bims-kracam Biomed News
on K-Ras in cancer metabolism
Issue of 2022‒08‒28
256 papers selected by
Yasmin Elkabani
Egyptian Foundation for Research and Community Development
  1. Nanocarriers: A Reliable Tool for the Delivery of Anticancer Drugs.
  2. Chitosan-Hyaluronic Acid Nanoparticles for Active Targeting in Cancer Therapy.
  3. Temperature-Ion-pH Triple Responsive Gellan Gum as In Situ Hydrogel for Long-Acting Cancer Treatment.
  4. Nanomedicines Targeting Metabolism in the Tumor Microenvironment.
  5. Receptor-Targeted Surface-Engineered Nanomaterials for Breast Cancer Imaging and Theranostic Applications.
  6. Enzyme-responsive nano-drug delivery system for combined antitumor therapy.
  7. Construction of magnetic drug delivery system and its potential application in tumor theranostics.
  8. Aptamer-functionalized Quercetin Thermosensitive Liposomes for Targeting Drug Delivery and Antitumor Therapy.
  9. Photoactive Herbal Compounds: A Green Approach to Photodynamic Therapy.
  10. Curcumin-Loaded Silica Nanoparticles: Applications in Infectious Disease and Food Industry.
  11. When Natural Compounds Meet Nanotechnology: Nature-Inspired Nanomedicines for Cancer Immunotherapy.
  12. Regulation of tumor metabolism by post translational modifications on metabolic enzymes.
  13. A Novel Diosgenin-Based Liposome Delivery System Combined with Doxorubicin for Liver Cancer Therapy.
  14. Recent Overview of Resveratrol's Beneficial Effects and Its Nano-Delivery Systems.
  15. Marine-Bioinspired Nanoparticles as Potential Drugs for Multiple Biological Roles.
  16. The Synergistic Effects of Curcumin and Chemotherapeutic Drugs in Inhibiting Metastatic, Invasive and Proliferative Pathways.
  17. A novel saponin liposomes based on the couplet medicines of Platycodon grandiflorum-Glycyrrhiza uralensis for targeting lung cancer.
  18. Nanoformulated bioactive compounds: A potential approach for cancer therapy.
  19. Saffron, Its Active Components, and Their Association with DNA and Histone Modification: A Narrative Review of Current Knowledge.
  20. Recent development in nanoencapsulation and delivery of natural bioactives through chitosan scaffolds for various biological applications.
  21. Curcumin-Based Nanoformulations: A Promising Adjuvant towards Cancer Treatment.
  22. Chitosan biguanide induced mitochondrial inhibition to amplify the efficacy of oxygen-sensitive tumor therapies.
  23. A Unifying Perspective in Blunting the Limited Oral Bioavailability of Curcumin: A Succinct Look.
  24. Diverse Metabolites and Pharmacological Effects from the Basidiomycetes Inonotus hispidus.
  25. Progress in Polymeric Micelles for Drug Delivery Applications.
  26. Herbal Ingredients in the Prevention of Breast Cancer: Comprehensive Review of Potential Molecular Targets and Role of Natural Products.
  27. Nanomedicine and versatile therapies for cancer treatment.
  28. MicroRNAs as Regulators of Cancer Cell Energy Metabolism.
  29. A spark to the powder keg: Microneedle-based antitumor nanomedicine targeting reactive oxygen species accumulation for chemodynamic/photothermal/chemotherapy.
  30. Melanin Nanoparticle-Actuated Redox-State Perturbation and Temporally Photoactivated Thermal Stress for Synergistic Tumor Therapy.
  31. Antioxidant Potential of Sea Cucumbers and Their Beneficial Effects on Human Health.
  32. Selected plant triterpenoids and their amide derivatives in cancer treatment: A review.
  33. Functionalized Magnetic Nanoparticles for Alternating Magnetic Field- or Near Infrared Light-Induced Cancer Therapies.
  34. Combinatorial Therapy of Letrozole- and Quercetin-Loaded Spanlastics for Enhanced Cytotoxicity against MCF-7 Breast Cancer Cells.
  35. Urolithins Modulate the Viability, Autophagy, Apoptosis, and Nephrin Turnover in Podocytes Exposed to High Glucose.
  36. Alginate as a Promising Biopolymer in Drug Delivery and Wound Healing: A Review of the State-of-the-Art.
  37. Sequentially Activatable Polypeptide Nanoparticles for Combinatory Photodynamic Chemotherapy of Breast Cancer.
  38. Stinging Nettle (Urtica dioica L.): Nutritional Composition, Bioactive Compounds, and Food Functional Properties.
  39. Application of Mesoporous Silica Nanoparticles in Cancer Therapy and Delivery of Repurposed Anthelmintics for Cancer Therapy.
  40. Apigenin in cancer therapy: From mechanism of action to nano-therapeutic agent.
  41. Albumin-Coated Framework Nucleic Acids as Bionic Delivery System for Triple-Negative Breast Cancer Therapy.
  42. Adapalene inhibits the growth of triple-negative breast cancer cells by S-phase arrest and potentiates the antitumor efficacy of GDC-0941.
  43. Disulfiram: A Food and Drug Administration-approved multifunctional role in synergistically drug delivery systems for tumor treatment.
  44. Synergistic anticancer effects of curcumin and crocin on human colorectal cancer cells.
  45. ROS triggered local delivery of stealth exosomes to tumors for enhanced chemo/photodynamic therapy.
  46. Liposomes as Multifunctional Nano-Carriers for Medicinal Natural Products.
  47. Nanoparticles-Based Strategies to Improve the Delivery of Therapeutic Small Interfering RNA in Precision Oncology.
  48. Gut Metabolites and Breast Cancer: The Continuum of Dysbiosis, Breast Cancer Risk, and Potential Breast Cancer Therapy.
  49. Carboxylated Graphene Oxide as a Nanocarrier for Drug Delivery of Quercetin as an Effective Anticancer Agent.
  50. Cauliflower bioactive compound sulforaphane inhibits breast cancer development by suppressing NF-κB /MMP-9 signaling pathway expression.
  51. Effects and Mechanisms of Curcumin for the Prevention and Management of Cancers: An Updated Review.
  52. Antitumor Activities of Aqueous Cinnamon Extract on 5637 Cell Line of Bladder Cancer through Glycolytic Pathway.
  53. Targeting Ferroptosis in Colorectal Cancer.
  54. Nano/Microcarriers in Drug Delivery: Moving the Timeline to Contemporary.
  55. High Drug-Loading Nanomedicines for Tumor Chemo-Photo Combination Therapy: Advances and Perspectives.
  56. Chemoprevention effect of the Mediterranean diet on colorectal cancer: Current studies and future prospects.
  57. The effect of magnesium alone or its combination with other supplements on the markers of inflammation, OS and metabolism in women with polycystic ovarian syndrome (PCOS): A systematic review.
  58. Vitamin D and curcumin-loaded PCL nanofibrous for engineering osteogenesis and immunomodulatory scaffold.
  59. Enhanced antitumor effect of icariin nanoparticles coated with iRGD functionalized erythrocyte membrane.
  60. Smart oral pH-responsive dual layer nano-hydrogel for dissolution enhancement and targeted delivery of naringenin using protein-polysaccharides complexation against colorectal cancer.
  61. A Review of Medicinal Plants of the Himalayas with Anti-Proliferative Activity for the Treatment of Various Cancers.
  62. Different mechanisms by which apigenin improves treatment of dermatological disorders Apigenin and its dermatological applications: A comprehensive review.
  63. Nanoformulations - Insights Towards Characterization Techniques.
  64. Application of Nanomicelles in Enhancing Bioavailability and Biological Efficacy of Bioactive Nutrients.
  65. Enhanced Delivery of Rose Bengal by Amino Acids Starvation and Exosomes Inhibition in Human Astrocytoma Cells to Potentiate Anticancer Photodynamic Therapy Effects.
  66. Plant-Derived Bioactive Compounds in Colorectal Cancer: Insights from Combined Regimens with Conventional Chemotherapy to Overcome Drug-Resistance.
  67. 5-ALA Is a Potent Lactate Dehydrogenase Inhibitor but Not a Substrate: Implications for Cell Glycolysis and New Avenues in 5-ALA-Mediated Anticancer Action.
  68. Mechanisms of natural products as potential antiepileptic drugs.
  69. Intestinal Absorption Study: Challenges and Absorption Enhancement Strategies in Improving Oral Drug Delivery.
  70. Tumor Selective Metabolic Reprogramming as a Prospective PD-L1 Depression Strategy to Reactivate Immunotherapy.
  71. Biofabrication of Silver Nanoparticles (AgNPs) Using Embelin for Effective Therapeutic Management of Lung Cancer.
  72. Novel Drug Delivery Systems as an Emerging Platform for Stomach Cancer Therapy.
  73. Mesona chinensis polysaccharide/zein nanoparticles to improve the bioaccesibility and in vitro bioactivities of curcumin.
  74. Beyond Formulation: Contributions of Nanotechnology for Translation of Anticancer Natural Products into New Drugs.
  75. Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases.
  76. Glutamine metabolism mediates sensitivity to respiratory complex II inhibition in acute myeloid leukemia.
  77. Injectable click-crosslinked hydrogel containing resveratrol to improve the therapeutic effect in triple negative breast cancer.
  78. Thymol has anticancer effects in U-87 human malignant glioblastoma cells.
  79. Porphyrin-Based Nanoparticles: A Promising Phototherapy Platform.
  80. Polyphenols and atherosclerosis: a critical review of clinical effects on LDL oxidation.
  81. New Advances in Biomedical Application of Polymeric Micelles.
  82. Nanoformulations of Plant-Derived Compounds as Emerging Therapeutic Approach for Colorectal Cancer.
  83. Inhibitory of active dual cancer targeting 5-Fluorouracil nanoparticles on liver cancer in vitro and in vivo.
  84. Hydrogel beads based on carboxymethyl cassava starch/alginate enriched with MgFe2O4 nanoparticles for controlling drug release.
  85. Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells.
  86. Research update on cell membrane camouflaged nanoparticles for cancer therapy.
  87. Bioactive Microbial Metabolites in Cancer Therapeutics: Mining, Repurposing, and Their Molecular Targets.
  88. Formulation, Characterization, and In Vitro/In Vivo Efficacy Studies of a Novel Liposomal Drug Delivery System of Amphiphilic Jaspine B for Treatment of Synovial Sarcoma.
  89. Spray drying encapsulation of essential oils; process efficiency, formulation strategies, and applications.
  90. An Updated Overview of Cyclodextrin-Based Drug Delivery Systems for Cancer Therapy.
  91. Polyamine-Based Nanostructures Share Polyamine Transport Mechanisms with Native Polyamines and Their Analogues: Significance for Polyamine-Targeted Therapy.
  92. In vitro antioxidant, anti-inflammatory, antimicrobial, and antidiabetic activities of synthesized chitosan-loaded p-coumaric acid nanoparticles.
  93. Commonalities in Metabolic Reprogramming between Tobacco Use and Oral Cancer.
  94. Recent progresses in the delivery of β-carotene: From nano/microencapsulation to bioaccessibility.
  95. Association of Indocyanine Green with Chitosan Oleate Coated PLGA Nanoparticles for Photodynamic Therapy.
  96. Directing ricin-based immunotoxins with targeting affibodies and KDEL signal peptide to cancer cells effectively induces apoptosis and tumor suppression.
  97. Nanotechnology-Based Combinatorial Anti-Glioblastoma Therapies: Moving from Terminal to Treatable.
  98. Mesoporous Polydopamine-Based Nanovehicles as a Versatile Drug Loading Platform to Enable Tumor-Sufficient Synergistic Therapy.
  99. Metabolic rewiring directs melanoma immunology.
  100. Levels of Vitamin D and Expression of the Vitamin D Receptor in Relation to Breast Cancer Risk and Survival.
  101. Antibacterial and wound healing applications of curcumin in micro and nano-scaffolds based on chitosan, cellulose, and collagen.
  102. Grafting of Natural Polymers and Gums for Drug Delivery Applications: A Perspective Review.
  103. Vanillic acid attenuates cell proliferation, xenobiotic enzyme activity, and the status of pulmonary mitochondrial enzymes in lung carcinoma.
  104. A self-activating nanoized vascular disrupting agent for selective anti-tumor therapy.
  105. Hybrid nanocarriers for neurological disorders: Diagnostic & therapeutic Approach.
  106. Fasting renders immunotherapy effective against low-immunogenic breast cancer while reducing side effects.
  107. Effect of nanovesicular surface-functionalization via chitosan and/or PEGylation on cytotoxicity of tamoxifen in induced-breast cancer model.
  108. KRAS-Mutant Non-Small-Cell Lung Cancer: From Past Efforts to Future Challenges.
  109. Resveratrol from Dietary Supplement to a Drug Candidate: An Assessment of Potential.
  110. Targeted cancer phototherapy using phthalocyanine-anticancer drug conjugates.
  111. Functional Nanoparticles for Enhanced Cancer Therapy.
  112. Research progress of bone-targeted drug delivery system on metastatic bone tumors.
  113. The journey of resveratrol from vineyards to clinics.
  114. Dual-Modulated Release of a Cytotoxic Photosensitizer Using Photogenerated Reactive Oxygen Species and Glutathione.
  115. Understanding the Mechanism of Action of Melatonin, Which Induces ROS Production in Cancer Cells.
  116. Antioxidant Activity of Fucoidan Modified with Gallic Acid Using the Redox Method.
  117. Diabetic ferroptosis and pancreatic cancer: Foe or Friend?
  118. Metastatic triple negative breast cancer adapts its metabolism to destination tissues while retaining key metabolic signatures.
  119. Multifunctional roles and pharmacological potential of β-sitosterol: Emerging evidence toward clinical applications.
  120. Nanomedicines for Overcoming Cancer Drug Resistance.
  121. Anti-Proliferative Potential of Quercetin Loaded Polymeric Mixed Micelles on Rat C6 and Human U87MG Glioma Cells.
  122. Vitamin D-Mediated Regulation of Intestinal Calcium Absorption.
  123. A Comprehensive Review on the Anti-Cancer Effects of Oleuropein.
  124. Anticancer and Antioxidant Activities in Ganoderma lucidum Wild Mushrooms in Poland, as Well as Their Phenolic and Triterpenoid Compounds.
  125. Peppermint essential oil: its phytochemistry, biological activity, pharmacological effect and application.
  126. The clinical impact of an extra virgin olive oil enriched mediterranean diet on metabolic syndrome: Lights and shadows of a nutraceutical approach.
  127. Mechanistic Insights into the Pharmacological Significance of Silymarin.
  128. The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions.
  129. Hazelnut extract-loaded nanostructured lipid carriers and evaluation of their antioxidant properties.
  130. Pyruvate as a Potential Beneficial Anion in Resuscitation Fluids.
  131. Silk sericin stabilized proanthocyanidins for synergetic alleviation of ulcerative colitis.
  132. Multimodal targeting of glioma with functionalized nanoparticles.
  133. The Genus Broussonetia: An Updated Review of Phytochemistry, Pharmacology and Applications.
  134. Evaluation of phenolic composition, antioxidant and cytotoxic activity of aronia melanocarpa leaf extracts.
  135. The current state of the art and future trends in RAS-targeted cancer therapies.
  136. Bioactive Effects of Curcumin in Human Immunodeficiency Virus Infection Along with the Most Effective Isolation Techniques and Type of Nanoformulations.
  137. Redox-Responsive Polymersomes as Smart Doxorubicin Delivery Systems.
  138. Protein-Delivering Nanocomplexes with Fenton Reaction-Triggered Cargo Release to Boost Cancer Immunotherapy.
  139. Cathepsin K: A Versatile Potential Biomarker and Therapeutic Target for Various Cancers.
  140. Understanding lactate sensing and signalling.
  141. An overview of vitamins as epidrugs for colorectal cancer prevention.
  142. Nanoparticles: attractive tools to treat colorectal cancer.
  143. The Current State of the Art in PARP Inhibitor-Based Delivery Nanosystems.
  144. Cruciferous vegetables as a treasure of functional foods bioactive compounds: Targeting p53 family in gastrointestinal tract and associated cancers.
  145. Fabrication, Characterization, and Antimicrobial Activity of Carvacrol-Loaded Zein Nanoparticles Using the pH-Driven Method.
  146. Fabrication and Preliminary In Vitro Evaluation of 3D-Printed Alginate Films with Cannabidiol (CBD) and Cannabigerol (CBG) Nanoparticles for Potential Wound-Healing Applications.
  147. Nutritional aspects in chronic non-cancer pain: A systematic review.
  148. Metabolic adaption of cancer cells toward autophagy: Is there a role for ER-phagy?
  149. Pharmacological Properties and Molecular Targets of Alisol Triterpenoids from Alismatis Rhizoma.
  150. Novel Fusidic Acid Cream Containing Metal Ions and Natural Products against Multidrug-Resistant Bacteria.
  151. Integration of cyclodextrins and associated toxicities: A roadmap for high quality biomedical applications.
  152. Encapsulation of miRNA and siRNA into Nanomaterials for Cancer Therapeutics.
  153. A Comparative Study of Quercetin-Loaded Nanocochleates and Liposomes: Formulation, Characterization, Assessment of Degradation and In Vitro Anticancer Potential.
  154. Fabrication of TPGS-Grafted Polyamidoamine Dendrimer for Enhanced Piperine Brain Delivery and Pharmacokinetics.
  155. Mini-Review on the Enzymatic Lipophilization of Phenolics Present in Plant Extracts with the Special Emphasis on Anthocyanins.
  156. Healthy and unhealthy plant-based diets in relation to the incidence of colorectal cancer overall and by molecular subtypes.
  157. Cratoxylumxanthone C, a natural xanthone, inhibits lung cancer proliferation and metastasis by regulating STAT3 and FAK signal pathways.
  158. The Nutraceuticals as Modern Key to Achieve Erythrocyte Oxidative Stress Fighting in Osteoarthritis.
  159. The effects of vegetarian diets on bone health: A literature review.
  160. Dapagliflozin Ameliorates Renal Tubular Ferroptosis in Diabetes via SLC40A1 Stabilization.
  161. Recent Advances in Nano-Formulations for Skin Wound Repair Applications.
  162. Research progress on classical traditional chinese medicine formula xiaoyaosan in the treatment of depression.
  163. Dietary Fructose and Fructose-Induced Pathologies.
  164. Evaluation of quaternization effect on chitosan-HAP composite for bone tissue engineering application.
  165. From Iron Metabolism to Ferroptosis: Pathologic Changes in Coronary Heart Disease.
  166. Increased PDT Efficacy When Associated with Nitroglycerin: A Study on Retinoblastoma Xenografted on Mice.
  167. Preparing simvastatin nanoparticles by a combination of pH-sensitive and timed-release approaches for the potential treatment of ulcerative colitis.
  168. The role of ferroptosis in esophageal cancer.
  169. Preparation and pharmacological effects of minor ginsenoside nanoparticles: a review.
  170. Exosomes: Small Vesicles with Important Roles in the Development, Metastasis and Treatment of Breast Cancer.
  171. Aptamer-Modified Erythrocyte Membrane-Coated pH-Sensitive Nanoparticles for c-Met-Targeted Therapy of Glioblastoma Multiforme.
  172. Combination Therapy Comprising Paclitaxel and 5-Fluorouracil by Using Folic Acid Functionalized Bovine Milk Exosomes Improves the Therapeutic Efficacy against Breast Cancer.
  173. The HbA1c and blood glucose response to selenium-rich polysaccharide from Fomes fomentarius loaded solid lipid nanoparticles as a potential antidiabetic agent in rats.
  174. Effect of Modified Chinese Diet Is Comparable to Antihypertensives.
  175. Strategies and Progresses for Enhancing Targeted Antibiotic Delivery.
  176. Recent advances in self-assembly behaviors of prolamins and their applications as functional delivery vehicles.
  177. An Insight on Novel Approaches & Perspectives for Gastro-Retentive Drug Delivery Systems.
  178. Leaves, seeds and exocarp of Ginkgo biloba L. (Ginkgoaceae): A Comprehensive Review of Traditional Uses, phytochemistry, pharmacology, resource utilization and toxicity.
  179. Functionalized bosutinib liposomes for target specific delivery in management of estrogen-positive cancer.
  180. Recent Advances in Fluorescent Methods for Polyamine Detection and the Polyamine Suppressing Strategy in Tumor Treatment.
  181. Ultrasonic Microbubble Cavitation Enhanced Tissue Permeability and Drug Diffusion in Solid Tumor Therapy.
  182. Micro-Encapsulation of Phytochemicals in Passion Fruit Peel Waste Generated on an Organic Farm: Effect of Carriers on the Quality of Encapsulated Powders and Potential for Value-Addition.
  183. Medical cannabis and cannabidiol: A new harvest for Malawi.
  184. Use of Saponinosomes from Ziziphus spina-christi as Anticancer Drug Carriers.
  185. Dual-source powered nanomotor with integrated functions for cancer photo-theranostics.
  186. Investigation of the Effects of the Endogenous Cannabinoid Anandamide on Luminal A Breast Cancer Cell Line MCF-7.
  187. Post-Diagnosis Vitamin D Supplement Use and Survival among Cancer Patients: A Meta-Analysis.
  188. Fermented Soy Products and Their Potential Health Benefits: A Review.
  189. Cancer Metabolism and Resistance to Cell Death: Novel Therapeutic Perspectives.
  190. Recent Advances in Nanoparticles-Based Platforms Targeting the PD-1/PD-L1 Pathway for Cancer Treatment.
  191. Targeting HIF-1α by Natural and Synthetic Compounds: A Promising Approach for Anti-Cancer Therapeutics Development.
  192. Melatonin Sensitizes OVCAR-3 Cells to Cisplatin through Suppression of PI3K/Akt Pathway.
  193. Metabolic heterogeneity protects metastatic mucosal melanomas cells from ferroptosis.
  194. Ferroptosis and Its Multifaceted Role in Cancer: Mechanisms and Therapeutic Approach.
  195. Tumor microenvironment-regulating nanomedicine design to fight multi-drug resistant tumors.
  196. Oxidative Stress Amplifying Polyprodrug Micelles as Drug Carriers for Combination Anticancer Therapy.
  197. Hypertension of liver-yang hyperactivity syndrome induced by a high salt diet by altering components of the gut microbiota associated with the glutamate/GABA-glutamine cycle.
  198. Punicalagin-Loaded Alginate/Chitosan-Gallol Hydrogels for Efficient Wound Repair and Hemostasis.
  199. Herb Polysaccharide-Based Drug Delivery System: Fabrication, Properties, and Applications for Immunotherapy.
  200. Dietary Supplement Use among Older Cancer Survivors: Socio-Demographic Associations, Supplement Types, Reasons for Use, and Cost.
  201. Preparation and characterization of chloridazon-loaded alginate/chitosan nanocapsules.
  202. Glycyrrhetinic acid proliposomes mediated by mannosylated ligand: Preparation, physicochemical characterization, environmental stability and bioactivity evaluation.
  203. The toxicity mechanism of glabridin in prostate cancer cells is involved in reactive oxygen species-dependent PI3K/Akt pathway: Integrated utilization of bioinformatic analysis and in vitro test validation.
  204. Cannabidiol attenuates hypersensitivity and oxidative stress after traumatic spinal cord injury in rats.
  205. Virgin coconut oil: A comprehensive review of antioxidant activity and mechanisms contributed by phenolic compounds.
  206. Antioxidant and pro-oxidant phytochemicals in ultrasound and microwave assisted extracts from hop cones: a statistical modelling approach.
  207. Bioactive polysaccharides from microalgae: A close look at the biomedical applications.
  208. Hybrid laser activated phycocyanin/capecitabine treatment of cancerous MCF7 cells.
  209. The Role of Myrrh Metabolites in Cancer, Inflammation, and Wound Healing: Prospects for a Multi-Targeted Drug Therapy.
  210. A comprehensive review on ethnopharmacological, phytochemical, pharmacological and toxicological evaluation, and quality control of Pinellia ternata (Thunb.) Breit.
  211. Lysionotin Induces Ferroptosis to Suppress Development of Colorectal Cancer via Promoting Nrf2 Degradation.
  212. Combined Effects of Tanshinone IIA and an Autophagy Inhibitor on the Apoptosis of Leukemia Cells via p53, Apoptosis-Related Proteins and Oxidative Stress Pathways.
  213. Nootropics as Cognitive Enhancers: Types, Dosage and Side Effects of Smart Drugs.
  214. Microalgae Photo-Protectants and Related Bio-Carriers Loaded with Bioactive Entities for Skin Applications-An Insight of Microalgae Biotechnology.
  215. Bisphenols A and S Alter the Bioenergetics and Behaviours of Normal Urothelial and Bladder Cancer Cells.
  216. Chitosan Grafted Poly (Ethylene Glycol) Methyl Ether Acrylate Particulate Hydrogels for Drug Delivery Applications.
  217. Functionalized Platinum Nanoparticles with Biomedical Applications.
  218. Anticancer potential and toxicity of the genus Handroanthus Mattos (Bignoniaceae): A systematic review.
  219. The effect of statin therapy in combination with ezetimibe on circulating C-reactive protein levels: a systematic review and meta-analysis of randomized controlled trials.
  220. Dietary Polyphenols Alleviate Autoimmune Liver Disease by Mediating the Intestinal Microenvironment: Challenges and Hopes.
  221. Characterization of anti-proliferative and anti-oxidant effects of nano-sized vesicles from Brassica oleracea L. (Broccoli).
  222. Ethnomedicinal Use, Phytochemistry, and Other Potential Application of Aquatic and Semiaquatic Medicinal Plants.
  223. Heteronemin and Tetrac Induce Anti-Proliferation by Blocking EGFR-Mediated Signaling in Colorectal Cancer Cells.
  224. A β-Sitosterol Encapsulated Biocompatible Alginate/Chitosan Polymer Nanocomposite for the Treatment of Breast Cancer.
  225. Bio-polymeric transferrin-targeted temozolomide nanoparticles in gel for synergistic post-surgical GBM therapy.
  226. The role of autophagy in the treatment of colon cancer by chlorin e6 photodynamic therapy combined with Oxaliplatin.
  227. Mitochondria dysfunction in circulating tumor cells.
  228. Effect of Thermal Treatment on the Physicochemical, Ultrastructural, and Antioxidant Characteristics of Euryale ferox Seeds and Flour.
  229. Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice.
  230. Chitosan-Based Scaffolds for Facilitated Endogenous Bone Re-Generation.
  231. Traditional Use, Phytochemical Profiles and Pharmacological Properties of Artemisia Genus from Central Asia.
  232. Modulatory role of dietary curcumin and resveratrol on growth performance, serum immunity responses, mucus enzymes activity, antioxidant capacity and serum and mucus biochemicals in the common carp, Cyprinus carpio exposed to abamectin.
  233. Oral administration of sodium bicarbonate can enhance the therapeutic outcome of Doxil® via neutralizing the acidic tumor microenvironment.
  234. Warburg-like metabolic transformation underlies neuronal degeneration in sporadic Alzheimer's disease.
  235. Rational surface modification of gadolinium borate nanoparticles enhancing colloidal stability in physiological media for potential neutron capture therapy and magnetic resonance imaging.
  236. Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency.
  237. Acriflavine, an Acridine Derivative for Biomedical Application: Current State of the Art.
  238. Anti-migratory effect of curcumin on A-549 lung cancer cells via epigenetic reprogramming of RECK/ matrix metalloproteinase axis.
  239. Recent Advances in Functionalized Nanoparticles in Cancer Theranostics.
  240. Polyhydroxyalkanoate Decelerates the Release of Paclitaxel from Poly(lactic-co-glycolic acid) Nanoparticles.
  241. Propolis: An update on its chemistry and pharmacological applications.
  242. Experimental Evidence for the Anti-Metastatic Action of Ginsenoside Rg3: A Systematic Review.
  243. Laser-induced breakdown spectroscopy-guided synergistic phototherapy: A theranostic platform mediated by a single laser wavelength.
  244. Role of Vitamin K in Selected Malignant Neoplasms in Women.
  245. Intracranial In Situ Thermosensitive Hydrogel Delivery of Temozolomide Accomplished by PLGA-PEG-PLGA Triblock Copolymer Blending for GBM Treatment.
  246. Promising effects of emoxypine and its succinate derivative in the management of various diseases-with insights on recent patent applications.
  247. The Potential of Pharmaceutical Hydrogels in the Formulation of Topical Administration Hormone Drugs.
  248. Structural Modifications and Strategies for Native Starch for Applications in Advanced Drug Delivery.
  249. Extracts of Common Vegetables Inhibit the Growth of Ovary Cancer Cells.
  250. Dynamic ginsenoside-sheltered nanocatalysts for safe ferroptosis-apoptosis combined therapy.
  251. β-Artemether and Lumefantrine Dual Drug Loaded Lipid Nanoparticles: Physicochemical Characterization, Pharmacokinetic Evaluation and Biodistribution Study.
  252. Optimization of ultrasound-assisted extraction of bioactive compounds from coffee pulp using propylene glycol as a solvent and their antioxidant activities.
  253. Antioxidant Effect of Coenzyme Q10 in the Prevention of Oxidative Stress in Arsenic-Treated CHO-K1 Cells and Possible Participation of Zinc as a Pro-Oxidant Agent.
  254. Autophagy-nutrient sensing pathways in diabetic complications.
  255. Phytochemical Composition and Cytoprotective Properties of the Endemic Sideritis sipylea Boiss Greek Species: A Valorization Study.
  256. Antitumor applications of polyphenol-conjugated turnip mosaic virus-derived nanoparticles.
  1. Pharmaceutics. 2022 Jul 28. pii: 1566. [Epub ahead of print]14(8):
    Nanocarriers: A Reliable Tool for the Delivery of Anticancer Drugs.
    Hussein Sabit, Mohamed Abdel-Hakeem, Tahsin Shoala, Shaimaa Abdel-Ghany, Mokhtar Mamdouh Abdel-Latif, Jawaher Almulhim, Mohamed Mansy.
      Nanomedicines have gained popularity due to their potential therapeutic applications, especially cancer treatment. Targeted nanoparticles can deliver drugs directly to cancer cells and enable prolonged drug release, reducing off-target toxicity and increasing therapeutic efficacy. However, translating nanomedicines from preclinical to clinical settings has been difficult. Rapid advancements in nanotechnology promise to enhance cancer therapies. Nanomedicine offers advanced targeting and multifunctionality. Nanoparticles (NPs) have several uses nowadays. They have been studied as drug transporters, tumor gene delivery agents, and imaging contrast agents. Nanomaterials based on organic, inorganic, lipid, or glycan substances and synthetic polymers have been used to enhance cancer therapies. This review focuses on polymeric nanoparticle delivery strategies for anticancer nanomedicines.
    Keywords:  anticancer; drug delivery; nanomedicine; polymer nanocarriers
    DOI:  https://doi.org/10.3390/pharmaceutics14081566
  2. Polymers (Basel). 2022 Aug 20. pii: 3410. [Epub ahead of print]14(16):
    Chitosan-Hyaluronic Acid Nanoparticles for Active Targeting in Cancer Therapy.
    Lisa Efriani Puluhulawa, I Made Joni, Khaled M Elamin, Ahmed Fouad Abdelwahab Mohammed, Muchtaridi Muchtaridi, Nasrul Wathoni.
      Cancer is the most common cause of death worldwide; therefore, there is a need to discover novel treatment modalities to combat it. One of the cancer treatments is nanoparticle technology. Currently, nanoparticles have been modified to have desirable pharmacological effects by using chemical ligands that bind with their specific receptors on the surface of malignant cells. Chemical grafting of chitosan nanoparticles with hyaluronic acid as a targeted ligand can become an attractive alternative for active targeting. Hence, these nanoparticles can control drug release with pH- responsive stimuli, and high selectivity of hyaluronic acid to CD44 receptors makes these nanoparticles accumulate more inside cells that overexpress these receptors (cancer cells). In this context, we discuss the benefits and recent findings of developing and utilizing chitosan-hyaluronic acid nanoparticles against distinct forms of cancer malignancy. From here we know that chitosan-hyaluronic acid nanoparticles (CHA-Np) can produce a nanoparticle system with good characteristics, effectiveness, and a good active targeting on various types of cancer cells. Therefore, this system is a good candidate for targeted drug delivery for cancer therapy, anticipating that CHA-Np could be further developed for various cancer therapy applications.
    Keywords:  cancer; chitosan; hyaluronic acid; nanoparticle; targeted delivery
    DOI:  https://doi.org/10.3390/polym14163410
  3. Gels. 2022 Aug 15. pii: 508. [Epub ahead of print]8(8):
    Temperature-Ion-pH Triple Responsive Gellan Gum as In Situ Hydrogel for Long-Acting Cancer Treatment.
    Shuwen Zhou, Xinmeng Zheng, Ke Yi, Xuancheng Du, Cheng Wang, Pengfei Cui, Pengju Jiang, Xinye Ni, Lin Qiu, Jianhao Wang.
      BACKGROUND: Promising cancer chemotherapy requires the development of suitable drug delivery systems (DDSs). Previous research has indicated that a hydrogel is a powerful DDS for tumor therapy and holds great potential to offer a feasible method for cancer management.METHODS: In this study, glutathione-gellan gum conjugate (GSH-GG) was synthesized through chemical reaction. Doxorubicin hydrochloride (DOX) was loaded into GSH-GG to accomplish DOX-loaded GSH-GG. The properties, injectability, drug release, and in vitro and in vivo anticancer effects of DOX-loaded GSH-GG were tested.
    RESULTS: DOX-loaded GSH-GG showed a temperature-ion dual responsive gelling property with good viscosity, strength, and injectability at an optimized gel concentration of 1.5%. In addition, lower drug release was found under acidic conditions, offering beneficial long-acting drug release in the tumor microenvironment. DOX-loaded GSH-GG presented selective action by exerting substantially higher cytotoxicity on cancer cells (4T1) than on normal epithelial cells (L929), signifying the potential of complete inhibition of tumor progression, without affecting the health quality of the subjects.
    CONCLUSIONS: GSH-GG can be applied as a responsive gelling material for delivering DOX for promising cancer therapy.
    Keywords:  cancer; doxorubicin; gellan gum; hydrogel; responsive
    DOI:  https://doi.org/10.3390/gels8080508
  4. Front Bioeng Biotechnol. 2022 ;10 943906
    Nanomedicines Targeting Metabolism in the Tumor Microenvironment.
    Mengdi Ren, Xiaoqiang Zheng, Huan Gao, Aimin Jiang, Yu Yao, Wangxiao He.
      Cancer cells reprogram their metabolism to meet their growing demand for bioenergy and biosynthesis. The metabolic profile of cancer cells usually includes dysregulation of main nutritional metabolic pathways and the production of metabolites, which leads to a tumor microenvironment (TME) having the characteristics of acidity, hypoxic, and/or nutrient depletion. Therapies targeting metabolism have become an active and revolutionary research topic for anti-cancer drug development. The differential metabolic vulnerabilities between tumor cells and other cells within TME provide nanotechnology a therapeutic window of anti-cancer. In this review, we present the metabolic characteristics of intrinsic cancer cells and TME and summarize representative strategies of nanoparticles in metabolism-regulating anti-cancer therapy. Then, we put forward the challenges and opportunities of using nanoparticles in this emerging field.
    Keywords:  cancer treatment; metabolic reprograming; metabolism; nanomedicine; tumor microenvironment
    DOI:  https://doi.org/10.3389/fbioe.2022.943906
  5. Crit Rev Ther Drug Carrier Syst. 2022 ;39(6): 1-44
    Receptor-Targeted Surface-Engineered Nanomaterials for Breast Cancer Imaging and Theranostic Applications.
    Javed Ahmad, Md Rizwanullah, Teeja Suthar, Hassan A Albarqi, Mohammad Zaki Ahmad, Parameswara Rao Vuddanda, Mohammad Ahmed Khan, Keerti Jain.
      Breast cancer is one of the most frequently diagnosed cancers in women and the major cause of worldwide cancer-related deaths among women. Various treatment strategies including conventional chemotherapy, immunotherapy, gene therapy, gene silencing and deliberately engineered nanomaterials for receptor mediated targeted delivery of anticancer drugs, antibodies, and small-molecule inhibitors, etc are being investigated by scientists to combat breast cancer. Smartly designed/fabricated nanomaterials are being explored to target breast cancer through enhanced permeation and retention effect; and also, being conjugated with suitable ligand for receptor-mediated endocytosis to target breast cancer for diagnostic, and theranostic applications. These receptor-targeted nanomedicines have shown efficacy to target specific tumor tissue/cells abstaining the healthy tissues/cells from cytotoxic effect of anticancer drug molecules. In the last few decades, theranostic nanomedicines have gained much attention among other nanoparticle systems due to their unique ability to deliver chemotherapeutic as well as diagnostic agents, simultaneously. Theranostic nanomaterials are emerging as novel paradigm with ability for concurrent delivery of imaging (with contrasting agents), targeting (with biomarkers), and anticancer therapeutics with one delivery system (as cancer theranostics) and can transpire as promising strategy to overcome various hurdles for effective management of breast cancer including its most aggressive form, triple-negative breast cancer.
    DOI:  https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2022040686
  6. Int J Biol Macromol. 2022 Aug 18. pii: S0141-8130(22)01826-8. [Epub ahead of print]
    Enzyme-responsive nano-drug delivery system for combined antitumor therapy.
    Fangyuan Guo, Yunlong Jiao, Yinzhou Du, Shuai Luo, Weiyong Hong, Qiafan Fu, Aiqin Li, Guoping Wang, Gensheng Yang.
      Efficient drug loading, tumor targeting, intratumoral penetration, and cellular uptake are the main factors affecting the effectiveness of drug delivery systems in oncotherapy. Based on the tumor microenvironment, we proposed to develop Curcumin (Cur)-loaded matrix metalloproteinase (MMP)-responsive nanoparticles (Cur-P-NPs) by static electricity, to enhance tumor targeting, cellular uptake, and drug loading efficiency. These nanoparticles combine the properties of both PEG-peptides (cleaved peptide + penetrating peptide) and star-shaped polyester (DPE-PCL) nanoparticles. Cur-P-NPs displayed good entrapment efficiency, drug loading and biocompatibility. Additionally, they showed an enhanced release rate, cellular uptake, and anti-proliferative activity by activating peptides under the simulated tumor microenvironment. Furthermore, intraperitoneal injection of losartan (LST) successfully enhanced intratumoral drug penetration by collagen I degradation. In vivo studies based on the systematic administration of the synergistic LST + Cur-P-NPs combination to mice confirmed that combined antitumor therapy with LST and Cur-P-NPs could further improve intratumor distribution, enhance anticancer efficacy, and reduce the toxicity and side effects. Therefore, LST + Cur-P-NPs represent a new and efficient system for clinical oncotherapy.
    Keywords:  Combined antitumor therapy; Curcumin-loaded MMP-responsive nanoparticles; Losartan; PEG-peptides; Star-shaped polyester nanoparticles; Tumor targeting
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.08.123
  7. Biomed Pharmacother. 2022 Aug 22. pii: S0753-3322(22)00934-9. [Epub ahead of print]154 113545
    Construction of magnetic drug delivery system and its potential application in tumor theranostics.
    Mingrui Jiang, Qianqian Liu, Yu Zhang, Huinan Wang, Jingqiu Zhang, Mengyu Chen, Zhuzhu Yue, Zhicheng Wang, Xiaotong Wei, Shuanghui Shi, Menglin Wang, Yanglong Hou, Zhiyi Wang, Fugeng Sheng, Ning Tian, Yingzi Wang.
      Magnetic nanoparticles(NPs) are characterized by a rich variety of properties. Because of their excellent physical and chemical properties, they have come to the fore in biomedicine and other fields. The magnetic NPs were extensively studied in magnetic separation of cells, targeted drug delivery, tumor hyperthermia, chemo-photothermal therapy, magnetic resonance imaging (MRI) and other biomedical fields. Magnetic NPs are increasingly used in magnetic resonance imaging (MRI) based on their inherent magnetic targeting, superparamagnetic enzyme-like catalytic properties and nanoscale size. Poly(lactic-co-glycolic acid) (PLGA) is a promising biodegradable material approved by FDA and EU for drug delivery. Currently, PLGA-based magnetic nano-drug delivery systems have attracted the attention of researchers. Herein, we achieved the effective encapsulation of sized-controlled polyethylene glycol-3,4-dihydroxy benzyl-amine-coated superparamagnetic iron oxide nanoparticles (SPIO NPs) and euphorbiasteroid into PLGA nanospheres via a modified multiple emulsion solvent evaporation method (W1/O2/W2). NPs with narrow size distribution and acceptable magnetic properties were developed that are very useful for applications involving cancer therapy and MRI. Furthermore, SPIO-PLGA NPs enhanced the MRI T2 relaxation properties of tumor sites.The prepared SPIO NPs and magnetic PLGA nanospheres can be promising magnetic drug delivery systems for tumor theranostics. This study has successfully constructed a tumor-targeting and magnetic-targeting smart nanocarrier with enhanced permeability and retention, multimodal anti-cancer therapeutics and biodegradability, which could be a hopeful candidate for anti-tumor therapy in the future.
    Keywords:  Active targeting; Cancer; MRI; Magnetic targeting; Superparamagnetic iron oxide nanoparticles; Theranostics
    DOI:  https://doi.org/10.1016/j.biopha.2022.113545
  8. Biomed Mater. 2022 Aug 24.
    Aptamer-functionalized Quercetin Thermosensitive Liposomes for Targeting Drug Delivery and Antitumor Therapy.
    Jian Li, Yanting Gao, Shihe Liu, Jiahui Cai, Qing Zhang, Kun Li, Zhiwei Liu, Ming Shi, Jidong Wang, Hongxia Cui.
      Chemo-thermotherapy, as a promising cancer combination therapy strategy, has attracted widespread attention. In this study, a novel aptamer functionalized thermosensitive liposome encapsulating hydrophobic drug quercetin was fabricated as an efficient drug delivery system. This aptamer-functionalized quercetin thermosensitive liposomes (AQTSL) combined the merits of high-loading yield, sustained drug release, long-term circulation in the body of PEGylated liposomes, passive targeting provided by 100-200 nm nanoparticles, active targeting and improved internalization effects offered by AS1411 aptamer, and temperature-responsive of quercetin release. In addition, AQTSL tail vein injection combined with 42℃ water bath heating on tumor site (AQTSL+42℃)treatment inhibited the tumor growth significantly compared with the normal saline administration (p<0.01), and the inhibition rate reached 75%. Furthermore, AQTSL+42℃ treatment also slowed down the tumor growth significantly compared with QTSL combined with 42℃ administration (p<0.05), confirming that AS1411 decoration on QTSL increased the active targeting and internalization effects of the drug delivery system, and AS1411 aptamer itself might also contribute to the tumor inhibition. These data indicate that AQTSL is a potential carrier candidate for different hydrophobic drugs and tumor targeting delivery, and this kind of targeted drug delivery system combined with temperature responsive drug release mode is expected to achieve an ideal tumor therapy effect.
    Keywords:  AS1411 aptamer; quercetin; thermosensitive liposomes; thermotherapy; tumor therapy
    DOI:  https://doi.org/10.1088/1748-605X/ac8c75
  9. Molecules. 2022 Aug 10. pii: 5084. [Epub ahead of print]27(16):
    Photoactive Herbal Compounds: A Green Approach to Photodynamic Therapy.
    Cheruthazhakkat Sulaiman, Blassan P George, Indira Balachandran, Heidi Abrahamse.
      Photodynamic therapy (PDT) is a minimally invasive, alternative, and promising treatment for various diseases, including cancer, actinic keratosis, Bowen's disease, macular degeneration, and atherosclerotic plaques. PDT involves three different components, photosensitizers (PS), molecular oxygen, and light. The photoactivation of administered PSs using a specific wavelength of light in the presence of molecular oxygen leads to the generation of reactive oxygen species that leads to tumour cell death. Photosensitizing potentials of many commercially available compounds have been reported earlier. However, the possibilities of PDT using herbal medicines, which contain many photosensitizing phytochemicals, are not much explored. Medicinal plants with complex phytochemical compound mixtures have the benefit over single compounds or molecules in the treatment of many diseases with the benefit of low or reduced toxic side effects. This review emphasizes the role of various herbal medicines either alone or in combination to enhance the therapeutic outcome of photodynamic therapy.
    Keywords:  herbal medicine; natural products; photodynamic therapy; photosensitizers; phytochemicals; plants
    DOI:  https://doi.org/10.3390/molecules27165084
  10. Nanomaterials (Basel). 2022 Aug 18. pii: 2848. [Epub ahead of print]12(16):
    Curcumin-Loaded Silica Nanoparticles: Applications in Infectious Disease and Food Industry.
    Solmaz Maleki Dizaj, Simin Sharifi, Fatemeh Tavakoli, Yaseen Hussain, Haleh Forouhandeh, Seyed Mahdi Hosseiniyan Khatibi, Mohammad Yousef Memar, Mina Yekani, Haroon Khan, Khang Wen Goh, Long Chiau Ming.
      Curcumin has multiple properties that are used to cure different diseases such as cancer, infections, inflammatory, arthritic disease, etc. Despite having many effects, the inherent physicochemical properties-such as poor water solubility, chemical instability, low bioavailability, photodegradation, fast metabolism, and short half-life-of curcumin's derivatives have limited its medical importance. Recently, unprecedented advances in biomedical nanotechnology have led to the development of nanomaterial-based drug delivery systems in the treatment of diseases and diagnostic goals that simultaneously enhance therapeutic outcomes and avoid side effects. Mesoporous silica nanoparticles (MSNs) are promising drug delivery systems for more effective and safer treatment of several diseases, such as infections, cancers, and osteoporosis. Achieving a high drug loading in MSNs is critical to the success of this type of treatment. Their notable inherent properties-such as adjustable size and porosity, high pore volume, large surface area, functionality of versatile surfaces, as well as biocompatibility-have prompted extraordinary research on MSNs as multi-purpose delivery platforms. In this review, we focused on curcumin-loaded silica nanoparticles and their effects on the diagnosis and treatment of infections as well as their use in food packaging.
    Keywords:  bacteria; drug delivery; food packaging; infections; mesoporous silica nanoparticles; phytochemicals
    DOI:  https://doi.org/10.3390/nano12162848
  11. Pharmaceutics. 2022 Jul 30. pii: 1589. [Epub ahead of print]14(8):
    When Natural Compounds Meet Nanotechnology: Nature-Inspired Nanomedicines for Cancer Immunotherapy.
    Linna Yu, Yi Jin, Mingjie Song, Yu Zhao, Huaqing Zhang.
      Recent significant strides of natural compounds in immunomodulation have highlighted their great potential against cancer. Despite many attempts being made for cancer immunotherapy, the biomedical application of natural compounds encounters a bottleneck because of their unclear mechanisms, low solubility and bioavailability, and limited efficacy. Herein, we summarize the immune regulatory mechanisms of different natural compounds at each step of the cancer-immunity cycle and highlight their anti-tumor potential and current limitations. We then propose and present various drug delivery strategies based on nanotechnology, including traditional nanoparticles (NPs)-based delivery strategies (lipid-based NPs, micelles, and polysaccharide/peptide/protein-based NPs) and novel delivery strategies (cell-derived NPs and carrier-free NPs), thus providing solutions to break through existing bottlenecks. Furthermore, representative applications of nature-inspired nanomedicines are also emphasized in detail with the advantages and disadvantages discussed. Finally, the challenges and prospects of natural compounds for cancer immunotherapy are provided, hopefully, to facilitate their far-reaching development toward clinical translation.
    Keywords:  cancer immunotherapy; controlled drug release; drug delivery; green materials; natural compounds
    DOI:  https://doi.org/10.3390/pharmaceutics14081589
  12. Cancer Gene Ther. 2022 Aug 23.
    Regulation of tumor metabolism by post translational modifications on metabolic enzymes.
    Abhisha Sawant Dessai, Poonam Kalhotra, Aaron T Novickis, Subhamoy Dasgupta.
      Metabolic reprogramming is a hallmark of cancer development, progression, and metastasis. Several metabolic pathways such as glycolysis, tricarboxylic acid (TCA) cycle, lipid metabolism, and glutamine catabolism are frequently altered to support cancer growth. Importantly, the activity of the rate-limiting metabolic enzymes in these pathways are specifically modulated in cancer cells. This is achieved by transcriptional, translational, and post translational regulations that enhance the expression, activity, stability, and substrate sensitivity of the rate-limiting enzymes. These mechanisms allow the enzymes to retain increased activity supporting the metabolic needs of rapidly growing tumors, sustain their survival in the hostile tumor microenvironments and in the metastatic lesions. In this review, we primarily focused on the post translational modifications of the rate-limiting enzymes in the glucose and glutamine metabolism, TCA cycle, and fatty acid metabolism promoting tumor progression and metastasis.
    DOI:  https://doi.org/10.1038/s41417-022-00521-x
  13. Pharmaceutics. 2022 Aug 12. pii: 1685. [Epub ahead of print]14(8):
    A Novel Diosgenin-Based Liposome Delivery System Combined with Doxorubicin for Liver Cancer Therapy.
    Lixia Chen, Jinshuai Lan, Zhe Li, Ruifeng Zeng, Yu Wang, Lu Zhen, Haojieyin Jin, Yue Ding, Tong Zhang.
      As a malignant tumor, liver cancer is mainly treated with chemotherapy, while chemotherapeutic drugs, such as doxorubicin (DOX), may lead to toxicity, drug resistance and poor prognosis. The targeted delivery systems of combining natural products and chemotherapeutic drugs are useful to eliminate cancers with reduced toxicity and increased efficiency. In this study, a diosgenin-based liposome loaded with DOX (Dios-DOX-LP) was developed for synergistic treatment of liver cancer, in which Dios not only replaced cholesterol as the membrane regulator to keep stability of liposomes, but also became the chemotherapy adjuvant of DOX for synergistic treatment. Dios-DOX-LP was characterized by particle size (99.4 ± 6.2 nm), zeta potential (-33.3 ± 2.5 mV), and entrapment efficiency (DOX: 98.77 ± 2.04%, Dios: 87.75 ± 2.93%), which had a good stability and slow-release effect. Compared with commercial DOX liposome (CHOL-DOX-LP), Dios-DOX-LP had an improved anti-tumor effect in vitro and in vivo by inducing the apoptosis and inhibiting the proliferation of the tumor cell, which was 1.6 times better than CHOL-DOX-LP in cytotoxicity, and had 78% of the tumor inhibition rate on tumor-bearing nude mice. Dios-DOX-LP provided a novel idea to achieve synergistic tumor treatment using diosgenin as a liposome material.
    Keywords:  diosgenin; doxorubicin; liposome; liver cancer; synergistic treatment
    DOI:  https://doi.org/10.3390/pharmaceutics14081685
  14. Molecules. 2022 Aug 12. pii: 5154. [Epub ahead of print]27(16):
    Recent Overview of Resveratrol's Beneficial Effects and Its Nano-Delivery Systems.
    Raghvendra A Bohara, Nazish Tabassum, Mohan P Singh, Giuseppe Gigli, Andrea Ragusa, Stefano Leporatti.
      Natural polyphenols have a wide variety of biological activities and are taken into account as healthcare materials. Resveratrol is one such natural polyphenol, belonging to a group known as stilbenoids (STBs). Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is mainly found in grapes, wine, nuts, and berries. A wide range of biological activities has been demonstrated by resveratrol, including antimicrobial, antioxidant, antiviral, antifungal, and antiaging effects, and many more are still under research. However, as with many other plant-based polyphenol products, resveratrol suffers from low bioavailability once administered in vivo due to its susceptibility to rapid enzyme degradation by the body's innate immune system before it can exercise its therapeutic influence. Therefore, it is of the utmost importance to ensure the best use of resveratrol by creating a proper resveratrol delivery system. Nanomedicine and nanodelivery systems utilize nanoscale materials as diagnostic tools or to deliver therapeutic agents in a controlled manner to specifically targeted locations. After a brief introduction about polyphenols, this review overviews the physicochemical characteristics of resveratrol, its beneficial effects, and recent advances on novel nanotechnological approaches for its delivery according to the type of nanocarrier utilized. Furthermore, the article summarizes the different potential applications of resveratrol as, for example, a therapeutic and disease-preventing anticancer and antiviral agent.
    Keywords:  drug delivery; nanocarriers; nanomedicine; polyphenols; resveratrol
    DOI:  https://doi.org/10.3390/molecules27165154
  15. Mar Drugs. 2022 Aug 18. pii: 527. [Epub ahead of print]20(8):
    Marine-Bioinspired Nanoparticles as Potential Drugs for Multiple Biological Roles.
    Geum-Jae Jeong, Sohail Khan, Nazia Tabassum, Fazlurrahman Khan, Young-Mog Kim.
      The increased interest in nanomedicine and its applicability for a wide range of biological functions demands the search for raw materials to create nanomaterials. Recent trends have focused on the use of green chemistry to synthesize metal and metal-oxide nanoparticles. Bioactive chemicals have been found in a variety of marine organisms, including invertebrates, marine mammals, fish, algae, plankton, fungi, and bacteria. These marine-derived active chemicals have been widely used for various biological properties. Marine-derived materials, either whole extracts or pure components, are employed in the synthesis of nanoparticles due to their ease of availability, low cost of production, biocompatibility, and low cytotoxicity toward eukaryotic cells. These marine-derived nanomaterials have been employed to treat infectious diseases caused by bacteria, fungi, and viruses as well as treat non-infectious diseases, such as tumors, cancer, inflammatory responses, and diabetes, and support wound healing. Furthermore, several polymeric materials derived from the marine, such as chitosan and alginate, are exploited as nanocarriers in drug delivery. Moreover, a variety of pure bioactive compounds have been loaded onto polymeric nanocarriers and employed to treat infectious and non-infectious diseases. The current review is focused on a thorough overview of nanoparticle synthesis and its biological applications made from their entire extracts or pure chemicals derived from marine sources.
    Keywords:  anticancer; antidiabetic; antiinflammatory; antimicrobial; antioxidant; infectious disease; marine; nanoparticles
    DOI:  https://doi.org/10.3390/md20080527
  16. Plants (Basel). 2022 Aug 17. pii: 2137. [Epub ahead of print]11(16):
    The Synergistic Effects of Curcumin and Chemotherapeutic Drugs in Inhibiting Metastatic, Invasive and Proliferative Pathways.
    Maria Younes, Rita Mardirossian, Liza Rizk, Tia Fazlian, Jean Paul Khairallah, Christopher Sleiman, Hassan Y Naim, Sandra Rizk.
      Curcumin, the main phytochemical identified from the Curcuma longa L. family, is one of the spices used in alternative medicine worldwide. It has exhibited a broad range of pharmacological activities as well as promising effects in the treatment of multiple cancer types. Moreover, it has enhanced the activity of other chemotherapeutic drugs and radiotherapy by promoting synergistic effects in the regulation of various cancerous pathways. Despite all the literature addressing the molecular mechanism of curcumin on various cancers, no review has specifically addressed the molecular mechanism underlying the effect of curcumin in combination with therapeutic drugs on cancer metastasis. The current review assesses the synergistic effects of curcumin with multiple drugs and light radiation, from a molecular perspective, in the inhibition of metastasis, invasion and proliferation. A systemic review of articles published during the past five years was performed using MEDLINE/PubMed and Scopus. The assessment of these articles evidenced that the combination therapy with various drugs, including doxorubicin, 5-fluorouracil, paclitaxel, berberine, docetaxel, metformin, gemcitabine and light radiation therapy on various types of cancer, is capable of ameliorating different metastatic pathways that are presented and evaluated. However, due to the heterogeneity of pathways and proteins in different cell lines, more research is needed to confirm the root causes of these pathways.
    Keywords:  cancer; combination therapy; curcumin; invasion; metastasis; phytotherapy
    DOI:  https://doi.org/10.3390/plants11162137
  17. Drug Deliv. 2022 Dec;29(1): 2743-2750
    A novel saponin liposomes based on the couplet medicines of Platycodon grandiflorum-Glycyrrhiza uralensis for targeting lung cancer.
    Chunjing Guo, Yanguo Su, Hui Wang, Min Cao, Ningning Diao, Zhongxin Liu, Daquan Chen, Ming Kong.
      Liposomes have been widely used for targeted drug delivery, but the disadvantages caused by cholesterol limit the application of conventional liposomes in cancer treatment. The compatibility basis of couplet medicines and the compatibility principle of the traditional Chinese medicine principle of 'monarch, minister, assistant and guide' are the important theoretical basis of Chinese medicine in the treatment of tumor and the important method to solve the problem of high toxicity. In this study, the active ingredients of the couplet medicines Platycodon grandiflorum and Glycyrrhiza uralensis were innovatively utilized, and glycyrrhizic acid (GA) was encapsulated in liposomes constructed by mixing saponin and lecithin, and cholesterol was replaced by platycodin and ginsenoside to construct saponin liposomes (RP-lipo) for the drug delivery system of Chinese medicine. Compared with conventional liposomes, PR-lipo@GA has no significant difference in morphological characteristics and drug release behavior, and also shows stronger targeting of lung cancer cells and anti-tumor ability in vitro, which may be related to the pharmacological properties of saponins themselves. Thus, PR-lipo@GA not only innovatively challenges the status of cholesterol as a liposome component, but also provides another innovative potential system with multiple functions for the clinical application of TCM couplet medicines.
    Keywords:  Couplet medicines; liposomes; platycodin; synergistic therapy
    DOI:  https://doi.org/10.1080/10717544.2022.2112997
  18. Chem Biol Interact. 2022 Aug 23. pii: S0009-2797(22)00323-4. [Epub ahead of print] 110118
    Nanoformulated bioactive compounds: A potential approach for cancer therapy.
    Baskar Venkidasamy, Rajakumar Govindasamy, Murugesan Krishnan, Muthu Thiruvengadam.
      
    Keywords:  Anticancer; Bioactives; Bioavailability; Drug delivery; Nanoformulations; Oral cancer
    DOI:  https://doi.org/10.1016/j.cbi.2022.110118
  19. Nutrients. 2022 Aug 12. pii: 3317. [Epub ahead of print]14(16):
    Saffron, Its Active Components, and Their Association with DNA and Histone Modification: A Narrative Review of Current Knowledge.
    Mudasir Rashid, Hassan Brim, Hassan Ashktorab.
      Intensive screening for better and safer medications to treat diseases such as cancer and inflammatory diseases continue, and some phytochemicals have been discovered to have anti-cancer and many therapeutical activities. Among the traditionally used spices, Crocus sativus (saffron) and its principal bioactive constituents have anti-inflammatory, antioxidant, and chemopreventive properties against multiple malignancies. Early reports have shown that the epigenetic profiles of healthy and tumor cells vary significantly in the context of different epigenetic factors. Multiple components, such as carotenoids as bioactive dietary phytochemicals, can directly or indirectly regulate epigenetic factors and alter gene expression profiles. Previous reports have shown the interaction between active saffron compounds with linker histone H1. Other reports have shown that high concentrations of saffron bind to the minor groove of calf thymus DNA, resulting in specific structural changes from B- to C-form of DNA. Moreover, the interaction of crocin G-quadruplex was reported. A recent in silico study has shown that residues of SIRT1 interact with saffron bio-active compounds and might enhance SIRT1 activation. Other reports have shown that the treatment of Saffron bio-active compounds increases γH2AX, decreases HDAC1 and phosphorylated histone H3 (p-H3). However, the question that still remains to be addressed how saffron triggers various epigenetic changes? Therefore, this review discusses the literature published till 2022 regarding saffron as dietary components and its impact on epigenetic mechanisms. Novel bioactive compounds such as saffron components that lead to epigenetic alterations might be a valuable strategy as an adjuvant therapeutic drug.
    Keywords:  DNA; HDAC1; SIRT1 and G-quadruplex; epigenetics; linker histone H1; phosphorylated H3; saffron; γH2AX
    DOI:  https://doi.org/10.3390/nu14163317
  20. Int J Biol Macromol. 2022 Aug 18. pii: S0141-8130(22)01801-3. [Epub ahead of print]220 537-572
    Recent development in nanoencapsulation and delivery of natural bioactives through chitosan scaffolds for various biological applications.
    Nisha Yadav, Deeksha Mudgal, Ritesh Anand, Simran Jindal, Vivek Mishra.
      Nowadays, nano/micro-encapsulation as a pioneering technique may significantly improve the bioavailability and durability of Natural bioactives. For this purpose, chitosan as a bioactive cationic natural polysaccharide has been frequently used as a carrier because of its distinct chemical and biological properties, including polycationic nature, biocompatibility, and biodegradability. Moreover, polysaccharide-based nano/micro-formulations are a new and extensive trend in scientific research and development in the disciplines of biomedicine, bioorganic/ medicinal chemistry, pharmaceutics, agrochemistry, and the food industry. It promises a new paradigm in drug delivery systems and nanocarrier formulations. This review aims to summarize current developments in approaches for designing innovative chitosan micro/nano-matrix, with an emphasis on the encapsulation of natural bioactives. The special emphasis led to a detailed integrative scientific achievement of the functionalities and abilities for encapsulating natural bioactives and mechanisms regulated in vitro/in vivo release in various biological/physiological environments.
    Keywords:  Carbohydrate; Encapsulation; Nanocarriers. Drug delivery; Natural bioactives; Polysaccharides
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.08.098
  21. Molecules. 2022 Aug 16. pii: 5236. [Epub ahead of print]27(16):
    Curcumin-Based Nanoformulations: A Promising Adjuvant towards Cancer Treatment.
    Salar Hafez Ghoran, Andrea Calcaterra, Milad Abbasi, Fatemeh Taktaz, Kay Nieselt, Esmaeil Babaei.
      Throughout the United States, cancer remains the second leading cause of death. Traditional treatments induce significant medical toxic effects and unpleasant adverse reactions, making them inappropriate for long-term use. Consequently, anticancer-drug resistance and relapse are frequent in certain situations. Thus, there is an urgent necessity to find effective antitumor medications that are specific and have few adverse consequences. Curcumin is a polyphenol derivative found in the turmeric plant (Curcuma longa L.), and provides chemopreventive, antitumor, chemo-, and radio-sensitizing properties. In this paper, we summarize the new nano-based formulations of polyphenolic curcumin because of the growing interest in its application against cancers and tumors. According to recent studies, the use of nanoparticles can overcome the hydrophobic nature of curcumin, as well as improving its stability and cellular bioavailability in vitro and in vivo. Several strategies for nanocurcumin production have been developed, each with its own set of advantages and unique features. Because the majority of the curcumin-based nanoformulation evidence is still in the conceptual stage, there are still numerous issues impeding the provision of nanocurcumin as a possible therapeutic option. To support the science, further work is necessary to develop curcumin as a viable anti-cancer adjuvant. In this review, we cover the various curcumin nanoformulations and nanocurcumin implications for therapeutic uses for cancer, as well as the current state of clinical studies and patents. We further address the knowledge gaps and future research orientations required to develop curcumin as a feasible treatment candidate.
    Keywords:  cancer immunotherapy; cancer treatment; curcumin nanoformulations; drug delivery system; nanocarriers; nanocurcumin
    DOI:  https://doi.org/10.3390/molecules27165236
  22. Carbohydr Polym. 2022 Nov 01. pii: S0144-8617(22)00783-4. [Epub ahead of print]295 119878
    Chitosan biguanide induced mitochondrial inhibition to amplify the efficacy of oxygen-sensitive tumor therapies.
    Zaigang Zhou, Chunjuan Zheng, Yu Liu, Wenjuan Luo, Hui Deng, Jianliang Shen.
      At present, the tumor's poor oxygen perfusion and limited tumor drug permeation are the major bottlenecks that limit the therapeutic effectiveness of the oxygen-sensitive antitumor therapies, like doxorubicin (Dox)-mediated chemotherapy and photodynamic therapy (PDT). To our best knowledge, the abnormal tumor mitochondria oxidative phosphorylation (OXPHOS) was the vital cause of such phenomenon, which induced the hypoxia tumor microenvironment and enhanced drug efflux from tumor cells via enhanced multidrug resistance protein 1 (MDR-1) expression. In this study, it was newly revealed that biguanide-modified chitosan (Bi-Ch) possessed ideal mitochondria depression capacity, leading to the following decreased dosage needed to disrupt mitochondrial function to reverse tumor hypoxia and depress MDR-1 expression. By doing this, Bi-Ch effectively enhanced Dox accumulation in tumor cells and amplified its cytotoxicity owing to the amplified ROS generation by Dox. Therefore, Bi-Ch could be used to improve the efficacy of oxygen-sensitive tumor therapies in vitro.
    Keywords:  Chitosan; Metformin; Mitochondria oxidative phosphorylation; Multidrug resistance; Oxygen-sensitive tumor therapies
    DOI:  https://doi.org/10.1016/j.carbpol.2022.119878
  23. Curr Drug Metab. 2022 Aug 25.
    A Unifying Perspective in Blunting the Limited Oral Bioavailability of Curcumin: A Succinct Look.
    Pitchai Balakumar, Taha Alqahtani, Ali Alqahtani, R Sulochana Lakshmiraj, Gurfateh Singh, Mani Rupeshkumar, A Thangathirupathi, Karupiah Sundram.
      BACKGROUND: Curcumin is a polyphenolic compound derived from rhizomes of Curcuma longa, the golden spice. Curcumin has drawn much attention in recent years of biomedical research owing to its wide-variety of biologic and pharmacologic actions. It exerts antiproliferative, antifibrogenic, anti-inflammatory, and antioxidative effects, among various imperative pharmacologic actions. In spite of its well-documented efficacies against numerous disease conditions, the limited systemic bioavailability of curcumin is a continuing concern. Perhaps, the poor bioavailability of curcumin may have curtailed its significant development from kitchen to clinic as a potential therapeutic agent. Subsequently, there have been a considerable number of studies over decades researching the scientific basis of curcumin's reduced bioavailability, and eventually improvement of its bioavailability employing a variety of therapeutic approaches, for instance, in combination with piperine, the bio-active constituent of black pepper. Piperine has remarkable potentials to modulate the functional activity of metabolic enzymes and drug transporters, and thus there has been a great interest in the therapeutic application of this widely used spice as an alternative medicine and bioavailability enhancer. Growing body of evidence supports the synergistic potential of curcumin against numerous pathologic conditions when administered with piperine.CONCLUSION: In light of current challenges, the major concern pertaining to poor systemic bioavailability of curcumin, its improvement especially in combination with piperine, and necessity of additional research in this setting are together described in this review. Besides, the recent advances on the potential therapeutic rationale and efficacy of curcumin-piperine combination, a promising duo, against various pathologic conditions are delineated.
    Keywords:  Bioavailability; Curcumin; Mechanistic insights; Piperine; Therapeutic rationale.; Turmeric
    DOI:  https://doi.org/10.2174/1389200223666220825101212
  24. Antibiotics (Basel). 2022 Aug 12. pii: 1097. [Epub ahead of print]11(8):
    Diverse Metabolites and Pharmacological Effects from the Basidiomycetes Inonotus hispidus.
    Zhenxin Wang, Xilong Feng, Chengwei Liu, Jinming Gao, Jianzhao Qi.
      Inonotus hispidus mushroom is a popular edible and medicinal mushroom with a long history of use. It is well known as a medicinal fungus with various health benefits for its significant anticancer and immunomodulatory activities. Over the last 60 years, secondary metabolites derived from I. hispidus and their biological activities have been discovered and investigated. Structurally, these compounds are mainly polyphenols and triterpenoids, which have anticancer, anti-inflammatory, antioxidant, antimicrobial, and enzyme inhibitor activities. Here, the secondary metabolites derived from I. hispidus and their activities were systematically and comprehensively classified and summarized, and the biosynthetic pathway of stylylpyrones was deduced and analyzed further. This review contributes to our understanding of I. hispidus and will help with research into natural product chemistry, pharmacology, and the biosynthesis of I. hispidus metabolites. According to this review, I. hispidus could be a promising source of bioactive compounds for health promotion and the development of functional foods.
    Keywords:  Inonotus hispidus; biological activity; medicinal fungi; natural product
    DOI:  https://doi.org/10.3390/antibiotics11081097
  25. Pharmaceutics. 2022 Aug 05. pii: 1636. [Epub ahead of print]14(8):
    Progress in Polymeric Micelles for Drug Delivery Applications.
    Sabna Kotta, Hibah Mubarak Aldawsari, Shaimaa M Badr-Eldin, Anroop B Nair, Kamal Yt.
      Polymeric micelles (PMs) have made significant progress in drug delivery applications. A robust core-shell structure, kinetic stability and the inherent ability to solubilize hydrophobic drugs are the highlights of PMs. This review presents the recent advances and understandings of PMs with a focus on the latest drug delivery applications. The types, methods of preparation and characterization of PMs are described along with their applications in oral, parenteral, transdermal, intranasal and other drug delivery systems. The applications of PMs for tumor-targeted delivery have been provided special attention. The safety, quality and stability of PMs in relation to drug delivery are also provided. In addition, advanced polymeric systems and special PMs are also reviewed. The in vitro and in vivo stability assessment of PMs and recent understandings in this area are provided. The patented PMs and clinical trials on PMs for drug delivery applications are considered indicators of their tremendous future applications. Overall, PMs can help overcome many unresolved issues in drug delivery.
    Keywords:  critical micelle concentration; drug delivery; oral; polymeric micelles; tumor-targeted
    DOI:  https://doi.org/10.3390/pharmaceutics14081636
  26. Oxid Med Cell Longev. 2022 ;2022 6044640
    Herbal Ingredients in the Prevention of Breast Cancer: Comprehensive Review of Potential Molecular Targets and Role of Natural Products.
    Esra Küpeli Akkol, Hilal Bardakci, Timur Hakan Barak, Michael Aschner, Gökçe Şeker Karatoprak, Haroon Khan, Yaseen Hussain.
      Among various cancers, breast cancer is the most prevalent type in women throughout the world. Breast cancer treatment is challenging due to complex nature of the etiology of disease. Cell division cycle alterations are often encountered in a variety of cancer types including breast cancer. Common treatments include chemotherapy, surgery, radiotherapy, and hormonal therapy; however, adverse effects and multidrug resistance lead to complications and noncompliance. Accordingly, there is an increasing demand for natural products from medicinal plants and foods. This review summarizes molecular mechanisms of signaling pathways in breast cancer and identifies mechanisms by which natural compounds may exert their efficacy in the treatment of breast cancer.
    DOI:  https://doi.org/10.1155/2022/6044640
  27. MedComm (2020). 2022 Sep;3(3): e163
    Nanomedicine and versatile therapies for cancer treatment.
    Aparna Shukla, Pralay Maiti.
      The higher prevalence of cancer is related to high rates of mortality and morbidity worldwide. By virtue of the properties of matter at the nanoscale, nanomedicine is proven to be a powerful tool to develop innovative drug carriers with greater efficacies and fewer side effects than conventional therapies. In this review, different nanocarriers for controlled drug release and their routes of administration have been discussed in detail, especially for cancer treatment. Special emphasis has been given on the design of drug delivery vehicles for sustained release and specific application methods for targeted delivery to the affected areas. Different polymeric vehicles designed for the delivery of chemotherapeutics have been discussed, including graft copolymers, liposomes, hydrogels, dendrimers, micelles, and nanoparticles. Furthermore, the effect of dimensional properties on chemotherapy is vividly described. Another integral section of the review focuses on the modes of administration of nanomedicines and emerging therapies, such as photothermal, photodynamic, immunotherapy, chemodynamic, and gas therapy, for cancer treatment. The properties, therapeutic value, advantages, and limitations of these nanomedicines are highlighted, with a focus on their increased performance versus conventional molecular anticancer therapies.
    Keywords:  administration routes; cancer; controlled drug delivery; nanomedicines
    DOI:  https://doi.org/10.1002/mco2.163
  28. J Pers Med. 2022 Aug 18. pii: 1329. [Epub ahead of print]12(8):
    MicroRNAs as Regulators of Cancer Cell Energy Metabolism.
    Natarajaseenivasan Suriya Muthukumaran, Prema Velusamy, Charles Solomon Akino Mercy, Dianne Langford, Kalimuthusamy Natarajaseenivasan, Santhanam Shanmughapriya.
      To adapt to the tumor environment or to escape chemotherapy, cancer cells rapidly reprogram their metabolism. The hallmark biochemical phenotype of cancer cells is the shift in metabolic reprogramming towards aerobic glycolysis. It was thought that this metabolic shift to glycolysis alone was sufficient for cancer cells to meet their heightened energy and metabolic demands for proliferation and survival. Recent studies, however, show that cancer cells rely on glutamine, lipid, and mitochondrial metabolism for energy. Oncogenes and scavenging pathways control many of these metabolic changes, and several metabolic and tumorigenic pathways are post-transcriptionally regulated by microRNA (miRNAs). Genes that are directly or indirectly responsible for energy production in cells are either negatively or positively regulated by miRNAs. Therefore, some miRNAs play an oncogenic role by regulating the metabolic shift that occurs in cancer cells. Additionally, miRNAs can regulate mitochondrial calcium stores and energy metabolism, thus promoting cancer cell survival, cell growth, and metastasis. In the electron transport chain (ETC), miRNAs enhance the activity of apoptosis-inducing factor (AIF) and cytochrome c, and these apoptosome proteins are directed towards the ETC rather than to the apoptotic pathway. This review will highlight how miRNAs regulate the enzymes, signaling pathways, and transcription factors of cancer cell metabolism and mitochondrial calcium import/export pathways. The review will also focus on the metabolic reprogramming of cancer cells to promote survival, proliferation, growth, and metastasis with an emphasis on the therapeutic potential of miRNAs for cancer treatment.
    Keywords:  TCA; cancer metabolism; fatty acid oxidation; glucose oxidation; miRNA; pentose-phosphate pathway
    DOI:  https://doi.org/10.3390/jpm12081329
  29. J Colloid Interface Sci. 2022 Aug 11. pii: S0021-9797(22)01413-8. [Epub ahead of print]628(Pt B): 189-203
    A spark to the powder keg: Microneedle-based antitumor nanomedicine targeting reactive oxygen species accumulation for chemodynamic/photothermal/chemotherapy.
    Kaixin Liao, Boyi Niu, Haibing Dong, Luxuan He, Yixian Zhou, Ying Sun, Dan Yang, Chuanbin Wu, Xin Pan, Guilan Quan.
      HYPOTHESIS: Chemodynamic therapy (CDT) can efficiently kill cancer cells by producing hydroxyl radical (•OH), a kind of high-toxic reactive oxygen species (ROS), via Fenton or Fenton-like reactions. This study involved a versatile nanomedicine, MSN@DOX/GA-Fe/PDA (M@DGP), delivered via microneedles, which was expected to combine chemodynamic/photothermal/chemotherapy and efficiently increase ROS accumulation to achieve significant therapeutic efficacy against melanoma.EXPERIMENTS: The composition of the synthesized nanoparticles was confirmed by a series of characterizations including transmission electron microscopy, Fourier transform infrared spectroscopy, and zeta potential. The photothermal properties of the nanomedicine was evaluated via infrared imaging, and •OH-producing ability was evaluated by UV-Vis and electron spin resonance. The mechanisms of ROS accumulation were studied in B16 cells by detecting intracellular •OH, glutathione, and ROS levels. The drug-loaded microneedles (M@DGP-MNs) were prepared, and their morphology and mechanical strength were characterized. The in vivo antimelanoma effect and biosafety evaluation of the nanomedicine were investigated in tumor-bearing C57 mice.
    FINDINGS: M@DGP was successfully prepared and could achieve ROS accumulation through a photothermal-enhanced Fenton reaction, polydopamine-induced glutathione consumption, and doxorubicin-mediated mitochondrial dysfunction which induced oxidative stress and apoptosis of tumor cells. M@DGP-MNs showed superior antitumor efficacy and good biosafety, providing a promising strategy for melanoma treatment.
    Keywords:  Chemodynamic therapy; Fenton reaction; Photothermal therapy; Polydopamine; Reactive oxygen species
    DOI:  https://doi.org/10.1016/j.jcis.2022.08.042
  30. ACS Biomater Sci Eng. 2022 Aug 24.
    Melanin Nanoparticle-Actuated Redox-State Perturbation and Temporally Photoactivated Thermal Stress for Synergistic Tumor Therapy.
    Hanyin Zhu, Yongyi Qu, Shuai Wang, Jixi Huang, Jing Zhu, Lu Wang, Kaiyong Cai, Jixi Zhang.
      The elevation of antioxidant defense systems by adaptation response to localized reactive oxygen species (ROS) accumulation may confer resistance to excessive oxidative stress and cause therapeutic lethality. Herein, a highly effective tumor therapy is developed through perturbation in cellular redox homeostasis. Specifically, metal-ion-assisted oxidation polymerization of the melanin precursor (l-DOPA) whose carboxyl groups exert a charge-shielding effect leads to the formation of catechol-rich but quinone-deficient nanoparticles (NPs). These NPs possess appreciable ROS-scavenging ability, and particularly the raised quinone group levels in oxidized products can then trigger subsequent depletion of antioxidative species (GSH) and, in turn, the redox-cycle consumption of catechol/quinone groups. After incubating with cells, varying degrees of redox-state and energy metabolism fluctuations with time (∼6 h) are observed, where ROS/GSH levels rebound to a maximum peak (up to ∼280%) higher than the normal redox state after hitting the bottom within a short time (1 h). Notably, systematically triggered redox stress response can sensitize cells to an extremely endangered metastable state. The synergy of temporally photoactivated thermal stress can produce overwhelming oxidative stress, thus leading to significant inhibition of cancer cells. This work established a new paradigm of redox perturbator-based programed and combined cancer therapy.
    Keywords:  melanin nanoparticles; redox perturbation; temporally photoactivated heat
    DOI:  https://doi.org/10.1021/acsbiomaterials.2c00614
  31. Mar Drugs. 2022 Aug 15. pii: 521. [Epub ahead of print]20(8):
    Antioxidant Potential of Sea Cucumbers and Their Beneficial Effects on Human Health.
    Abul Hossain, Deepika Dave, Fereidoon Shahidi.
      Sea cucumbers are considered a luxury food item and used locally in traditional medication due to their impressive nutritional profile and curative effects. Sea cucumbers contain a wide range of bioactive compounds, namely phenolics, polysaccharides, proteins (collagen and peptides), carotenoids, and saponins, demonstrating strong antioxidant and other activities. In particular, phenolic compounds, mainly phenolic acids and flavonoids, are abundant in this marine invertebrate and exhibit antioxidant activity. Protein hydrolysates and peptides obtained from sea cucumbers exhibit antioxidant potential, mainly dependent on the amino acid compositions and sequences as well as molecular weight, displayed for those of ≤20 kDa. Moreover, the antioxidant activity of sea cucumber polysaccharides, including fucosylated chondroitin sulfate and fucan, is a combination of numerous factors and is mostly associated with molecular weight, degree of sulfation, and type of major sugars. However, the activity of these bioactive compounds typically depends on the sea cucumber species, harvesting location, food habit, body part, and processing methods employed. This review summarizes the antioxidant activity of bioactive compounds obtained from sea cucumbers and their by-products for the first time. The mechanism of actions, chemical structures, and factors affecting the antioxidant activity are also discussed, along with the associated health benefits.
    Keywords:  antioxidants; carotenoids; phenolics and polyphenolics; polysaccharides; protein hydrolysates and peptides; sea cucumber
    DOI:  https://doi.org/10.3390/md20080521
  32. Phytochemistry. 2022 Aug 17. pii: S0031-9422(22)00256-4. [Epub ahead of print] 113340
    Selected plant triterpenoids and their amide derivatives in cancer treatment: A review.
    Zulal Özdemir, Zdeněk Wimmer.
      Medicinal plants have been used to treat different diseases throughout the human history namely in traditional medicine. Most of the plants mentioned in this review article belong among them, including those that are widely spread in the nature, counted frequently to be food and nutrition plants and producing pharmacologically important secondary metabolites. Triterpenoids represent an important group of plant secondary metabolites displaying emerging pharmacological importance. This review article sheds light on four selected triterpenoids, oleanolic, ursolic, betulinic and platanic acid, and on their amide derivatives as important natural or semisynthetic agents in cancer treatment, and, in part, in pathogenic microbe treatment. A literature search was made in the Web of Science for the given key words covering the required area of secondary plant metabolites and their amide derivatives. The most recently published findings on the biological activity of the selected triterpenoids, and on the structures and biological activity of their relevant amide derivatives have been summarized therein. Mainly anti-cancer effects, and, in part, antimicrobial and other effects of the four selected triterpenoids and their amide derivatives have also been reviewed. A comparison of the effects of the parent plant products and those of their amide derivatives has been made.
    Keywords:  Amide; Antimalarial activity; Antimicrobial activity; Cytotoxicity; Hepatitis a virus; Medicinal plant; Pentacyclic triterpenoid; Secondary metabolite
    DOI:  https://doi.org/10.1016/j.phytochem.2022.113340
  33. Micromachines (Basel). 2022 Aug 08. pii: 1279. [Epub ahead of print]13(8):
    Functionalized Magnetic Nanoparticles for Alternating Magnetic Field- or Near Infrared Light-Induced Cancer Therapies.
    Anilkumar Thaghalli Shivanna, Banendu Sunder Dash, Jyh-Ping Chen.
      The multi-faceted nature of functionalized magnetic nanoparticles (fMNPs) is well-suited for cancer therapy. These nanocomposites can also provide a multimodal platform for targeted cancer therapy due to their unique magnetic guidance characteristics. When induced by an alternating magnetic field (AMF), fMNPs can convert the magnetostatic energy to heat for magnetic hyperthermia (MHT), as well as for controlled drug release. Furthermore, with the ability to convert near-infrared (NIR) light energy to heat energy, fMNPs have attracted interest for photothermal therapy (PTT). Other than MHT and PTT, fMNPs also have a place in combination cancer therapies, such as chemo-MHT, chemo-PTT, and chemo-PTT-photodynamic therapy, among others, due to their versatile properties. Thus, this review presents multifunctional nanocomposites based on fMNPs for cancer therapies, induced by an AMF or NIR light. We will first discuss the different fMNPs induced with an AMF for cancer MHT and chemo-MHT. Secondly, we will discuss fMNPs irradiated with NIR lasers for cancer PTT and chemo-PTT. Finally, fMNPs used for dual-mode AMF + NIR-laser-induced magneto-photo-hyperthermia (MPHT) will be discussed.
    Keywords:  alternating magnetic field; magnetic hyperthermia; magnetic nanoparticles; magnetic targeting; near-infrared; photothermal therapy
    DOI:  https://doi.org/10.3390/mi13081279
  34. Pharmaceutics. 2022 Aug 18. pii: 1727. [Epub ahead of print]14(8):
    Combinatorial Therapy of Letrozole- and Quercetin-Loaded Spanlastics for Enhanced Cytotoxicity against MCF-7 Breast Cancer Cells.
    Aml I Mekkawy, Nermin E Eleraky, Ghareb M Soliman, Mohamed G Elnaggar, Marwa G Elnaggar.
      Breast cancer is the most widespread cancer in women with rising incidence, prevalence, and mortality in developed regions. Most breast cancers (80%) are estrogen receptor-positive, indicating that disease progression could be controlled by estrogen inhibition in the breast tissue. However, drug resistance limits the benefits of this approach. Combinatorial treatment could overcome the resistance and improve the outcome of breast cancer treatment. In the current study, we prepared letrozole-(LTZSPs) and quercetin-loaded spanlastics (QuSPs) using different edge activators-Tween 80, Brij 35, and Cremophor RH40-with different concentrations. The spanlastics were evaluated for their average particles size, surface charge, and percent encapsulation efficiency. The optimized formulations were further examined using transmission electron microscopy, Fourier transform infrared spectroscopy, in vitro drug release and ex vivo skin permeation studies. The prepared spherical LTZSPs and QuSPs had average particle sizes ranged between 129-310 nm and 240-560 nm, respectively, with negative surface charge and high LTZ and Qu encapsulation (94.3-97.2% and 97.9-99.6%, respectively). The in vitro release study of LTZ and Qu from the selected formulations showed a sustained drug release for 24 h with reasonable flux and permeation through the rat skin. Further, we evaluated the in vitro cytotoxicity, cell cycle analysis, and intracellular reactive oxygen species (ROS) of the combination therapy of letrozole and quercetin either in soluble form or loaded in spanlastics against MCF-7 breast cancer cells. The LTZSPs and QuSPs combination was superior to the individual treatments and the soluble free drugs in terms of in vitro cytotoxicity, cell cycle analysis, and ROS studies. These results confirm the potential of LTZSPs and QuSPs combination for transdermal delivery of drugs for enhanced breast cancer management.
    Keywords:  breast cancer; combination therapy; letrozole; quercetin; spanlastics
    DOI:  https://doi.org/10.3390/pharmaceutics14081727
  35. Cells. 2022 Aug 09. pii: 2471. [Epub ahead of print]11(16):
    Urolithins Modulate the Viability, Autophagy, Apoptosis, and Nephrin Turnover in Podocytes Exposed to High Glucose.
    Milena Kotewicz, Mirosława Krauze-Baranowska, Agnieszka Daca, Agata Płoska, Sylwia Godlewska, Leszek Kalinowski, Barbara Lewko.
      Urolithins are bioactive compounds generated in human and animal intestines because of the bacterial metabolism of dietary ellagitannins (and their constituent, ellagic acid). Due to their multidirectional effects, including anti-inflammatory, antioxidant, anti-cancer, neuroprotective, and antiglycative properties, urolithins are potential novel therapeutic agents. In this study, while considering the future possibility of using urolithins to improve podocyte function in diabetes, we assessed the results of exposing mouse podocytes cultured in normal (NG, 5.5 mM) and high (HG, 25 mM) glucose concentrations to urolithin A (UA) and urolithin B (UB). Podocytes metabolized UA to form glucuronides in a time-dependent manner; however, in HG conditions, the metabolism was lower than in NG conditions. In HG milieu, UA improved podocyte viability more efficiently than UB and reduced the reactive oxygen species level. Both types of urolithins showed cytotoxic activity at high (100 µM) concentration. The UA upregulated total and surface nephrin expression, which was paralleled by enhanced nephrin internalization. Regulation of nephrin turnover was independent of ambient glucose concentration. We conclude that UA affects podocytes in different metabolic and functional aspects. With respect to its pro-survival effects in HG-induced toxicity, UA could be considered as a potent therapeutic candidate against diabetic podocytopathy.
    Keywords:  diabetic nephropathy; high glucose; nephrin; podocytes; urolithin A; urolithins
    DOI:  https://doi.org/10.3390/cells11162471
  36. Int J Mol Sci. 2022 Aug 12. pii: 9035. [Epub ahead of print]23(16):
    Alginate as a Promising Biopolymer in Drug Delivery and Wound Healing: A Review of the State-of-the-Art.
    Mohammad A S Abourehab, Rahul R Rajendran, Anshul Singh, Sheersha Pramanik, Prachi Shrivastav, Mohammad Javed Ansari, Ravi Manne, Larissa Souza Amaral, A Deepak.
      Biopolymeric nanoparticulate systems hold favorable carrier properties for active delivery. The enhancement in the research interest in alginate formulations in biomedical and pharmaceutical research, owing to its biodegradable, biocompatible, and bioadhesive characteristics, reiterates its future use as an efficient drug delivery matrix. Alginates, obtained from natural sources, are the colloidal polysaccharide group, which are water-soluble, non-toxic, and non-irritant. These are linear copolymeric blocks of α-(1→4)-linked l-guluronic acid (G) and β-(1→4)-linked d-mannuronic acid (M) residues. Owing to the monosaccharide sequencing and the enzymatically governed reactions, alginates are well-known as an essential bio-polymer group for multifarious biomedical implementations. Additionally, alginate's bio-adhesive property makes it significant in the pharmaceutical industry. Alginate has shown immense potential in wound healing and drug delivery applications to date because its gel-forming ability maintains the structural resemblance to the extracellular matrices in tissues and can be altered to perform numerous crucial functions. The initial section of this review will deliver a perception of the extraction source and alginate's remarkable properties. Furthermore, we have aspired to discuss the current literature on alginate utilization as a biopolymeric carrier for drug delivery through numerous administration routes. Finally, the latest investigations on alginate composite utilization in wound healing are addressed.
    Keywords:  administration route; alginate; controlled release; drug delivery system; extraction methods; formulations; wound healing
    DOI:  https://doi.org/10.3390/ijms23169035
  37. ACS Appl Mater Interfaces. 2022 Aug 24.
    Sequentially Activatable Polypeptide Nanoparticles for Combinatory Photodynamic Chemotherapy of Breast Cancer.
    Huijuan Zhang, Jiaxing Pan, Tingting Wang, Yi Lai, Xiaoying Liu, Fangmin Chen, Leiming Xu, Xiongwei Qu, Xiuli Hu, Haijun Yu.
      Stimuli-activatable nanomaterials hold significant promise for tumor-specific drug delivery by recognizing the internal or external stimulus. Herein, we reported a dual-responsive and biodegradable polypeptide nanoparticle (PPTP@PTX2 NP) for combinatory chemotherapy and photodynamic therapy (PDT) of breast cancer. The NPs were engineered by encapsulating diselenide bond linked dimeric prodrug of paclitaxel (PTX2) in an intracellular acidity-activatable polypeptide micelle. Specifically, the acid-responsive polypeptide was synthesized by grafting a tetraphenyl porphyrin (TPP) photosensitizer and N,N-diisopropylethylenediamine (DPA) onto the poly(ethylene glycol)-block-poly(glutamic acid) diblock copolymer by the amidation reaction, which self-assembled into micellar NPs and was activated inside the acidic endocytic vesicles to perform PDT. The paclitaxel dimer can be stably loaded into the polypeptide NPs and be restored by PDT inside the tumor cells. The formed PPTP@PTX2 NPs remained inert during blood circulation and passively accumulated in the tumor foci, which could be activated within the endocytic vesicles via acid-triggered protonation of DPA groups to generate fluorescence signal and release PTX2 in 4T1 murine breast tumor cells. Upon 660 nm laser irradiation, the activated NPs carried out PDT via TPP and chemotherapy via PTX to induce apoptosis of 4T1 cells and thereby efficiently inhibited 4T1 tumor growth and prevented metastasis of tumor cells.
    Keywords:  breast cancer; photodynamic therapy; polypeptide nanoparticles; precise tumor therapy; stimulus responsive
    DOI:  https://doi.org/10.1021/acsami.2c09064
  38. Molecules. 2022 Aug 16. pii: 5219. [Epub ahead of print]27(16):
    Stinging Nettle (Urtica dioica L.): Nutritional Composition, Bioactive Compounds, and Food Functional Properties.
    Hari Prasad Devkota, Keshav Raj Paudel, Shristi Khanal, Ananda Baral, Nisha Panth, Anjana Adhikari-Devkota, Niraj Kumar Jha, Niranjan Das, Sachin Kumar Singh, Dinesh Kumar Chellappan, Kamal Dua, Philip M Hansbro.
      Stinging nettle (Urtica dioica L., Urticaceae) is commonly found in Asia, Africa, and Europe and has a long history of being used as food and traditional medicine. Recently, this plant is gaining attention as a highly nutritious food, where fresh leaves are dried and used as powder or in other forms. Leaves are rich in many bioactive compounds. This review aims to cover the traditional uses in food and medicine, as well as its nutritional composition, including its bioactive chemical constituents and reported food functional activities. Various bioactive chemical constituents have been isolated from stinging nettle to date, such as flavonoids, phenolic acids, amino acid, carotenoids, and fatty acids. Stinging nettle extracts and its compounds, such as rutin, kaempferol, and vitamin A, are also used for their nutritional properties and as anti-inflammatory and antioxidant agents. Future studies should focus on the proper formulation and stability testing of the functional foods containing stinging nettle and their detailed activities in clinical studies.
    Keywords:  Urtica dioica; anti-bacterial; anti-inflammatory; anti-ulcer; antioxidant; nettle; nutraceuticals; stinging nettle
    DOI:  https://doi.org/10.3390/molecules27165219
  39. Pharmaceutics. 2022 Jul 29. pii: 1579. [Epub ahead of print]14(8):
    Application of Mesoporous Silica Nanoparticles in Cancer Therapy and Delivery of Repurposed Anthelmintics for Cancer Therapy.
    Maedeh Koohi Moftakhari Esfahani, Seyed Ebrahim Alavi, Peter J Cabot, Nazrul Islam, Emad L Izake.
      This review focuses on the biomedical application of mesoporous silica nanoparticles (MSNs), mainly focusing on the therapeutic application of MSNs for cancer treatment and specifically on overcoming the challenges of currently available anthelmintics (e.g., low water solubility) as repurposed drugs for cancer treatment. MSNs, due to their promising features, such as tunable pore size and volume, ability to control the drug release, and ability to convert the crystalline state of drugs to an amorphous state, are appropriate carriers for drug delivery with the improved solubility of hydrophobic drugs. The biomedical applications of MSNs can be further improved by the development of MSN-based multimodal anticancer therapeutics (e.g., photosensitizer-, photothermal-, and chemotherapeutics-modified MSNs) and chemical modifications, such as poly ethyleneglycol (PEG)ylation. In this review, various applications of MSNs (photodynamic and sonodynamic therapies, chemotherapy, radiation therapy, gene therapy, immunotherapy) and, in particular, as the carrier of anthelmintics for cancer therapy have been discussed. Additionally, the issues related to the safety of these nanoparticles have been deeply discussed. According to the findings of this literature review, the applications of MSN nanosystems for cancer therapy are a promising approach to improving the efficacy of the diagnostic and chemotherapeutic agents. Moreover, the MSN systems seem to be an efficient strategy to further help to decrease treatment costs by reducing the drug dose.
    Keywords:  anthelmintic; cancer; drug delivery; mesoporous silica nanoparticle; nanomaterial; nanotechnology
    DOI:  https://doi.org/10.3390/pharmaceutics14081579
  40. Food Chem Toxicol. 2022 Aug 22. pii: S0278-6915(22)00583-X. [Epub ahead of print] 113385
    Apigenin in cancer therapy: From mechanism of action to nano-therapeutic agent.
    Yun Zhou, Yijun Yu, He Lv, Hao Zhang, Tianzi Liang, Guoer Zhou, Liping Huang, Yizhou Tian, Wenqing Liang.
      Apigenin (APG) is a flavonoid presence in beverages, vegetables, and fruits containing anti-diabetic, anti-oxidant, and anti-viral activities, as well as cancer management properties. There is growing evidence that APG presented extensive anti-cancer effects in several cancer types by modulating various cellular processes, including angiogenesis, apoptosis, metastasis, autophagy, cell cycle, and immune responses, through activation or inhibition of different cell signaling pathways and molecules. By emerging nanotechnology and its advent in the biomedicine field, cancer therapy has been changed based on nanotechnology-based delivery systems. APG nanoformulations have been used to target tumor cells specifically, improve cellular uptake of APG, and overcome limitations of the free form of APG, such as low solubility and poor bioavailability. In this review, the biotherapeutic activity of APG and its mechanisms, both in free form and nanoformulation, toward cancer cells are discussed to shed some light on APG anti-tumor activity in different cancers.
    Keywords:  Angiogenesis; Anti-cancer; Apigenin; Autophagy; Immune response; Nanoformulation
    DOI:  https://doi.org/10.1016/j.fct.2022.113385
  41. ACS Appl Mater Interfaces. 2022 Aug 24.
    Albumin-Coated Framework Nucleic Acids as Bionic Delivery System for Triple-Negative Breast Cancer Therapy.
    Yuxin Zhang, Chenchen Mao, Yuxi Zhan, Yuxuan Zhao, Ye Chen, Yunfeng Lin.
      Triple-negative breast cancer (TNBC) is a subtype of breast cancer, and it has aggressive and more frequent tissue metastases than other breast cancer subtypes. Because the proliferation of TNBC tumor cells does not depend on estrogen receptor (ER), progesterone receptor (PR), and Erb-B2 receptor tyrosine kinase 2 (HER2) and lacks accurate drug targets, conventional chemotherapy is challenging to be effective, and adverse reactions are severe. At present, the treatment strategy for TNBC generally depends on a combination of surgery, radiotherapy, and chemotherapy. Conventional administration methods have minimal effects on TNBC and cause severe damage to normal tissues. Therefore, it is an urgent task to develop an efficient and practical way of drug delivery and open up a new horizon of targeted therapy for TNBC. In our work, bovine serum albumin (BSA) acted as the protective film to prolong the circulation time of the tetrahedral framework nucleic acid (tFNA) delivery system and resist immune clearance in vivo. tFNA was used as a carrier loaded with DOX and AS1411 aptamers for the targeted treatment of triple-negative breast cancer. Compared with existing approaches, this optimized system exhibits stronger tumor-targeting so that tFNAs can be more concentrated around the tumor tissue, reducing DOX toxicity to other organs. This bionic delivery system exhibited effective tumor growth inhibition in the TNBC mice model, offering the clinical potential to promote the treatment of TNBC with great potential for clinical translation.
    Keywords:  albumin; drug delivery system; long circulation; tetrahedral framework nucleic acid; triple-negative breast cancer
    DOI:  https://doi.org/10.1021/acsami.2c10612
  42. Front Pharmacol. 2022 ;13 958443
    Adapalene inhibits the growth of triple-negative breast cancer cells by S-phase arrest and potentiates the antitumor efficacy of GDC-0941.
    Umar Mehraj, Nissar Ahmad Wani, Abid Hamid, Mustfa Alkhanani, Abdullah Almilaibary, Manzoor Ahmad Mir.
      Although advances in diagnostics and therapeutics have prolonged the survival of triple-negative breast cancer (TNBC) patients, metastasis, therapeutic resistance, and lack of targeted therapies remain the foremost hurdle in the effective management of TNBC. Thus, evaluation of new therapeutic agents and their efficacy in combination therapy is urgently needed. The third-generation retinoid adapalene (ADA) has potent antitumor activity, and using ADA in combination with existing therapeutic regimens may improve the effectiveness and minimize the toxicities and drug resistance. The current study aimed to assess the anticancer efficacy of adapalene as a combination regimen with the PI3K inhibitor (GDC-0941) in TNBC in vitro models. The Chou-Talalay's method evaluated the pharmacodynamic interactions (synergism, antagonism, or additivity) of binary drug combinations. Flow cytometry, Western blotting, and in silico studies were used to analyze the mechanism of GDC-ADA synergistic interactions in TNBC cells. The combination of GDC and ADA demonstrated a synergistic effect in inhibiting proliferation, migration, and colony formation of tumor cells. Accumulation of reactive oxygen species upon co-treatment with GDC and ADA promoted apoptosis and enhanced sensitivity to GDC in TNBC cells. The findings indicate that ADA is a promising therapeutic agent in treating advanced BC tumors and enhance sensitivity to GDC in inhibiting tumor growth in TNBC models while reducing therapeutic resistance.
    Keywords:  Breast cancer; Chou–Talalay; GDC-0941; adapalene; combination therapy; triple-negative breast cancer
    DOI:  https://doi.org/10.3389/fphar.2022.958443
  43. Int J Pharm. 2022 Aug 22. pii: S0378-5173(22)00683-4. [Epub ahead of print] 122130
    Disulfiram: A Food and Drug Administration-approved multifunctional role in synergistically drug delivery systems for tumor treatment.
    Lushuang Xu, Yue Sun, Yue Li, Junli Sun, Yong Guo, Qiying Shen, Qiaolin Wei, Jia-Wei Shen.
      Disulfiram (DSF), a Food and Drug Administration (FDA)-approved drug for the treatment of alcoholism, has been found to have antitumor activity. DSF showed better antitumor efficiency when it was used in combination with certain antitumor drugs. DSF plays an important role in cancer treatment. It has been used as multidrug resistance (MDR) modulator to reverse MDR and can also combine with copper ions (Cu2+), which will produce copper diethyldithiocarbamate (Cu[DDC]2) complex with antitumor activity. The synergistic targeted drug delivery for cancer treatment based on DSF, especially the combination with exogenous Cu2+ and its forms of administration, has attracted extensive attention in the biomedical field. In this review, we summarize these synergistic delivery systems, in the hope that they will contribute to the continuous optimization and development of more advanced drug delivery systems. Furthermore, we discuss the current limitation and future directions of DSF-based drug delivery systems in the field of tumor therapy. Hopefully, our work may inspire further innovation of DSF-based antitumor drug delivery systems.
    Keywords:  Cancer therapy; Copper diethyldithiocarbamate; Disulfiram; Multidrug resistance modulator; Synergistic drug delivery systems
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.122130
  44. Mol Biol Rep. 2022 Aug 21.
    Synergistic anticancer effects of curcumin and crocin on human colorectal cancer cells.
    Seyed Samad Hosseini, Robab Zare Reihani, Mohammad Amin Doustvandi, Mohammad Amini, Felor Zargari, Behzad Baradaran, AmirHossein Yari, Maryam Hashemi, Maryam Tohidast, Ahad Mokhtarzadeh.
      BACKGROUND: Curcumin, a polyphenol compound derived from the Curcuma longa L, and crocin, a hydrophilic carotenoid from Crocus Sativus Linnaeus, are traditionally used in food preparations in many countries and could act as chemopreventive compounds against several diseases, including cancer. In this study, the synergistic effect of curcumin and crocin was investigated for the first time on inducing apoptosis and suppressing colorectal cancer cells (SW-480 cell line).METHODS AND RESULTS: MTT, Annexin V-FITC/PI, and DAPI staining tests were employed to evaluate cell viability and apoptosis induction, respectively. The combined effect of curcumin and crocin on the expression of genes involved in apoptosis and proliferation was quantified using real-time PCR. The combination therapy effect on cell cycle progression was also evaluated by flow cytometry. Based on the obtained results, curcumin and crocin treatment could cooperatively reduce cell viability and induce apoptosis in SW-480 cells by modulating the expression of Bax, Bcl-2, Caspase-3, Caspase-8, Caspase-9, Jak2, Stat3, and Akt1 genes. Besides, curcumin and crocin were able to synergistically increase the cell cycle arrest at the sub G1 phase, induce autophagy and decrease the clonogenic ability of SW-480 cells.
    CONCLUSIONS: These results suggested that curcumin and crocin combination could be considered a more effective therapeutic strategy for inhibiting colorectal cancer.
    Keywords:  AKT1; Anticancer; Colorectal cancer; Crocin; Curcumin; JAK/STAT signaling; Synergism
    DOI:  https://doi.org/10.1007/s11033-022-07719-0
  45. J Nanobiotechnology. 2022 Aug 23. 20(1): 385
    ROS triggered local delivery of stealth exosomes to tumors for enhanced chemo/photodynamic therapy.
    Zhuo Wan, Xueqi Gan, Ruiyan Mei, Jianbin Du, Wen Fan, Mengying Wei, Guodong Yang, Weiwei Qin, Zhuoli Zhu, Li Liu.
      BACKGROUND: Exosomes are recognized as effective platforms for targeted delivery for their high physicochemical stability and biocompatibility. However, most of the exosomes are inevitably and rapidly cleared by mononuclear phagocytic system (MPS) during cancer therapy. How to engineer exosome to enhance the delivery efficiency is being intensively explored. In this study, we have constructed mPEG2000-TK-CP05 decorated exosomes as effective delivery platforms to achieve enhanced photodynamic/chemical cancer therapy.RESULTS: Exosomes were coated with CP05-TK-mPEG2000, in which CP05 is a peptide with high affinity to exosomal CD63 and TK could be cleaved by ROS. The resulted exosomes, namely stealth Exo, were electroporated to load RB (photosensitizer Rose Bengal) and Dox (Doxorubicin). We verified that the Stealth Exo@RB (Stealth Exo additionally loaded with RB) could escape MPS while accumulate in the tumor region efficiently in the xenograft model when laser irradiation conducted locally. Additionally, we revealed that the Stealth Exo serves as an efficient platform for Dox delivery. Dox, together with the RB mediated photodynamic therapy induce tumor cell damage synergistically in the tumor region. Moreover, the proposed switchable stealth exosomes minimized the dose of toxic Dox and thus allowed robust tumor immune response.
    CONCLUSIONS: Our results indicated that the proposed Stealth Exo greatly improves both the accessibility and efficiency of drug delivery, with minimal chemical or genetic engineering. The proposed Stealth Exo serve as a promising and powerful drug delivery nanoplatform in cancer treatment.
    Keywords:  Cancer; Exosomes; Photodynamic therapy; ROS-responsive; Targeted delivery
    DOI:  https://doi.org/10.1186/s12951-022-01591-7
  46. Front Chem. 2022 ;10 963004
    Liposomes as Multifunctional Nano-Carriers for Medicinal Natural Products.
    Xiamin Cheng, Hui Yan, Songhao Pang, Mingjun Ya, Feng Qiu, Pinzhu Qin, Chao Zeng, Yongna Lu.
      Although medicinal natural products and their derivatives have shown promising effects in disease therapies, they usually suffer the drawbacks in low solubility and stability in the physiological environment, low delivery efficiency, side effects due to multi-targeting, and low site-specific distribution in the lesion. In this review, targeted delivery was well-guided by liposomal formulation in the aspects of preparation of functional liposomes, liposomal medicinal natural products, combined therapies, and image-guided therapy. This review is believed to provide useful guidance to enhance the targeted therapy of medicinal natural products and their derivatives.
    Keywords:  liposome; nano-carrier; natural product; targeted-delivery; traditional Chinese medicine
    DOI:  https://doi.org/10.3389/fchem.2022.963004
  47. Pharmaceutics. 2022 Jul 29. pii: 1586. [Epub ahead of print]14(8):
    Nanoparticles-Based Strategies to Improve the Delivery of Therapeutic Small Interfering RNA in Precision Oncology.
    Jinxing Huang, Kai Xiao.
      Small interfering RNA (siRNA) can selectively suppress the expression of disease-causing genes, holding great promise in the treatment of human diseases, including malignant cancers. In recent years, with the development of chemical modification and delivery technology, several siRNA-based therapeutic drugs have been approved for the treatment of non-cancerous liver diseases. Nevertheless, the clinical development of siRNA-based cancer therapeutics remains a major translational challenge. The main obstacles of siRNA therapeutics in oncology include both extracellular and intracellular barriers, such as instability under physiological conditions, insufficient tumor targeting and permeability (particularly for extrahepatic tumors), off-target effects, poor cellular uptake, and inefficient endosomal escape. The development of clinically suitable and effective siRNA delivery systems is expected to overcome these challenges. Herein, we mainly discuss recent strategies to improve the delivery and efficacy of therapeutic siRNA in cancer, including the application of non-viral nanoparticle-based carriers, the selection of target genes for therapeutic silencing, and the combination with other therapeutic modalities. In addition, we also provide an outlook on the ongoing challenges and possible future developments of siRNA-based cancer therapeutics during clinical translation.
    Keywords:  cancer; combination strategies; gene delivery; nanoparticles; small interfering RNA; targeting
    DOI:  https://doi.org/10.3390/pharmaceutics14081586
  48. Int J Mol Sci. 2022 Aug 22. pii: 9490. [Epub ahead of print]23(16):
    Gut Metabolites and Breast Cancer: The Continuum of Dysbiosis, Breast Cancer Risk, and Potential Breast Cancer Therapy.
    Kayla Jaye, Dennis Chang, Chun Guang Li, Deep Jyoti Bhuyan.
      The complex association between the gut microbiome and cancer development has been an emerging field of study in recent years. The gut microbiome plays a crucial role in the overall maintenance of human health and interacts closely with the host immune system to prevent and fight infection. This review was designed to draw a comprehensive assessment and summary of recent research assessing the anticancer activity of the metabolites (produced by the gut microbiota) specifically against breast cancer. In this review, a total of 2701 articles were screened from different scientific databases (PubMed, Scopus, Embase and Web of Science) with 72 relevant articles included based on the predetermined inclusion and exclusion criteria. Metabolites produced by the gut microbial communities have been researched for their health benefits and potential anticancer activity. For instance, the short-chain fatty acid, butyrate, has been evaluated against multiple cancer types, including breast cancer, and has demonstrated anticancer potential via various molecular pathways. Similarly, nisin, a bacteriocin, has presented with a range of anticancer properties primarily against gastrointestinal cancers, with nominal evidence supporting its use against breast cancer. Comparatively, a natural purine nucleoside, inosine, though it has not been thoroughly investigated as a natural anticancer agent, has shown promise in recent studies. Additionally, recent studies demonstrated that gut microbial metabolites influence the efficacy of standard chemotherapeutics and potentially be implemented as a combination therapy. Despite the promising evidence supporting the anticancer action of gut metabolites on different cancer types, the molecular mechanisms of action of this activity are not well established, especially against breast cancer and warrant further investigation. As such, future research must prioritise determining the dose-response relationship, molecular mechanisms, and conducting animal and clinical studies to validate in vitro findings. This review also highlights the potential future directions of this field.
    Keywords:  breast cancer; butyrate; cancer; gut microbial metabolites; inosine; nisin; sodium butyrate; standard chemotherapy
    DOI:  https://doi.org/10.3390/ijms23169490
  49. Iran Biomed J. 2022 Aug 13.
    Carboxylated Graphene Oxide as a Nanocarrier for Drug Delivery of Quercetin as an Effective Anticancer Agent.
    Fatemeh Yaghoubi, Najmeh Sadat Hosseini Motlagh, Ali Moradi, Fateme Haghiralsadat.
      Background: Enhancing the therapeutic profile of hydrophobic drugs using the development of biocompatible drug delivery systems is an urgent need. Many types of research have been conducted on graphene derivatives owing to their unique characteristics.Methods: In this survey, QUER, a natural medicine, was loaded on carboxylated GO, and cytotoxicity assay and the uptake of QUER into prostate cancer cells (PC3) were evaluated.
    Results: The release behavior of QUER was temperature- and pH-sensitive. Although QUER was loaded with high efficiency, the released rate was low (23.25% at pH 5.5 and 42 °C). The toxicity and intensity of fluorescence in the FREE QUER were higher than the loaded form.
    Conclusion: High-capacity loading and controlled release of GO QUER can be recognized as a proper candidate in treating cancer.
    Keywords:  Drug delivery systems; Graphene oxide; Nanoparticle; Quercetin
    DOI:  https://doi.org/10.52547/ibj.3598
  50. Cell Mol Biol (Noisy-le-grand). 2022 Apr 30. 68(4): 134-143
    Cauliflower bioactive compound sulforaphane inhibits breast cancer development by suppressing NF-κB /MMP-9 signaling pathway expression.
    Taoqi Zhou, Minming Zhou, Chaochao Tong, Mali Zhuo.
      In recent years, anti-cancer plant food development and research have received increasing attention, and cauliflower is one of the vegetables with anti-cancer effects. Sulforaphane (SFN) is one of the main anti-cancer components in cauliflower. In this study, the mechanism of action of SFN in anti-breast cancer was investigated using SFN, a bioactive compound extracted from cauliflower. For this purpose, SFN was extracted from cauliflower using rotary evaporation and silica gel chromatography, and the extracted SFN was used for in vitro and in vivo experiments. Breast cancer cells MCF-7, MDA-MB-231 and MDA-MB-231 xenograft tumor model mice were treated with SFN, pcDNA3.1-MMP-9, Si-RNA- MMP-9 and Si-RNA-NF-κB, respectively, and the corresponding saline treatment or blank plasmid treatment was used as control. The gene expression of NF-κB and MMP-9 in each group was detected by RT-PCR, and the protein phosphorylation level of MMP-9 was measured by Western bloting assay. WST 1 assay, MTT assay and flow cytometric analysis were used to detect the activity, proliferation and apoptosis levels of breast cancer cells. The tumor histopathology of the xenograft tumor model mice after SFN treatment was examined by HE staining. Results showed that Breast cancer cells treated with SFN showed reduced cell proliferation, decreased cell activity, increased apoptosis ratio, and inhibited gene expression and protein phosphorylation of MMP-9 as well as gene expression of NF-κB (P < 0.05). The same effect occurred with transfection of Si-RNA- MMP-9 and Si-RNA-NF-κB in breast cancer cells, while transfection of pcDNA3.1-MMP-9 plasmid significantly redeemed the inhibitory effect of SFN on breast cancer cells (P < 0.05). MDA-MB-231 xenograft tumor model mice treated with SFN showed significant improvement in the pathological condition of the tumor tissue. Then, SFN may inhibit breast cancer development by regulating the NF-κB /MMP-9 signaling pathway.
    DOI:  https://doi.org/10.14715/cmb/2022.68.4.17
  51. Antioxidants (Basel). 2022 Jul 28. pii: 1481. [Epub ahead of print]11(8):
    Effects and Mechanisms of Curcumin for the Prevention and Management of Cancers: An Updated Review.
    Zhi-Jun Yang, Si-Yu Huang, Dan-Dan Zhou, Ruo-Gu Xiong, Cai-Ning Zhao, Ai-Ping Fang, Yun-Jian Zhang, Hua-Bin Li, Hui-Lian Zhu.
      Cancer is the leading cause of death in the world. Curcumin is the main ingredient in turmeric (Curcuma longa L.), and is widely used in the food industry. It shows anticancer properties on different types of cancers, and the underlying mechanisms of action include inhibiting cell proliferation, suppressing invasion and migration, promoting cell apoptosis, inducing autophagy, decreasing cancer stemness, increasing reactive oxygen species production, reducing inflammation, triggering ferroptosis, regulating gut microbiota, and adjuvant therapy. In addition, the anticancer action of curcumin is demonstrated in clinical trials. Moreover, the poor water solubility and low bioavailability of curcumin can be improved by a variety of nanotechnologies, which will promote its clinical effects. Furthermore, although curcumin shows some adverse effects, such as diarrhea and nausea, it is generally safe and tolerable. This paper is an updated review of the prevention and management of cancers by curcumin with a special attention to its mechanisms of action.
    Keywords:  anticancer; bioavailability; curcumin; mechanism; safety
    DOI:  https://doi.org/10.3390/antiox11081481
  52. Int J Inflam. 2022 ;2022 3855368
    Antitumor Activities of Aqueous Cinnamon Extract on 5637 Cell Line of Bladder Cancer through Glycolytic Pathway.
    Zeynab Aminzadeh, Nasrin Ziamajidi, Roghayeh Abbasalipourkabir, Sajedeh Daei, Sobhan Helbi, Abbas Moridnia.
      Background: Pharmacotherapy with medicinal plants is a promising approach to treat cancer. Cinnamon is a medicinal plant whose properties have been proven in various fields of medical sciences. Among its biological activities, its antioxidant and antiviral effects can be mentioned. In this study, the antitumor effects of Cinnamon with a focus on glucose metabolism in bladder cancer carcinoma cell-line 5637 were investigated.Methods: Aqueous extract of Cinnamon was prepared from Cinnamon bark. Bladder cancer 5637cell line were treated with different concentrations of aqueous extract of Cinnamon. MTT was used to evaluate cell viability at 24, 48, and 72 h. The concentration of 1.25, 2.50, and 5 mg/ml was used. Apoptosis was assessed with Hochest33258 staining. For evaluating of aqueous extract of Cinnamon effect on glycolysis, the gene expression of epidermal growth factor receptor 2 (ErbB2), heat shock protein transcription factor1 (HSF1), and lactate dehydrogenase A (LDHA), as well as protein levels of HSF1 and LDHA, LDH activity, glucose consumption, and lactate production, were measured.
    Results: Aqueous extract of Cinnamon significantly decreased ErbB2, HSF1, and LDHA gene expression and also decreased the protein level of HSF1 and LDHA, LDH activity, glucose consumption, and lactate production dose-dependently (p < 0.05).
    Conclusion: Our finding showed that the aqueous extract of Cinnamon can inhibit proliferation in 5637 cells by inhibition of glycolysis and induction of apoptosis.
    DOI:  https://doi.org/10.1155/2022/3855368
  53. Metabolites. 2022 Aug 12. pii: 745. [Epub ahead of print]12(8):
    Targeting Ferroptosis in Colorectal Cancer.
    Xiaojie Liang, Zhihuan You, Xinhao Chen, Jun Li.
      Ferroptosis is a unique way of regulating cell death (RCD), which is quite different from other programmed cell deaths such as autophagy. It presents iron overload, accumulation of reactive oxygen species (ROS), and lipid peroxidation. A ferroptotic cell usually has an intact cell structure as well as shrinking mitochondria with decreased or vanishing cristae, concentrated membrane density, and ruptured outer membrane. Recently, increasing investigations have discovered that tumor cells have a much greater iron demand than the normal ones, making them more sensitive to ferroptosis. In other words, ferroptosis may inhibit the progress of the tumor, which can be used in the therapy of tumor patients, especially for those with chemotherapy resistance. Therefore, ferroptosis has become one hot spot in the field of tumor research in recent years. Colorectal cancer (CRC) is one common type of gastrointestinal malignancy. The incidence of CRC appears to have an upward trend year by year since the enhancement of living standards. Although surgery and chemoradiotherapy have largely improved the prognosis of patients with CRC, some patients still appear to have severe adverse reactions and drug resistance. Moreover, much research has verified that ferroptosis has a necessary association with the occurrence and progression of gastrointestinal tumors. In this review, we provide a comprehensive evaluation of the main mechanisms of iron metabolism, lipid metabolism, and amino acid metabolism involved in the occurrence of ferroptosis, as well as the research progress of ferroptosis in CRC.
    Keywords:  colorectal cancer 2; ferroptosis 1; iron ions 3; lipid peroxides 4
    DOI:  https://doi.org/10.3390/metabo12080745
  54. Curr Med Chem. 2022 Aug 21.
    Nano/Microcarriers in Drug Delivery: Moving the Timeline to Contemporary.
    Ana Vujačić Nikezić, Jasmina Grbović Novaković.
      Treatment of various diseases, especially cancer treatment, includes the potential use of different types of nanoparticles and nanostructures as drug carriers. However, searching for the less toxic and more efficient therapy requires further progress wherein recent developments in medicine increasingly include the use of various advanced nanostructures. Their more successful application might be achieved by leveling imbalances between the potentiality of different nanostructures and demands required for their safe use. Biocompatibility, biodegradability, prolonged circulation time and enhanced accumulation and uptake by cells are some of the key preconditions for their usage in efficient drug delivery. Thanks to their greatly tunable functions, they are major building blocks for manufacturing novel materials. Nevertheless, given that their toxicity is questionable their practical application is challenging. Hereof, before entering in the sphere of human consumption it is of critical importance to perform more studies regarding their toxicity and drug distribution. This review emphasizes some recent advances in the field of nanomedicine employing different kinds of conventionally used nanoparticles as well as novel nanoparticles and nanostructures. Special emphasis is placed on micro/nanomotors (MNMs) discussing their opportunities, limitations, challenges and possible applications in drug delivery and outlining some perspectives in nanomedicine area.
    Keywords:  Biomedical application; Drug delivery vehicles; Micro/nanorobots; Smart nanocarriers; Targeted therapy; Toxicity
    DOI:  https://doi.org/10.2174/0929867329666220821193938
  55. Pharmaceutics. 2022 Aug 19. pii: 1735. [Epub ahead of print]14(8):
    High Drug-Loading Nanomedicines for Tumor Chemo-Photo Combination Therapy: Advances and Perspectives.
    Ya Wang, Yujie Zhang, Xiaojiang Zhang, Zhe Zhang, Junjun She, Daocheng Wu, Wei Gao.
      The combination of phototherapy and chemotherapy (chemo-photo combination therapy) is an excellent attempt for tumor treatment. The key requirement of this technology is the high drug-loading nanomedicines, which can load either chemotherapy drugs or phototherapy agents at the same nanomedicines and simultaneously deliver them to tumors, and play a multimode therapeutic role for tumor treatment. These nanomedicines have high drug-loading efficiency (&gt;30%) and good tumor combination therapeutic effect with important clinical application potential. Although there are many reports of high drug-loading nanomedicines for tumor therapy at present, systematic analyses on those nanomedicines remain lacking and a comprehensive review is urgently needed. In this review, we systematically analyze the current status of developed high drug-loading nanomedicines for tumor chemo-photo combination therapy and summarize their types, methods, drug-loading properties, in vitro and in vivo applications. The shortcomings of the existing high drug-loading nanomedicines for tumor chemo-photo combination therapy and the possible prospective development direction are also discussed. We hope to attract more attention for researchers in different academic fields, provide new insights into the research of tumor therapy and drug delivery system and develop these nanomedicines as the useful tool for tumor chemo-photo combination therapy in the future.
    Keywords:  chemotherapy; combination therapy; high drug-loading nanomedicines; phototherapy
    DOI:  https://doi.org/10.3390/pharmaceutics14081735
  56. Front Nutr. 2022 ;9 924192
    Chemoprevention effect of the Mediterranean diet on colorectal cancer: Current studies and future prospects.
    Asma Ismail Mahmod, Shatha Khaled Haif, Ayah Kamal, Israa A Al-Ataby, Wamidh H Talib.
      Colorectal cancer (CRC) is the third most common cancer and the second most deadly cancer worldwide. Nevertheless, more than 70% of CRC cases are resulted from sporadic tumorigenesis and are not inherited. Since adenoma-carcinoma development is a slow process and may take up to 20 years, diet-based chemoprevention could be an effective approach in sporadic CRC. The Mediterranean diet is an example of a healthy diet pattern that consists of a combination of nutraceuticals that prevent several chronic diseases and cancer. Many epidemiological studies have shown the correlation between adherence to the Mediterranean diet and low incidence of CRC. The goal of this review is to shed the light on the anti-inflammatory and anti-colorectal cancer potentials of the natural bioactive compounds derived from the main foods in the Mediterranean diet.
    Keywords:  Mediterranean diet; chemoprevention; colorectal cancer; inflammation; natural compounds
    DOI:  https://doi.org/10.3389/fnut.2022.924192
  57. Front Endocrinol (Lausanne). 2022 ;13 974042
    The effect of magnesium alone or its combination with other supplements on the markers of inflammation, OS and metabolism in women with polycystic ovarian syndrome (PCOS): A systematic review.
    Ruiyun Li, Zhiyuan Li, Yi Huang, Kaiyan Hu, Bin Ma, Yuan Yang.
      The objective of this systematic review is to synthesize the available evidence on the effectiveness of magnesium supplements on the markers of inflammation, oxidative stress (OS), and metabolism in PCOS patients and to provide a basis for its clinical treatment. Electronic databases (PubMed, Cochrane Library databases, Embase, Web of science, CMB, CNKI, VIP, Wan Fang and ClinicalTrials.gov) were searched from their inception until January 2022. Randomized controlled trials (RCTs) for PCOS undergoing therapy with magnesium supplementation alone or in combination with other agents. The primary outcomes were the markers of blood glucose and OS.363 patients from nine RCTs were included in the current systematic review. Four of the nine studies reported the effects of magnesium supplementation alone on OS or metabolic markers in women with PCOS. Whilemagnesium supplementation alone did not show any significant improvement in the markers of inflammation, OS or metabolism in PCOS, seven of the nine articles reported the effect of magnesium co-supplementation on OS or metabolic markers in PCOS patients. Magnesium combined with vitamin E or zinc-calcium-vitamin D significantly improved glucose and lipid metabolism in PCOS patients. Magnesium intake alone did not lead to a significant improvement in the markers of OS, blood glucose, or serum lipids in PCOS. However, magnesium combined with other supplements (vitamin E, zinc, zinc-calcium-vitamin D) significantly improved serum hs-CRP, insulin, HOMA-IR, TG, TC levels, and the improvement in OS markers was inconclusive. The effect of magnesium and melatonin supplementation on the markers of metabolism needs to be further verified.System Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/#myprospero, CRD42022303410.
    Keywords:  inflammation; insulin resistance; lipid profile; magnesium; oxidative stress; polycystic ovarian syndrome
    DOI:  https://doi.org/10.3389/fendo.2022.974042
  58. Front Bioeng Biotechnol. 2022 ;10 975431
    Vitamin D and curcumin-loaded PCL nanofibrous for engineering osteogenesis and immunomodulatory scaffold.
    Abdullrahman M Al-Bishari, Bilal A Al-Shaaobi, Aisha A Al-Bishari, Mohammed A Al-Baadani, Liang Yu, Jiating Shen, Lei Cai, Yiding Shen, Zhennan Deng, Peng Gao.
      The accelerating bone healing process is still a major challenge in clinical orthopedics, especially in critical-sized bone defects. Recently, Nanofiber membranes are showing increasing attention in the biomedical field due to their good biocompatibility, mechanical stability, and the ability to work as a drug carrier to achieve localized and sustained drug delivery. Herein, a multifunction nanofiber membrane loaded with vitamin D (Vit D) and curcumin (Cur) was successfully fabricated using electrospinning technology. In addition, we innovatively modified Vit D with PEG to improve the hydrophilicity of PCL nanofibers. The vitro results of CCK-8, alkaline phosphatase (ALP) and mineralization demonstrated that the PCL/Vit D-Cur membrane had great potential for enhancing the proliferation/differentiation of osteoblasts. Moreover, the synergistic effect of Vit D-Cur loaded PCL nanofiber membrane showed a superior ability to improve the anti-inflammatory activity through M2 polarization. Furthermore, in vivo results confirmed that the defect treated with PCL/Vit D-Cur nanofiber membrane was filled with the newly formed bone after 1 month. These results indicate that the Vit D/Cur loaded membrane can be applied for potential bone regeneration therapy.
    Keywords:  anti-inflammatory; bone regeneration; curcumin; electrospinning; vitamin D
    DOI:  https://doi.org/10.3389/fbioe.2022.975431
  59. Eur J Pharmacol. 2022 Aug 21. pii: S0014-2999(22)00486-1. [Epub ahead of print] 175225
    Enhanced antitumor effect of icariin nanoparticles coated with iRGD functionalized erythrocyte membrane.
    You Ji, Ziting Zhang, Wenjun Hou, Min Wu, Haisi Wu, Nan Hu, Mengnan Ni, Chunming Tang, Fenglei Wu, Huae Xu.
      Lung cancer is the most common cause of incidence and mortality among tumor diseases. Icariin (ICA), a potential Chinese medicine monomer, has been reported to show outstanding antitumor effects. However, the hydrophobic nature and less tumor penetration limit its potential as a topical healing agent. There are few studies report the efficacy of ICA on lung cancer, moreover, there is no biomimetic targeted delivery system in the application of ICA. Herein, we firstly develop a novel ICA bionic targeted nano-preparation, camouflaged by the tumor penetrating peptide iRGD (cRGDKGPDC), functionalized red blood cell membrane (RBCM), has the increased solubility, utilized biocompatibility, and aggravated tumor penetration of ICA. In this study, we constructed the iRGD functionalized RBCM mimetic targeted ICA-loaded nanoparticles (iRINPs) and explored the anti-tumor effect of iRINPs against lung cancer with biochemical and behavioral analysis. The results suggested that iRINPs showed improved biocompatibility and stability, and reduced phagocytic uptakes by macrophages. Besides, the modification of iRGD significantly improved the targeting ability of iRINPs. In vitro and in vivo the treatment effects and safety assays showed that iRINPs attained better therapeutic effects than ICA by inhibiting A549 cell migration, proliferation and invasion, as well as reducing side effects of ICA. Overall, we expected that the new bionic nanocarriers would be a promising nano-platform for ICA in the precise therapy of lung cancer.
    Keywords:  Antitumor efficiency; Bionic nanoparticles; Icariin; Lung cancer; iRGD
    DOI:  https://doi.org/10.1016/j.ejphar.2022.175225
  60. J Pharm Sci. 2022 Aug 22. pii: S0022-3549(22)00356-2. [Epub ahead of print]
    Smart oral pH-responsive dual layer nano-hydrogel for dissolution enhancement and targeted delivery of naringenin using protein-polysaccharides complexation against colorectal cancer.
    Shadab Md, Samaa Abdullah, Zuheir Awan, Nabil A Alhakamy.
      Naringenin (NAR) is a natural anticancer, but it has not been developed for clinical use despite its therapeutic potential due to its low water solubility, low membrane permeability, first-pass metabolism, and low bioavailability. To overcome these problems, the optimization and preparation of NAR-Soy protein complex (NAR-Sp) led to the optimum ratio of their interaction using Fourier Transform-Infrared spectroscopy (FT-IR) as the first level and layer of the formulation. The second layer of the formulation was to incorporate the NAR-Sp complex in aqueous-based gel-forming. The most optimum nanosuspension was determined using the gel sedimentation, sustained-release, pH-selective and targeted system. The most optimum components combinations and complex were characterized using different characterization tools, such as, the particle size analysis, SEM, TEM, PXRD and FT-IR. In addition, the optimum nanosuspension was characterized for its nanoparticle sensitivity against colorectal cancer cells using MTT assay in comparison to the untreated, naringenin, and blank groups. The complex enhanced the NAR's dissolution. The complex incorporation in the optimum nano-encapsulating system was characterized by the sustained-release and pH-selective behaviors to target the NAR release at the site of action or absorption. Interestingly, the optimum nano-encapsulating system was showing better colorectal cytotoxicity results in comparison to the other groups.
    Keywords:  Naringenin; complex; controlled delivery; dissolution enhancement; nanohydrogel; nanosuspension
    DOI:  https://doi.org/10.1016/j.xphs.2022.08.019
  61. Cancers (Basel). 2022 Aug 12. pii: 3898. [Epub ahead of print]14(16):
    A Review of Medicinal Plants of the Himalayas with Anti-Proliferative Activity for the Treatment of Various Cancers.
    Hailemeleak Regassa, Anuradha Sourirajan, Vikas Kumar, Sadanand Pandey, Deepak Kumar, Kamal Dev.
      Cancer is a serious and significantly progressive disease. Next to cardiovascular disease, cancer has become the most common cause of mortality in the entire world. Several factors, such as environmental factors, habitual activities, genetic factors, etc., are responsible for cancer. Many cancer patients seek alternative and/or complementary treatments because of the high death rate linked with cancer and the adverse side effects of chemotherapy and radiation therapy. Traditional medicine has a long history that begins with the hunt for botanicals to heal various diseases, including cancer. In the traditional medicinal system, several plants used to treat diseases have many bioactive compounds with curative capability, thereby also helping in disease prevention. Plants also significantly contributed to the modern pharmaceutical industry throughout the world. In the present review, we have listed 33 medicinal plants with active and significant anticancer activity, as well as their anticancer compounds. This article will provide a basic set of information for researchers interested in developing a safe and nontoxic active medicinal plant-based treatment for cancer. The research will give a scientific foundation for the traditional usage of these medicinal herbs to treat cancer.
    Keywords:  Himalayas; cancer; cytotoxicity; immunotherapies; medicinal plants; phytocompounds
    DOI:  https://doi.org/10.3390/cancers14163898
  62. Phytochemistry. 2022 Aug 20. pii: S0031-9422(22)00306-5. [Epub ahead of print] 113390
    Different mechanisms by which apigenin improves treatment of dermatological disorders Apigenin and its dermatological applications: A comprehensive review.
    Pantea Majma Sanaye, Mohammad Reza Mojaveri, Roohollah Ahmadian, Mehdi Sabet Jahromi, Roodabeh Bahramsoltani.
      Apigenin is one of the abundant flavonoids in fruits and vegetables of human diet with several demonstrated health benefits. The aim of the present study is to provide an overview of the current evidence regarding the effect of apigenin on different dermatological complications. Electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve all papers assessing the dermatological effects of apigenin. Preclinical studies support beneficial effects of apigenin on UV-induced skin damage, vitiligo, dermatitis, wounds, skin aging, and some types of skin cancer. The compound mostly acts via inhibition of inflammation through suppression of pro-inflammatory cytokines and intracellular inflammatory mediators, as well as antioxidant properties such as improvement of endogenous antioxidant defense mechanisms. There are also some studies for the design and development of novel drug delivery systems for apigenin to improve its oral and topical bioavailability. Nevertheless, no clinical study has evaluated apigenin as a natural supplement for skin conditions. Considering the benefits of apigenin in preclinical models of dermatological disorders, as well as the acceptable safety of this compound, apigenin maybe a future candidate to be used in dermatological disorders. Future clinical studies are needed to further confirm the safety and efficacy of apigenin in skin care products.
    Keywords:  Antioxidant; Apigenin; Cancer; Flavonoid; Inflammation; Skin
    DOI:  https://doi.org/10.1016/j.phytochem.2022.113390
  63. Curr Drug Targets. 2022 Aug 22.
    Nanoformulations - Insights Towards Characterization Techniques.
    Venkateshwaran Krishnaswami, Abimanyu Sugumaran, Venkatesan Perumal, Murugan Manavalan, Durga Prasad Kondeti, Shaik Kamil Basha, Mohammed Akmal Ahmed, Munish Kumar, Sivakumar Vijayaraghavalu.
      BACKGROUND: Drug-loaded novel nanoformulations are gaining importance due to their versatile properties compared to conventional pharmaceutical formulations. Nanomaterials, apart from their multifactorial benefits, have a wider scope in the prevention, treatment, and diagnosis of cancer. Understanding the chemistry of drug-loaded nano-formulations to elicit its behaviour both at molecular and systemic levels is critical in the present scenario. Drug-loaded nanoformulations are controlled by their size, shape, surface chemistry, and release behavior. The major pharmaceutical drug loaded nanocarriers reported for anticancer drug delivery for the treatment of various forms of cancers such as lung cancer, liver cancer, breast cancer, colon cancer, etc include nanoparticles, nanospheres, nanodispersions, nanocapsules, nanomicelles, cubosomes, nanoemulsions, liposomes and niosomes. The major objectives in designing anticancer drug-loaded nanoformulations are to manage the particle size/morphology correlating with the drug release to fulfil the specific objectives. Hence, nano characterizations are very critical both at in vitro and in vivo levels.OBJECTIVE: The main objective of this review paper is to summarise the major characterization techniques used for the characterization of drug-loaded nanoformulations. Even though information on characterization techniques of various nano-formulations is available in the literature, it is scattered. The proposed review will provide a comprehensive understanding of nanocharacterization techniques.
    CONCLUSION: To conclude, the proposed review will provide insights towards the different nano characterization techniques along with their recent updates, such as particle size, zeta potential, entrapment efficiency, in vitro release studies (chromatographic HPLC, HPTLC, and LC-MS/MS analysis), EPR analysis, X-ray diffraction analysis, thermal analysis, rheometric, morphological analysis etc. Additionally, the challenges encountered by the nano characterization techniques will also be discussed.
    Keywords:  EPR spectra; Nanocharacterization; Nanomaterial; Nanoparticles; Raman Spectra.; Zeta potential
    DOI:  https://doi.org/10.2174/1389450123666220822094248
  64. Polymers (Basel). 2022 Aug 11. pii: 3278. [Epub ahead of print]14(16):
    Application of Nanomicelles in Enhancing Bioavailability and Biological Efficacy of Bioactive Nutrients.
    Lei Li, Yun Zeng, Minyi Chen, Gang Liu.
      Nutraceuticals provide many biological benefits besides their basic nutritional value. However, their biological efficacies are often limited by poor absorption and low bioavailability. Nanomaterials have received much attention as potential delivery systems of nutrients and phytonutrients for multiple applications. Nanomicelles are nanosized colloidal structures with a hydrophobic core and hydrophilic shell. Due to their unique characteristics, they have shown great perspectives in food and nutraceutical science. In this review, we discussed the unique properties of nanomicelles. We also emphasized the latest advances on the design of different nanomicelles for efficient delivery and improved bioavailability of various nutrients. The role of nanomicelles in the efficacy improvement of bioactive components from nutraceutical and health foods has been included. Importantly, the safety concerns on nano-processed food products were highlighted.
    Keywords:  bioactive nutrients; bioavailability; delivery systems; nanomaterials; nanomicelles
    DOI:  https://doi.org/10.3390/polym14163278
  65. Cells. 2022 Aug 11. pii: 2502. [Epub ahead of print]11(16):
    Enhanced Delivery of Rose Bengal by Amino Acids Starvation and Exosomes Inhibition in Human Astrocytoma Cells to Potentiate Anticancer Photodynamic Therapy Effects.
    Bianca Slivinschi, Federico Manai, Carolina Martinelli, Francesca Carriero, Camilla D'Amato, Martina Massarotti, Giorgia Bresciani, Claudio Casali, Gloria Milanesi, Laura Artal, Lisa Zanoletti, Federica Milella, Davide Arfini, Alberto Azzalin, Sara Demartis, Elisabetta Gavini, Sergio Comincini.
      Photodynamic therapy (PDT) is a promising anticancer strategy based on the light energy stimulation of photosensitizers (PS) molecules within a malignant cell. Among a multitude of recently challenged PS, Rose bengal (RB) has been already reported as an inducer of cytotoxicity in different tumor cells. However, RB displays a low penetration capability across cell membranes. We have therefore developed a short-term amino acids starvation protocol that significantly increases RB uptake in human astrocytoma cells compared to normal rat astrocytes. Following induced starvation uptake, RB is released outside cells by the exocytosis of extracellular vesicles (EVs). Thus, we have introduced a specific pharmacological treatment, based on the GW4869 exosomes inhibitor, to interfere with RB extracellular release. These combined treatments allow significantly reduced nanomolar amounts of administered RB and a decrease in the time interval required for PDT stimulation. The overall conditions affected astrocytoma viability through the activation of apoptotic pathways. In conclusion, we have developed for the first time a combined scheme to simultaneously increase the RB uptake in human astrocytoma cells, reduce the extracellular release of the drug by EVs, and improve the effectiveness of PDT-based treatments. Importantly, this strategy might be a valuable approach to efficiently deliver other PS or chemotherapeutic drugs in tumor cells.
    Keywords:  drug delivery; glioblastoma; nanomedicine; photosensitizers; rose bengal
    DOI:  https://doi.org/10.3390/cells11162502
  66. Biomedicines. 2022 Aug 11. pii: 1948. [Epub ahead of print]10(8):
    Plant-Derived Bioactive Compounds in Colorectal Cancer: Insights from Combined Regimens with Conventional Chemotherapy to Overcome Drug-Resistance.
    Laura Ioana Gavrilas, Daniel Cruceriu, Andrei Mocan, Felicia Loghin, Doina Miere, Ovidiu Balacescu.
      Acquired drug resistance represents a major clinical problem and one of the biggest limitations of chemotherapeutic regimens in colorectal cancer. Combination regimens using standard chemotherapeutic agents, together with bioactive natural compounds derived from diet or plants, may be one of the most valuable strategies to overcome drug resistance and re-sensitize chemoresistant cells. In this review, we highlight the effect of combined regimens based on conventional chemotherapeutics in conjunction with well-tolerated plant-derived bioactive compounds, mainly curcumin, resveratrol, and EGCG, with emphasis on the molecular mechanisms associated with the acquired drug resistance.
    Keywords:  chemotherapy resistance; colorectal cancer; combination therapy; curcumin; drug resistance; epigallocatechin gallate; resveratrol
    DOI:  https://doi.org/10.3390/biomedicines10081948
  67. Cancers (Basel). 2022 Aug 18. pii: 4003. [Epub ahead of print]14(16):
    5-ALA Is a Potent Lactate Dehydrogenase Inhibitor but Not a Substrate: Implications for Cell Glycolysis and New Avenues in 5-ALA-Mediated Anticancer Action.
    Mantas Grigalavicius, Somayeh Ezzatpanah, Athanasios Papakyriakou, Tine Therese Henriksen Raabe, Konstantina Yannakopoulou, Theodossis A Theodossiou.
      In a course of metabolic experiments, we determined that the addition of δ-aminolevulinic acid (5-ALA) to a panel of glioblastoma multiforme (GBM) cells caused a steep reduction in their glycolytic activity. This reduction was accompanied by a decrease in adenosine triphosphate (ATP) production from glycolysis. These results suggested that 5-ALA is an inhibitor of glycolysis; due to the structural similarity of 5-ALA to the established lactate dehydrogenase (LDH) inhibitors oxamate (OXM) and tartronate (TART), we initially investigated LDH inhibition by 5-ALA in silico. The modelling revealed that 5-ALA could indeed be a competitive inhibitor of LDH but not a substrate. These theoretical findings were corroborated by enzymatic and cell lysate assays in which 5-ALA was found to confer a potent LDH inhibition comparable to that of OXM and TART. We subsequently evaluated the effect of 5-ALA-induced glycolysis inhibition on the viability of GBM cells with diverse metabolic phenotypes. In the Warburg-type cell lines Ln18 and U87, incubation with 5-ALA elicited profound and irreversible cell death (90-98%) at 10 mM after merely 24 h. In T98G, however, which exhibited both high respiratory and glycolytic rates, LD95 was achieved after 72 h of incubation with 20 mM 5-ALA. We additionally examined the production of the 5-ALA photosensitive metadrug protoporphyrin IX (PpIX), with and without prior LDH inhibition by TART. These studies revealed that ~20% of the 5-ALA taken up by the cells was engaged in LDH inhibition. We subsequently performed 5-ALA photodynamic therapy (PDT) on Ln18 GBM cells, again with and without prior LDH inhibition with TART, and found a PDT outcome enhancement of ~15% upon LDH pre-inhibition. We expect our findings to have a profound impact on contemporary oncology, particularly for the treatment of otherwise incurable brain cancers such as GBM, where the specific accumulation of 5-ALA is very high compared to the surrounding normal tissue.
    Keywords:  glioblastoma multiforme; glioblastoma treatment; glycolysis; glycolysis inhibition; lactate dehydrogenase; metabolism; δ-aminolevulinic acid
    DOI:  https://doi.org/10.3390/cancers14164003
  68. Pak J Pharm Sci. 2022 Jul;35(4): 1043-1053
    Mechanisms of natural products as potential antiepileptic drugs.
    Nurulumi Ahmad, Yow Hui-Yin, Mohd Makmor-Bakry.
      The universal epileptogenic cascade remains unknown and most modern treatments focus on the reduction of symptoms and the prevention of seizure recurrence. Experimental studies have demonstrated that herbal medicines may act as antiepileptogenic agents. In this study, the possibilities of plants with antiepileptic properties were reviewed and discussed on their structures and related mechanism of actions. This work constituted a literature review of medicinal plants showing antiepileptic properties by literature searching in Science Direct, PubMed and Wiley Online Library. The keywords of search included epilepsy, antiepileptogenesis, antiepilepsy, natural compounds, extract, herbal medicines and medicinal plants in epilepsy treatment. Only articles published in English were reviewed. Mechanism of action of the natural plants were described according to experimental studies. From the databases, we found 135 natural plants with antiepileptic properties. In this review, the highly studied natural plants were selected. These included Acorus calamus, Bacopa monnieri, Boerhaavia diffusa, Curcuma longa, Gastrodia elata, Ginseng, Uncaria rhynchophylla, Pinellia ternatae, Withania somnifera, Magnolia bark and Resveratrol-related products. From the evidences, natural products may potentially be developed as antiepileptic or antiepileptogenic agents. However, several issues in drug development should be considered such as safety, formulations, pharmacokinetic characteristics and possible interactions.
  69. Pharmaceuticals (Basel). 2022 Aug 08. pii: 975. [Epub ahead of print]15(8):
    Intestinal Absorption Study: Challenges and Absorption Enhancement Strategies in Improving Oral Drug Delivery.
    Maisarah Azman, Akmal H Sabri, Qonita Kurnia Anjani, Mohd Faiz Mustaffa, Khuriah Abdul Hamid.
      The oral route is the most common and practical means of drug administration, particularly from a patient's perspective. However, the pharmacokinetic profile of oral drugs depends on the rate of drug absorption through the intestinal wall before entering the systemic circulation. However, the enteric epithelium represents one of the major limiting steps for drug absorption, due to the presence of efflux transporters on the intestinal membrane, mucous layer, enzymatic degradation, and the existence of tight junctions along the intestinal linings. These challenges are more noticeable for hydrophilic drugs, high molecular weight drugs, and drugs that are substrates of the efflux transporters. Another challenge faced by oral drug delivery is the presence of first-pass hepatic metabolism that can result in reduced drug bioavailability. Over the years, a wide range of compounds have been investigated for their permeation-enhancing effect in order to circumvent these challenges. There is also a growing interest in developing nanocarrier-based formulation strategies to enhance the drug absorption. Therefore, this review aims to provide an overview of the challenges faced by oral drug delivery and selected strategies to enhance the oral drug absorption, including the application of absorption enhancers and nanocarrier-based formulations based on in vitro, in vivo, and in situ studies.
    Keywords:  absorption enhancers; intestinal absorption; nanocarriers; oral delivery; pharmacokinetic profile
    DOI:  https://doi.org/10.3390/ph15080975
  70. Adv Mater. 2022 Aug 26. e2206121
    Tumor Selective Metabolic Reprogramming as a Prospective PD-L1 Depression Strategy to Reactivate Immunotherapy.
    Yu Liu, Zaigang Zhou, Jiting Hou, Wei Xiong, Heejeong Kim, Jiashe Chen, Chunjuan Zheng, Xin Jiang, Juyoung Yoon, Jianliang Shen.
      Currently, the role of the lysosome, endoplasmic reticulum (ER), or dictyosome in the transcription and translation of Programmed cell death ligand 1 (PD-L1) was well revealed, but the role and function of mitochondria in the PD-L1 expression in tumors was still not fully researched, making it hard to offer a novel PD-L1 regulation strategy. In this research, we newly revealed that mitochondria oxidative phosphorylation (OXPHOS) depression could be used as an effective PD-L1 downregulation method. To offer an ideal and high-effective tumor mitochondria-targeted OXPHOS depression nanosystem, IR-LND was prepared by conjugating mitochondria-targeted heptamethine cyanine dye IR-68 with mitochondrial complexes Ⅰ and Ⅱ depression agent Lonidamine (LND), which then further self-assembled with albumin (Alb) to form IR-LND@Alb nanoparticles. By doing this, PD-L1 expression in tumors was selectively and effectively depressed by IR-LND@Alb nanoparticles. As we expected, the anti-tumor efficacy of such a PD-L1 depression strategy was superior to conventional anti-PD-L1 monoclonal antibodies. Interestingly, IR-LND could also be served as a novel ideal promising photodynamic therapy (PDT) drug with self-oxygen and self-PD-L1 regulation capacity. All in all, this tumor-selective metabolic reprogramming platform to reactivate immunotherapy and sensitize for PDT effect, which would open a new window for mitochondrial immunotherapy for cancer patients. This article is protected by copyright. All rights reserved.
    Keywords:  immunotherapy; mitochondria; photodynamic therapy; programmed death ligand-1; tumor targeting
    DOI:  https://doi.org/10.1002/adma.202206121
  71. Front Nutr. 2022 ;9 960674
    Biofabrication of Silver Nanoparticles (AgNPs) Using Embelin for Effective Therapeutic Management of Lung Cancer.
    Rutika R Jagtap, Aniket Garud, Shubhangi S Puranik, Mithun Rudrapal, Mohammad Azam Ansari, Mohammad N Alomary, Meshal Alshamrani, Ahmad Salawi, Yosif Almoshari, Johra Khan, Bhagyashri Warude.
      Nanobiotechnology is a burgeoning field of research with applications in cancer treatment, targeted chemotherapy, and molecular diagnosis. This study aims at the fabrication of silver nanoparticles using embelin derived from Embelia ribes to evaluate its anticancer property. Silver nanoparticles (AgNPs) have emerged as a novel nano-carrier for therapeutic agents with a wide range of medical capabilities due to their unique structural, physicochemical, and optical features. In our study, the particle size of fabricated AgNPs was measured as 25 nm, and the zeta potential was recorded as -5.42 mV, which indicates the good stability of embelin-derived AgNPs. The crystalline surface morphology was observed by SEM analysis. The FT-IR spectrum confirmed the reduction in silver ions (Ag+) by embelin, and the TEM analysis exhibited polydispersed Ag+ of 20-30 nm. The anticancer potential of embelin-fabricated AgNPs was investigated using in vitro studies on lung cancer cells by the MTT assay. The results revealed significant dose-dependent inhibition of cell proliferation against A549 cell lines. Embelin AgNP-induced apoptosis was measured by the annexin-V PI apoptosis assay, which exhibited significantly low necrotic cells as compared to apoptotic cells. Finally, the findings of our study suggest the anticancer potential of biofabricated embelin AgNPs, particularly against lung cancer cells.
    Keywords:  MTT assay; anticancer; apoptosis assay; biofabrication; embelin; lung cancer; silver nanoparticles
    DOI:  https://doi.org/10.3389/fnut.2022.960674
  72. Pharmaceutics. 2022 Jul 29. pii: 1576. [Epub ahead of print]14(8):
    Novel Drug Delivery Systems as an Emerging Platform for Stomach Cancer Therapy.
    Umme Hani, Riyaz Ali M Osmani, Sabina Yasmin, B H Jaswanth Gowda, Hissana Ather, Mohammad Yousuf Ansari, Ayesha Siddiqua, Mohammed Ghazwani, Adel Al Fatease, Ali H Alamri, Mohamed Rahamathulla, M Yasmin Begum, Shadma Wahab.
      Cancer has long been regarded as one of the world's most fatal diseases, claiming the lives of countless individuals each year. Stomach cancer is a prevalent cancer that has recently reached a high number of fatalities. It continues to be one of the most fatal cancer forms, requiring immediate attention due to its low overall survival rate. Early detection and appropriate therapy are, perhaps, of the most difficult challenges in the fight against stomach cancer. We focused on positive tactics for stomach cancer therapy in this paper, and we went over the most current advancements and progressions of nanotechnology-based systems in modern drug delivery and therapies in great detail. Recent therapeutic tactics used in nanotechnology-based delivery of drugs aim to improve cellular absorption, pharmacokinetics, and anticancer drug efficacy, allowing for more precise targeting of specific agents for effective stomach cancer treatment. The current review also provides information on ongoing research aimed at improving the curative effectiveness of existing anti-stomach cancer medicines. All these crucial matters discussed under one overarching title will be extremely useful to readers who are working on developing multi-functional nano-constructs for improved diagnosis and treatment of stomach cancer.
    Keywords:  novel drug delivery systems; pathophysiology; stomach cancer; therapies
    DOI:  https://doi.org/10.3390/pharmaceutics14081576
  73. Carbohydr Polym. 2022 Nov 01. pii: S0144-8617(22)00780-9. [Epub ahead of print]295 119875
    Mesona chinensis polysaccharide/zein nanoparticles to improve the bioaccesibility and in vitro bioactivities of curcumin.
    Jun Yang, Jieqiong Lin, Xianxiang Chen, Liyuan Rong, Mingyue Shen, Yuanxing Wang, Jianhua Xie.
      The aim of this study was to enhance the stability, bioaccesibility, and bioactivities of curcumin using a composite nanoparticle prepared from zein and Mesona chinensis polysaccharide (MCP). Curcumin-loaded nanoparticles (ZMC NPs) were prepared. ZMC NPs showed smooth spherical structure with a high encapsulation efficiency (94 %), a small average particle size (223 nm), and surface negative charge (-34.53 mV). Compared with free curcumin, encapsulated curcumin has been shown to have better environmental stability, higher antioxidant activity and bioaccesibility. The surface coating of zein NPs with MCP makes them more amenable to uptake by intestinal epithelial cells. Studies on in vitro antitumor activity of ZMC NPs showed that they could enter hepatocellular carcinoma cells, induce cell apoptosis, promote ROS production, and alter mitochondrial membrane potential, showing higher in vitro antitumor activity compared to free curcumin. These results may contribute to the development of novel curcumin oral delivery systems.
    Keywords:  Antitumor; Curcumin delivery; Mesona chinensis polysaccharide; Zein
    DOI:  https://doi.org/10.1016/j.carbpol.2022.119875
  74. Pharmaceutics. 2022 Aug 17. pii: 1722. [Epub ahead of print]14(8):
    Beyond Formulation: Contributions of Nanotechnology for Translation of Anticancer Natural Products into New Drugs.
    Rodrigo Dos A Miguel, Amanda S Hirata, Paula C Jimenez, Luciana B Lopes, Leticia V Costa-Lotufo.
      Nature is the largest pharmacy in the world. Doxorubicin (DOX) and paclitaxel (PTX) are two examples of natural-product-derived drugs employed as first-line treatment of various cancer types due to their broad mechanisms of action. These drugs are marketed as conventional and nanotechnology-based formulations, which is quite curious since the research and development (R&D) course of nanoformulations are even more expensive and prone to failure than the conventional ones. Nonetheless, nanosystems are cost-effective and represent both novel and safer dosage forms with fewer side effects due to modification of pharmacokinetic properties and tissue targeting. In addition, nanotechnology-based drugs can contribute to dose modulation, reversion of multidrug resistance, and protection from degradation and early clearance; can influence the mechanism of action; and can enable drug administration by alternative routes and co-encapsulation of multiple active agents for combined chemotherapy. In this review, we discuss the contribution of nanotechnology as an enabling technology taking the clinical use of DOX and PTX as examples. We also present other nanoformulations approved for clinical practice containing different anticancer natural-product-derived drugs.
    Keywords:  anticancer drugs; doxorubicin; drug delivery; nanotechnology; natural products; paclitaxel
    DOI:  https://doi.org/10.3390/pharmaceutics14081722
  75. Biomedicines. 2022 Aug 05. pii: 1904. [Epub ahead of print]10(8):
    Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases.
    Gemma Di Pompo, Katsuyuki Kusuzaki, Marco Ponzetti, Vito Ferdinando Leone, Nicola Baldini, Sofia Avnet.
      Current multimodal treatment of bone metastases is partially effective and often associated with side effects, and novel therapeutic options are needed. Acridine orange is a photosensitizing molecule that accumulates in acidic compartments. After photo- or radiodynamic activation (AO-PDT or AO-RDT), acridine orange can induce lysosomal-mediated cell death, and we explored AO-RDT as an acid-targeted anticancer therapy for bone metastases. We used osteotropic carcinoma cells and human osteoclasts to assess the extracellular acidification and invasiveness of cancer cells, acridine orange uptake and lysosomal pH/stability, and the AO-RDT cytotoxicity in vitro. We then used a xenograft model of bone metastasis to compare AO-RDT to another antiacid therapeutic strategy (omeprazole). Carcinoma cells showed extracellular acidification activity and tumor-derived acidosis enhanced cancer invasiveness. Furthermore, cancer cells accumulated acridine orange more than osteoclasts and were more sensitive to lysosomal death. In vivo, omeprazole did not reduce osteolysis, whereas AO-RDT promoted cancer cell necrosis and inhibited tumor-induced bone resorption, without affecting osteoclasts. In conclusion, AO-RDT was selectively toxic only for carcinoma cells and effective to impair both tumor expansion in bone and tumor-associated osteolysis. We therefore suggest the use of AO-RDT, in combination with the standard antiresorptive therapies, to reduce disease burden in bone metastasis.
    Keywords:  acridine orange; bone metastases; radiodynamic therapy; tumor acidosis; tumor microenvironment
    DOI:  https://doi.org/10.3390/biomedicines10081904
  76. Mol Cancer Res. 2022 Aug 22. pii: MCR-21-1032. [Epub ahead of print]
    Glutamine metabolism mediates sensitivity to respiratory complex II inhibition in acute myeloid leukemia.
    Alessia Roma, Matthew Tcheng, Nawaz Ahmed, Sarah Walker, Preethi Jayanth, Mark D Minden, Kristin Hope, Praveen P Nekkar Rao, Jessica Luc, Andrew C Doxey, Julie A Reisz, Rachel Culp-Hill, Angelo D'Alessandro, Paul A Spagnuolo.
      Acute myeloid leukemia (AML) is a hematological malignancy metabolically dependent on oxidative phosphorylation and mitochondrial electron transport chain (ETC) activity. AML cells are distinct from their normal hematopoietic counterparts by this metabolic reprogramming, which presents targets for new selective therapies. Here, metabolic changes in AML cells after ETC impairment are investigated. Genetic knockdown of the ETC complex II (CII) chaperone protein SDHAF1 (succinate dehydrogenase assembly factor 1) suppressed CII activity and delayed AML cell growth in vitro and in vivo. As a result, a novel small molecule that directly binds to the ubiquinone binding site of CII and inhibits its activity was identified. Pharmacological inhibition of CII induced selective cell death in AML cells while sparing normal hematopoietic progenitors. Through stable isotope tracing, results show that genetic or pharmacological inhibition of CII truncates the tricarboxylic acid cycle (TCA) and leads to anaplerotic glutamine metabolism to reestablish the truncated cycle. The inhibition of CII showed divergent fates of AML cells since they lacked the metabolic plasticity to adequately utilize glutamine metabolism, resulting in preferential depletion of key metabolites in the TCA cycle and death; normal cells were unaffected. These findings provide insight into the metabolic mechanisms that underlie AML's selective inhibition of CII. Implications: This work highlights the effects of direct CII inhibition in mediating selective AML cell death and provides insights into glutamine anaplerosis as a metabolic adaptation that can be therapeutically targeted.
    DOI:  https://doi.org/10.1158/1541-7786.MCR-21-1032
  77. Mater Today Bio. 2022 Dec;16 100386
    Injectable click-crosslinked hydrogel containing resveratrol to improve the therapeutic effect in triple negative breast cancer.
    Gi Ru Shin, Hee Eun Kim, Hyeon Jin Ju, Jae Ho Kim, Sangdun Choi, Hak Soo Choi, Moon Suk Kim.
      Triple-negative breast cancer (TNBC) patients are considered intractable, as this disease has few effective treatments and a very poor prognosis even in its early stages. Here, intratumoral therapy with resveratrol (Res), which has anticancer and metastasis inhibitory effects, was proposed for the effective treatment of TNBC. An injectable Res-loaded click-crosslinked hyaluronic acid (Res-Cx-HA) hydrogel was designed and intratumorally injected to generate a Res-Cx-HA depot inside the tumor. The Res-Cx-HA formulation exhibited good injectability into the tumor tissue, quick depot formation inside the tumor, and the depot remained inside the injected tumor for extended periods. In vivo formed Res-Cx-HA depots sustained Res inside the tumor for extended periods. More importantly, the bioavailability and therapeutic efficacy of Res remained almost exclusively within the tumor and not in other organs. Intratumoral injection of Res-Cx-HA in animal models resulted in significant negative tumor growth rates (i.e., the tumor volume decreased over time) coupled with large apoptotic cells and limited angiogenesis in tumors. Therefore, Res-Cx-HA intratumoral injection is a promising way to treat TNBC patients with high efficacy and minimal adverse effects.
    Keywords:  Click-crosslinking; Injectable hydrogel; Intratumoral injection; Resveratrol; Triple-negative breast cancer
    DOI:  https://doi.org/10.1016/j.mtbio.2022.100386
  78. Mol Biol Rep. 2022 Aug 23.
    Thymol has anticancer effects in U-87 human malignant glioblastoma cells.
    Farid Qoorchi Moheb Seraj, Niloofar Heravi-Faz, Arash Soltani, Seyed Sajad Ahmadi, Fatemeh Shahbeiki, Amir Talebpour, Amir R Afshari, Gordon A Ferns, Afsane Bahrami.
      BACKGROUND: Thymol (2-isopropyl-5-methylphenol) is a colorless crystalline derivative of cymene, that possesses pleotropic pharmacological properties, including analgesic, antibacterial, antispasmodic, and anti-inflammatory activities. Thymol has also been recognized for its beneficial effect as an anti-tumor agent, but the precise mechanism for this has not been fully elucidated. We aimed to identifying whether thymol exerts anti-cancer activity in human U-87 malignant glioblastoma (GB) cells (U-87).METHODS AND RESULTS: Cell viability and apoptosis was evaluated in U-87 cells treated with thymol at different concentrations. Reactive oxygen species (ROS) production, mRNA expressions of apoptosis-related genes and cell cycle characteristics were assessed. The cytotoxic activity of the co-exposure of thymol and temozolomide (TMZ) was also evaluated. The half-maximal inhibitory concentration (IC50) of thymol in the U-87 cells was 230 μM assessed at 24 h after exposure. Thymol did not exhibit any cytotoxic effects on normal L929 cells at this concentration. Thymol treatment increased the expression of Bax and p53, and also increased apoptotic cell death, and excessive generation of ROS. Moreover, the cytotoxic activity of thymol on the U-87 cells may be related to the arrest of the cell cycle at the G0/G1 interface. Combination therapy showed that the cytotoxic effects of thymol synergized with TMZ, and combined treatment had more cytotoxic potential compared to either of the agents alone.
    CONCLUSIONS: Our data indicate the potential cytotoxic activities of thymol on U-87 cells. Further studies are required to evaluate the spectrum of the antitumor activity of thymol on GB cells.
    Keywords:  Apoptosis; Cell cycle arrest; Glioma; ROS; Thymol
    DOI:  https://doi.org/10.1007/s11033-022-07867-3
  79. Chempluschem. 2022 Jul 29. 87(8): e202200156
    Porphyrin-Based Nanoparticles: A Promising Phototherapy Platform.
    Zhenhua Liu, Hui Li, Zejie Tian, Xin Liu, Yu Guo, Jun He, Zhenyu Wang, Tao Zhou, Yunmei Liu.
      Phototherapy, including photodynamic therapy and photothermal therapy, is an emerging form of non-invasive treatment. The combination of imaging technology and phototherapy is becoming an attractive development in the treatment of cancer, as it allows for highly effective therapeutic results through image-guided phototherapy. Porphyrins have attracted significant interest in the treatment and diagnosis of cancer due to their excellent phototherapeutic effects in phototherapy and their remarkable imaging capabilities in fluorescence imaging, magnetic resonance imaging and photoacoustic imaging. However, porphyrins suffer from poor water solubility, low near-infrared absorption and insufficient tumor accumulation. The development of nanotechnology provides an effective way to improve the bioavailability, phototherapeutic effect and imaging capability of porphyrins. This review highlights the research results of porphyrin-based small molecule nanoparticles in phototherapy and image-guided phototherapy in the last decade and discusses the challenges and directions for the development of porphyrin-based small molecule nanoparticles in phototherapy.
    Keywords:  imaging guided phototherapy; nanostructures; photodynamic therapy; photothermal therapy; porphyrins
    DOI:  https://doi.org/10.1002/cplu.202200156
  80. Pharmacol Res. 2022 Aug 23. pii: S1043-6618(22)00359-0. [Epub ahead of print] 106414
    Polyphenols and atherosclerosis: a critical review of clinical effects on LDL oxidation.
    Ali Ahmadi, Tannaz Jamialahmadi, Amirhossein Sahebkar.
      Atherosclerosis is a major etiology of cardiovascular disease that causes considerable mortality. Oxidized low-density lipoprotein (oxLDL) is a fundamental attributor to atherosclerosis. Therefore, there seems to be an essential place for antioxidant therapy besides the current treatment protocols for coronary heart disease. Polyphenols are a class of compounds with substantial antioxidant properties that have shown the ability to reduce LDL oxidation in preclinical studies. However, clinical evidence has not been as conclusive although offering many promising signs. This review aims to examine the trials that have evaluated how dietary intake of polyphenols in different forms might influence the oxidation of LDL. Lowering the circulating cholesterol, incorporation into LDL particles, and enhancing systemic antioxidant activity are among the main mechanisms of action for polyphenols for lowering oxLDL. On the other hand, the population under study significantly affects the impact on oxLDL, as the type of the supplement and phenolic content. To conclude, although the polyphenols might decrease inflammation and enhance endothelial function via lowering oxLDL, there are still many gaps in our knowledge that need to be filled with further high-quality studies.
    Keywords:  LDL oxidation; atherosclerosis; polyphenols
    DOI:  https://doi.org/10.1016/j.phrs.2022.106414
  81. Pharmaceutics. 2022 Aug 15. pii: 1700. [Epub ahead of print]14(8):
    New Advances in Biomedical Application of Polymeric Micelles.
    Ana Figueiras, Cátia Domingues, Ivana Jarak, Ana Isabel Santos, Ana Parra, Alberto Pais, Carmen Alvarez-Lorenzo, Angel Concheiro, Alexander Kabanov, Horacio Cabral, Francisco Veiga.
      In the last decade, nanomedicine has arisen as an emergent area of medicine, which studies nanometric systems, namely polymeric micelles (PMs), that increase the solubility and the stability of the encapsulated drugs. Furthermore, their application in dermal drug delivery is also relevant. PMs present unique characteristics because of their unique core-shell architecture. They are colloidal dispersions of amphiphilic compounds, which self-assemble in an aqueous medium, giving a structure-type core-shell, with a hydrophobic core (that can encapsulate hydrophobic drugs), and a hydrophilic shell, which works as a stabilizing agent. These features offer PMs adequate steric protection and determine their hydrophilicity, charge, length, and surface density properties. Furthermore, due to their small size, PMs can be absorbed by the intestinal mucosa with the drug, and they transport the drug in the bloodstream until the therapeutic target. Moreover, PMs improve the pharmacokinetic profile of the encapsulated drug, present high load capacity, and are synthesized by a reproducible, easy, and low-cost method. In silico approaches have been explored to improve the physicochemical properties of PMs. Based on this, a computer-aided strategy was developed and validated to enable the delivery of poorly soluble drugs and established critical physicochemical parameters to maximize drug loading, formulation stability, and tumor exposure. Poly(2-oxazoline) (POx)-based PMs display unprecedented high loading concerning water-insoluble drugs and over 60 drugs have been incorporated in POx PMs. Among various stimuli, pH and temperature are the most widely studied for enhanced drug release at the site of action. Researchers are focusing on dual (pH and temperature) responsive PMs for controlled and improved drug release at the site of action. These dual responsive systems are mainly evaluated for cancer therapy as certain malignancies can cause a slight increase in temperature and a decrease in the extracellular pH around the tumor site. This review is a compilation of updated therapeutic applications of PMs, such as PMs that are based on Pluronics®, micelleplexes and Pox-based PMs in several biomedical applications.
    Keywords:  biomedical applications; cancer-target delivery; copolymers; nanocarrier; polymeric micelles; theranostic
    DOI:  https://doi.org/10.3390/pharmaceutics14081700
  82. Curr Drug Deliv. 2022 Aug 23.
    Nanoformulations of Plant-Derived Compounds as Emerging Therapeutic Approach for Colorectal Cancer.
    Hossein Biganeh, Sahand Mirzaei Dizaji, Yasamin Davatgaran Taghipour, Ghulam Murtaza, Roja Rahimi.
      BACKGROUND: Colorectal cancer (CRC) represents one of the most daunting health problems accompanied by progressive undesirable socio-economic effects. Phytochemicals, bioactive ingredients majorly found in plants, have gained momentum for their potential against CRC occurrence and regression. However, these phytoconstituents are not exempt of biopharmaceutical drawbacks; therefore, novel strategies, especially nanotechnology, are exploited to surmount the aforementioned bottlenecks. The current paper aims to comprehensively review the phytochemical-based nanoformulations and their mechanisms in the setting of CRC.METHODS: Electronic databases including Scopus, PubMed, and Web of Science were searched with the keywords "colon cancer" or "colorectal cancer", and "plant", "phytochemical", "extract", or "herb", and "nano", "nanoformulation", "Nanoencapsulation", "nanoparticle", "nanostructure", or "nanoliposome", until January 2021.
    RESULTS: Of the 1230 research hits, only 69 articles were consequently analyzed. The results indicated nanoformulations of several secondary plant metabolites such as berberine, camptothecin, colchicine, apigenin, chrysin, fisetin, quercetin, curcumin, gallic acid, resveratrol, and ursolic acid have profound effects in a broad range of preclinical models of CRC. A wide variety of nanoformulations have been utilized to deliver these phytochemicals, such as nanocomposite, nanocolloids, and mesoporous silica nanoparticles, which have consequently decreased tumor angiogenesis and mitochondrial membrane potential, increased radical scavenging activity, induced cell cycle arrest at different phases of the cancer cell cycle, and induction of apoptosis process via decreased anti-apoptotic proteins (BRAF, CD44, and Bcl-2) and increased in pro-apoptotic ones (Bax, Fas, caspase 3,8, and 9), as well as modulated biopharmaceutical properties. Chitosan and PEG and their derivatives are among the most polymers exploited in the phytochemicals' nanoformulations.
    CONCLUSION AND PERSPECTIVE: To conclude, nanoformulated forms of natural ingredients depicted outstanding anti-CRC activity that could hold promise for help in treating CRC. However, well-designed clinical trials are needed to build up a whole picture of the health profits of nanoformulation of natural products in CRC management.
    Keywords:  Colon cancer; chemotherapeutic; drug delivery; nanoformulation; nanotechnology; phytochemical
    DOI:  https://doi.org/10.2174/1567201819666220823155526
  83. Front Oncol. 2022 ;12 971475
    Inhibitory of active dual cancer targeting 5-Fluorouracil nanoparticles on liver cancer in vitro and in vivo.
    Mingrong Cheng, Dejian Dai.
      The chitosan (CS) material as the skeleton nano-drug delivery system has the advantages of sustained release, biodegradability, and modifiability, and has broad application prospects. In the previous experiments, biotin (Bio) was grafted onto CS to synthesize biotin-modified chitosan (Bio-CS), and it was confirmed that it has liver cancer targeting properties. Single-targeted nanomaterials are susceptible to pathological and physiological factors, resulting in a state of ineffective binding between ligands and receptors, so there is still room for improvement in the targeting of liver cancer. Based on the high expression of folate (FA) receptors on the surface of liver cancers, FA was grafted onto Bio-CS by chemical synthesis to optimize the synthesis of folic acid-modified biotinylated chitosan (FA-CS-Bio), verified by infrared spectroscopy and hydrogen-1 nuclear magnetic resonance spectroscopy. The release of FA-CS-Bio/fluorouracil (5-FU) had three obvious stages: fast release stage, steady release stage, and slow release stage, with an obvious sustained release effect. Compared with Bio-CS, FA-CS-Bio could promote the inhibition of the proliferation and migration of liver cancer by 5-FU, and the concentration of 5-FU in hepatoma cells was significantly increased dose-dependently. Laser confocal experiments confirmed that FA-CS-Bio caused a significant increase in the fluorescence intensity in liver cancer cells. In terms of animal experiments, FA-CS-Bio increased the concentration of 5-FU in liver cancer tissue by 1.6 times on the basis of Bio-CS and the number of monophotons in liver cancer tissue by in vivo dynamic imaging experiments was significantly stronger than that of Bio-CS, indicating that the targeting ability of FA-CS-Bio was further improved. Compared with Bio-CS, FA-CS-Bio can significantly prolong the survival time of 5-FU in the orthotopic liver cancer transplantation model in mice, and has a relieving effect on liver function damage and bone marrow suppression caused by 5-FU. In conclusion, FA-CS-Bio nanomaterials have been optimized for synthesis. In vivo and in vitro experiments confirmed that FA-CS-Bio can significantly improve the targeting of liver cancer compared with Bio-CS. FA-CS-Bio/5-FU nanoparticles can improve the targeted inhibition of the proliferation and migration of liver cancer cells, prolong the survival period of tumor-bearing mice, and alleviate the toxic and side effects.
    Keywords:  biotin; chitosan; drug delivery system; folic acid; liver cancer; nanotechnology
    DOI:  https://doi.org/10.3389/fonc.2022.971475
  84. Int J Biol Macromol. 2022 Aug 19. pii: S0141-8130(22)01784-6. [Epub ahead of print]220 573-588
    Hydrogel beads based on carboxymethyl cassava starch/alginate enriched with MgFe2O4 nanoparticles for controlling drug release.
    Kun Fang, Yuqi Zhang, Jiangyu Yin, Tonghan Yang, Kai Li, Li Wei, Jianbin Li, Wei He.
      Implementing novel oral drug delivery systems with controlled drug release behavior is valuable in cancer therapy. Herein, a green synthetic approach based on the sol-gel technique was adopted to prepare MgFe2O4 nanoparticles at different calcination temperatures using citric acid as a chelating/combustion agent. In this context, pH-responsive and magnetic carboxymethyl starch/alginate hydrogel beads (CMCS-SA) containing the MgFe2O4 nanoparticles were developed as potential drug carriers for the anticancer drug (Doxorubicin, Dox) release in simulated gastrointestinal fluids. Furthermore, in vitro release behaviors validated that these beads illustrated excellent stability in the simulated stomach liquids. In contrast, the data in simulated intestinal fluids showed sustained release of Dox because of their pH-sensitive swelling characteristics. Notably, applying an external magnetic field (EMF) could accelerate drug release from the beads. The in vitro release of drugs from gel beads was mainly accomplished by a combination of diffusion, swelling and erosion. Moreover, the cell cytotoxicity test and laser confocal results showed no harmful effects on normal cells (3T3) but were significant cytotoxic to colon cancer cell lines (HCT116) by drug-loaded hydrogel beads. Therefore, the prepared gel beads could be qualified as latent platforms for controlling the release of anticancer drugs in cancer treatment.
    Keywords:  Carboxymethyl cassava starch; Controlled-release; Doxorubicin; Magnesium ferrite; Sodium alginate
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.08.081
  85. Int J Mol Sci. 2022 Aug 21. pii: 9440. [Epub ahead of print]23(16):
    Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells.
    Shaimaa M Badr-Eldin, Hibah M Aldawsari, Usama A Fahmy, Osama A A Ahmed, Nabil A Alhakamy, Omar D Al-Hejaili, Alhanoof A Alhassan, Ghadeer A Ammari, Shouq I Alhazmi, Raghad M Alawadi, Rana Bakhaidar, Abdulmohsen J Alamoudi, Thikryat Neamatallah, Singkome Tima.
      Ellagic acid has recently attracted increasing attention regarding its role in the prevention and treatment of cancer. Surface functionalized nanocarriers have been recently studied for enhancing cancer cells' penetration and achieving better tumor-targeted delivery of active ingredients. Therefore, the present work aimed at investigating the potential of APA-functionalized emulsomes (EGA-EML-APA) for enhancing cytototoxic activity of EGA against human breast cancer cells. Phospholipon® 90 G: cholesterol molar ratio (PC: CH; X1, mole/mole), Phospholipon® 90 G: Tristearin weight ratio (PC: TS; X2, w/w) and apamin molar concentration (APA conc.; X3, mM) were considered as independent variables, while vesicle size (VS, Y1, nm) and zeta potential (ZP, Y2, mV) were studied as responses. The optimized formulation with minimized vs. and maximized absolute ZP was predicted successfully utilizing a numerical technique. EGA-EML-APA exhibited a significant cytotoxic effect with an IC50 value of 5.472 ± 0.21 µg/mL compared to the obtained value from the free drug 9.09 ± 0.34 µg/mL. Cell cycle profile showed that the optimized formulation arrested MCF-7 cells at G2/M and S phases. In addition, it showed a significant apoptotic activity against MCF-7 cells by upregulating the expression of p53, bax and casp3 and downregulating bcl2. Furthermore, NF-κB activity was abolished while the expression of TNfα was increased confirming the significant apoptotic effect of EGA-EML-APA. In conclusion, apamin-functionalized emulsomes have been successfully proposed as a potential anti-breast cancer formulation.
    Keywords:  apamin; breast cancer; central composite design; cytotoxicity; ellagic acid; emulsomes; nanotechnology; phospholipon; tristearin
    DOI:  https://doi.org/10.3390/ijms23169440
  86. Front Bioeng Biotechnol. 2022 ;10 944518
    Research update on cell membrane camouflaged nanoparticles for cancer therapy.
    Chengfang Wang, Size Wu.
      Cell membrane-camouflaged biomimetic functionalization of nanoparticles has emerged as a promising strategy for cancer theranostics. These cell membranes used for camouflaging are generally isolated from natural or engineered erythrocytes, neutrophils, macrophages, T lymphatic cells, stem cells, and cancer cells. The camouflaging strategy of coating nanoparticles with cell membranes allows for tumor homotypic targeting through self-recognition as source cells, immune evasion, and a prolonged blood circulation time, thereby improving the effective payload delivery and tumor therapy. More so, some engineered cell membranes with functionalized peptides, proteins and moieties on membrane surface can be transferred for therapy in the same time. In this review, we summarize the latest research on various types of cell membrane-camouflaged nanoparticles aimed at anti-cancer therapy, focusing on the biological advantages of different cell membranes, constitutions of nanoparticles, fabrication processes, key findings, potential therapies, and discuss the major challenges and future opportunities.
    Keywords:  biomimetic; cell membrane-coated nanoparticle; homotypic targeting; immune evasion; tumor therapy
    DOI:  https://doi.org/10.3389/fbioe.2022.944518
  87. Curr Microbiol. 2022 Aug 24. 79(10): 300
    Bioactive Microbial Metabolites in Cancer Therapeutics: Mining, Repurposing, and Their Molecular Targets.
    Subhaswaraj Pattnaik, Madangchanok Imchen, Ranjith Kumavath, Ram Prasad, Siddhardha Busi.
      The persistence and resurgence of cancer, characterized by abnormal cell growth and differentiation, continues to be a serious public health concern critically affecting public health, social life, and the global economy. Hundreds of putative drug molecules of synthetic and natural origin were approved for anticancer therapy in the last few decades. Although conventional anticancer treatment strategies have promising aspects, several factors such as their limitations, drug resistance, and side effects associated with them demand more effort in repositioning or developing novel therapeutic regimens. The rich heritage of microbial bioactive components remains instrumental in providing novel avenues for cancer therapeutics. Actinobacteria, Firmicutes, and fungi have a plethora of bioactive compounds, which received attention for their efficacy in cancer treatment targeting different pathways responsible for abnormal cell growth and differentiation. Yet the full potential remains underexplored to date, and novel compounds from such microbes are reported regularly. In addition, the advent of computational tools has further augmented the mining of microbial secondary metabolites and identifying their molecular targets in cancer cells. Furthermore, the drug-repurposing strategy has facilitated the use of approved drugs of microbial origin in regulating cancer cell growth and progression. The wide diversity of microbial compounds, different mining approaches, and multiple modes of action warrant further investigations on the current status of microbial metabolites in cancer therapeutics. Hence, in this review, we have critically discussed the untapped potential of microbial products in mitigating cancer progression. The review also summarizes the impact of drug repurposing in cancer therapy and discusses the novel avenues for future therapeutic drug development against cancer.
    DOI:  https://doi.org/10.1007/s00284-022-02990-7
  88. Mar Drugs. 2022 Aug 10. pii: 509. [Epub ahead of print]20(8):
    Formulation, Characterization, and In Vitro/In Vivo Efficacy Studies of a Novel Liposomal Drug Delivery System of Amphiphilic Jaspine B for Treatment of Synovial Sarcoma.
    Sana Khajeh Pour, Sameena Mateen, Srinath Pashikanti, Jared J Barrott, Ali Aghazadeh-Habashi.
      Sphingomyelin is a cell membrane sphingolipid that is upregulated in synovial sarcoma (SS). Jaspine B has been shown to inhibit sphingomyelin synthase, which synthesizes sphingomyelin from ceramide, a critical signal transducer; however, jaspine B's low bioavailability limits its application as a promising treatment option. To address this shortcoming, we used microfluidics to develop a liposomal delivery system with increased anticancer efficacy. The nano-liposome size was determined by transmission electron microscopy. The jaspine B liposome was tested for its tumor inhibitory efficacy compared to plain jaspine B in in vitro and in vivo studies. The human SS cell line was tested for cell viability using varying jaspine B concentrations. In a mouse model of SS, tumor growth suppression was evaluated during four weeks of treatment (3 times/week). The results show that jaspine B was successfully formulated in the liposomes with a size ranging from 127.5 ± 61.2 nm. The MTT assay and animal study results indicate that jaspine B liposomes dose-dependently lowers cell viability in the SS cell line and effectively suppresses tumor cell growth in the SS animal model. The novel liposome drug delivery system addresses jaspine B's low bioavailability issues and improves its therapeutic efficacy.
    Keywords:  drug delivery; jaspine B; liposomes; microfluidic method; synovial sarcoma
    DOI:  https://doi.org/10.3390/md20080509
  89. Crit Rev Food Sci Nutr. 2022 Aug 25. 1-19
    Spray drying encapsulation of essential oils; process efficiency, formulation strategies, and applications.
    Özgül Altay, Özgün Köprüalan, Işıl İlter, Mehmet Koç, Figen Kaymak Ertekin, Seid Mahdi Jafari.
      Essential oils (EOs) have many beneficial qualities, including antimicrobial, antioxidant, antiviral, and antifungal activities, along with good aroma, which have played a significant role in pharmaceutical, textile, and food industries. However, their high volatility and sensibility to external factors, as well as susceptibility to deterioration caused by environmental and storage conditions, or even common processing, and consequently limited water solubility, makes it difficult to incorporate them into aqueous food matrices and limits their industrial application. Spray-drying encapsulation has been proposed as a solution and a challenging research field to retard oil oxidation, extend EO's shelf life, improve their physicochemical stability, achieve controlled release, suggest novel uses, and therefore boost their added value. The objective of this review is to discuss various used wall materials, infeed emulsion properties, the main formulation and process variables affecting the physicochemical properties and release characteristics of the EOs-loaded particles obtained by spray-drying, the stability of EOs during storage, and the applications of encapsulated EOs powders in foods and nutrition, pharmaceuticals, and textile industries. The current review also summarizes recent advances in spray drying approaches for improving encapsulation efficiency, flavor retention, controlled release, and applicability of encapsulated EOs, thereby expanding their use and functionalities.
    Keywords:  Applications; aroma retention; encapsulation efficiency; essential oils; spray drying
    DOI:  https://doi.org/10.1080/10408398.2022.2113364
  90. Pharmaceutics. 2022 Aug 22. pii: 1748. [Epub ahead of print]14(8):
    An Updated Overview of Cyclodextrin-Based Drug Delivery Systems for Cancer Therapy.
    Dan Nicolae Păduraru, Adelina-Gabriela Niculescu, Alexandra Bolocan, Octavian Andronic, Alexandru Mihai Grumezescu, Rodica Bîrlă.
      Encompassing a group of complex and heterogeneous diseases, cancer continues to be a challenge for patients and healthcare systems worldwide. Thus, it is of vital importance to develop advanced treatment strategies that could reduce the trends of cancer-associated morbidity and mortality rates. Scientists have focused on creating performant delivery vehicles for anti-cancer agents. Among the possible materials, cyclodextrins (CDs) attracted increasing interest over the past few years, leading to the emergence of promising anti-tumor nanomedicines. Tackling their advantageous chemical structure, ease of modification, natural origin, biocompatibility, low immunogenicity, and commercial availability, researchers investigated CD-based therapeutical formulations against many types of cancer. In this respect, in this paper, we briefly present the properties of interest of CDs for designing performant nanocarriers, further reviewing some of the most recent potential applications of CD-based delivery systems in cancer management.
    Keywords:  anti-cancer drug formulations; cancer treatment; cyclodextrins; delivery systems
    DOI:  https://doi.org/10.3390/pharmaceutics14081748
  91. Med Sci (Basel). 2022 Aug 22. pii: 44. [Epub ahead of print]10(3):
    Polyamine-Based Nanostructures Share Polyamine Transport Mechanisms with Native Polyamines and Their Analogues: Significance for Polyamine-Targeted Therapy.
    Cassandra E Holbert, Jackson R Foley, Ao Yu, Tracy Murray Stewart, Otto Phanstiel, David Oupicky, Robert A Casero.
      Polyamines are small polycationic alkylamines involved in many fundamental cellular processes, including cell proliferation, survival, and protection from oxidative stress. Polyamine homeostasis is tightly regulated through coordinated biosynthesis, catabolism, and transport. Due to their continual proliferation, cancer cells maintain elevated intracellular polyamine pools. Both polyamine metabolism and transport are commonly dysregulated in cancer, and as such, polyamine analogues are a promising strategy for exploiting the increased polyamine requirement of cancer cells. One potential polyamine analogue resistance mechanism is the downregulation of the poorly defined polyamine transport system. Recent advances in nanomedicine have produced nanostructures with polyamine analogue-based backbones (nanopolyamines). Similar nanostructures with non-polyamine backbones have been shown to be transported by endocytosis. As these polyamine-based nanoparticles could be a method for polyamine analogue delivery that bypasses polyamine transport, we designed the current studies to determine the efficacy of polyamine-based nanoparticles in cells lacking intact polyamine transport. Utilizing polyamine transport-deficient derivatives of lung adenocarcinoma lines, we demonstrated that cells unable to transport natural polyamines were also resistant to nanopolyamine-induced cytotoxicity. This resistance was a result of transport-deficient cells being incapable of importing and accumulating nanopolyamines. Pharmacological modulation of polyamine transport confirmed these results in polyamine transport competent cells. These studies provide additional insight into the polyamine transport pathway and suggest that receptor-mediated endocytosis is a likely mechanism of transport for higher-order polyamines, polyamine analogues and the nanopolyamines.
    Keywords:  cancer therapy; drug delivery system; drug transport; nanoparticle; nanopolyamine; polyamine; polyamine analogue; polyamine transport
    DOI:  https://doi.org/10.3390/medsci10030044
  92. Curr Pharm Biotechnol. 2022 Aug 22.
    In vitro antioxidant, anti-inflammatory, antimicrobial, and antidiabetic activities of synthesized chitosan-loaded p-coumaric acid nanoparticles.
    Amalan Venkatesan, Jose Vinoth Raja Antony Samy, Karthikeyan Balakrishnan, Vijayakumar Natesan, Sung-Jin Kim.
      BACKGROUND: p-Coumaric acid is a phenolic compound widely distributed in fruits and vegetables that displays an array of therapeutic properties, including antidiabetic effects. Prominent application in diabetes is limited due to its suboptimal pharmacokinetics, poor aqueous solubility, and poor bioavailability. Nanotechnology-based delivery methods have been developed to address these limitations and improve the therapeutic uses of p-coumaric acid, and the nanoencapsulation method is emerging as a feasible alternative.OBJECTIVE: The objective of this study is to synthesize p-coumaric acid nanoparticles (PCNPs) and to evaluate their in vitro activities.
    METHODS: The PCNPs were synthesized by the nanoprecipitation method and characterized by UV-visible spectroscopy, zeta potential, Fourier-transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM) with dispersive energy X-ray (EDX) analysis. In addition, the PCNPs were analyzed for in vitro antioxidant activity using six different free radical scavenging assays and were also analyzed for antimicrobial, anti-inflammatory, antithrombotic, and antidiabetic effects.
    RESULT: The formation of PCNPs was confirmed by UV-Visible spectra at 283 nm, and FTIR analysis revealed the reduction and capping of the chitosan nanoparticles. SEM was used to assess the size and shape of the PCNPs, and the high absorption property of the PCNPs was investigated using EDX analysis. The PCNPs had significant antioxidant, hydrogen peroxide (H2O2), lipid peroxidation (LPO), superoxide and nitric oxide (NO) radical scavenging power activities, and showed potent antimicrobial, anti-inflammatory, antithrombotic, and antidiabetic activities.
    CONCLUSION: The present study suggests that PCNPs can be used as a potential medication delivery approach to provide a greater nephroprotective effect in the treatment of diabetic nephropathy. To the best of our knowledge, this is the first attempt at the synthesis of chitosan-loaded PCNPs.
    Keywords:  antioxidant; chitosan; encapsulation; nanoprecipitation; p-coumaric acid
    DOI:  https://doi.org/10.2174/1389201023666220822112923
  93. Int J Environ Res Public Health. 2022 Aug 18. pii: 10261. [Epub ahead of print]19(16):
    Commonalities in Metabolic Reprogramming between Tobacco Use and Oral Cancer.
    Blake R Rushing, Spencer Tilley, Sabrina Molina, Madison Schroder, Susan Sumner.
      Tobacco use is a major public health concern and is linked to myriad diseases, including cancer. The link between tobacco use and oral cancer, specifically, is very strong, making tobacco use one of the primary risk factors for oral cancer. While this association is well known, the underlying biochemical changes that result from tobacco use, and how this links to metabolic phenotypes of oral cancer, is not well understood. To address this knowledge gap, a combination of literature reviews and metabolomics studies were performed to identify commonalities in metabolic perturbations between tobacco use and oral cancers. Metabolomics analysis was performed on pooled reference urine from smokers and non-smokers, healthy and malignant oral tissues, and cultured oral cells with or without treatment of the well-known tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Alterations in amino acid metabolism, carbohydrates/oxidative phosphorylation, fatty acid oxidation, nucleotide metabolism, steroid metabolism, and vitamin metabolism were found to be shared between tobacco use and oral cancer. These results support the conclusion that tobacco use metabolically reprograms oral cells to support malignant transformation through these pathways. These metabolic reprogramming events may be potential targets to prevent or treat oral cancers that arise from tobacco use.
    Keywords:  cancer; carcinogen; metabolic reprogramming; metabolism; metabolomics; oral cancer; smoking; tobacco use
    DOI:  https://doi.org/10.3390/ijerph191610261
  94. Adv Colloid Interface Sci. 2022 Aug 12. pii: S0001-8686(22)00152-X. [Epub ahead of print]307 102750
    Recent progresses in the delivery of β-carotene: From nano/microencapsulation to bioaccessibility.
    Mehdi Jalali-Jivan, Hadis Rostamabadi, Elham Assadpour, Merve Tomas, Esra Capanoglu, Mahmood Alizadeh-Sani, Mohammad Saeed Kharazmi, Seid Mahdi Jafari.
      Beta-carotene (BC) as an efficient pro-vitamin is effective in improving vision, immune system and cognitive function as well as preventing coronary diseases and cancer. However, besides its poor chemical stability, the high lipophilic nature of BC reduces its dispersibility and consequently bioavailability which limits its application into food, pharmaceutical and nutraceuticals. Different carriers with vesicular or particulate structures have been studied and utilized for promoting BC solubility, dispersibility, and protection against diverse operational or environmental stresses and also controlling BC release and subsequent bioaccessibility. The current study, therefore reviews different micro/nanocarriers reported on BC encapsulation with special focusing on its bioavailability. Liposomal structures have been successfully used for enhancing BC stability and bioavailability. Besides, emulsion-based carriers including Pickering emulsions, nanoemulsions and microemulsions have been widely evaluated for BC encapsulation and protection. In addition, lipid-based nanoparticles and nanostructural carriers have also been applied successfully for this context. Moreover, gel structures including emulgels, hydrogels and oleogels are studied in some researches. Most of these delivery systems led to higher hydro-solubility and dispersibility of BC which consequently increased its bioavailability; thereupon could promote its application into food, cosmetic and nutraceutical products. However, for remarkable incorporation of BC and other bioactive compounds into edible products, the safety and toxicological aspects of these delivery system especially those designed in nano scale should be addressed in the further researches.
    Keywords:  Bioavailability; Encapsulation; Nanocarriers; Nanoemulsions; Nanoliposomes; β-Carotene
    DOI:  https://doi.org/10.1016/j.cis.2022.102750
  95. Pharmaceutics. 2022 Aug 20. pii: 1740. [Epub ahead of print]14(8):
    Association of Indocyanine Green with Chitosan Oleate Coated PLGA Nanoparticles for Photodynamic Therapy.
    Dalila Miele, Milena Sorrenti, Laura Catenacci, Paolo Minzioni, Giorgio Marrubini, Valeria Amendola, Marcello Maestri, Paolo Giunchedi, Maria Cristina Bonferoni.
      Indocyanine green (ICG) is a safe dye widely used in the biomedical field. Its photodynamic effect (PDT), originating from laser irradiation at 803 nm, opens interesting perspectives in theranostic applications. To overcome its low water stability, ICG can be shielded with nanoparticles (NPs). In this work, previously developed NPs based on poly lactic-co-glycolic acid (PLGA) coated with chitosan oleate (CS-OA) and loaded with resveratrol as a hydrophobic model drug have been proposed as an ICG carrier. These systems have been selected for their observed immunostimulatory properties. The possible loading of the dye by adsorption onto NP surface by electrostatic interaction was studied here in comparison with the encapsulation into the PLGA core. The ICG-chitosan (CS) interaction has been characterized by spectrophotometry, spectroscopy and in-cell in vitro assays. Fluorescence quenching was observed due to the ionic interaction between ICG and CS and was studied considering the dye:polymer stoichiometry and the effect of the NP dilution in cell culture medium (DMEM). The NP systems have been compared in vitro, assessing their behaviour in Caco-2 cell lines. A reduction in cell viability was observed after irradiation of ICG associated with NPs, evident also for the samples loaded by adsorption. These findings open the opportunity to exploit the association of PDT's effect on ICG with the properties of CS-OA coated NPs, whose immunostimulatory effect can be associated with PDT mechanism in cancer therapy.
    Keywords:  PLGA nanoparticles; chitosan oleate; indocyanine green; photodynamic effect
    DOI:  https://doi.org/10.3390/pharmaceutics14081740
  96. J Nanobiotechnology. 2022 Aug 23. 20(1): 387
    Directing ricin-based immunotoxins with targeting affibodies and KDEL signal peptide to cancer cells effectively induces apoptosis and tumor suppression.
    Seong Guk Park, Heeyeon Kim, Heejin Jun, Sun Young Choi, Eunhee Kim, Sebyung Kang.
      The plant toxin ricin, especially its cytotoxic A chain (RTA), can be genetically engineered with targeting ligands to develop specific anti-cancer recombinant immunotoxins (RITs). Here, we used affibody molecules targeting two cancer biomarkers, the receptors HER2 and EGFR, along with the KDEL signal peptide to construct two cancer-specific ricin-based RITs, HER2Afb-RTA-KDEL and EGFRAfb-RTA-KDEL. The affibodies successfully provided target-specificity and subsequent receptor-mediated endocytosis and the KDEL signal peptide routed the RITs through the retrograde transport pathway, effectively delivering RTA to the cytosol as well as avoiding the alternate recycling pathway that typical cancer cells frequently have. The in vivo efficacy of RITs was enhanced by introducing the albumin binding domain (AlBD) to construct AlBD/HER2Afb/RTA-KDEL. Systemic administration of AlBD-containing RITs to tumor-bearing mice significantly suppressed tumor growth without any noticeable side-effects. Collectively, combining target-selective affibody molecules, a cytotoxic RTA, and an intracellularly designating peptide, we successfully developed cancer-specific and efficacious ricin-based RITs. This approach can be applied to develop novel protein-based "magic bullets" to effectively suppress tumors that are resistant to conventional anti-cancer drugs.
    Keywords:  Affibody molecule; Drug delivery; Intracellular delivery; KDEL; Recombinant immunotoxin; Ricin; Tumor suppression
    DOI:  https://doi.org/10.1186/s12951-022-01601-8
  97. Pharmaceutics. 2022 Aug 15. pii: 1697. [Epub ahead of print]14(8):
    Nanotechnology-Based Combinatorial Anti-Glioblastoma Therapies: Moving from Terminal to Treatable.
    Amir Barzegar Behrooz, Zahra Talaie, Amir Syahir.
      Aggressive glioblastoma (GBM) has no known treatment as a primary brain tumor. Since the cancer is so heterogeneous, an immunosuppressive tumor microenvironment (TME) exists, and the blood-brain barrier (BBB) prevents chemotherapeutic chemicals from reaching the central nervous system (CNS), therapeutic success for GBM has been restricted. Drug delivery based on nanocarriers and nanotechnology has the potential to be a handy tool in the continuing effort to combat the challenges of treating GBM. There are various new therapies being tested to extend survival time. Maximizing therapeutic effectiveness necessitates using many treatment modalities at once. In the fight against GBM, combination treatments outperform individual ones. Combination therapies may be enhanced by using nanotechnology-based delivery techniques. Nano-chemotherapy, nano-chemotherapy-radiation, nano-chemotherapy-phototherapy, and nano-chemotherapy-immunotherapy for GBM are the focus of the current review to shed light on the current status of innovative designs.
    Keywords:  drug delivery; glioblastoma; nanocarriers; nanomedicine; nanotechnology
    DOI:  https://doi.org/10.3390/pharmaceutics14081697
  98. ChemMedChem. 2022 Aug 24. e202200360
    Mesoporous Polydopamine-Based Nanovehicles as a Versatile Drug Loading Platform to Enable Tumor-Sufficient Synergistic Therapy.
    Suhua Jiang, Fukai Zhu, Xiaoxuan Ji, Jiaqi Li, Haina Tian, Bingli Wang, Luanmei Lu, Peiyuan Wang.
      The combination of photothermal therapy and chemotherapy are developing as a promising clinical strategy but it urgently needs the high exploration of intelligent multifunctional drug delivery nanovectors. In this paper, we used a versatile method to construct mesoporous polydopamine nanovehicles (MPDA) with the dendritic mesopores loaded with a clinical chemotherapeutic drug, Doxorubicin (MPDA@DOX). The monodisperse nanoagents are spherical with a size of ∼160 nm and pore size of approximately 10 nm. MPDA could efficiently delivery DOX with π-π stacking interaction and acts as the potent photothermal agents. Importantly, MPDA@DOX are preferentially internalized by cancerous cells, then bursting drug release and local hyperthermia generation were observed in conditions representative of the cytoplasm in tumor cells that highly synergistic cell killing effect were found under 808 nm laser irradiation. The fluorescent imaging results of human breast tumor bearing murine model evidenced that MPDA delivery platform have excellent tumor precise targeting effect and in vivo tumor ablation experiment further revealed that MPDA@DOX showed markedly eradicated tumor growth capability under laser exposure. Therefore, this work provided a fascinating strategy based on biocompatible MPDA based drug delivery system for malignant tumors eradication via synergistic therapy.
    Keywords:  Dox; Mesoporous polydopamine; Photothermal therapy; Synergistic effect; Tumor eradication
    DOI:  https://doi.org/10.1002/cmdc.202200360
  99. Front Immunol. 2022 ;13 909580
    Metabolic rewiring directs melanoma immunology.
    Ningyue Sun, Yangzi Tian, Yuhan Chen, Weinan Guo, Chunying Li.
      Melanoma results from the malignant transformation of melanocytes and accounts for the most lethal type of skin cancers. In the pathogenesis of melanoma, disordered metabolism is a hallmark characteristic with multiple metabolic paradigms involved in, e.g., glycolysis, lipid metabolism, amino acid metabolism, oxidative phosphorylation, and autophagy. Under the driving forces of oncogenic mutations, melanoma metabolism is rewired to provide not only building bricks for macromolecule synthesis and sufficient energy for rapid proliferation and metastasis but also various metabolic intermediates for signal pathway transduction. Of note, metabolic alterations in tumor orchestrate tumor immunology by affecting the functions of surrounding immune cells, thereby interfering with their antitumor capacity, in addition to the direct influence on tumor cell intrinsic biological activities. In this review, we first introduced the epidemiology, clinical characteristics, and treatment proceedings of melanoma. Then, the components of the tumor microenvironment, especially different populations of immune cells and their roles in antitumor immunity, were reviewed. Sequentially, how metabolic rewiring contributes to tumor cell malignant behaviors in melanoma pathogenesis was discussed. Following this, the proceedings of metabolism- and metabolic intermediate-regulated tumor immunology were comprehensively dissertated. Finally, we summarized currently available drugs that can be employed to target metabolism to intervene tumor immunology and modulate immunotherapy.
    Keywords:  glycolysis; immunology; immunotherapy; melanoma; metabolism
    DOI:  https://doi.org/10.3389/fimmu.2022.909580
  100. Nutrients. 2022 Aug 16. pii: 3353. [Epub ahead of print]14(16):
    Levels of Vitamin D and Expression of the Vitamin D Receptor in Relation to Breast Cancer Risk and Survival.
    Linnea Huss, Salma Tunå Butt, Signe Borgquist, Karin Elebro, Malte Sandsveden, Jonas Manjer, Ann Rosendahl.
      Previous research suggests associations between low systemic levels of vitamin D and poor breast cancer prognosis and between expression of the vitamin D receptor (VDR) in breast cancers and survival. This study aimed to study associations between pre-diagnostic systemic levels of vitamin D and expression of VDR in subsequent breast tumors, and interactions between vitamin D and VDR on breast cancer mortality. Systemic vitamin D levels were measured in women within the Malmö Diet and Cancer Study. The expression of VDR was evaluated immunohistochemically in a tissue microarray of subsequent breast cancers. Statistical analyses followed. Women with high levels of vitamin D had a smaller proportion of VDR negative breast tumors compared to women with low levels of vitamin D (odds ratio: 0.68; 95% confidence interval: 0.41-1.13). Vitamin D levels were not found to modify the association between low VDR expression and high breast cancer mortality. To conclude, there was no statistical evidence for an association between pre-diagnostic levels of vitamin D and the expression of VDRs in breast cancer, nor did vitamin D levels influence the association between VDR expression and breast cancer mortality. Further studies are needed in order to establish the effects of vitamin D on breast cancer.
    Keywords:  breast cancer; incidence; survival; vitamin D; vitamin D receptor
    DOI:  https://doi.org/10.3390/nu14163353
  101. Cell Mol Biol (Noisy-le-grand). 2022 Mar 31. 68(3): 9-14
    Antibacterial and wound healing applications of curcumin in micro and nano-scaffolds based on chitosan, cellulose, and collagen.
    Mehran Alavi, Musa Moetasam Zorab, Morahem Ashengroph, Qassim Hassan Aubais Aljelehawy, Danial Kahrizi.
      About 80% higher risk of amputation resulted from microbial infection was indicated for patients with diabetic foot ulcers (DFUs). Micro and nano-scaffolds made of natural polymers specifically cellulose, chitosan, and collagen can donate the biocompatibility, biodegradability, and bioavailability properties appropriate to  accelerate wound closure before microbial biofilm formation. Antimicrobial activity of these wound dressings can be improved by incorporation of bioactive compounds extracted from medicinal plant species such as curcumin. Low water solubility and poor bioavailability are recognized as two main disadvantages of curcumin, lipophilic phytopolyphenol, which could be controlled by targeted polymeric micro and nano-scaffolds. Consequently, this review has discussed the capacity and challenges of these types of formulations according to recent investigations.
    DOI:  https://doi.org/10.14715/cmb/2022.68.3.2
  102. Crit Rev Ther Drug Carrier Syst. 2022 ;39(6): 45-83
    Grafting of Natural Polymers and Gums for Drug Delivery Applications: A Perspective Review.
    Baburao N Chandakavathe, Ravindra G Kulkarni, Shivsharan B Dhadde.
      Natural polymers have received more attention because of their advantages over synthetic polymers such as abundant availability, low cost, biodegradability and non-toxicity. However, natural polymers suffer some limitations such as drop-in viscosity upon storage, uncontrolled hydration, solubility, inability to perform under high temperature and pressure (thermal stability), etc. In many instances above mentioned drawbacks of natural polymers limits their applications in drug delivery systems. Grafting of natural polymer leads to improved properties and characteristics of backbones of macromolecules such as improvement in gel strength, swelling index, mucoadhesion, drug targeting and drug release profile. Therefore, in recent decades grafting of the natural polymer has gained immense importance for the development of drug delivery systems. In addition to the pharmaceutical applications graft copolymers are extensively utilized in diversified fields. The present review is an attempt to define the grafting, various methods of polymer grafting and their application in drug delivery.
    DOI:  https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2022035905
  103. J Food Biochem. 2022 Aug 25. e14366
    Vanillic acid attenuates cell proliferation, xenobiotic enzyme activity, and the status of pulmonary mitochondrial enzymes in lung carcinoma.
    Sathesh Kanna V, Jagan S, Sharmila S, Palanisamy K, Nirmala S, Devaki T.
      The purpose of the study is to determine the anti-proliferative and mitochondrial status of benzo(a)pyrene-induced lung cancer in Swiss albino mice, as well as the modulatory effect of vanillic acid on it. B(a)P had altered levels of lysosomal enzymes, xenobiotic-metabolizing enzymes, cell proliferation, inflammation, and mitochondrial abnormalities, whereas treatment with VA treatment significantly reversed the aforementioned activities. According to the findings, VA greatly reduces lung carcinogenesis by restoring antioxidants and xenobiotic-enzyme levels, consequently proving to be an anti-proliferative and anti-inflammatory drug against lung cancer in mice. PRACTICAL APPLICATIONS: As we all know, lung cancer is on the rise all over the world. A recent study demonstrated that vanillic acid protects against B(a)P in experimental mice. According to the findings, VA considerably suppresses lung carcinogenesis by restoring lysosomal enzyme levels, xenobiotic-metabolizing enzyme levels, and mitochondrial activities, effectively functioning as an anti-proliferative and anti-inflammatory therapy against lung cancer. According to the most recent study, vanillic acid can be used as a defensive medicine in the treatment of lung cancer.
    Keywords:  inflammation; lung cancer; lysosomal enzymes; proliferation; xenobiotic enzymes
    DOI:  https://doi.org/10.1111/jfbc.14366
  104. Biomaterials. 2022 Aug 14. pii: S0142-9612(22)00376-3. [Epub ahead of print] 121736
    A self-activating nanoized vascular disrupting agent for selective anti-tumor therapy.
    Yajun Xu, Jianlin Lv, Na Shen, Zhaohui Tang, Xuesi Chen.
      Vascular disrupting agents (VDAs) have great potential in antitumor therapy, while the efficiency is limited by cardiovascular toxicity. In this study, a self-activating nanoized plinabulin (poly (l-glutamic acid) grafted Azo-Plinabulin, AzoP-NP) was constructed. The AzoP-NPs can selectively be activated to an amino derivative of plinabulin (AmP) by intrinsic tumor hypoxia, disrupting tumor vessels and amplifying hypoxia, whilst be activated by self-amplified tumor hypoxia, then selectively inhibit tumor growth. In 4T1 tumor model, the AzoP-NPs had a selective biodistribution in tumor, as the free AmP in tumors at 24 h after AzoP-NPs treatment was 18.6 fold of that after AmP treatment and significantly higher than that in other tissues. Accordingly, AzoP-NPs resulted in no obvious acute cardiovascular toxicity (plasma von Willebrand factor in PBS, AzoP-NPs and AmP group: 143.1, 184.0 and 477.6 ng/mL) and a significantly stronger tumor inhibition than AmP. And the sustained release of drug in AzoP-NPs led to a higher maximum tolerated dose (MTD) (MTD of AzoP-NPs and AmP: > 80 vs 20 mg/kg). In addition, AzoP-NPs amplified tumor hypoxic, and synergized the anti-tumor effect of Tirapazamine (TPZ), a hypoxia-activated drug in clinical trials, with an inhibition rate of 97.7% and Q value of 1.89. Therefore, our findings provide new insights into next generation VDAs and their application in tumor therapy.
    Keywords:  Hypoxia-activated; Plinabulin; Self-activating; Tumor selectivity; Vascular disrupting agents
    DOI:  https://doi.org/10.1016/j.biomaterials.2022.121736
  105. Recent Pat Nanotechnol. 2022 Aug 25.
    Hybrid nanocarriers for neurological disorders: Diagnostic & therapeutic Approach.
    Anuradha Mishra, Rabiya Ahsan, Anas Islam, Rohit Kumar Tiwari, Pragyandip P Dash.
      BACKGROUND: Around 1.5 billion people in the world were affected by complex neurological disorders and the figure is increasing alarmingly due to unsatisfactory clinical outcomes. To date, no conventional formulation is able to show a promising effect on the control or prevention of neurodegeneration. However, Nano delivery tools have shown better penetration and profound action on the targeted area of the brain.METHODS: Although existing Nano therapeutic approaches are abundant but would not reach the clinic due to their improper bioavailability, BBB restricts its entry and causes improper biodistribution, so it's a challenge to use certain bioactive as a potential therapy in neurodegenerative disorders. Hybrid nanocarriers are nano-vesicular transported systems, which could be utilized as carriers for the delivery of both hydrophilic and hydrophobic compounds. Available patents on nanodelivery for therapeutic approach will also include in this review.
    RESULTS: Hybrid Nano delivery system may provide good stability to polar and nonpolar compounds and improve their stability.
    CONCLUSION: This manuscript updates the available findings on the Nano vesicular system to deliver drugs for neurodegenerative disorders.
    Keywords:  Bioactive; Bioavailability; Hybrid; Nanocarriers; neurodegeneration
    DOI:  https://doi.org/10.2174/1872210516666220825170125
  106. Cell Rep. 2022 Aug 23. pii: S2211-1247(22)01074-9. [Epub ahead of print]40(8): 111256
    Fasting renders immunotherapy effective against low-immunogenic breast cancer while reducing side effects.
    Salvatore Cortellino, Alessandro Raveane, Claudia Chiodoni, Gloria Delfanti, Federica Pisati, Vanessa Spagnolo, Euplio Visco, Giuseppe Fragale, Federica Ferrante, Serena Magni, Fabio Iannelli, Federica Zanardi, Giulia Casorati, Francesco Bertolini, Paolo Dellabona, Mario P Colombo, Claudio Tripodo, Valter D Longo.
      Immunotherapy is improving the prognosis and survival of cancer patients, but despite encouraging outcomes in different cancers, the majority of tumors are resistant to it, and the immunotherapy combinations are often accompanied by severe side effects. Here, we show that a periodic fasting-mimicking diet (FMD) can act on the tumor microenvironment and increase the efficacy of immunotherapy (anti-PD-L1 and anti-OX40) against the poorly immunogenic triple-negative breast tumors (TNBCs) by expanding early exhausted effector T cells, switching the cancer metabolism from glycolytic to respiratory, and reducing collagen deposition. Furthermore, FMD reduces the occurrence of immune-related adverse events (irAEs) by preventing the hyperactivation of the immune response. These results indicate that FMD cycles have the potential to enhance the efficacy of anti-cancer immune responses, expand the portion of tumors sensitive to immunotherapy, and reduce its side effects.
    Keywords:  CP: Cancer; CP: Immunology; differential stress sensitization; fasting; fasting-mimicking diet; immunotherapy; inflammation; nutrition; side effects; triple-negative breast cancer
    DOI:  https://doi.org/10.1016/j.celrep.2022.111256
  107. Life Sci. 2022 Aug 23. pii: S0024-3205(22)00608-7. [Epub ahead of print] 120908
    Effect of nanovesicular surface-functionalization via chitosan and/or PEGylation on cytotoxicity of tamoxifen in induced-breast cancer model.
    Mohamed A Megahed, Hossam S El-Sawy, Ahmed M Reda, Fathy I Abd Allah, Sherif K Abu Elyazid, Ahmed E Lila, Hatem R Ismael, Khalid M El-Say.
      AIMS: The effect of surface-modification of Tamoxifen (Tam)-loaded-niosomes on drug cytotoxicity and bio-distribution, via functionalization with chitosan and/or PEGylation, was investigated.MATERIALS AND METHODS: Tam-loaded hybrid-nanocarriers (Tam-loaded niosomes, chitosomes, PEGylated niosomes, and PEGylated chitosomes) were formulated and characterized.
    KEY FINDINGS: Chitosanization with/without PEGylation proved to selectively enhance Tam-release at the cancerous-acidic micromilieu. Cytotoxic activity study showed that Tam-loaded PEGylated niosomes had a lower IC50 value on MCF-7 cell line (0.39, 0.35, and 0.27 times) than Tam-loaded PEGylated chitosomes, Tam-loaded niosomes, and Tam-loaded chitosomes, respectively. Cell cycle analysis showed that PEGylation and/or Chitosanization significantly impact Tam efficiency in inducing apoptosis, with a preferential influence of PEGylation over chitosanization. The assay of Annexin-V/PI double staining revealed that chitosanized-nanocarriers had a significant role in increasing the incidence of apoptosis over necrosis. Besides, PEGylated-nanocarriers increased apoptosis, as well as total death and necrosis percentages more than what was shown from free Tam. Moreover, the average changes in both Bax/Bcl-2 ratio and Caspase 9 were best improved in cells treated by Tam-loaded PEGylated niosomes over all other formulations. The in-vivo study involving DMBA-induced-breast cancer rats revealed that PEGylation made the highest tumor-growth inhibition (84.9 %) and breast tumor selectivity, while chitosanization had a lower accumulation tendency in the blood (62.3 ng/ml) and liver tissues (103.67 ng/ml). The histopathological specimens from the group treated with Tam-loaded PEGylated niosomes showed the best improvement over other formulations.
    SIGNIFICANCE: All these results concluded the crucial effect of both PEGylation and chitosan-functionalization of Tam-loaded niosomes in enhancing effectiveness, targetability, and safety.
    Keywords:  Apoptosis and necrosis detection; In-vitro/in-vivo correlation; Induced-breast cancer rats; Niosomes; Surface modification; Tamoxifen
    DOI:  https://doi.org/10.1016/j.lfs.2022.120908
  108. Int J Mol Sci. 2022 Aug 20. pii: 9391. [Epub ahead of print]23(16):
    KRAS-Mutant Non-Small-Cell Lung Cancer: From Past Efforts to Future Challenges.
    Serena Ceddia, Lorenza Landi, Federico Cappuzzo.
      KRAS is the most frequently mutated oncogene identified in human cancers. Despite the numerous efforts to develop effective specific inhibitors against KRAS, this molecule has remained "undruggable" for decades. The development of direct KRAS inhibitors, such as sotorasib, the first FDA-approved drug targeting KRAS G12C, or adagrasib, was made possible with the discovery of a small pocket in the binding switch II region of KRAS G12C. However, a new challenge is represented by the necessity to overcome resistance mechanisms to KRAS inhibitors. Another area to be explored is the potential role of co-mutations in the selection of the treatment strategy, particularly in the setting of immune checkpoint inhibitors. The aim of this review was to analyze the state-of-the-art of KRAS mutations in non-small-cell lung cancer by describing the biological structure of KRAS and exploring the clinical relevance of KRAS as a prognostic and predictive biomarker. We reviewed the different treatment approaches, focusing on the novel therapeutic strategies for the treatment of KRAS-mutant lung cancers.
    Keywords:  KRAS mutations; KRASG12C inhibitors; molecular biology; non-small-cell lung cancer; targeted therapy
    DOI:  https://doi.org/10.3390/ijms23169391
  109. Pharmaceuticals (Basel). 2022 Aug 01. pii: 957. [Epub ahead of print]15(8):
    Resveratrol from Dietary Supplement to a Drug Candidate: An Assessment of Potential.
    Shivani Khattar, Sauban Ahmed Khan, Syed Amir Azam Zaidi, Mahdi Darvishikolour, Uzma Farooq, Punnoth Poonkuzhi Naseef, Mohamed Saheer Kurunian, Mohammed Zaafar Khan, Athar Shamim, Mohd Masih Uzzaman Khan, Zeenat Iqbal, Mohd Aamir Mirza.
      Resveratrol (RVT) is a well known phyto-chemical and is widely used in dietary supplements and botanical products. It shows a wide range of pharmacological/beneficial effects. Therefore, it can be a potential candidate to be developed as phyto-pharmaceutical. Multiple diseases are reported to be treated by the therapeutic effect of RVT since it has antioxidant, anti-cancer activity and anti-inflammatory activities. It also has a major role in diabetes, arthritis, cardiac disorder and platelet aggregation etc. The major requirements are establishments regarding safety, efficacy profile and physicochemical characterization. As it is already being consumed in variable maximum daily dose, there should not be a major safety concern but the dose needs to be established for different indications. Clinical trials are also being reported in different parts of the world. Physicochemical properties of the moiety are also well reported. Moreover, due to its beneficial effect on health it leads to the development of some intellectual property in the form of patents.
    Keywords:  anti-thrombogenic; antioxidants; carcinogenic and anti-aging; cardioprotective; neuroprotective
    DOI:  https://doi.org/10.3390/ph15080957
  110. Dalton Trans. 2022 Aug 26.
    Targeted cancer phototherapy using phthalocyanine-anticancer drug conjugates.
    Christopher C Rennie, Robert M Edkins.
      Phototherapy, the use of light to selectively ablate cancerous tissue, is a compelling prospect. Phototherapy is divided into two major domains: photodynamic and photothermal, whereby photosensitizer irradiation generates reactive oxygen species or heat, respectively, to disrupt the cancer microenvironment. Phthalocyanines (Pcs) are prominent phototherapeutics due to their desirable optical properties and structural versatility. Targeting of Pc photosensitizers historically relied on the enhanced permeation and retention effect, but the weak specificity engendered by this approach has hindered bench-to-clinic translation. To improve specificity, antibody and peptide active-targeting groups have been employed to some effect. An alternative targeting method exploits the binding of anticancer drugs to direct the photosensitizer close to essential cellular components, allowing for precise, synergistic phototherapy. This Perspective explores the use of Pc-drug conjugates as targeted anticancer phototherapeutic systems with examples of Pc-platin, Pc-kinase, and Pc-anthracycline conjugates discussed in detail.
    DOI:  https://doi.org/10.1039/d2dt02040h
  111. Pharmaceutics. 2022 Aug 12. pii: 1682. [Epub ahead of print]14(8):
    Functional Nanoparticles for Enhanced Cancer Therapy.
    Chenchen Li, Yuqing Li, Guangzhi Li, Song Wu.
      Cancer is the leading cause of death in people worldwide. The conventional therapeutic approach is mainly based on chemotherapy, which has a series of side effects. Compared with traditional chemotherapy drugs, nanoparticle-based delivery of anti-cancer drugs possesses a few attractive features. The application of nanotechnology in an interdisciplinary manner in the biomedical field has led to functional nanoparticles achieving much progress in cancer therapy. Nanoparticles have been involved in the diagnosis and targeted and personalized treatment of cancer. For example, different nano-drug strategies, including endogenous and exogenous stimuli-responsive, surface conjugation, and macromolecular encapsulation for nano-drug systems, have successfully prevented tumor procession. The future for functional nanoparticles is bright and promising due to the fast development of nanotechnology. However, there are still some challenges and limitations that need to be considered. Based on the above contents, the present article analyzes the progress in developing functional nanoparticles in cancer therapy. Research gaps and promising strategies for the clinical application are discussed.
    Keywords:  cancer therapy; functional nanoparticles; nanotechnology
    DOI:  https://doi.org/10.3390/pharmaceutics14081682
  112. J Control Release. 2022 Aug 22. pii: S0168-3659(22)00539-9. [Epub ahead of print]
    Research progress of bone-targeted drug delivery system on metastatic bone tumors.
    Beibei Hu, Yongkang Zhang, Guogang Zhang, Zhongqiu Li, Yongshuai Jing, Jun Yao, Shiguo Sun.
      Bone metastases are common in malignant tumors and the effect of conventional treatment is limited. How to effectively inhibit tumor bone metastasis and deliver the drug to the bone has become an urgent issue to be solved. While bone targeting drug delivery systems have obvious advantages in the treatment of bone tumors. The research on bone-targeted anti-tumor therapy has made significant progress in recent years. We introduced the related tumor pathways of bone metastases. The tumor microenvironment plays an important role in metastatic bone tumors. We introduce a drug-loading systems based on different environment-responsive nanocomposites for anti-tumor and anti-metastatic research. According to the process of bone metastases and the structure of bone tissue, we summarized the information on bone-targeting molecules. Bisphosphate has become the first choice of bone-targeted drug delivery carrier because of its affinity with hydroxyapatite in bone. Therefore, we sought to summarize the bone-targeting molecule of bisphosphate to identify the modification effect on bone-targeting. And this paper discusses the relationship between bisphosphate bone targeting molecular structure and drug delivery carriers, to provide some new ideas for the research and development of bone-targeting drug delivery carriers. Targeted therapy will make a more outstanding contribution to the treatment of tumors.
    Keywords:  Bisphosphonates; Bone metastases; Bone-targeting molecules; Tumor microenvironment; cancer
    DOI:  https://doi.org/10.1016/j.jconrel.2022.08.034
  113. Cancer Invest. 2022 Aug 22. 1-66
    The journey of resveratrol from vineyards to clinics.
    Ramya Venkat, Elika Verma, Uzini Devi Daimary, Aviral Kumar, Sosmitha Girisa, Uma Dutta, Kwang Seok Ahn, Ajaikumar B Kunnumakkara.
      With rising technological advancements, several factors influence the lifestyle of people and stimulate chronic inflammation that severely affects the human body. Chronic inflammation leads to a broad range of physical and pathophysiological distress. For many years non-steroidal drugs and corticosteroids were most frequently used in treating inflammation and related ailments. However, long-term usage of these drugs aggravates the conditions of chronic diseases and is presented with morbid side effects, especially in old age. Hence, the quest for safe and less toxic anti-inflammatory compounds of high therapeutic potential with least adverse side effects has shifted researchers' attention to ancient medicinal system. Resveratrol (RSV) - 3,4,5' trihydroxystilbene is one such naturally available polyphenolic stilbene derivative obtained from various plant sources. For over 2000 years, these plants have been used in Asian medicinal system for curing inflammation-associated disorders. There is a wealth of in vitro, in vivo and clinical evidence that shows RSV could induce anti-aging health benefits including, anti-cancer, anti-inflammatory, anti-oxidant, phytoesterogenic, and cardio protective properties. However, the issue of rapid elimination of RSV through the metabolic system and its low bio-availability is of paramount importance which is being studied extensively. Therefore, in the present article, we scientifically reviewed the molecular targets, biological activities, beneficial and contradicting effects of RSV as evinced by clinical studies for the prevention and treatment of inflammation-mediated chronic disorders.
    Keywords:  Resveratrol; anti-aging; chronic diseases; inflammation; molecular targets
    DOI:  https://doi.org/10.1080/07357907.2022.2115057
  114. Angew Chem Int Ed Engl. 2022 Aug 25.
    Dual-Modulated Release of a Cytotoxic Photosensitizer Using Photogenerated Reactive Oxygen Species and Glutathione.
    Chae Gyu Lee, Chaiheon Lee, Joonhee Lee, Jung Seung Nam, Byeong-Su Kim, Tae-Hyuk Kwon.
      Reversible thiol-disulfide exchange chemistry is of particular interest in drug delivery systems. However, high levels of glutathione (GSH) in cancer cells are hardly distinguished from GSH in normal cells, resulting in unmanageable cytotoxic drug release. This study investigates the spatiotemporally-controlled irreversible degradation of Ir-based photosensitizer (TIr3)-encapsulating nanogels (IrNG) through the hyperoxidation of resulting intracellular thiols using reactive oxygen species (ROS). A highly cytotoxic TIr3 was stably encapsulated within IrNG through hydrophobic interactions and reversible crosslinking between its disulfide bonds and thiols in the absence of light, resulting in high biocompatibility under normal cellular conditions. However, upon photoirradiation, TIr3 generated high levels of ROS, irreversibly oxidizing the thiols to induce electrostatic repulsion between the polymer molecules, resulting in the TIr3 release and induction of cancer cell apoptosis.
    Keywords:  Cytotoxicity, Drug delivery, Nanoparticles, Photooxidation, Redox chemistry
    DOI:  https://doi.org/10.1002/anie.202210623
  115. Antioxidants (Basel). 2022 Aug 20. pii: 1621. [Epub ahead of print]11(8):
    Understanding the Mechanism of Action of Melatonin, Which Induces ROS Production in Cancer Cells.
    Javier Florido, César Rodriguez-Santana, Laura Martinez-Ruiz, Alba López-Rodríguez, Darío Acuña-Castroviejo, Iryna Rusanova, Germaine Escames.
      Reactive oxygen species (ROS) constitute a group of highly reactive molecules that have evolved as regulators of important signaling pathways. In this context, tumor cells have an altered redox balance compared to normal cells, which can be targeted as an antitumoral therapy by ROS levels and by decreasing the capacity of the antioxidant system, leading to programmed cell death. Melatonin is of particular importance in the development of innovative cancer treatments due to its oncostatic impact and lack of adverse effects. Despite being widely recognized as a pro-oxidant molecule in tumor cells, the mechanism of action of melatonin remains unclear, which has hindered its use in clinical treatments. The current review aims to describe and clarify the proposed mechanism of action of melatonin inducing ROS production in cancer cells in order to propose future anti-neoplastic clinical applications.
    Keywords:  apoptosis; cancer; melatonin; mitochondria; reactive oxygen species
    DOI:  https://doi.org/10.3390/antiox11081621
  116. Mar Drugs. 2022 Jul 29. pii: 490. [Epub ahead of print]20(8):
    Antioxidant Activity of Fucoidan Modified with Gallic Acid Using the Redox Method.
    Keylla Dayanne Coelho Marinho de Melo, Lucas Dos Santos Lisboa, Moacir Fernandes Queiroz, Weslley Souza Paiva, Ana Carolina Luchiari, Rafael Barros Gomes Camara, Leandro Silva Costa, Hugo Alexandre Oliveira Rocha.
      Antioxidant compounds decrease the amount of intracellular reactive oxygen species (ROS) and, consequently, reduce the deleterious effects of ROS in osteoblasts. Here, we modified a 21 kDa fucoidan (FucA) with gallic acid (GA) using the redox method, to potentiate its antioxidant/protective capacity on pre-osteoblast-like cells (MC3T3) against oxidative stress. The 20 kDa FucA-GA contains 37 ± 3.0 mg GA per gram of FucA. FucA-GA was the most efficient antioxidant agent in terms of total antioxidant capacity (2.5 times), reducing power (five times), copper chelation (three times), and superoxide radical scavenging (2 times). Exposure of MC3T3 cells to H2O2 increased ROS levels and activated caspase-3 along with caspase-9. In addition, the cell viability decreased approximately 80%. FucA-GA also provided the most effective protection against oxidative damage caused by H2O2. Treatment with FucA-GA (1.0 mg/mL) increased cell viability (~80%) and decreased intracellular ROS (100%) and caspase activation (~80%). In addition, Fuc-GA (0.1 mg/mL) abolished H2O2-induced oxidative stress in zebra fish embryos. Overall, FucA-GA protected MC3T3 cells from oxidative stress and could represent a possible adjuvant for the treatment of bone fragility by counteracting oxidative phenomena.
    Keywords:  antioxidant activity; oxidative damage; sulfated fucan; sulfated polysaccharides
    DOI:  https://doi.org/10.3390/md20080490
  117. Antioxid Redox Signal. 2022 Aug 23.
    Diabetic ferroptosis and pancreatic cancer: Foe or Friend?
    Le Li, Xing-Jia Yu, Lei Gao, Long Cheng, Bei Sun, Gang Wang.
      Significance Pancreatic cancer and diabetes are of reciprocal causation. As a potential risk factor, diabetes increases the morbidity and promote pancreatic cancer progression. The main mechanisms include islet dysfunction-induced systemic metabolic disorder, pancreatic stellate cell activation and immunosuppression. Ferroptosis is regarded as a regulated cell death which participates in chemotherapy resistance and refractory to radiation therapy and immunotherapy. Diabetes-induced ferroptosis causes many complications, but the underlying mechanism of diabetes-related ferroptosis in pancreatic cancer has not been discussed. Recent Advances Ferroptosis alleviates pancreatic intraepithelial neoplasia (PanIN) progression by activating chronic inflammation. The specific drugs that cause ferroptosis achieve tumor suppression by inducing lipid peroxidation. Ferroptosis presents pros and cons roles in cancers. Both ferroptosis inhibitor and inducer exhibit anti-tumor effects through killing cancer cells or directly affecting tumor growth. Diabetes-induced ferroptosis contributes to tumor cell death by different components, including tumor cells, fibroblasts, immune cells and adipocytes. Better demonstrating its roles on modulating tumor microenvironment will reveal diabetes-associated ferroptotic features in cancer development, and figure out possible strategies for cancer treatments in hyperglycaemia. Critical Issues We demonstrate the potential roles of diabetes-related ferroptosis in pancreatic cancer progression, and discussing ferroptosis-related anti-tumor effects and therapeutics for pancreatic cancer treatment. Future Directions Further studies are required to highlight mechanisms of diabetes-medicated ferroptosis in pancreatic cancer tumorigenesis and progression. The anti-tumor effects of ferroptosis regulators combined with chemotherapy, targeted therapy or immunotherapy in diabetic patients should be investigated. We hope that pancreatic cancer patients with diabetes will benefit from the ferroptosis-related therapies.
    DOI:  https://doi.org/10.1089/ars.2022.0101
  118. Proc Natl Acad Sci U S A. 2022 Aug 30. 119(35): e2205456119
    Metastatic triple negative breast cancer adapts its metabolism to destination tissues while retaining key metabolic signatures.
    Fariba Roshanzamir, Jonathan L Robinson, Daniel Cook, Mohammad Hossein Karimi-Jafari, Jens Nielsen.
      Triple negative breast cancer (TNBC) metastases are assumed to exhibit similar functions in different organs as in the original primary tumor. However, studies of metastasis are often limited to a comparison of metastatic tumors with primary tumors of their origin, and little is known about the adaptation to the local environment of the metastatic sites. We therefore used transcriptomic data and metabolic network analyses to investigate whether metastatic tumors adapt their metabolism to the metastatic site and found that metastatic tumors adopt a metabolic signature with some similarity to primary tumors of their destinations. The extent of adaptation, however, varies across different organs, and metastatic tumors retain metabolic signatures associated with TNBC. Our findings suggest that a combination of anti-metastatic approaches and metabolic inhibitors selected specifically for different metastatic sites, rather than solely targeting TNBC primary tumors, may constitute a more effective treatment approach.
    Keywords:  gene expression; genome-scale metabolic models; metastasis; systems biology; triple negative breast cancer
    DOI:  https://doi.org/10.1073/pnas.2205456119
  119. Chem Biol Interact. 2022 Aug 19. pii: S0009-2797(22)00322-2. [Epub ahead of print] 110117
    Multifunctional roles and pharmacological potential of β-sitosterol: Emerging evidence toward clinical applications.
    Zidan Khan, Nikhil Nath, Abdur Rauf, Talha Bin Emran, Saikat Mitra, Fahadul Islam, Deepak Chandran, Jackie Barua, Mayeen Uddin Khandaker, Abubakr M Idris, Polrat Wilairatana, Muthu Thiruvengadam.
      Currently, available therapeutic medications are both costly as well as not entirely promising in terms of potency. So, new candidates from natural resources are of research interest to find new alternative therapeutics. A well-known combination is a β-sitosterol, a plant-derived nutrient with anticancer properties against breast, prostate, colon, lung, stomach, and leukemia. Studies have shown that β-sitosterol interferes with multiple cell signaling pathways, including cell cycle, apoptosis, proliferation, survival, invasion, angiogenesis, metastasis, anti-inflammatory, anticancer, hepatoprotective, antioxidant, cardioprotective, and antidiabetic effects have been discovered during pharmacological screening without significant toxicity. The pharmacokinetic profile of β-sitosterol has also been extensively investigated. However, a comprehensive review of the pharmacology, phytochemistry and analytical methods of β-sitosterol is desired. Because β-sitosterol is a significant component of most plant materials, humans use it for various reasons, and numerous β-sitosterol-containing products have been commercialized. To offset the low efficacy of β-sitosterol, designing β-sitosterol delivery for "cancer cell-specific" therapy holds great potential. Delivery of β-sitosterol via liposomes is a demonstration that has shown great promise. But further research has not progressed on the drug delivery of β-sitosterol or how it can enhance β-sitosterol mediated anti-inflammatory activity, thus making β-sitosterol an orphan nutraceutical. Therefore, extensive research on β-sitosterol as an anticancer nutraceutical is recommended.
    Keywords:  Biological characteristics; Pharmacological potential; Pharmacology; Toxicity; β-Sitosterol
    DOI:  https://doi.org/10.1016/j.cbi.2022.110117
  120. Pharmaceutics. 2022 Aug 01. pii: 1606. [Epub ahead of print]14(8):
    Nanomedicines for Overcoming Cancer Drug Resistance.
    Tingting Hu, Hanlin Gong, Jiayue Xu, Yuan Huang, Fengbo Wu, Zhiyao He.
      Clinically, cancer drug resistance to chemotherapy, targeted therapy or immunotherapy remains the main impediment towards curative cancer therapy, which leads directly to treatment failure along with extended hospital stays, increased medical costs and high mortality. Therefore, increasing attention has been paid to nanotechnology-based delivery systems for overcoming drug resistance in cancer. In this respect, novel tumor-targeting nanomedicines offer fairly effective therapeutic strategies for surmounting the various limitations of chemotherapy, targeted therapy and immunotherapy, enabling more precise cancer treatment, more convenient monitoring of treatment agents, as well as surmounting cancer drug resistance, including multidrug resistance (MDR). Nanotechnology-based delivery systems, including liposomes, polymer micelles, nanoparticles (NPs), and DNA nanostructures, enable a large number of properly designed therapeutic nanomedicines. In this paper, we review the different mechanisms of cancer drug resistance to chemotherapy, targeted therapy and immunotherapy, and discuss the latest developments in nanomedicines for overcoming cancer drug resistance.
    Keywords:  chemotherapy; drug resistance; immunotherapy; nanomedicine; nanotechnology; targeted therapy
    DOI:  https://doi.org/10.3390/pharmaceutics14081606
  121. Pharmaceutics. 2022 Aug 06. pii: 1643. [Epub ahead of print]14(8):
    Anti-Proliferative Potential of Quercetin Loaded Polymeric Mixed Micelles on Rat C6 and Human U87MG Glioma Cells.
    Sathishbabu Paranthaman, Chinnappa A Uthaiah, Riyaz Ali M Osmani, Umme Hani, Mohammed Ghazwani, Ali H Alamri, Adel Al Fatease, SubbaRao V Madhunapantula, Devegowda Vishkante Gowda.
      Quercetin (Qu) is a natural flavonoid present in many commonly consumed food items and is also identified as a potential anticancer agent. The present study evaluates the Qu-loaded polymeric mixed micelles (Qu-PMMs) against C6 and U87MG glioma cell lines. The Box-Behnken Design (BBD) was employed to study the influence of independent variables such as Soluplus, Vitamin-E polyethyleneglycol-1000 succinate (E-TPGS), and poloxamer 407 concentrations on dependent variables including particle size (PS), polydispersity index (PDI), and percentage entrapment efficiency (%EE) of the prepared Qu-PMMs. The Qu-PMMs were further characterized by Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscope (SEM), and were assessed for in vitro drug release, effect on cell viability, migration, cellular uptake, and apoptosis assays. The PS, PDI, and % EE of the optimized PMMs were 107.16 ± 1.06 nm, 0.236 ± 0.053, and 77.46 ± 1.94%, respectively. The FTIR and XRD revealed that the Qu was completely entrapped inside the PMMs. The SEM analysis confirmed the spherical shape of micelles. The in vitro cell viability study showed that the Qu-PMMs had 1.7 times higher cytotoxicity against C6 and U87MG cells than Qu pure drug (Qu-PD). Furthermore, Qu-PMMs demonstrated superior cellular uptake, inhibited migration, and induced apoptosis when tested against C6 and U87MG cells than pure Qu. Thus, the polymeric mixed micelle (PMMs) enhanced the therapeutic effect of Qu and can be considered an effective therapeutic strategy to treat Glioma.
    Keywords:  Box–Behnken Design; anticancer activity; glioma; polymeric mixed micelles; quercetin
    DOI:  https://doi.org/10.3390/pharmaceutics14081643
  122. Nutrients. 2022 Aug 16. pii: 3351. [Epub ahead of print]14(16):
    Vitamin D-Mediated Regulation of Intestinal Calcium Absorption.
    James C Fleet.
      Vitamin D is a critical regulator of calcium and bone homeostasis. While vitamin D has multiple effects on bone and calcium metabolism, the regulation of intestinal calcium (Ca) absorption efficiency is a critical function for vitamin D. This is necessary for optimal bone mineralization during growth, the protection of bone in adults, and the prevention of osteoporosis. Intestinal Ca absorption is regulated by 1,25 dihydroxyvitamin D (1,25(OH)2 D), a hormone that activates gene transcription following binding to the intestinal vitamin D receptor (VDR). When dietary Ca intake is low, Ca absorption follows a vitamin-D-regulated, saturable pathway, but when dietary Ca intake is high, Ca absorption is predominately through a paracellular diffusion pathway. Deletion of genes that mediate vitamin D action (i.e., VDR) or production (CYP27B1) eliminates basal Ca absorption and prevents the adaptation of mice to low-Ca diets. Various physiologic or disease states modify vitamin-D-regulated intestinal absorption of Ca (enhanced during late pregnancy, reduced due to menopause and aging).
    Keywords:  absorption; diet; diffusion; homeostasis; intestine; parathyroid hormone; transcellular
    DOI:  https://doi.org/10.3390/nu14163351
  123. Life (Basel). 2022 Jul 28. pii: 1140. [Epub ahead of print]12(8):
    A Comprehensive Review on the Anti-Cancer Effects of Oleuropein.
    Sabreen Rishmawi, Fatma Haddad, Ghadeer Dokmak, Rafik Karaman.
      In Mediterranean cuisine and culture, olive oil and olive fruits play a significant role. Many people believe that those who consume olive oil and its fruit live longer and have a decreased risk of illness. Olive leaves were used to treat a range of diseases in ancient times, including malaria fever and lower earaches. Although it was not understood at the time what key components were responsible for these effects because they had not yet been discovered, Oleuropein is now recognized as one of the primary elements in immature olive fruits and leaves. Later research was carried out to determine the effects of this molecule, and it was determined that it functions as an antioxidant. Oleuropein consumption has aided in cancer treatment over the years, and this was assumed to be owing to its antioxidant properties. Oleuropein's effects on cancer, however, go beyond that; it is now known that Oleuropein functions as both an anti-proliferative and an apoptotic promoter in many cancer cells. The kinetics and dosages of Oleuropein and the mechanisms behind its involvement and effects in cancer are explored in this review. Finally, the effects of Oleuropein in combination with anticancer medicines are investigated.
    Keywords:  Olea europaea; Oleuropein; angiogenesis; antioxidant; antiproliferative; apoptosis; cancer; olive oil
    DOI:  https://doi.org/10.3390/life12081140
  124. Int J Mol Sci. 2022 Aug 19. pii: 9359. [Epub ahead of print]23(16):
    Anticancer and Antioxidant Activities in Ganoderma lucidum Wild Mushrooms in Poland, as Well as Their Phenolic and Triterpenoid Compounds.
    Joanna Kolniak-Ostek, Jan Oszmiański, Anna Szyjka, Helena Moreira, Ewa Barg.
      The goal of this study was to the assess anti-cancer and antioxidant properties of the Ganoderma lucidum fruiting body, and to identify bioactive compounds found in their extracts. Significant antiproliferative activity was observed against MCF-7, MCF-7/DX, LOVO, LOVO/DX, MDA-MB 231, SW 620, and NHDF cell lines. With IC50 values of 25.38 µg/mL and 47.90 µg/mL, respectively, the extract was most effective against MDA-MB 231 and SW 620 cell lines. The bioactive compounds were identified using an ACQUITY UPLC-PDA-MS system. The extracts contained 13 triterpenoids and 28 polyphenols from the flavonols, phenolic acids, flavones, flavan-3-ols, and stilbenes families. Ganoderic acid derivative was found to be the most abundant triterpenoid (162.4 mg/g DW), followed by ganoderic acid B (145.6 mg/g DW). Resveratrol was the most abundant phenolic in the extract (5155.7 mg/100 g DM). The findings could explain why G. lucidum extracts are used in folk medicine.
    Keywords:  LC-MS; antioxidants; bioactive compounds; lingzhi; mushrooms; reishi
    DOI:  https://doi.org/10.3390/ijms23169359
  125. Biomed Pharmacother. 2022 Aug 19. pii: S0753-3322(22)00948-9. [Epub ahead of print]154 113559
    Peppermint essential oil: its phytochemistry, biological activity, pharmacological effect and application.
    Hui Zhao, Shan Ren, Han Yang, Shun Tang, Chenyang Guo, Maolun Liu, Qiu Tao, Tianqi Ming, Haibo Xu.
      Mentha (also known as peppermint), a genus of plants in the taxonomic family Lamiaceae (mint family), is widely distributed throughout temperate regions of the world. Mentha contains various constituents that are classified as peppermint essential oil (PEO) and non-essential components. PEO, consisting mainly of menthol, menthone, neomenthol and iso-menthone, is a mixture of volatile metabolites with anti-inflammatory, antibacterial, antiviral, scolicidal, immunomodulatory, antitumor, neuroprotective, antifatigue and antioxidant activities. Mounting evidence indicates that PEO may pharmacologically protect gastrointestinal, liver, kidney, skin, respiratory, brain and nervous systems, and exert hypoglycemic and hypolipidemic effects. Clinically, PEO is used for gastrointestinal and dermatological diseases, postoperative adjuvant therapy and other fields. This review aims to address the advances in the extraction and isolation of PEO, its biological activities, pharmacological effects, toxicity and applications, with an emphasis on the efficacy of PEO on burn wounds and psoriasis, providing a comprehensive foundation for research, development and application of PEO in future.
    Keywords:  Application; Biological activity; Mentha; Pharmacological effect; Phytochemistry; peppermint essential oil
    DOI:  https://doi.org/10.1016/j.biopha.2022.113559
  126. Front Nutr. 2022 ;9 980429
    The clinical impact of an extra virgin olive oil enriched mediterranean diet on metabolic syndrome: Lights and shadows of a nutraceutical approach.
    Aurelio Seidita, Maurizio Soresi, Lydia Giannitrapani, Vita Di Stefano, Roberto Citarrella, Luigi Mirarchi, Antonella Cusimano, Giuseppa Augello, Antonio Carroccio, Juan Lucio Iovanna, Melchiorre Cervello.
      For years it has been established that the only truly effective treatment of metabolic syndrome (MS) is lifestyle modification to prevent its cardiovascular (e.g., coronary artery disease and atherosclerosis), metabolic (e.g., diabetes mellitus), and hepatic (e.g., steatosis and non-alcoholic steatohepatitis) complications. The focal points of this approach are to increase physical activity and intake of a diet characterized by high quantities of fruits, vegetables, grains, fish, and low-fat dairy products, the so called mediterranean diet (MD); however, the added value of MD is the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations (range 50-800 mg/kg) of phenols (oleuropein, ligstroside, and oleocanthal, and their derivatives, phenolic alcohols, such as hydroxytyrosol and tyrosol). Phenolic compounds not only determine EVOO's main organoleptic qualities (oxidative stability, specific flavor, and taste features) but, theoretically, make it a source of antioxidant, anti-inflammatory, insulin-sensitizing, cardioprotective, antiatherogenic, neuroprotective, immunomodulatory, and anticancer activity. Although many studies have been carried out on EVOO's clinical effects and attention toward this dietary approach (healthy and palatable food with strong nutraceutical activity) has become increasingly pressing, there are still many dark sides to be clarified, both in terms of actual clinical efficacy and biochemical and molecular activity. Thus, we reviewed the international literature, trying to show the state of the art about EVOO's clinical properties to treat MS (along with correlated complications) and the future prospective of its nutraceutical use.
    Keywords:  cardiovascular disease; extra virgin olive oil (EVOO); functional foods; insulin resistance; metabolic syndrome; nutraceuticals
    DOI:  https://doi.org/10.3389/fnut.2022.980429
  127. Molecules. 2022 Aug 21. pii: 5327. [Epub ahead of print]27(16):
    Mechanistic Insights into the Pharmacological Significance of Silymarin.
    Karan Wadhwa, Rakesh Pahwa, Manish Kumar, Shobhit Kumar, Prabodh Chander Sharma, Govind Singh, Ravinder Verma, Vineet Mittal, Inderbir Singh, Deepak Kaushik, Philippe Jeandet.
      Medicinal plants are considered the reservoir of diverse therapeutic agents and have been traditionally employed worldwide to heal various ailments for several decades. Silymarin is a plant-derived mixture of polyphenolic flavonoids originating from the fruits and akenes of Silybum marianum and contains three flavonolignans, silibinins (silybins), silychristin and silydianin, along with taxifolin. Silybins are the major constituents in silymarin with almost 70-80% abundance and are accountable for most of the observed therapeutic activity. Silymarin has also been acknowledged from the ancient period and is utilized in European and Asian systems of traditional medicine for treating various liver disorders. The contemporary literature reveals that silymarin is employed significantly as a neuroprotective, hepatoprotective, cardioprotective, antioxidant, anti-cancer, anti-diabetic, anti-viral, anti-hypertensive, immunomodulator, anti-inflammatory, photoprotective and detoxification agent by targeting various cellular and molecular pathways, including MAPK, mTOR, β-catenin and Akt, different receptors and growth factors, as well as inhibiting numerous enzymes and the gene expression of several apoptotic proteins and inflammatory cytokines. Therefore, the current review aims to recapitulate and update the existing knowledge regarding the pharmacological potential of silymarin as evidenced by vast cellular, animal, and clinical studies, with a particular emphasis on its mechanisms of action.
    Keywords:  anti-inflammatory; antioxidant; pharmacological interventions; pro-apoptotic; silybin; silymarin
    DOI:  https://doi.org/10.3390/molecules27165327
  128. Pharmaceutics. 2022 Aug 10. pii: 1666. [Epub ahead of print]14(8):
    The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions.
    Jelena B Đoković, Sotiria Demisli, Sanela M Savić, Bojan D Marković, Nebojša D Cekić, Danijela V Randjelovic, Jelena R Mitrović, Dominique Jasmin Lunter, Vassiliki Papadimitriou, Aristotelis Xenakis, Snežana D Savić.
      A nanotechnology-based approach to drug delivery presents one of the biggest trends in biomedical science that can provide increased active concentration, bioavailability, and safety compared to conventional drug-delivery systems. Nanoemulsions stand out amongst other nanocarriers for being biodegradable, biocompatible, and relatively easy to manufacture. For improved drug-delivery properties, longer circulation for the nanoemulsion droplets should be provided, to allow the active to reach the target site. One of the strategies used for this purpose is PEGylation. The aim of this research was assessing the impact of the oil phase selection, soybean or fish oil mixtures with medium chain triglycerides, on the physicochemical characteristics and injectability of curcumin-loaded PEGylated nanoemulsions. Electron paramagnetic resonance spectroscopy demonstrated the structural impact of the oil phase on the stabilizing layer of nanoemulsions, with a more pronounced stabilizing effect of curcumin observed in the fish oil nanoemulsion compared to the soybean oil one. The design of the experiment study, employed to simultaneously assess the impact of the oil phase, different PEGylated phospholipids and their concentrations, as well as the presence of curcumin, showed that not only the investigated factors alone, but also their interactions, had a significant influence on the critical quality attributes of the PEGylated nanoemulsions. Detailed physicochemical characterization of the NEs found all formulations were appropriate for parenteral administration and remained stable during two years of storage, with the preserved antioxidant activity demonstrated by DPPH and FRAP assays. In vitro release studies showed a more pronounced release of curcumin from the fish oil NEs compared to that from the soybean oil ones. The innovative in vitro injectability assessment, designed to mimic intravenous application, proved that all formulations tested in selected experimental setting could be employed in prospective in vivo studies. Overall, the current study shows the importance of oil phase selection when formulating PEGylated nanoemulsions.
    Keywords:  D-optimal experimental design; PEGylated nanoemulsions; curcumin; electron paramagnetic resonance spectroscopy; fish oil; injectability
    DOI:  https://doi.org/10.3390/pharmaceutics14081666
  129. Front Bioeng Biotechnol. 2022 ;10 953867
    Hazelnut extract-loaded nanostructured lipid carriers and evaluation of their antioxidant properties.
    Melis Emanet, Özlem Şen, Francesca Pignatelli, Chiara Lavarello, Andrea Petretto, Gianni Ciofani.
      Reactive oxygen species (ROS) are a common hallmark of many degenerative diseases, developing in all those cases where a failure of physiological antioxidant mechanisms occurs (in particular, antioxidant enzymes and the glutathione system), or in case of exposure to an extremely high level of oxidants. In this regard, antioxidant natural extracts are promising compounds as preventive or therapeutic agents against ROS-dependent degenerations. In this study, a deep investigation of hazelnut (Corylus avellana) extract has been performed in terms of mass spectroscopy, evaluation of phenolic content, and antioxidant capacity. Then, nanostructured lipid carriers (NLCs) have been exploited for encapsulation of the hazelnut extracts in order to achieve prolonged bioactivity, increased stability, and targeting through a sustainable delivery approach. The hazelnut extract-loaded NLCs (NE_NLCs) have been deeply characterized for their stability, production yield, and encapsulation efficiency. Moreover, NE_NLCs showed optimal cytocompatibility on human dermal fibroblast (HDF) cells, as well as excellent antioxidant activity, upon pro-oxidant stimulus on HDF cells.
    Keywords:  antioxidant agents; choline; hazelnut extract; nanostructured lipid carriers; natural materials
    DOI:  https://doi.org/10.3389/fbioe.2022.953867
  130. Front Med (Lausanne). 2022 ;9 905978
    Pyruvate as a Potential Beneficial Anion in Resuscitation Fluids.
    Fang-Qiang Zhou.
      There have been ongoing debates about resuscitation fluids because each of the current fluids has its own disadvantages. The debates essentially reflect an embarrassing clinical status quo that all fluids are not quite ideal in most clinical settings. Therefore, a novel fluid that overcomes the limitations of most fluids is necessary for most patients, particularly diabetic and older patients. Pyruvate is a natural potent antioxidant/nitrosative and anti-inflammatory agent. Exogenous pyruvate as an alkalizer can increase cellular hypoxia and anoxia tolerance with the preservation of classic glycolytic pathways and the reactivation of pyruvate dehydrogenase activity to promote oxidative metabolism and reverse the Warburg effect, robustly preventing and treating hypoxic lactic acidosis, which is one of the fatal complications in critically ill patients. In animal studies and clinical reports, pyruvate has been shown to play a protective role in multi-organ functions, especially the heart, brain, kidney, and intestine, demonstrating a great potential to improve patient survival. Pyruvate-enriched fluids including crystalloids and colloids and oral rehydration solution (ORS) may be ideal due to the unique beneficial properties of pyruvate relative to anions in contemporary existing fluids, such as acetate, bicarbonate, chloride, citrate, lactate, and even malate. Preclinical studies have demonstrated that pyruvate-enriched saline is superior to 0.9% sodium chloride. Moreover, pyruvate-enriched Ringer's solution is advantageous over lactated Ringer's solution. Furthermore, pyruvate as a carrier in colloids, such as hydroxyethyl starch 130/0.4, is more beneficial than its commercial counterparts. Similarly, pyruvate-enriched ORS is more favorable than WHO-ORS in organ protection and shock resuscitation. It is critical that pay attention first to improving abnormal saline with pyruvate for ICU patients. Many clinical trials with a high dose of intravenous or oral pyruvate were conducted over the past half century, and results indicated its effectiveness and safety in humans. The long-term instability of pyruvate aqueous solutions and para-pyruvate cytotoxicity is not a barrier to the pharmaceutical manufacturing of pyruvate-enriched fluids for ICU patients. Clinical trials with sodium pyruvate-enriched solutions are urgently warranted.
    Keywords:  fluid therapy; hypoxia; metabolic acidosis; oral rehydration solution; pyruvate; resuscitation
    DOI:  https://doi.org/10.3389/fmed.2022.905978
  131. Int J Biol Macromol. 2022 Aug 22. pii: S0141-8130(22)01837-2. [Epub ahead of print]
    Silk sericin stabilized proanthocyanidins for synergetic alleviation of ulcerative colitis.
    Chunru Wang, Junyao Li, Xiangsheng Han, Shuai Liu, Xintao Gao, Chuanlong Guo, Xiaochen Wu.
      Silk sericin (SS) has become a noticeable drug nanocarrier due to its excellent biocompatibility and bioactivity. To further extend the application of SS, a facile one-step process was constructed to fabricate SS-stabilized-drug composites. Various insoluble drugs can be encapsulated into SS with high loading amount, and showed good dispersity in aqueous solution. For example, proanthocyanidins (PAC), a natural polyphenol with initial antioxidant and anti-inflammatory effects, can be loaded on SS to form SS/PAC composites. The SS/PAC can disperse uniformly in aqueous solution with an average particle diameter of ~136 nm, and showed high drug loading amount of 1767 mg/g. The SS/PAC exhibited high antioxidant efficiency and excellent biocompatibility (non-irritant, non-hemolysis, and non-cytotoxicity) both in vitro and in vivo, could remarkably alleviate the symptoms of dextran sulfate sodium-induced ulcerative colitis by decreasing the disease activity index scores, inhibiting the shortening of colon length, regulating oxidative stress, suppressing inflammation, and reversing the histopathological injuries. This work provides a simple method to fabricate SS-stabilized-drug composites, promises high potential in therapeutic and pharmaceutical applications.
    Keywords:  Proanthocyanidins; Silk sericin; Ulcerative colitis
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.08.134
  132. Cancer Cell Int. 2022 Aug 23. 22(1): 265
    Multimodal targeting of glioma with functionalized nanoparticles.
    Hany E Marei.
      The most common and aggressive primitive intracranial tumor of the central nervous system is the glioma. The blood-brain barrier (BBB) has proven to be a significant obstacle to the effective treatment of glioma. To effectively treat glioma, different ways have been used to cross the BBB to deliver drugs to the brain. Drug delivery through nanocarriers proves to be an effective and non-invasive technique for the treatment of glioma and has great potential in the treatment of glioma. In this review, we will provide an overview of nanocarrier-mediated drug delivery and related glioma therapy. Nanocarrier-mediated drug delivery techniques to cross the BBB (liposomes, micelles, inorganic systems, polymeric nanoparticles, nanogel system, and biomimetic nanoparticles) are explored. Finally, the use of nanotherapeutic approaches in the treatment of glioblastoma including chemotherapy, radiotherapy, photothermal therapy, gene therapy, glioma genome editing, immunotherapy, chimeric antigen receptor (CAR) T-cells, immune checkpoint modulators, immune photothermal therapy, vaccine-based immunotherapy, and combination therapy is summarized. Furthermore, this article offers various views on the clinical applicability of nanomedicine.
    Keywords:  CAR T cells; Chemotherapy; Glioma; Immune checkpoint modulators; Immunotherapy; Nanoparticles; Radiotherapy; Vaccine-based immunotherapy
    DOI:  https://doi.org/10.1186/s12935-022-02687-8
  133. Molecules. 2022 Aug 22. pii: 5344. [Epub ahead of print]27(16):
    The Genus Broussonetia: An Updated Review of Phytochemistry, Pharmacology and Applications.
    Yueru Chen, Lu Wang, Xue Liu, Fulin Wang, Ying An, Wei Zhao, Jinli Tian, Degang Kong, Wenru Zhang, Yang Xu, Yahui Ba, Honglei Zhou.
      The Broussonetia genus (Moraceae), recognized for its value in many Chinese traditional herbs, mainly includes Broussonetia papyrifera (L.) L'Hér. ex Vent. (BP), Broussonetia kazinoki Siebold (BK), and Broussonetia luzonica (Blanco) Bureau (BL). Hitherto, researchers have found 338 compounds isolated from BP, BK, and BL, which included flavonoids, polyphenols, phenylpropanoids, alkaloids, terpenoids, steroids, and others. Moreover, its active compounds and extracts have exhibited a variety of pharmacological effects such as antitumor, antioxidant, anti-inflammatory, antidiabetic, anti-obesity, antibacterial, and antiviral properties, and its use against skin wrinkles. In this review, the phytochemistry and pharmacology of Broussonetia are updated systematically, after its applications are first summarized. In addition, this review also discusses the limitations of investigations and the potential direction of Broussonetia. This review can help to further understand the phytochemistry, pharmacology, and other applications of Broussonetia, which paves the way for future research.
    Keywords:  Broussonetia; applications; pharmacology; phytochemistry
    DOI:  https://doi.org/10.3390/molecules27165344
  134. J Physiol Pharmacol. 2022 Apr;73(2):
    Evaluation of phenolic composition, antioxidant and cytotoxic activity of aronia melanocarpa leaf extracts.
    K Owczarek, D Sosnowska, D Kajszczak, U Lewandowska.
      The objective of this study was to investigate the phytochemical composition, antioxidant and cytotoxic potential of aronia leaf crude phenolic-extract (ACE) and purified phenolic-rich extract (APE) on human intestinal cells (CCD 841 CoN) and colon cancer cells (SW-480 and HT-29). UPLC-Q-TOF-MS analysis confirmed that aronia leaves are rich in structurally diverse polyphenols (25 and 42 compounds for ACE and APE, respectively). Chlorogenic acid and quercetin-3-rutinoside were most abundant in both aronia extracts. The sum of detected polyphenols varied significantly between extracts ranging from 32.8 mg/g (ACE) to 436.3 mg/g (APE). The biological potential of aronia extracts was confirmed by applying in vitro antioxidant and cytotoxic assays. The results of antioxidant activity (ABTS and FRAP) indicate that APE showed 2-fold stronger antioxidant properties compared to ACE. APE revealed a stronger cytotoxic effect on SW-480 and HT-29 cells than ACE (MTT test). After 48 -hours of incubation, APE was found to inhibit SW-480 cell growth by 50% vs. control at 194.35 μg/mL, while for HT-29 cells it was observed at 552.02 μg/mL. In the case of ACE, IC50 has not been reached for SW-480 cells after 48 -hours of treatment, but for HT-29 it was 794.84 μg/mL. Moreover, the viability was significantly decreased in a concentration- and time-dependent manner for both cancer cell lines. Examined extracts showed selective inhibitory potential against colon cancer cells. However, after 72 h incubation with CCD 841 CoN cells, the obtained IC50 values for APE and ACE were 594 μg/mL and 709 μg/mL respectively. This suggests that aronia leaves are valuable natural-based products that may support the treatment as chemopreventive agents in colorectal cancer.
    DOI:  https://doi.org/10.26402/jpp.2022.2.06
  135. Nat Rev Clin Oncol. 2022 Aug 26.
    The current state of the art and future trends in RAS-targeted cancer therapies.
    Salman R Punekar, Vamsidhar Velcheti, Benjamin G Neel, Kwok-Kin Wong.
      Despite being the most frequently altered oncogenic protein in solid tumours, KRAS has historically been considered 'undruggable' owing to a lack of pharmacologically targetable pockets within the mutant isoforms. However, improvements in drug design have culminated in the development of inhibitors that are selective for mutant KRAS in its active or inactive state. Some of these inhibitors have proven efficacy in patients with KRASG12C-mutant cancers and have become practice changing. The excitement associated with these advances has been tempered by drug resistance, which limits the depth and/or duration of responses to these agents. Improvements in our understanding of RAS signalling in cancer cells and in the tumour microenvironment suggest the potential for several novel combination therapies, which are now being explored in clinical trials. Herein, we provide an overview of the RAS pathway and review the development and current status of therapeutic strategies for targeting oncogenic RAS, as well as their potential to improve outcomes in patients with RAS-mutant malignancies. We then discuss challenges presented by resistance mechanisms and strategies by which they could potentially be overcome.
    DOI:  https://doi.org/10.1038/s41571-022-00671-9
  136. Int J Nanomedicine. 2022 ;17 3619-3632
    Bioactive Effects of Curcumin in Human Immunodeficiency Virus Infection Along with the Most Effective Isolation Techniques and Type of Nanoformulations.
    Monica Butnariu, Cristina Quispe, Niranjan Koirala, Sujan Khadka, Carla Marina Salgado-Castillo, Muhammad Akram, Rabia Anum, Balakyz Yeskaliyeva, Natália Cruz-Martins, Miquel Martorell, Manoj Kumar, Radu Vasile Bagiu, Ahmad Faizal Abdull Razis, Usman Sunusi, Ramla Muhammad Kamal, Javad Sharifi-Rad.
      Human immunodeficiency virus (HIV) is one of the leading causes of death worldwide, with African countries being the worst affected by this deadly virus. Curcumin (CUR) is a Curcuma longa-derived polyphenol that has attracted the attention of researchers due to its antimicrobial, anti-inflammatory, antioxidant, immunomodulatory and antiviral effects. CUR also demonstrates anti-HIV effects by acting as a possible inhibitor of gp120 binding, integrase, protease, and topoisomerase II activities, besides also exerting a protective action against HIV-associated diseases. However, its effectiveness is limited due to its poor water solubility, rapid metabolism, and systemic elimination. Nanoformulations have been shown to be useful to enhance curcumin's bioavailability and its effectiveness as an anti-HIV agent. In this sense, bioactive effects of CUR in HIV infection are carefully reviewed, along with the most effective isolation techniques and type of nanoformulations available.
    Keywords:  HIV therapy; bioactivities; curcumin; nanoformulations; nanoparticles
    DOI:  https://doi.org/10.2147/IJN.S364501
  137. Pharmaceutics. 2022 Aug 18. pii: 1724. [Epub ahead of print]14(8):
    Redox-Responsive Polymersomes as Smart Doxorubicin Delivery Systems.
    Carmen Ferrero, Marta Casas, Isidoro Caraballo.
      Stimuli-responsive polymersomes have emerged as smart drug delivery systems for programmed release of highly cytotoxic anticancer agents such as doxorubicin hydrochloride (Dox·HCl). Recently, a biodegradable redox-responsive triblock copolymer (mPEG-PDH-mPEG) was synthesized with a central hydrophobic block containing disulfide linkages and two hydrophilic segments of poly(ethylene glycol) methyl ether. Taking advantage of the self-assembly of this amphiphilic copolymer in aqueous solution, in the present investigation we introduce a solvent-exchange method that simultaneously achieves polymersome formation and drug loading in phosphate buffer saline (10 mM, pH 7.4). Blank and drug-loaded polymersomes (5 and 10 wt.% feeding ratios) were prepared and characterized for morphology, particle size, surface charge, encapsulation efficiency and drug release behavior. Spherical vesicles of uniform size (120-190 nm) and negative zeta potentials were obtained. Dox·HCl was encapsulated into polymersomes with a remarkably high efficiency (up to 98 wt.%). In vitro drug release studies demonstrated a prolonged and diffusion-driven release at physiological conditions (~34% after 48 h). Cleavage of the disulfide bonds in the presence of 50 mM glutathione (GSH) enhanced drug release (~77%) due to the contribution of the erosion mechanism. Therefore, the designed polymersomes are promising candidates for selective drug release in the reductive environment of cancer cells.
    Keywords:  doxorubicin hydrochloride; drug release kinetics; polymersome; redox-responsive; smart drug delivery systems; triblock copolymer mPEG–PDH–mPEG
    DOI:  https://doi.org/10.3390/pharmaceutics14081724
  138. ACS Nano. 2022 Aug 26.
    Protein-Delivering Nanocomplexes with Fenton Reaction-Triggered Cargo Release to Boost Cancer Immunotherapy.
    Xiang Li, Qinghao Zhou, Abd Al-Wali Mohammed M Japir, Debabrata Dutta, Nannan Lu, Zhishen Ge.
      Immunotherapeutic efficacy of tumors based on immune checkpoint blockade (ICB) therapy is frequently limited by an immunosuppressive tumor microenvironment and cross-reactivity with normal tissues. Herein, we develop reactive oxygen species (ROS)-responsive nanocomplexes with the function of ROS production for delivery and triggered release of anti-mouse programmed death ligand 1 antibody (αPDL1) and glucose oxidase (GOx). GOx and αPDL1 were complexed with oligomerized (-)-epigallocatechin-3-O-gallate (OEGCG), which was followed by chelation with Fe3+ and coverage of the ROS-responsive block copolymer, POEGMA-b-PTKDOPA, consisting of poly(oligo(ethylene glycol)methacrylate) (POEGMA) and the block with thioketal bond-linked dopamine moieties (PTKDOPA) as the side chains. After intravenous injection, the nanocomplexes show prolonged circulation in the bloodstream with a half-life of 8.72 h and efficient tumor accumulation. At the tumor sites, GOx inside the nanocomplexes can produce H2O2 via oxidation of glucose for Fenton reaction to generate hydroxyl radicals (•OH) which further trigger the release of the protein cargos through ROS-responsive cleavage of thioketal bonds. The released GOx improves the production efficiency of •OH to kill cancer cells for release of tumor-associated antigens via chemodynamic therapy (CDT). The enhanced immunogenic cell death (ICD) can activate the immunosuppressive tumor microenvironment and improve the immunotherapy effect of the released αPDL1, which significantly suppresses primary and metastatic tumors. Thus, the nanocomplexes with Fenton reaction-triggered protein release show great potentials to improve the immunotherapeutic efficacy of ICB via combination with CDT.
    Keywords:  ROS-responsive; chemodynamic therapy; immune checkpoint blockade; immunotherapy; nanocomplex
    DOI:  https://doi.org/10.1021/acsnano.2c06026
  139. Curr Oncol. 2022 Aug 22. 29(8): 5963-5987
    Cathepsin K: A Versatile Potential Biomarker and Therapeutic Target for Various Cancers.
    Die Qian, Lisha He, Qing Zhang, Wenqing Li, Dandan Tang, Chunjie Wu, Fei Yang, Ke Li, Hong Zhang.
      Cancer, a common malignant disease, is one of the predominant causes of diseases that lead to death. Additionally, cancer is often detected in advanced stages and cannot be radically cured. Consequently, there is an urgent need for reliable and easily detectable markers to identify and monitor cancer onset and progression as early as possible. Our aim was to systematically review the relevant roles of cathepsin K (CTSK) in various possible cancers in existing studies. CTSK, a well-known key enzyme in the bone resorption process and most studied for its roles in the effective degradation of the bone extracellular matrix, is expressed in various organs. Nowadays, CTSK has been involved in various cancers such as prostate cancer, breast cancer, bone cancer, renal carcinoma, lung cancer and other cancers. In addition, CTSK can promote tumor cells proliferation, invasion and migration, and its mechanism may be related to RANK/RANKL, TGF-β, mTOR and the Wnt/β-catenin signaling pathway. Clinically, some progress has been made with the use of cathepsin K inhibitors in the treatment of certain cancers. This paper reviewed our current understanding of the possible roles of CTSK in various cancers and discussed its potential as a biomarker and/or novel molecular target for various cancers.
    Keywords:  CTSK; biomarker; cancer; cathepsin K; therapeutic target
    DOI:  https://doi.org/10.3390/curroncol29080471
  140. Trends Endocrinol Metab. 2022 Aug 20. pii: S1043-2760(22)00136-9. [Epub ahead of print]
    Understanding lactate sensing and signalling.
    Michelangelo Certo, Alba Llibre, Wheeseong Lee, Claudio Mauro.
      Metabolites generated from cellular and tissue metabolism have been rediscovered in recent years as signalling molecules. They may act as cofactor of enzymes or be linked to proteins as post-translational modifiers. They also act as ligands for specific receptors, highlighting that their neglected functions have, in fact, a long standing in evolution. Lactate is one such metabolite that has been considered for long time a waste product of metabolism devoid of any biological function. However, in the past 10 years, lactate has gained much attention in several physio-pathological processes. Mechanisms of sensing and signalling have been discovered and implicated in a broad range of diseases, from cancer to inflammation and fibrosis, providing opportunities for novel therapeutic avenues. Here, we review some of the most recently discovered mechanisms of lactate sensing and signalling.
    Keywords:  G protein-coupled receptor; acidity; lactylation; metabolic reprogramming
    DOI:  https://doi.org/10.1016/j.tem.2022.07.004
  141. Nutr Rev. 2022 Aug 26. pii: nuac065. [Epub ahead of print]
    An overview of vitamins as epidrugs for colorectal cancer prevention.
    Hatim Boughanem, Pallavi Kompella, Francisco J Tinahones, Manuel Macias-Gonzalez.
      Gene expression altering epigenomic modifications such as DNA methylation, histone modification, and chromosome remodeling is crucial to regulating many biological processes. Several lifestyle factors, such as diet and natural, bioactive food compounds, such as vitamins, modify epigenetic patterns. However, epigenetic dysregulation can increase the risk of many diseases, including cancer. Various studies have provided supporting and contrasting evidence on the relationship between vitamins and cancer risk. Though there is a gap in knowledge about whether dietary vitamins can induce epigenetic modifications in the context of colorectal cancer (CRC), the possibility of using them as epidrugs for CRC treatment is being explored. This is promising because such studies might be informative about the most effective way to use vitamins in combination with DNA methyltransferase inhibitors and other approved therapies to prevent and treat CRC. This review summarizes the available epidemiological and observational studies involving dietary, circulating levels, and supplementation of vitamins and their relationship with CRC risk. Additionally, using available in vitro, in vivo, and human observational studies, the role of vitamins as potential epigenetic modifiers in CRC is discussed. This review is focused on the action of vitamins as modifiers of DNA methylation because aberrant DNA methylation, together with genetic alterations, can induce the initiation and progression of CRC. Although this review presents some studies with promising results, studies with better study designs are necessary. A thorough understanding of the underlying molecular mechanisms of vitamin-mediated epigenetic regulation of CRC genes can help identify effective therapeutic targets for CRC prevention and treatment.
    Keywords:  colorectal cancer prevention; epidrugs; epigenetics; vitamins
    DOI:  https://doi.org/10.1093/nutrit/nuac065
  142. Semin Cancer Biol. 2022 Aug 23. pii: S1044-579X(22)00192-4. [Epub ahead of print]
    Nanoparticles: attractive tools to treat colorectal cancer.
    Nour K Younis, Rami Roumieh, Emmanuel P Bassil, Joseph A Ghoubaira, Firas Kobeissy, Ali H Eid.
      Colorectal Cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Despite the notable advances achieved over the last few decades, CRC remains a hard-to-treat deadly disease in many patients. This is attributed mainly to chemo- and immuno-resistance, which frequently emerge soon after treatment with conventional therapeutics. Systemic treatments are also constrained by their many undesired and serious side effects. More recently, nanomedicine has emerged as an attractive modality that can overcome issues of therapeutic resistance, improper delivery, or suboptimal targeting of tumor cells. Many nanomaterials, having already been examined in pre-clinical and clinical studies, are now considered biocompatible and relatively safe. Indeed, around 50 nano-formulations have so far been approved as diagnostic and therapeutic agents in humans. Here, in this review, we describe a set of imperative nanoparticles (NPs) involved in diagnosing and treating CRC. In particular, we discuss the theragnostic roles of quantum dots, iron oxide NPs, Polylactide-co-glycolic acid (PLGA) NPs, dendrimer NPs, carbon nanotubes, liposomes, and gold NPs. We dissect the molecular and clinical evidence supporting the use of these NPs in CRC. We also highlight their implications in targeted drug delivery as well as their anti-tumorigenic properties and effects on the cardinal hallmarks of CRC. We conclude by highlighting the notion that nanomedicine is emerging as an attractive approach to address the unmet needs in managing several diseases, including CRC.
    Keywords:  Colorectal Cancer; Drug delivery; Nanomedicine; Nanoparticles; Theragnostics; Theranostics
    DOI:  https://doi.org/10.1016/j.semcancer.2022.08.006
  143. Pharmaceutics. 2022 Aug 08. pii: 1647. [Epub ahead of print]14(8):
    The Current State of the Art in PARP Inhibitor-Based Delivery Nanosystems.
    Lisha Cai, Xiaoling Xu, Wei Chen.
      Poly (adenosine diphosphate [ADP]-ribose) polymerases inhibitors (PARPi), the first clinically approved drug that exhibits synthetic lethality, are moving to the forefront of cancer treatments. Currently, the oral bioavailability of PARPi is quite low; thus, it is a major challenge to effectively and safely deliver PARPi during clinical cancer therapy. Nanotechnology has greatly advanced the development of drug delivery. Based on the basic characteristics and various forms of nanoparticles, drug delivery systems can prolong the time that drugs circulate, realize the controlled release of drugs, provide drugs with an active targeting ability, and spatiotemporally present combination treatment. Furthermore, nanosystems may not only enhance drug efficiency but also reduce adverse side effects. This review focuses on strategies involving nanoparticle-based delivery for PARPi, including single administration and codelivery with other agents. We believe that nanosystems have great potential in advancing PARPi efficacy for cancer therapy.
    Keywords:  PARP inhibitor; cancer therapy; drug delivery; nanosystem
    DOI:  https://doi.org/10.3390/pharmaceutics14081647
  144. Front Nutr. 2022 ;9 951935
    Cruciferous vegetables as a treasure of functional foods bioactive compounds: Targeting p53 family in gastrointestinal tract and associated cancers.
    Saikat Mitra, Talha Bin Emran, Deepak Chandran, B M Redwan Matin Zidan, Rajib Das, Sukamto S Mamada, Ayu Masyita, Mirnawati Salampe, Firzan Nainu, Mayeen Uddin Khandaker, Abubakr M Idris, Jesus Simal-Gandara.
      In the past few years, phytochemicals from natural products have gotten the boundless praise in treating cancer. The promising role of cruciferous vegetables and active components contained in these vegetables, such as isothiocyanates, indole-3-carbinol, and isothiocyanates, has been widely researched in experimental in vitro and in vivo carcinogenesis models. The chemopreventive agents produced from the cruciferous vegetables were recurrently proven to affect carcinogenesis throughout the onset and developmental phases of cancer formation. Likewise, findings from clinical investigations and epidemiological research supported this statement. The anticancer activities of these functional foods bioactive compounds are closely related to their ability to upregulate p53 and its related target genes, e.g., p21. As the "guardian of the genome," the p53 family (p53, p63, and p73) plays a pivotal role in preventing the cancer progression associated with DNA damage. This review discusses the functional foods bioactive compounds derived from several cruciferous vegetables and their use in altering the tumor-suppressive effect of p53 proteins. The association between the mutation of p53 and the incidence of gastrointestinal malignancies (gastric, small intestine, colon, liver, and pancreatic cancers) is also discussed. This review contains crucial information about the use of cruciferous vegetables in the treatment of gastrointestinal tract malignancies.
    Keywords:  apoptosis; cruciferous vegetables; foods bioactive compounds; gastrointestinal cancer; p53 family
    DOI:  https://doi.org/10.3389/fnut.2022.951935
  145. Int J Mol Sci. 2022 Aug 17. pii: 9227. [Epub ahead of print]23(16):
    Fabrication, Characterization, and Antimicrobial Activity of Carvacrol-Loaded Zein Nanoparticles Using the pH-Driven Method.
    Huaming Zheng, Jiangli Wang, Feng You, Mingyu Zhou, Shengwei Shi.
      To reduce the application of synthetic additives in the field of food preservation, this study utilized carvacrol as an antibacterial agent, and zein and sodium caseinate as carriers, to prepare composite nanoparticles loaded with carvacrol by the pH-driven method. The composite nanoparticles of zein/sodium caseinate had an excellent encapsulation efficiency (77.96~82.19%) for carvacrol, and it had remarkable redispersibility. The results of Fourier transform infrared spectroscopy showed that the formation of the composite nanoparticles mainly depended on the hydrogen bond and the hydrophobic zone force, and thermal gravimetric analysis showed that carvacrol was loaded successfully into nanoparticles, and loading efficiency reached 24.9%. Scanning electron microscopy showed that the composite nanoparticles were spherical, with a particle size range of 50~200 nm, and through the free radical scavenging method and the plate counting method to confirm the particle has stronger antioxidant and antibacterial properties, and with the composite nanoparticles with poly (vinyl alcohol) film applied to the preservation of banana together, it was found that PVA film containing 5 wt% CA-loaded composite NPs can significantly extend the storage period of banana. Therefore, when the composite nanoparticles were applied to food packaging, they could effectively inhibit food spoilage and lengthen the shelf life of food, which displays potential application prospects in the food industry.
    Keywords:  antimicrobial activity; carvacrol; composite nanoparticles; pH-driven; sodium caseinate; zein
    DOI:  https://doi.org/10.3390/ijms23169227
  146. Pharmaceutics. 2022 Aug 05. pii: 1637. [Epub ahead of print]14(8):
    Fabrication and Preliminary In Vitro Evaluation of 3D-Printed Alginate Films with Cannabidiol (CBD) and Cannabigerol (CBG) Nanoparticles for Potential Wound-Healing Applications.
    Paraskevi Kyriaki Monou, Anastasia Maria Mamaligka, Emmanuil K Tzimtzimis, Dimitrios Tzetzis, Souzan Vergkizi-Nikolakaki, Ioannis S Vizirianakis, Eleftherios G Andriotis, Georgios K Eleftheriadis, Dimitrios G Fatouros.
      In this study, drug carrier nanoparticles comprised of Pluronic-F127 and cannabidiol (CBD) or cannabigerol (CBG) were developed, and their wound healing action was studied. They were further incorporated in 3D printed films based on sodium alginate. The prepared films were characterized morphologically and physicochemically and used to evaluate the drug release profiles of the nanoparticles. Additional studies on their water loss rate, water retention capacity, and 3D-printing shape fidelity were performed. Nanoparticles were characterized physicochemically and for their drug loading performance. They were further assessed for their cytotoxicity (MTT Assay) and wound healing action (Cell Scratch Assay). The in vitro wound-healing study showed that the nanoparticles successfully enhanced wound healing in the first 6 h of application, but in the following 6 h they had an adverse effect. MTT assay studies revealed that in the first 24 h, a concentration of 0.1 mg/mL nanoparticles resulted in satisfactory cell viability, whereas CBG nanoparticles were safe even at 48 h. However, in higher concentrations and after a threshold of 24 h, the cell viability was significantly decreased. The results also presented mono-disperse nano-sized particles with diameters smaller than 200 nm with excellent release profiles and enhanced thermal stability. Their entrapment efficiency and drug loading properties were higher than 97%. The release profiles of the active pharmaceutical ingredients from the films revealed a complete release within 24 h. The fabricated 3D-printed films hold promise for wound healing applications; however, more studies are needed to further elucidate their mechanism of action.
    Keywords:  3D-printing; Pluronic-F127; cannabidiol; cannabigerol; cannabinoids; sodium alginate; wound-healing
    DOI:  https://doi.org/10.3390/pharmaceutics14081637
  147. Front Nutr. 2022 ;9 931090
    Nutritional aspects in chronic non-cancer pain: A systematic review.
    Inmaculada Xu Lou, Eugenia Gil-García, Rocío Cáceres-Matos, Kamran Ali, Esther Molina.
      Objectives: Chronic pain (CP) is an unpleasant emotional and sensory experience that can be accompanied by tissue damage that persists for more than 3 months. Recent studies show that certain nutritional strategies can help to improve pain, so this study is aimed to systematically review scientific evidence to understand and map the effect of the use of nutritional strategies on the presence or intensity of chronic non-cancer pain (CNCP) and the association of these nutritional aspects with the presence or intensity of CNCP.Study design: A systematic review.
    Methods: Two independent researchers searched for randomized clinical trials (RCTs) and observational studies that explored the relationship between nutrition and CNCP in adults from 2010 to 2020 in PubMed, Web of Science, Scopus, and Cochrane Library databases. A total of 24 studies were included, of which 20 were RCTs and 4 were observational studies. They are classified into the administration of nutritional supplements, dietary modification, and incorporation of food.
    Results: Of these studies, those that have a significant effect on pain are dietary modification and the use of nutritional supplements. On the other hand, the main results from the few observational studies included in this review point to the existence of an association relationship between less pain and a ketogenic or hypocaloric diet or adherence to the Mediterranean diet.
    Conclusion: Dietary modification seems to be one plausible therapeutic option to improve and relieve CNCP. However, more research is needed in this regard to obtain better conclusions.
    Systematic Review Registration: [www.crd.york.ac.uk/prospero], identifier [CRD42021226431].
    Keywords:  chronic pain; diet; feeding; nutrients; nutrition; supplements
    DOI:  https://doi.org/10.3389/fnut.2022.931090
  148. Front Mol Biosci. 2022 ;9 930223
    Metabolic adaption of cancer cells toward autophagy: Is there a role for ER-phagy?
    Debora Gentile, Marianna Esposito, Paolo Grumati.
      Autophagy is an evolutionary conserved catabolic pathway that uses a unique double-membrane vesicle, called autophagosome, to sequester cytosolic components, deliver them to lysosomes and recycle amino-acids. Essentially, autophagy acts as a cellular cleaning system that maintains metabolic balance under basal conditions and helps to ensure nutrient viability under stress conditions. It is also an important quality control mechanism that removes misfolded or aggregated proteins and mediates the turnover of damaged and obsolete organelles. In this regard, the idea that autophagy is a non-selective bulk process is outdated. It is now widely accepted that forms of selective autophagy are responsible for metabolic rewiring in response to cellular demand. Given its importance, autophagy plays an essential role during tumorigenesis as it sustains malignant cellular growth by acting as a coping-mechanisms for intracellular and environmental stress that occurs during malignant transformation. Cancer development is accompanied by the formation of a peculiar tumor microenvironment that is mainly characterized by hypoxia (oxygen < 2%) and low nutrient availability. Such conditions challenge cancer cells that must adapt their metabolism to survive. Here we review the regulation of autophagy and selective autophagy by hypoxia and the crosstalk with other stress response mechanisms, such as UPR. Finally, we discuss the emerging role of ER-phagy in sustaining cellular remodeling and quality control during stress conditions that drive tumorigenesis.
    Keywords:  ER stress; ER-phagy; UPR; autophagy; cancer; endoplasmic reticulum; hypoxia
    DOI:  https://doi.org/10.3389/fmolb.2022.930223
  149. Biomedicines. 2022 Aug 11. pii: 1945. [Epub ahead of print]10(8):
    Pharmacological Properties and Molecular Targets of Alisol Triterpenoids from Alismatis Rhizoma.
    Christian Bailly.
      More than 100 protostane triterpenoids have been isolated from the dried rhizomes of Alisma species, designated Alismatis rhizoma (AR), commonly used in Asian traditional medicine to treat inflammatory and vascular diseases. The main products are the alisols, with the lead compounds alisol-A/-B and their acetate derivatives being the most abundant products in the plant and the best-known bioactive products. The pharmacological effects of Ali-A, Ali-A 24-acetate, Ali-B, Ali-B 23-acetate, and derivatives have been analyzed to provide an overview of the medicinal properties, signaling pathways, and molecular targets at the origin of those activities. Diverse protein targets have been proposed for these natural products, including the farnesoid X receptor, soluble epoxide hydrolase, and other enzymes (AMPK, HCE-2) and functional proteins (YAP, LXR) at the origin of the anti-atherosclerosis, anti-inflammatory, antioxidant, anti-fibrotic, and anti-proliferative activities. Activities were classified in two groups. The lipid-lowering and anti-atherosclerosis effects benefit from robust in vitro and in vivo data (group 1). The anticancer effects of alisols have been largely reported, but, essentially, studies using tumor cell lines and solid in vivo data are lacking (group 2). The survey shed light on the pharmacological properties of alisol triterpenoids frequently found in traditional phytomedicines.
    Keywords:  Alismatis rhizoma; alisol; cancer; inflammation; molecular targets; pharmacology; protostane triterpenoids
    DOI:  https://doi.org/10.3390/biomedicines10081945
  150. Pharmaceutics. 2022 Aug 05. pii: 1638. [Epub ahead of print]14(8):
    Novel Fusidic Acid Cream Containing Metal Ions and Natural Products against Multidrug-Resistant Bacteria.
    Hani Naseef, Yousef Sahoury, Mohammad Farraj, Moammal Qurt, Abdallah D Abukhalil, Nidal Jaradat, Israr Sabri, Abdullah K Rabba, Mahmmoud Sbeih.
      BACKGROUND: Drug design and development to overcome antimicrobial resistance continues to be an area of research due to the evolution of microbial resistance mechanisms and the necessity for new treatments. Natural products have been used since the dawn of medicine to heal skin infections. The antimicrobial properties of fusidic acid, zinc sulfate, and copper sulfate have been studied and are well known. Furthermore, these compounds have different mechanisms of action in targeting microorganisms, either by inhibiting protein synthesis or bacterial cell walls. Therefore, their combination is expected to have synergistic activity in killing bacteria. However, the synergistic antimicrobial activity has not been evaluated in a cream formulation. Therefore, the objectives of this in vitro study were to develop and evaluate the synergistic efficacy of fusidic acid in combinations with natural products, including oleuropein, thyme oil, zinc sulfate, and copper sulfate, as a cream to eradicate fusidic-acid-resistant microorganisms in skin infections.METHODS: Three different cream formulations were developed, compared, and labeled F1, F2, and F3. The compounds were studied for their antibacterial activity. In addition, the stability of the cream was investigated at 25 °C and 40 °C in plastic jars over three months.
    RESULTS: The F2 formula has adequate physicochemical properties. Furthermore, it displays stable and better results than the marketed trade product and has potential inhibition zones (ZOI). Interestingly, considerable numbers (9.5%) of fusidic-acid-resistant Staphylococcus aureus (FRSA) isolates possessed a high resistance pattern with MIC ≥ 128 μg/mL. In contrast, most tested FRSA isolates (90.5%) had a low resistance pattern with MIC ≤ 8 μg/mL.
    CONCLUSION: In conclusion, the F2 cream made with fusidic acid, oleuropein, thyme oil, zinc sulfate, and copper sulfate in the right amounts has stable physical and chemical properties and has potential against FRSA as an antimicrobial agent.
    Keywords:  FRSA; MRSA; antimicrobial activity; formulation; fusidic acid; natural products; skin infections
    DOI:  https://doi.org/10.3390/pharmaceutics14081638
  151. Carbohydr Polym. 2022 Nov 01. pii: S0144-8617(22)00785-8. [Epub ahead of print]295 119880
    Integration of cyclodextrins and associated toxicities: A roadmap for high quality biomedical applications.
    Francesco Trotta, Thorsteinn Loftsson, R S Gaud, Riddhi Trivedi, Pravin Shende.
      Cyclodextrins are extensively employed in drug delivery systems like inclusion complexes, metal-organic frameworks, functionalized or PEGylated conjugates, and other nanocarrier systems such as nanosponges or hydrogel nanoparticles for targeted effect or prolonged release action. Applications of CDs range from drug-loaded nanocarrier systems useful for disease conditions (such as cancer, diabetes, and bacterial infections, etc.) to supramolecular chemistry, diagnostics, imaging, biosensors, and medical devices. However, there is a limited data and information on the adverse effects caused by cyclodextrins and their toxicities in the medical field. Various in-vitro and ex-vivo toxic effects such as cytotoxicity, ototoxicity, etc. as well as the adverse and toxic effects depend on the role of administration of cyclodextrins. This review article focuses on the advancement of characteristics, properties and chemistry of cyclodextrins and addresses the new challenges faced in cyclodextrin-based delivery systems and the various toxicities induced by them.
    Keywords:  Adverse effect; Complexation; Cytotoxicity; Functionalization; Inclusion
    DOI:  https://doi.org/10.1016/j.carbpol.2022.119880
  152. Pharmaceutics. 2022 Aug 03. pii: 1620. [Epub ahead of print]14(8):
    Encapsulation of miRNA and siRNA into Nanomaterials for Cancer Therapeutics.
    Mina Zare, Rakesh Pemmada, Maya Madhavan, Aswathy Shailaja, Seeram Ramakrishna, Sumodan Padikkala Kandiyil, James M Donahue, Vinoy Thomas.
      Globally, cancer is amongst the most deadly diseases due to the low efficiency of the conventional and obsolete chemotherapeutic methodologies and their many downsides. The poor aqueous solubility of most anticancer medications and their low biocompatibility make them ineligible candidates for the design of delivery systems. A significant drawback associated with chemotherapy is that there are no advanced solutions to multidrug resistance, which poses a major obstacle in cancer management. Since RNA interference (RNAi) can repress the expression of genes, it is viewed as a novel tool for advanced drug delivery. this is being explored as a promising drug targeting strategy for the treatment of multiple diseases, including cancer. However, there are many obstructions that hinder the clinical uses of siRNA drugs due to their low permeation into cells, off-target impacts, and possible unwanted immune responses under physiological circumstances. Thus, in this article, we review the design measures for siRNA conveyance frameworks and potential siRNA and miRNA drug delivery systems for malignant growth treatment, including the use of liposomes, dendrimers, and micelle-based nanovectors and functional polymer-drug delivery systems. This article sums up the advancements and challenges in the use of nanocarriers for siRNA delivery and remarkably centers around the most critical modification strategies for nanocarriers to build multifunctional siRNA and miRNA delivery vectors. In short, we hope this review will throw light on the dark areas of RNA interference, which will further open novel research arenas in the development of RNAi drugs for cancer.
    Keywords:  RNA delivery; cancer therapy; nanocarriers; nanomedicine
    DOI:  https://doi.org/10.3390/pharmaceutics14081620
  153. Pharmaceutics. 2022 Jul 31. pii: 1601. [Epub ahead of print]14(8):
    A Comparative Study of Quercetin-Loaded Nanocochleates and Liposomes: Formulation, Characterization, Assessment of Degradation and In Vitro Anticancer Potential.
    Neha Munot, Ujjwala Kandekar, Prabhanjan S Giram, Kavita Khot, Abhinandan Patil, Simona Cavalu.
      Quercetin, a flavonoid, has antioxidant and anti-inflammatory properties and the potential to inhibit the proliferation of cancer, but its therapeutic efficacy is lowered due to poor solubility and bioavailability. Quercetin-loaded nanocochleates (QN) were developed using a trapping method by the addition of calcium ions into preformed negatively charged liposomes (QL) prepared by a thin-film hydration method. Liposomes were optimized by varying the concentration of Dimyristoyl phosphatidyl glycerol and quercetin by applying D-optimal factorial design using Design-Expert® software. Stable rods were observed using TEM with an average particle size, zeta potential and encapsulation efficiency of 502 nm, -18.52 mV and 88.62%, respectively, for QN which were developed from spherical QL showing 111.06 nm, -40.33 mV and 74.2%, respectively. In vitro release of quercetin from QN and QL was extended to 24 h. Poor bioavailability of quercetin is due to its degradation in the liver, so to mimic in vivo conditions, the degradation of quercetin released from QL and QN was studied in the presence of rat liver homogenate (S9G) and results revealed that QN, due to its unique structure, i.e., series of rolled up solid layers, shielded quercetin from the external environment and protected it. The safety and biocompatibility of QL and QN were provenby performing cytotoxicity studies on fibroblast L929 cell lines. QN showed superior anticancer activity compared to QL, as seen for human mouth cancerKB cell lines. Stability studies proved that nanocochleates were more stable than liposomal formulations. Thus, nanocochleates might serve as pharmaceutical nanocarriers for the improved efficacy of drugs with low aqueous solubility, poor bioavailability, poor targeting ability and stability.
    Keywords:  dimyristoyl phosphatidyl glycerol; human mouth cancerKB cell lines; liposomes; nanocochleates; quercetin; rat liver homogenate (S9G)
    DOI:  https://doi.org/10.3390/pharmaceutics14081601
  154. AAPS PharmSciTech. 2022 Aug 24. 23(7): 236
    Fabrication of TPGS-Grafted Polyamidoamine Dendrimer for Enhanced Piperine Brain Delivery and Pharmacokinetics.
    Ajit Singh, Akshada Mhaske, Rahul Shukla.
      Piperine (PIP) is a neuroprotective phytomedicine that has profound acetylcholine esterase and reactive oxygen species inhibition effect in Alzheimer's disease (AD) model. However, the oral delivery of PIP is limited by poor aqueous solubility and low bioavailability in systemic circulation. To improve the PIP bioavailability, the polyamidoamine (PAMAM) G4 dendrimer is grafted with tocopheryl polyethylene glycol succinate-1000 (TPGS) through carbodiimide chemistry to form TPGS-PAMAM conjugate. The TPGS-PAMAM coupling was confirmed through proton NMR and FTIR techniques. PIP was encapsulated in the TPGS-PAMAM through solvent diffusion method to form PIP-TPGS-PAMAM. The particle size for PIP-TPGS-PAMAM found the less than 50 nm, whereas entrapment efficiency found to 87 ± 3.5% and 10.6 ± 2.9% drug loading. The powder differential scanning calorimetry and powder X-ray diffraction characterization were employed to evaluate the amorphous encapsulation of the PIP in TPGS-PAMAM. The PIP-TPGS-PAMAM stability was studied in the gastric fluids which showed no drastic difference in particle size and encapsulation efficiency compared to PIP-PAMAM. The in vitro release analysis revealed 37 ± 4.1% PIP release from the PIP-TPGS-PAMAM matrix, and 71 ± 4.9% PIP release from the PIP-PAMAM dendrimer was observed in 48 h. The single-dose oral gavage to Wistar rats of PIP-TPGS-PAMAM showed the AUC0-∞ 14.38 µg/mL.h, Cmax 7.77 ± 1.65 µg/mL, Tmax, 1.6 ± 0.18 h, and half-life 3.47 ± 0.64 h for PIP in systemic circulation. PIP-PAMAM and free PIP showed significantly poor AUC0-∞ compared to PIP-TPGS-PAMAM. The brain uptake studies revealed PIP-TPGS-PAMAM treated group showed 2.2 ± 0.37 µg/g PIP content compared to free PIP administered group which was 0.4 ± 0.10 µg/g. Therefore, PIP-TPGS-PAMAM can offer excellent prospect for the delivery hydrophobic drugs to brain in AD.
    Keywords:  PAMAM dendrimer; TPGS; bioavailability; brain uptake; conjugation; piperine
    DOI:  https://doi.org/10.1208/s12249-022-02393-8
  155. Antioxidants (Basel). 2022 Aug 05. pii: 1528. [Epub ahead of print]11(8):
    Mini-Review on the Enzymatic Lipophilization of Phenolics Present in Plant Extracts with the Special Emphasis on Anthocyanins.
    Karina Jasińska, Agata Fabiszewska, Ewa Białecka-Florjańczyk, Bartłomiej Zieniuk.
      Different plant extracts have the potential to be important sources of phenolic compounds. Their antibacterial, antifungal and antioxidant properties are of interest to researchers due to various possibilities for use in the pharmacy, cosmetic and food industries. Unfortunately, the direct application of phenolics in food is limited because of their hydrophilic nature and low solubility. The review is devoted to the recent advances in the methods of lipophilization of phenolic extracts along with the use of enzymes. The concept of extract modification instead of single compound modification is based on the expected synergistic effect of many phenolic compounds. The main focus is on the phenolic compounds found in fruits, flowers and leaves of different common and underutilized as well as medicinal, folk-medicinal or endemic plants. The compiled papers point to the great interest in the modification of anthocyanins, highly active but often unstable phenolics. Some examples of other flavonoids are also outlined. The possible applications of the lipophilized plant extracts are presented for improving the stability of edible oils, decreasing the content of acrylamide, exhibiting higher color stability in thermal processing and increasing the nutritional value.
    Keywords:  anthocyanins; esterification; lipase; lipophilization; phenolic compounds; plant extracts
    DOI:  https://doi.org/10.3390/antiox11081528
  156. Clin Transl Med. 2022 Aug;12(8): e893
    Healthy and unhealthy plant-based diets in relation to the incidence of colorectal cancer overall and by molecular subtypes.
    Fenglei Wang, Tomotaka Ugai, Koichiro Haruki, Yi Wan, Naohiko Akimoto, Kota Arima, Rong Zhong, Tyler S Twombly, Kana Wu, Kanhua Yin, Andrew T Chan, Marios Giannakis, Jonathan A Nowak, Jeffrey A Meyerhardt, Liming Liang, Mingyang Song, Stephanie A Smith-Warner, Xuehong Zhang, Edward L Giovannucci, Walter C Willett, Shuji Ogino.
      BACKGROUND: Plant-based foods have been recommended for health. However, not all plant foods are healthy, and little is known about the association between plant-based diets and specific molecular subtypes of colorectal cancer (CRC). We examined the associations of healthy and unhealthy plant-based diets with the incidence of CRC and its molecular subtypes.METHODS: While 123 773 participants of the Nurses' Health Study and the Health Professionals Follow-up Study had been followed up (3 143 158 person-years), 3077 of them had developed CRC. Healthy and unhealthy plant-based diet indices (hPDI and uPDI, respectively) were calculated using repeated food frequency questionnaire data. We determined the tumoural status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations.
    RESULTS: Higher hPDI was associated with lower CRC incidence (multivariable hazard ratio [HR] comparing extreme quartiles, 0.86, 95% confidence interval [CI]: 0.77, 0.96; P-trend = .04), whereas higher uPDI was associated with higher CRC incidence (multivariable HR comparing extreme quartiles, 1.16, 95% CI: 1.04, 1.29; P-trend = .005). The association of hPDI significantly differed by KRAS status (P-heterogeneity = .003) but not by other tumour markers. The hPDI was associated with lower incidence of KRAS-wildtype CRC (multivariable HR comparing extreme quartiles, 0.74, 95% CI: 0.57, 0.96; P-trend = .004) but not KRAS-mutant CRC (P-trend = .22).
    CONCLUSIONS: While unhealthy plant-based diet enriched with refined grains and sugar is associated with higher CRC incidence, healthy plant-based diet rich in whole grains, fruits and vegetables is associated with lower incidence of CRC, especially KRAS-wildtype CRC.
    Keywords:  colorectal carcinoma; inverse probability weighting; molecular pathological epidemiology; sustainability
    DOI:  https://doi.org/10.1002/ctm2.893
  157. Front Pharmacol. 2022 ;13 920422
    Cratoxylumxanthone C, a natural xanthone, inhibits lung cancer proliferation and metastasis by regulating STAT3 and FAK signal pathways.
    Yeling Li, Huimei Wang, Wenhui Liu, Jiantong Hou, Jing Xu, Yuanqiang Guo, Ping Hu.
      To discover phytochemicals as lead compounds for cancer treatment, cratoxylumxanthone C, a natural xanthone, was obtained from Cratoxylum cochinchinense (Lour.) Bl., for which there have been no reports on the biological effects against cancer. Our study revealed that cratoxylumxanthone C had significant anti-tumor activity by inducing apoptosis, augmenting cellular reactive oxygen species (ROS), and arresting cell circle. The mechanistic examination showed the inhibition of A549 cell proliferation and metastasis by cratoxylumxanthone C was coupled with the signal transducer and activator of transcription 3 (STAT3) and focal adhesion kinase (FAK) signaling pathways. Furthermore, the zebrafish models confirmed its significant in vivo anti-tumor activity, in which cratoxylumxanthone C inhibited tumor proliferation and metastasis and suppressed the angiogenesis. Comprehensively, these cellular and zebrafish experiments implied that cratoxylumxanthone C may have the potential to become an anti-tumor agent for lung cancer, especially non-small cell lung cancer (NSCLC).
    Keywords:  FAK; anti-tumor; cratoxylumxanthone C; natural xanthone; stat3; zebrafish
    DOI:  https://doi.org/10.3389/fphar.2022.920422
  158. Curr Issues Mol Biol. 2022 Aug 05. 44(8): 3481-3495
    The Nutraceuticals as Modern Key to Achieve Erythrocyte Oxidative Stress Fighting in Osteoarthritis.
    Alessia Mariano, Irene Bigioni, Francesco Misiti, Luigi Fattorini, Anna Scotto d'Abusco, Angelo Rodio.
      Osteoarthritis (OA), the most common joint disease, shows an increasing prevalence in the aging population in industrialized countries. OA is characterized by low-grade chronic inflammation, which causes degeneration of all joint tissues, such as articular cartilage, subchondral bone, and synovial membrane, leading to pain and loss of functionality. Erythrocytes, the most abundant blood cells, have as their primary function oxygen transport, which induces reactive oxygen species (ROS) production. For this reason, the erythrocytes have several mechanisms to counteract ROS injuries, which cause damage to lipids and proteins of the cell membrane. Oxidative stress and inflammation are highly correlated and are both causes of joint disorders. In the synovial fluid and blood of osteoarthritis patients, erythrocyte antioxidant enzyme expression is decreased. To date, OA is a non-curable disease, treated mainly with non-steroidal anti-inflammatory drugs and corticosteroids for a prolonged period of time, which cause several side effects; thus, the search for natural remedies with anti-inflammatory and antioxidant activities is always ongoing. In this review, we analyze several manuscripts describing the effect of traditional remedies, such as Harpagophytum procumbens, Curcumin longa, and Boswellia serrata extracts, in the treatments of OA for their anti-inflammatory, analgesic, and antioxidant activity. The effects of such remedies have been studied both in in vitro and in vivo models, considering both joint cells and erythrocytes.
    Keywords:  Boswellia serrata; Curcuma longa; Harpagophytum procumbens; erythrocytes; nutraceuticals; osteoarthritis; oxidative stress
    DOI:  https://doi.org/10.3390/cimb44080240
  159. Front Endocrinol (Lausanne). 2022 ;13 899375
    The effects of vegetarian diets on bone health: A literature review.
    Alberto Falchetti, Guido Cavati, Roberto Valenti, Christian Mingiano, Roberta Cosso, Luigi Gennari, Iacopo Chiodini, Daniela Merlotti.
      In these recent years many people are adopting a vegetarian type diet due to the numerous positive health effects of this regimen such as the reduction of the incidence of many chronic disorders like diabetes, hypertension, obesity and cancer. However this diet is quite restrictive and so it could be possible to have a deficiency in some specific nutrients, increasing the risk of osteoporosis and fractures. Although there are conflicting results on the effects of the vegetarian diet on bone health and fracture incidence, it is always recommendable in vegetarian people to have an adequate intake of calcium and vitamin D, through an increased intake of supplements, natural and fortified foods, an adequate intake of protein, fruit, vegetables, as well as vitamin B12. The aim of this literature review is to revise the actual knowledge of the effect of some nutrients and vegetarian diets on bone health.
    Keywords:  adults; bone; bone density; elderly, review; fracture; nutrients; vegetarian diets
    DOI:  https://doi.org/10.3389/fendo.2022.899375
  160. Oxid Med Cell Longev. 2022 ;2022 9735555
    Dapagliflozin Ameliorates Renal Tubular Ferroptosis in Diabetes via SLC40A1 Stabilization.
    Bin Huang, Wenjie Wen, Shandong Ye.
      Tubular injury has been shown to play a critical role in the morbidity of diabetic kidney disease (DKD); ferroptosis often occurs in tubules during renal disease development. This study was aimed at evaluating the inhibitory effects and potential mechanism of dapagliflozin (DAPA) against diabetic-related ferroptosis in the kidney. C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks, administered a small dose of streptozocin (STZ) for three consecutive days by intraperitoneal injection, and then orally administered dapagliflozin (10 mg/kg/day) for 8 weeks. Mouse blood and urine samples were collected, and their renal cortices were harvested for subsequent investigations. The effects of DAPA were also evaluated in HK-2 cells subjected to simulated diabetic conditions through excess glucose or palmitic acid (PA) administration. DAPA significantly ameliorated tubular injury independently of glycemic control in diabetic model mice. In vivo and in vitro investigations showed that dapagliflozin ameliorated tubular injury by inhibiting ferroptosis. Docking experiments demonstrated that dapagliflozin and SLC40A1 could bind with each other and may consequently reduce ubiquitination degradation. In conclusion, in this study, the tubular protective effects of DAPA, irrespective of glycemic control, were observed in a diabetic mouse model. DAPA ameliorated ferroptosis during diabetic tubular injury via SLC40A1 stabilization, and this may be the mechanism underlying its action. To the best of our knowledge, this is the first study to investigate the ferroptosis inhibitory effects of DAPA in the treatment of DKD.
    DOI:  https://doi.org/10.1155/2022/9735555
  161. Drug Des Devel Ther. 2022 ;16 2707-2728
    Recent Advances in Nano-Formulations for Skin Wound Repair Applications.
    Yue Lin, Zheyan Chen, Yinai Liu, Jiawen Wang, Wang Lv, Renyi Peng.
      Skin injuries caused by accidents and acute or chronic diseases place a heavy burden on patients and health care systems. Current treatments mainly depend on preventing infection, debridement, and hemostasis and on supplementing growth factors, but patients will still have scar tissue proliferation or difficulty healing and other problems after treatment. Conventional treatment usually focuses on a single factor or process of wound repair and often ignores the influence of the wound pathological microenvironment on the final healing effect. Therefore, it is of substantial research value to develop multifunctional therapeutic methods that can actively regulate the wound microenvironment and reduce the oxidative stress level at the wound site to promote the repair of skin wounds. In recent years, various bioactive nanomaterials have shown great potential in tissue repair and regeneration due to their properties, including their unique surface interface effect, small size effect, enzyme activity and quantum effect. This review summarizes the mechanisms underlying skin wound repair and the defects in traditional treatment methods. We focus on analyzing the advantages of different types of nanomaterials and comment on their toxicity and side effects when used for skin wound repair.
    Keywords:  nano-formulations; nanomaterials; nanomedicine; skin injury; wound repair
    DOI:  https://doi.org/10.2147/DDDT.S375541
  162. Front Pharmacol. 2022 ;13 925514
    Research progress on classical traditional chinese medicine formula xiaoyaosan in the treatment of depression.
    Jianbei Chen, Chaofang Lei, Xiaojuan Li, Qian Wu, Chenyue Liu, Qingyu Ma, Jiaxu Chen.
      Depression is an emotional disorder that is problematic in psychiatry owing to its unclear etiology and unknown pathogenesis. Traditional Chinese medicine formulations such as Xiaoyaosan have been widely used throughout history to treat depression. In this review, we have focused on recent evidences elucidating the links between Xiaoyaosan and the treatment of depression. Data from animal and clinical studies, focusing on the pharmacological mechanisms, clinical applications, and effective materials that form the basis for the treatment of depression are presented and discussed. We found that the antidepressant effects of Xiaoyaosan are related to the effects of monoamine neurotransmitters, regulation of the hypothalamic-pituitary-adrenal axis, neuroplasticity, synaptic plasticity, inflammatory response, neuroprotection, brain-gut axis, regulation of intestinal microbiota, oxidative stress, and autophagy for reducing neuronal apoptosis. This review highlights the current evidence supporting the use of Xiaoyaosan as an antidepressant and provides an overview of the potential mechanisms involved.
    Keywords:  TCM; clinical application; depression; pharmacological mechanism; research progress; review; xiaoyaosan
    DOI:  https://doi.org/10.3389/fphar.2022.925514
  163. Annu Rev Nutr. 2022 Aug 22. 42 45-66
    Dietary Fructose and Fructose-Induced Pathologies.
    Sunhee Jung, Hosung Bae, Won-Suk Song, Cholsoon Jang.
      The consumption of fructose as sugar and high-fructose corn syrup has markedly increased during the past several decades. This trend coincides with the exponential rise of metabolic diseases, including obesity, nonalcoholic fatty liver disease, cardiovascular disease, and diabetes. While the biochemical pathways of fructose metabolism were elucidated in the early 1990s, organismal-level fructose metabolism and its whole-body pathophysiological impacts have been only recently investigated. In this review, we discuss the history of fructose consumption, biochemical and molecular pathways involved in fructose metabolism in different organs and gut microbiota, the role of fructose in the pathogenesis of metabolic diseases, and the remaining questions to treat such diseases.
    Keywords:  fatty liver; fructose; gut microbiota; intestine; ketohexokinase; lipogenesis
    DOI:  https://doi.org/10.1146/annurev-nutr-062220-025831
  164. Colloids Surf B Biointerfaces. 2022 Aug 09. pii: S0927-7765(22)00450-7. [Epub ahead of print]218 112767
    Evaluation of quaternization effect on chitosan-HAP composite for bone tissue engineering application.
    E Murugan, C R Akshata, R Ilangovan, Manju Mohan.
      This study attempts to improve the aqueous solubility of chitosan and utilizes it in the fabrication of composites with hydroxyapatite (HAP). The composites were evaluated as a curcumin delivery vehicle for bone regeneration. The chitosan was modified by quaternization, with a quaternization degree of 5 % for low quaternized chitosan (LQC) and 11 % for high quaternized chitosan (HQC). The modified chitosan, at alkaline pH 11, facilitated in situ HAP growth and formed LQC-HAP and HQC-HAP composites. The quaternization weakens intermolecular hydrogen bonds, facilitates interaction with the apatite precursor ions and promotes the growth of HAP. The modification significantly improved drug encapsulation (2.6 fold) but at the cost of a slight decrease in mechanical strength and increase in drug release. The in vitro studies with human osteoblast-like MG-63 cells established that the curcumin-loaded composites, LQC-HAP-C and HQC-HAP-C are biocompatible, encourage proliferation and promote a 2-fold increase in calcium mineralization over drug-free composites. The study exemplifies the reciprocity between quaternization degree and drug load/release properties and also illustrates that the magnitude of the latter reflects bioactivity. Thus, the quaternized chitosan-based HAP composite with tailorable bio-physicochemical properties becomes an interesting drug delivery system in bone regeneration.
    Keywords:  Chitosan; Curcumin; HAP; Quaternization
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112767
  165. Oxid Med Cell Longev. 2022 ;2022 6291889
    From Iron Metabolism to Ferroptosis: Pathologic Changes in Coronary Heart Disease.
    Xinbiao Fan, Aolin Li, Zhipeng Yan, Xiaofei Geng, Lu Lian, Hao Lv, Dongjie Gao, Junping Zhang.
      Coronary heart disease (CHD) is closely related to oxidative stress and inflammatory response and is the most common cardiovascular disease (CVD). Iron is an essential mineral that participates in many physiological and biochemical reactions in the human body. Meanwhile, on the negative side, iron has an active redox capacity, which leads to the accumulation of reactive oxygen species (ROS) and lipid peroxidation. There is growing evidence that disordered iron metabolism is involved in CHD's pathological progression. And the result of disordered iron metabolism is associated with iron overload-induced programmed cell death, often called ferroptosis. That features iron-dependent lipid peroxidation. Ferroptosis may play a crucial role in the development of CHD, and targeting ferroptosis may be a promising option for treating CHD. Here, we review the mechanisms of iron metabolism in cardiomyocytes (CMs) and explain the correlation between iron metabolism and ferroptosis. Meanwhile, we highlight the specific roles of iron metabolism and ferroptosis in the main pathological progression of CHD.
    DOI:  https://doi.org/10.1155/2022/6291889
  166. Pharmaceuticals (Basel). 2022 Aug 10. pii: 985. [Epub ahead of print]15(8):
    Increased PDT Efficacy When Associated with Nitroglycerin: A Study on Retinoblastoma Xenografted on Mice.
    Carole D Thomas, Mihaela Lupu, Florent Poyer, Philippe Maillard, Joël Mispelter.
      PURPOSES: The aim of the study was to assess the efficacy of a treatment protocol that combines photodynamic therapy (PDT) and nitroglycerin (NG) on human retinoblastoma tumors xenografted on mice. We aimed to increase the PDT efficiency (in our least treatment-responsive retinoblastoma line) with better PS delivery to the tumor generated by NG, which is known to dilate vessels and enhance the permeability and retention of macromolecules in solid tumors.METHODS: In vivo follow-up of the therapeutic effects was performed by sodium MRI, which directly monitors variations in sodium concentrations non-invasively and can be used to track the tumor response to therapy. NG ointment was applied one hour before PDT. The PDT protocol involves double-tumor targeting, i.e., cellular and vascular. The first PS dose was injected followed by a second one, separated by a 3 h interval. The timelapse allowed the PS molecules to penetrate tumor cells. Ten minutes after the second dose, the PS was red-light-activated.
    RESULTS: In this study, we observed that the PDT effect was enhanced by applying nitroglycerin ointment to the tumor-bearing animal's skin. PDT initiates the bystander effect on retinoblastomas, and NG increases this effect by increasing the intratumoral concentration of PS, which induces a higher production of ROS in the illuminated region and thus increases the propagation of the cell death signal deeper into the tumor (bystander effect).
    Keywords:  PDT; mice; nitroglycerin ointment; retinoblastoma; sodium MRI
    DOI:  https://doi.org/10.3390/ph15080985
  167. J Biomater Appl. 2022 Aug 23. 8853282221122907
    Preparing simvastatin nanoparticles by a combination of pH-sensitive and timed-release approaches for the potential treatment of ulcerative colitis.
    Fereshteh Fardafshari, Somayeh Taymouri, Mohsen Minaiyan, Naser Tavakoli.
      In this study, an emulsion solvent evaporation method was used to produce Eudragit RL (ERL) nanoparticles (NPs) loaded with simvastatin (SIM) for the treatment of ulcerative colitis (UC). Accordingly, the effects of different formulation variables on the properties of NPs were evaluated using the Box-Behnken design. The optimized NPs were then coated by Eudragit FS30D (EFS30D). Drug release was studied in different physiological environments. Colitis was induced by 3% of acetic acid in rats, which received NPs of SIM (10 mg/kg/day), mesalazine (150 mg/kg/day), blank NPs and normal saline orally for 5 days. Macroscopic histopathological evaluation and biochemical analysis, including myeloperoxidase (MPO) activity and malondialdehyde (MDA) level in the colon tissues, were carried out in this study. The optimized SIM-ERL NPs showed the particle size of 182.48 ± 4.57 nm, the polydispersity index of 0.29 ± 0.12, the zeta potential of 26.45 ± 4.57 mV, drug loading % of 34.64 ± 0.48, the encapsulation efficiency % of 98.68 ± 0.69, and the release efficiency % of 35.78 ± 1.37. Coating the optimized NPs with EFS30D caused an increase in particle size and a decrease in the zeta potential of NPs. The optimized SIM-EFS30D/RL NPs improved the macroscopic and histopathological scores. Also, MPO activity and MDA level were reduced significantly by NPs, as compared to the control group. Therefore, this drug delivery system can be an alternative to the previous treatments of UC.
    Keywords:  Eudragit RL; acetic acid-induced colitis; eudragit FS30D; experimental design; nanoparticles; simvastatin
    DOI:  https://doi.org/10.1177/08853282221122907
  168. Cancer Cell Int. 2022 Aug 23. 22(1): 266
    The role of ferroptosis in esophageal cancer.
    Zimin Wang, Sikai Wu, Chengchu Zhu, Jianfei Shen.
      Esophageal cancer is one of the most common cancers with high mortality rate around the world. Although the treatment strategy of this disease has made great progress, the prognosis of advanced patients is not ideal. Ferroptosis, a novel regulatory cell death model, that is different from traditional apoptosis and characterized by increased Fenton reaction mediated by intracellular free iron and lipid peroxidation of cell membrane. Ferroptosis has been proved to be closely linked to a variety of diseases, especially cancer. This review aims to summarize the core mechanism of ferroptosis in esophageal cancer, the regulation of ferroptosis signaling pathway and its current application. At the same time, we emphasize the potential and prospect of ferroptosis in the treatment of esophageal cancer. Collectively, targeting ferroptosis pathway may provide new insights into the diagnosis, treatment and prognosis of esophageal cancer.
    Keywords:  Cell death; Esophageal cancer; Ferroptosis; Iron; Lipid peroxidation
    DOI:  https://doi.org/10.1186/s12935-022-02685-w
  169. Front Pharmacol. 2022 ;13 974274
    Preparation and pharmacological effects of minor ginsenoside nanoparticles: a review.
    Yue Ke, Lei Huang, Yu Song, Zhenxin Liu, Linshuang Liang, Linmao Wang, Taoyun Wang.
      Ginseng (Panax ginseng) is a perennial herbaceous plant belonging to Panax genus of Araliaceae. Ginsenosides are a kind of important compounds in ginseng and minor ginsenosides are secondary metabolic derivatives of ginsenosides. Studies have shown that minor ginsenosides have many pharmacological effects, such as antioxidant, anti-tumor, anti-platelet aggregation, and neuroprotective effects. However, the therapeutic effects of minor ginsenosides are limited due to poor solubility in water, short half-life, and poor targeting accuracy. In recent years, to improve the application efficiency, the research on the nanocrystallization of minor ginsenosides have attracted extensive attention from researchers. This review focuses on the classification, preparation methods, pharmacological effects, and action mechanisms of minor ginsenoside nanoparticles, as well as existing problems and future direction of relevant research, which provides a reference for the in-depth research of minor ginsenoside nanoparticles.
    Keywords:  action mechanism; minor ginsenosides; nanoparticles; pharmacological effects; preparation
    DOI:  https://doi.org/10.3389/fphar.2022.974274
  170. Membranes (Basel). 2022 Aug 12. pii: 775. [Epub ahead of print]12(8):
    Exosomes: Small Vesicles with Important Roles in the Development, Metastasis and Treatment of Breast Cancer.
    Ling'ao Meng, Kedong Song, Shenglong Li, Yue Kang.
      Breast cancer (BC) has now overtaken lung cancer as the most common cancer, while no biopredictive marker isolated from biological fluids has yet emerged clinically. After traditional chemotherapy, with the huge side effects brought by drugs, patients also suffer from the double affliction of drugs to the body while fighting cancer, and they often quickly develop drug resistance after the drug, leading to a poor prognosis. And the treatment of some breast cancer subtypes, such as triple negative breast cancer (TNBC), is even more difficult. Exosomes (Exos), which are naturally occurring extracellular vesicles (EVs) with nanoscale acellular structures ranging in diameter from 40 to 160 nm, can be isolated from various biological fluids and have been widely studied because they are derived from the cell membrane, have extremely small diameter, and are widely involved in various biological activities of the body. It can be used directly or modified to make derivatives or to make some analogs for the treatment of breast cancer. This review will focus on the involvement of exosomes in breast cancer initiation, progression, invasion as well as metastasis and the therapeutic role of exosomes in breast cancer.
    Keywords:  breast cancer; cancer therapeutics; drug resistance; exosome; targeted delivery
    DOI:  https://doi.org/10.3390/membranes12080775
  171. Membranes (Basel). 2022 Jul 29. pii: 744. [Epub ahead of print]12(8):
    Aptamer-Modified Erythrocyte Membrane-Coated pH-Sensitive Nanoparticles for c-Met-Targeted Therapy of Glioblastoma Multiforme.
    Xianping Liu, Yixin Chen, Daoying Geng, Haichun Li, Ting Jiang, Zimiao Luo, Jianhong Wang, Zhiqing Pang, Jun Zhang.
      Biomimetic drug delivery systems, especially red blood cell (RBC) membrane-based nanoparticle drug delivery systems (RNP), have been extensively utilized in tumor drug delivery because of their excellent biocompatibility and prolonged circulation. In this study, we developed an active targeting pH-sensitive RNP loaded with DOX by decorating an aptamer SL1 on RBC membranes (SL1-RNP-DOX) for c-Met-targeted therapy of glioblastoma multiforme (GBM). SL1 could specifically bind to c-Met, which is highly expressed in GBM U87MG cells and facilitate DOX delivery to GBM cells. In vitro studies demonstrated that U87MG cells had a higher uptake of SL1-RNP-DOX (3.25 folds) and a stronger pro-apoptosis effect than unmodified RNP-DOX. In vivo fluorescence imaging and tissue distribution further demonstrated the higher tumor distribution of SL1-RNP-DOX (2.17 folds) compared with RNP-DOX. As a result, SL1-RNP-DOX presented the best anti-GBM effect with a prolonged median survival time (23 days vs. 15.5 days) and the strongest tumor cell apoptosis in vivo among all groups. In conclusion, SL1-RNP-DOX exhibited a promising targeting delivery strategy for GBM therapy.
    Keywords:  aptamer; biomimetic drug delivery system; c-Met; chemotherapy; glioblastoma multiforme (GBM)
    DOI:  https://doi.org/10.3390/membranes12080744
  172. Life (Basel). 2022 Jul 28. pii: 1143. [Epub ahead of print]12(8):
    Combination Therapy Comprising Paclitaxel and 5-Fluorouracil by Using Folic Acid Functionalized Bovine Milk Exosomes Improves the Therapeutic Efficacy against Breast Cancer.
    Dulla Naveen Kumar, Aiswarya Chaudhuri, Deepa Dehari, Anusmita Shekher, Subash C Gupta, Shreyasi Majumdar, Sairam Krishnamurthy, Sanjay Singh, Dinesh Kumar, Ashish Kumar Agrawal.
      Paclitaxel (PAC) has been approved by FDA for clinical use (Taxol®), yet dose-dependent severe toxicity due to the adjuvant Cremophor EL® in combination with ethanol is a major drawback. The drawbacks of the current therapy can be overcome by (i) finding a suitable vehicle that cannot only bypass the above adjuvant but also be used to deliver drugs orally and (ii) combining the PAC with some other chemotherapeutics to have the enhanced therapeutic efficacy. In the current work, we have used folic acid (FA) functionalized bovine milk-derived exosomes for oral delivery of PAC in combination with 5-fluorouracil (5-FU). Exosomes before and after the drug loading were found to have a particle size in the range of 80-100 nm, polydispersity index (PDI ~0.20), zeta potential (~-25 mV), entrapment efficiency (~82%), practical drug loading (~28%) and sustained drug release for 48 h. Significant decreases in IC50 were observed in the case of exosomes loaded drugs which further improved following the FA functionalization. FA functionalized coumarin-6-loaded exosomes showed remarkably higher cellular uptake in comparison with free coumarin-6. Moreover, FA-functionalized drug-loaded exosomes showed a higher apoptotic index with better control over cell migration. Collectively, data suggested the enhanced efficacy of the combination following its loading to the folic acid functionalized exosomes against breast cancer.
    Keywords:  5-fluorouracil; breast cancer; chemotherapy; co-delivery; exosomes; paclitaxel
    DOI:  https://doi.org/10.3390/life12081143
  173. Biomater Adv. 2022 Aug 20. pii: S2772-9508(22)00361-2. [Epub ahead of print]140 213084
    The HbA1c and blood glucose response to selenium-rich polysaccharide from Fomes fomentarius loaded solid lipid nanoparticles as a potential antidiabetic agent in rats.
    Mohammad Keshavarz-Rezaei, Ashrafalsadat Hatamian-Zarmi, Hale Alvandi, Bahman Ebrahimi-Hosseinzadeh, Zahra Beagom Mokhtari-Hosseini.
      Fomes fomentarius is a medicinal fungus used in traditional Chinese medicine to treat various illnesses. Antidiabetic effects of F. fomentarius extracts have been reported recently. In this study, F. fomentarius extracellular polysaccharide (PS) was prepared, and then to enhance its antidiabetic effects, Na2SeO3 was added to the culture medium, and selenium-polysaccharide (PS-Se) was obtained. Also, solid lipid nanoparticles containing PS (SLN-PS) and PS-Se (SLN-PS-Se) were synthesized by the microemulsion method to compare their effects with free polysaccharides in streptozotocin (STZ) diabetic rats. Optimized SLNs had a size of 170.5 nm and drug loading of 9.27 %. EDS analysis confirmed that Se presence in PS-Se. Characterization analyses such as FTIR, DSC, TGA, and XRD suggested that SLNs have good thermal stability and crystalline nature. Release of PS from SLNs demonstrated sustained profile, and MTT assay proved that PSs and SLNs have no cytotoxicity. Furthermore, oral administration of PS, PS-Se, SLN-PS, and SLN-PS-Se for 28 days to diabetic rats significantly declined blood glucose by 48.24 %, 49.96 %, 55.50 %, and 60.47 %, respectively. Also, insulin secretion and body weight improved, and HbA1c levels decreased. Treatment by PS, PS-Se, SLN-PS, and SLN-PS-Se alleviated lipid profiles, liver enzymes, and serum proteins. Liver anti-oxidant parameters and histopathological observation of the liver, pancreas, and kidney confirmed that F. fomentarius PSs and SLNs have antidiabetic impacts. Moreover, supplementation of PS with selenium improves its anti-hyperglycemic effects. Finally, SLN-PS and SLN-PS-Se showed a higher antidiabetic impact than free PS and PS-Se.
    Keywords:  Anti-diabetic; Medicinal mushrooms; SLNs; Selenium-polysaccharide
    DOI:  https://doi.org/10.1016/j.bioadv.2022.213084
  174. JAMA. 2022 08 23. 328(8): 700
    Effect of Modified Chinese Diet Is Comparable to Antihypertensives.
    Anita Slomski.
      
    DOI:  https://doi.org/10.1001/jama.2022.14322
  175. Adv Drug Deliv Rev. 2022 Aug 20. pii: S0169-409X(22)00392-1. [Epub ahead of print] 114502
    Strategies and Progresses for Enhancing Targeted Antibiotic Delivery.
    Adila Nazli, David L He, Dandan Liao, Muhammad Zafar Irshad Khan, Chao Huang, Yun He.
      Antibiotic resistance is a global health issue and a potential risk for society. Antibiotics administered through conventional formulations are devoid of targeting effect and often spread to various undesired body sites, leading to sub-lethal concentrations at the site of action and thus resulting in emergence of resistance, as well as side effects. Moreover, we have a very slim antibiotic pipeline. Drug-delivery systems have been designed to control the rate, time, and site of drug release, and innovative approaches for antibiotic delivery provide a glint of hope for addressing these issues. This review elaborates different delivery strategies and approaches employed to overcome the limitations of conventional antibiotic therapy. These include antibiotic conjugates, prodrugs, and nanocarriers for local and targeted antibiotic release. In addition, a wide range of stimuli-responsive nanocarriers and biological carriers for targeted antibiotic delivery are discussed. The potential advantages and limitations of targeted antibiotic delivery strategies are described along with possible solutions to avoid these limitations. A number of antibiotics successfully delivered through these approaches with attained outcomes and potentials are reviewed.
    Keywords:  Antibiotic delivery; Antibiotic resistance; Nanoparticle; Prodrug; Siderophore; Stimuli-responsive; Trojan Horse
    DOI:  https://doi.org/10.1016/j.addr.2022.114502
  176. Crit Rev Food Sci Nutr. 2022 Aug 25. 1-28
    Recent advances in self-assembly behaviors of prolamins and their applications as functional delivery vehicles.
    Abdullah, Jieping Fang, Xidong Liu, Hafiz Umer Javed, Jiyang Cai, Qize Zhou, Qingrong Huang, Jie Xiao.
      Prolamins are a group of storage proteins (zeins, kafirins, hordeins, secalins, gliadins, glutenins, and avenins) found in the endosperm of cereal grains and characterized by high glutamine and proline content. With the high proportion of nonpolar amino acids (40-80%) and peculiar solubility (alcohol (60-90%), acetic acid, and alkaline solutions), prolamins exhibit tunable self-assembly behaviors. In recent years, research practices of utilizing prolamins as green building materials of functional delivery vehicles to improve the health benefits of bioactive compounds have surged due to their attractive advantages (e.g. sustainability, biocompatibility, fabrication potential, and cost-competitiveness). This article covers the recent advances in self-assembly behaviors leading to the fabrication of nanoparticles, fibers, and films in the bulk water phase, at the air-liquid interface, and under the electrostatic field. Different fabrication methods, including antisolvent precipitation, evaporation induced self-assembly, thermal treatment, pH-modulation, electrospinning, and solvent casting for assembling nanoarchitectures as functional delivery vehicles are highlighted. Emerging industrial applications by mapping patents, including encapsulation and delivery of bioactive compounds and probiotics, active packaging, Pickering emulsions, and as functional additives to develop safer, healthier, and sustainable food products are discussed. A future perspective concerning the fabrication of prolamins as advanced materials to promote their commercial food applications is proposed.
    Keywords:  Pickering emulsions; electrospun fibers; films; nanoparticles; prolamins; self-assembly
    DOI:  https://doi.org/10.1080/10408398.2022.2113031
  177. Curr Drug Deliv. 2022 Aug 19.
    An Insight on Novel Approaches & Perspectives for Gastro-Retentive Drug Delivery Systems.
    Sonia Dhiman, Nincy Philip, Thakur Gurjeet Singh, Ritchu Babbar, Nikhil Garg, Vanshika Diwan, Prabha Singh.
      The conventional oral drug delivery systems face a lot of difficulties in the gastrointestinal tract, such as inappropriate drug release and reduction in the efficacy of the doses, which makes this system less susceptible to the delivery of drug formulation. For the enhancement of therapeutic efficacy and bioavailability of the drug, many efforts have been made. The drug candidates which are not stable at alkaline pH and soluble in acidic medium were selected to increase their therapeutic effectiveness through gastro retentive drug delivery systems (GRDDS). This article discusses various factors which alter the gastro retention time (GRT) of the gastro retentive drug delivery system in the stomach and intestine (duodenum). It emphasizes on the novel approaches made for the delivery and release of drugs with the use of magnetic systems, floating (low-density) systems, super porous hydrogels, raft systems, mucoadhesive systems, high-density systems and expandable systems. Along with the applications, the key aspects of in vivo, in vitro & clinical studies in different approaches to GRDDS have been ad- dressed. In addition, future perspectives have been summarized to reduce gastric transit time in fasting and fed conditions.
    Keywords:  Bioavailability; floating systems; gastric transit time; gastroretentive drug delivery systems; hydro- gels; raft systems
    DOI:  https://doi.org/10.2174/1567201819666220819200236
  178. J Ethnopharmacol. 2022 Aug 19. pii: S0378-8741(22)00684-5. [Epub ahead of print]298 115645
    Leaves, seeds and exocarp of Ginkgo biloba L. (Ginkgoaceae): A Comprehensive Review of Traditional Uses, phytochemistry, pharmacology, resource utilization and toxicity.
    Yanxia Liu, Huawei Xin, Yunchao Zhang, Fengyuan Che, Na Shen, Yulei Cui.
      ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. (Ginkgoaceae) is a treasure species with high medicinal value. The Ming Dynasty "Compendium of Materia Medica" and Qing Dynasty "Bencao Fengyuan" in China recorded this herbal medicine can reduce phlegm, clear poison, treat diarrhea and frequent urination, etc. AIM OF THE STUDY: Until now, there is no painstakingly summarized review on leaves, seeds and exocarp of G. biloba simultaneously. This review will systematically summarize and compare current knowledge of G. biloba.MATERIALS AND METHODS: Ample original publications related to traditional uses, phytochemistry, pharmacology, resource utilization and toxicity of G. biloba leaves, seeds and exocarp till the end of 2021 were searched and collected by using various literature databases, including China National Knowledge Infrastructure, PubMed, Elsevier, Springer, Google Scholar and Web of Science database.
    RESULTS: According to classical Chinese herbal books and Chinese Pharmacopoeia, relieving cough, reducing phlegm, clearing poison and relieving diarrhea are the main pharmacological effects of G. biloba. The common chemical ingredients in different parts of G. biloba are flavonoids, terpenoids, phenolic acids, polysaccharides and endotoxin, etc. Among them, flavonoids and terpenoids are the main bioactive compounds in G. biloba leaves. Phenolic acids are the main bioactive compounds in G. biloba exocarp. G. biloba seeds are rich in nutritional ingredients, such as starch, adipose, protein, etc. Modern pharmacological studies showed that the crude extracts or compounds of G. biloba leaves, seeds and exocarp can be used for treating cardiovascular and cerebrovascular diseases, Alzheimer's disease, atherosclerosis, cancer, asthma, non-alcoholic fatty liver, diabetic complications and other diseases. In daily life, G. biloba seeds were usually used as raw material or additives for commodities, healthy food, drinks, even insecticides and antibacterial agents, etc. G. biloba leaves and seeds have been mainly applied for treating cardiovascular and cerebrovascular diseases, cough and asthma in clinical. However, endotoxins and ginkgolic acids have been identified as the dominating toxic ingredients in different parts of G. biloba. Besides, flavonoids and ginkgolides also have been proved to have toxicity recently.
    CONCLUSIONS: This review systematically sums up and compares the traditional uses, phytochemistry, pharmacology, resource utilization and toxicity research progress of G. biloba leaves, seeds and exocarp for the first time. It will provide some comprehensive reference data and suggestions for future research on this herbal medicine.
    Keywords:  Ginkgo biloba; Pharmacology; Phytochemistry; Resource utilization; Toxicity; Traditional uses
    DOI:  https://doi.org/10.1016/j.jep.2022.115645
  179. Colloids Surf B Biointerfaces. 2022 Aug 06. pii: S0927-7765(22)00446-5. [Epub ahead of print]218 112763
    Functionalized bosutinib liposomes for target specific delivery in management of estrogen-positive cancer.
    Priya Singh, Neelu Singh, Nidhi Mishra, Raquibun Nisha, Alka, Priyanka Maurya, Ravi Raj Pal, Samipta Singh, Shubhini A Saraf.
      This study was designed to create surface-functionalized bosutinib liposomes that could be used for the management of estrogen-positive cancers. The novelty of this work was the anti-cancer activity of bosutinib-loaded liposomes (Bos-LPs) in estrogen-positive cancer via estrogen response elements, responsible for the malignancy of cancer cells. Biotin effectively delivers active moiety to tumor tissues because it interacts with the biotin receptor and operates through the Sodium-dependent multivitamin transporters (SMVT) transporter. The prepared liposomes had a 257.73 ± 4.50 nm particle size, - 28.07 ± 5.81 mV zeta potential, 87.78 ± 1.16 % encapsulation efficiency and 85.56 ± 0.95 % drug release for 48 h. The surface architecture of biotin-modified bosutinib-loaded liposomes (b-Bos-LPs) was confirmed using scanning electron and transmission electron microscopies. In-vitro experiments revealed that b-Bos-LPs outperformed Bos and Bos-LPs in terms of significantly reduced cell viability in MCF-7 cells. According to biodistribution and pharmacokinetic studies, b-Bos-LPs have a higher Bos concentration in tumor tissues as compared to the other organs and also possess better pharmacokinetic activity, indicating that they can be used to treat carcinogen-induced estrogen-positive cancers. This is the first study to show that b-Bos-LPs can display activity against estrogen-positive cancer via biotin targeting. As evidenced by various parameters, b-Bos-LPs showed improved anticancer targeting, therapeutic safety and efficacy in carcinogen-induced estrogen-positive cancer. The receptor protein estrogen, which is primarily responsible for this cancer was downregulated by b-Bos-LPs in an immunoblotting assay. The results showed that biotinylated distearoylphosphatidylcholine (DSPC) augmented LPs loaded with Bosutinib can cause apoptosis in estrogen-positive breast cancer and be an effective way to treat estrogen-positive cancer.
    Keywords:  Bosutinib; Breast cancer; Estrogen-positive; Liposomes
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112763
  180. Biosensors (Basel). 2022 Aug 12. pii: 633. [Epub ahead of print]12(8):
    Recent Advances in Fluorescent Methods for Polyamine Detection and the Polyamine Suppressing Strategy in Tumor Treatment.
    Bingli Lu, Lingyun Wang, Xueguang Ran, Hao Tang, Derong Cao.
      The biogenic aliphatic polyamines (spermine, spermidine, and putrescine) are responsible for numerous cell functions, including cell proliferation, the stabilization of nucleic acid conformations, cell division, homeostasis, gene expression, and protein synthesis in living organisms. The change of polyamine concentrations in the urine or blood is usually related to the presence of malignant tumors and is regarded as a biomarker for the early diagnosis of cancer. Therefore, the detection of polyamine levels in physiological fluids can provide valuable information in terms of cancer diagnosis and in monitoring therapeutic effects. In this review, we summarize the recent advances in fluorescent methods for polyamine detection (supramolecular fluorescent sensing systems, fluorescent probes based on the chromophore reaction, fluorescent small molecules, and fluorescent nanoparticles). In addition, tumor polyamine-suppressing strategies (such as polyamine conjugate, polyamine analogs, combinations that target multiple components, spermine-responsive supramolecular chemotherapy, a combination of polyamine consumption and photodynamic therapy, etc.) are highlighted. We hope that this review promotes the development of more efficient polyamine detection methods and provides a comprehensive understanding of polyamine-based tumor suppressor strategies.
    Keywords:  detection; polyamines; suppressor strategies; tumor
    DOI:  https://doi.org/10.3390/bios12080633
  181. Pharmaceutics. 2022 Aug 06. pii: 1642. [Epub ahead of print]14(8):
    Ultrasonic Microbubble Cavitation Enhanced Tissue Permeability and Drug Diffusion in Solid Tumor Therapy.
    Jide He, Zenan Liu, Xuehua Zhu, Haizhui Xia, Huile Gao, Jian Lu.
      Chemotherapy has an essential role not only in advanced solid tumor therapy intervention but also in society's health at large. Chemoresistance, however, seriously restricts the efficiency and sensitivity of chemotherapeutic agents, representing a significant threat to patients' quality of life and life expectancy. How to reverse chemoresistance, improve efficacy sensitization response, and reduce adverse side effects need to be tackled urgently. Recently, studies on the effect of ultrasonic microbubble cavitation on enhanced tissue permeability and retention (EPR) have attracted the attention of researchers. Compared with the traditional targeted drug delivery regimen, the microbubble cavitation effect, which can be used to enhance the EPR effect, has the advantages of less trauma, low cost, and good sensitization effect, and has significant application prospects. This article reviews the research progress of ultrasound-mediated microbubble cavitation in the treatment of solid tumors and discusses its mechanism of action to provide new ideas for better treatment strategies.
    Keywords:  EPR effect; cavitation effect; microbubbles; permeability; tumor therapy; ultrasound
    DOI:  https://doi.org/10.3390/pharmaceutics14081642
  182. Antioxidants (Basel). 2022 Aug 15. pii: 1579. [Epub ahead of print]11(8):
    Micro-Encapsulation of Phytochemicals in Passion Fruit Peel Waste Generated on an Organic Farm: Effect of Carriers on the Quality of Encapsulated Powders and Potential for Value-Addition.
    Gift Kabelo Kobo, Tafadzwa Kaseke, Olaniyi Amos Fawole.
      The passion (Passiflora edulis Sims) fruit peel is rich in phenolics and other bioactive compounds and has great potential as a natural food preservative. The present study investigated the value-adding potential of passion fruit peel waste generated on an organic farm. The effect of carriers in encapsulating the peel extract to develop a polyphenolic-rich powder was investigated. The passion fruit peel extracts were prepared using 70% ethanol (1:10 w/v), and encapsulated using waxy starch (WS), gum arabic (GA), and maltodextrin (MT) before freeze-drying. The effects of carriers on the passion fruit peel powder (PFPP) production yield, physicochemical, rheological, phytochemical, and antioxidant properties were investigated. GA-and MT-encapsulated powders had better physical, phytochemical, and antioxidant properties, including yield, total soluble solids, solubility, bulk density, total phenolic content, and ferric reducing antioxidant powder. A total of 18 metabolites, including phenolic acids (10), flavonoids (6), and stilbenes (2), were tentatively identified in all the PFPP samples, with WS exhibiting a higher concentration of the compounds compared to GA and MT. Our results indicated that no single carrier was associated with all the quality attributes; therefore, better results could be produced by compositing these carriers. Nonetheless, our results highlight the potential of passion fruit peels as a source of polyphenols and functional ingredient in formulating natural food additives.
    Keywords:  carriers; flavonoids; passion fruit peel; phenolic acids; solubility; total monomeric anthocyanin; total phenolic content
    DOI:  https://doi.org/10.3390/antiox11081579
  183. Malawi Med J. 2022 06;34(2): 138-142
    Medical cannabis and cannabidiol: A new harvest for Malawi.
    Gama Bandawe.
      In February 2020 parliament passed the Cannabis Regulation Bill (2020) which regulates the cultivation and production of industrial hemp and medical cannabis. The country will only fully benefit from this development if the medical and scientific community can take the lead in enabling the country to exploit the plant's potential to help address some of our economic and public health challenges. This special communication provides some basic information on cannabis and discusses its history and medical uses. Cannabidiol (CBD) has emerged as one of the most important cannabis-derived phytochemicals and has formed the basis for the growth of the medical cannabis industry. The scientific data on the mechanisms of the effects of CBD on the human neuroendocrine-immune network is reviewed and the first effective cannabis-based FDA-approved treatment for epilepsy discussed. Some clinical research that is being done on the antipsychotic and neuroprotective properties of CBD is also reviewed. A case is made for the potential of CBD as a neuroprotective adjunctive therapy for the prevention of neuropsychological sequelae associated with complicated malaria. The safety profile of CBD is reviewed and finally, the potential importance of the re-medicalization of cannabis-based therapies for the broader field of phytomedicine is pointed out.
    Keywords:  Cannabis sativa; cannabidiol; endocannabinoid; industrial hemp; marijuana; medical cannabis
    DOI:  https://doi.org/10.4314/mmj.v34i2.10
  184. ACS Omega. 2022 Aug 16. 7(32): 28421-28433
    Use of Saponinosomes from Ziziphus spina-christi as Anticancer Drug Carriers.
    Zahra Nazemoroaya, Mohsen Sarafbidabad, Athar Mahdieh, Darya Zeini, Bo Nyström.
      Saponins are plant glycosides with different structures and biological activities, such as anticancer effects. Ziziphus spina-christi is a plant rich in saponin, and this compound is used to treat malignant melanoma in the present study. Nanophytosomes can be used as an advantageous nanodrug delivery system for plant extracts. The aim of this work is to use the saponin-rich fraction (SRF) from Z. spina-christi and prepare SRF-loaded nanophytosomes (saponinosomes) and observe the in vitro and in vivo effects of these carriers. First, the SRF was obtained from Z. spina-christi by a solvent-solvent fractionation method. Then, Fourier transform infrared (FTIR) analyses were performed to confirm the presence of saponins in the extracted material. Subsequently, the saponinosomes were prepared by the solvent injection method (ether injection method) using a 1:1:1 ratio of lecithin/cholesterol/SRF in the mixture. Characterization of the prepared saponinosomes was performed by FTIR, dynamic light scattering (DLS), field-emission scanning electron microscopy (FE-SEM), and atomic force microscopy (AFM) analyses. In addition, a UV-vis spectrophotometer was used to determine the entrapment efficiency (EE) and in vitro release of the SRF. Finally, cell cytotoxicity of the different formulations was evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay on both mouse melanoma cells (B16F10) and fibroblasts (L929). Using DLS, AFM, and FE-SEM analyses, the particle size was determined to be 58 ± 6 nm with a zeta potential of -32 ± 2 mV. The calculated EE was 85 ± 3%. The results of the in vitro release profile showed that 68.2% of the SRF was released from the saponinosome after 48 h. The results of the MTT assay showed that the SRF and saponinosomes have high toxicity on B16F10 melanoma cells, but saponinosomes showed a significant decrease in cytotoxicity on L929 fibroblast cells compared with that of the SRF. Our results indicate that the SRF from Z. spina-christi has anticancer activity, and the saponinosomes prepared in this work can control tumor growth, improve therapeutic efficacy, and reduce the side effects of saponins.
    DOI:  https://doi.org/10.1021/acsomega.2c03109
  185. Biomaterials. 2022 Aug 15. pii: S0142-9612(22)00384-2. [Epub ahead of print] 121744
    Dual-source powered nanomotor with integrated functions for cancer photo-theranostics.
    Shuqin Chen, Xiang Sun, Mingming Fu, Xiaoxia Liu, Shiyao Pang, Yongqiang You, Xiaojia Liu, Yong Wang, Xiaohui Yan, Xing Ma.
      While the miniaturization and motility of artificial nanomotors made them popular tools for exploring novel and innovative biomedical cancer treatment strategies, the integration of multiple functions on the small motor bodies is key to achieve further progress but remains unresolved. Here, we propose a dual-source powered Janus nanomotor whose composition integrates multiple photo-theranostic functions such as surface-enhanced Raman scattering (SERS) sensing, fluorescence imaging/photoacoustic imaging (PAI), photodynamic therapy (PDT), and photothermal therapy (PTT). This nanomotor can be fabricated by sputtering a thin gold layer onto one side of mesoporous silica (mSiO2) combined with surface modification by photo-sensitizer, Raman reporter, and catalase. Upon illumination with 808 nm near-infrared light, the half-coated gold nanoshell serves as PAI/PTT agent, and by upconverting NIR to visible light, the pre-loaded photosensitizer can be excited by the upconverted light of UCNPs to convert the dissolved oxygen (O2) into reactive oxygen species for efficient PDT. Furthermore, ratiometric SERS signal can be captured to quantitatively detect the tumor marker, H2O2, in cellular microenvironments. The immobilized catalase as a nano-engine can catalyze endogenous H2O2 to O2. This function not only improves the hypoxic tumor microenvironment and therefore enhances PDT efficiency, but also provides a thrust force for deep penetration. As a proof of concept for the in vivo trial we performed cancer photo-theranostics where our nanomotors successfully treated a mouse breast tumor in a subcutaneous tumor model. The results are promising and encourage the use of an integrated nanomotor platform that could be further developed into a photo-theranostic agent for superficial cancer treatment.
    Keywords:  Cancer photo-theranostics; In vivo imaging; Micro-/nanomotors; Photothermal/photodynamic effects; SERS sensing
    DOI:  https://doi.org/10.1016/j.biomaterials.2022.121744
  186. Cell Mol Biol (Noisy-le-grand). 2022 Apr 30. 68(4): 129-133
    Investigation of the Effects of the Endogenous Cannabinoid Anandamide on Luminal A Breast Cancer Cell Line MCF-7.
    İdil Çetin, Mehmet Topçul.
      The present study was carried out to investigate anti-tumoral effects of Anandamide (AEA) in luminal A breast cancer cell line MCF-7. Cell viability was measured by MTT assay and cell index was measured by xCelligence DP analyzer system. The Feulgen method was used to determine the mitotic index parameter, and the 3H-Thymidine method was used to determine the labeling index parameter. The apoptotic index parameter was determined using a fluorescent dye DAPI. The results of this study showed that 25 µM Anandamide concentration was the optimum concentration for MCF-7 cells. While this concentration decreased the proportion of cells in the mitotic phase and synthesis phase, it increased the proportion of apoptotic cells.
    DOI:  https://doi.org/10.14715/cmb/2022.68.4.16
  187. Nutrients. 2022 Aug 19. pii: 3418. [Epub ahead of print]14(16):
    Post-Diagnosis Vitamin D Supplement Use and Survival among Cancer Patients: A Meta-Analysis.
    Qiao-Yi Chen, Sohyun Kim, Bohyoon Lee, Gyeongin Jeong, Dong Hoon Lee, NaNa Keum, JoAnn E Manson, Edward L Giovannucci.
      Vitamin D administered pre-diagnostically has been shown to reduce mortality. Emerging evidence suggests a role of post-diagnosis vitamin D supplement intake for survival among cancer patients. Thus, we conducted a meta-analysis to evaluate the relationship. PubMed and Embase were searched for relevant observational cohort studies and randomized trials published through April 2022. Summary relative risk (SRR) and 95% confidence interval (CI) were estimated using the DerSimonian-Laird random-effects model. The SRR for post-diagnosis vitamin D supplement use vs. non-use, pooling cohort studies and randomized trials, was 0.87 (95% CI, 0.78-0.98; p = 0.02; I2 = 0%) for overall survival, 0.81 (95% CI, 0.62-1.06; p = 0.12; I2 = 51%) for progression-free survival, 0.86 (95% CI, 0.72-1.03; p = 0.10; I2 = 0%) for cancer-specific survival, and 0.86 (95% CI, 0.64-1.14; p = 0.29; I2 = 0%) for relapse. Albeit not significantly heterogeneous by variables tested, a significant inverse association was limited to cohort studies and supplement use during cancer treatment for overall survival, and to studies with ≤3 years of follow-up for progression-free survival. Post-diagnosis vitamin D supplement use was associated with improved overall survival, but not progression-free or cancer-specific survival or relapse. Our findings require confirmation, as randomized trial evidence was insufficient to establish cause-and-effect relationships.
    Keywords:  cancer-specific survival; cohort study; meta-analysis; overall survival; post-diagnosis; progression-free survival; randomized controlled trial; relapse; vitamin D supplement use
    DOI:  https://doi.org/10.3390/nu14163418
  188. Microorganisms. 2022 Aug 09. pii: 1606. [Epub ahead of print]10(8):
    Fermented Soy Products and Their Potential Health Benefits: A Review.
    Fernanda Guilherme do Prado, Maria Giovana Binder Pagnoncelli, Gilberto Vinícius de Melo Pereira, Susan Grace Karp, Carlos Ricardo Soccol.
      In the growing search for therapeutic strategies, there is an interest in foods containing natural antioxidants and other bioactive compounds capable of preventing or reversing pathogenic processes associated with metabolic disease. Fermentation has been used as a potent way of improving the properties of soybean and their components. Microbial metabolism is responsible for producing the β-glucosidase enzyme that converts glycosidic isoflavones into aglycones with higher biological activity in fermented soy products, in addition to several end-metabolites associated with human health development, including peptides, phenolic acids, fatty acids, vitamins, flavonoids, minerals, and organic acids. Thus, several products have emerged from soybean fermentation by fungi, bacteria, or a combination of both. This review covers the key biological characteristics of soy and fermented soy products, including natto, miso, tofu, douchi, sufu, cheonggukjang, doenjang, kanjang, meju, tempeh, thua-nao, kinema, hawaijar, and tungrymbai. The inclusion of these foods in the diet has been associated with the reduction of chronic diseases, with potential anticancer, anti-obesity, antidiabetic, anticholesterol, anti-inflammatory, and neuroprotective effects. These biological activities and the recently studied potential of fermented soybean molecules against SARS-CoV-2 are discussed. Finally, a patent landscape is presented to provide the state-of-the-art of the transfer of knowledge from the scientific sphere to the industrial application.
    Keywords:  bioactive compounds; daidzein; fermented soybean foods; genistein; oxidative stress
    DOI:  https://doi.org/10.3390/microorganisms10081606
  189. Biomedicines. 2022 Jul 29. pii: 1828. [Epub ahead of print]10(8):
    Cancer Metabolism and Resistance to Cell Death: Novel Therapeutic Perspectives.
    Francesco Ciccarese.
      Deregulation of metabolism and resistance to cell death are two hallmarks of cancer [...].
    DOI:  https://doi.org/10.3390/biomedicines10081828
  190. Pharmaceutics. 2022 Jul 29. pii: 1581. [Epub ahead of print]14(8):
    Recent Advances in Nanoparticles-Based Platforms Targeting the PD-1/PD-L1 Pathway for Cancer Treatment.
    Xin Yu, Chao Fang, Kun Zhang, Chunxia Su.
      Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis showed remarkable improvements in overall response and patient survival, which changed the treatment landscape for multiple cancer types. However, the majority of patients receiving ICIs are either non-responders or eventually develop secondary resistance. Meanwhile, immunological homeostasis would be destroyed as T cell functions are activated excessively, leading to immune-related adverse events (irAEs). Clinically, a large number of irAEs caused by ICIs occurred and affected almost every organ system, resulting in the discontinuation or even the termination of the ongoing therapy. Therefore, researchers are exploring methods to overcome the situations of insufficient accumulation of these drugs in tumor sites and severe side effects. PD-1/PD-L1-targeted agents encapsulated in nanoparticles have emerged as novel drug delivery systems for improving the delivery efficacy, enhancing immune response and minimizing side effects in cancer treatment. Nanocarriers targeting the PD-1/PD-L1 axis showed enhanced functionalities and improved the technical weaknesses based on their reduced off-target effects, biocompatible properties, multifunctional potential and biomimetic modifications. Here, we summarize nanoparticles which are designed to directly target the PD-1/PD-L1 axis. We also discuss the combination of anti-PD-1/PD-L1 agents and other therapies using nanomedicine-based treatments and their anticancer effects, safety issues, and future prospects.
    Keywords:  PD-1/PD-L1; cancer immunotherapy; delivery nanoplatforms; immune checkpoint; nanoparticles
    DOI:  https://doi.org/10.3390/pharmaceutics14081581
  191. Molecules. 2022 Aug 15. pii: 5192. [Epub ahead of print]27(16):
    Targeting HIF-1α by Natural and Synthetic Compounds: A Promising Approach for Anti-Cancer Therapeutics Development.
    Rituparna Ghosh, Priya Samanta, Rupali Sarkar, Souradeep Biswas, Prosenjit Saha, Subhadip Hajra, Arijit Bhowmik.
      Advancement in novel target detection using improved molecular cancer biology has opened up new avenues for promising anti-cancer drug development. In the past two decades, the mechanism of tumor hypoxia has become more understandable with the discovery of hypoxia-inducible factor-1α (HIF-1α). It is a major transcriptional regulator that coordinates the activity of various transcription factors and their downstream molecules involved in tumorigenesis. HIF-1α not only plays a crucial role in the adaptation of tumor cells to hypoxia but also regulates different biological processes, including cell proliferation, survival, cellular metabolism, angiogenesis, metastasis, cancer stem cell maintenance, and propagation. Therefore, HIF-1α overexpression is strongly associated with poor prognosis in patients with different solid cancers. Hence, pharmacological targeting of HIF-1α has been considered to be a novel cancer therapeutic strategy in recent years. In this review, we provide brief descriptions of natural and synthetic compounds as HIF-1α inhibitors that have the potential to accelerate anticancer drug discovery. This review also introduces the mode of action of these compounds for a better understanding of the chemical leads, which could be useful as cancer therapeutics in the future.
    Keywords:  HIF-1α; angiogenesis; cancer stem cells; hypoxia; metastasis; natural compounds; synthetic drugs
    DOI:  https://doi.org/10.3390/molecules27165192
  192. Cell Mol Biol (Noisy-le-grand). 2022 Apr 30. 68(4): 158-169
    Melatonin Sensitizes OVCAR-3 Cells to Cisplatin through Suppression of PI3K/Akt Pathway.
    Sahar Baghal-Sadriforoush, Morteza Bagheri, Isa Abdi Rad, Fattah Sotoodehnejadnematalahi.
      This study examined the effect of melatonin on oxidative stress, expression of pro-apoptotic protein, anti-apoptotic proteins, and the activity of the PI3K/Akt signaling pathway in the human ovarian cancer cell line (OVCAR3). OVCAR3 cells were treated with cisplatin, melatonin, cisplatin + melatonin, and siRNA Akt. Reactive oxygen species levels were assessed. The expression of the proteins was determined by Western blot. Melatonin administration significantly increased intracellular ROS generation, the cleavage of caspase 3 and decreased phosphorylation of Akt. Combination therapy of cisplatin and melatonin increases apoptosis in the OVCAR-3 cells by inhibiting of PI3K/Akt signaling pathway and exacerbating oxidative stress.
    DOI:  https://doi.org/10.14715/cmb/2022.68.4.19
  193. Int J Mol Med. 2022 Oct;pii: 124. [Epub ahead of print]50(4):
    Metabolic heterogeneity protects metastatic mucosal melanomas cells from ferroptosis.
    Weifan Lin, Xiangwan Lu, Hang Yang, Linxuan Huang, Wuheng Huang, Yuluan Tang, Situn Liu, Hua Wang, Yan Zhang.
      Cancer heterogeneity has been proposed to be one of the main causes of metastatic dissemination and therapy failure. However, the underlying mechanisms of this phenomenon remain poorly understood. Melanoma is an aggressive malignancy with a high heterogeneity and metastatic potential. Therefore, the present study investigated the possible association between cancer heterogeneity and metastasis in melanoma. In total, two novel Chinese oral mucosal melanoma (COMM) cell lines, namely COMM‑1 and COMM‑2, were established for exploring methods into preventing the loss of cellular heterogeneity caused by long‑term cell culture. Each cell line was grown under two different models of culture, which yielded two subtypes, one exhibited an adhesive morphology (COMM‑AD), whereas the other was grown in suspension (COMM‑SUS). Compared with the COMM‑AD cells, the COMM‑SUS cells exhibited higher metastatic capacities and autofluorescence. Further investigations indicated that the COMM‑SUS cells exhibited metabolic reprogramming by taking up lactate produced by COMM‑AD cells at increased levels to accumulate NADH through monocarboxylate transporter 1, whilst also increasing NADPH levels through the pentose phosphate pathway (PPP). Additionally, increased NADH and NADPH levels in the COMM‑SUS cells, coupled with the upregulation of the anti‑ferroptotic proteins, glutathione peroxidase 4 and ferrop-tosis suppressor protein 1, enabled them to resist ferroptotic cell death induced by oxidative stress during hematogenous dissemination. The inhibition of ferroptosis was found to substantially increase the metastatic capacity of COMM‑AD cells. Furthermore, suppressing lactate uptake and impairing PPP activation significantly decreased the metastatic potential of the COMM‑SUS cells. Thus, the present study on metabolic heterogeneity in COMM cells potentially provides a novel perspective for exploring this mechanism underlying cancer metastasis.
    Keywords:  cancer heterogeneity; ferroptosis; inflammation; metabolic reprogramming; metastasis; mucosal melanomas
    DOI:  https://doi.org/10.3892/ijmm.2022.5180
  194. Antioxidants (Basel). 2022 Jul 31. pii: 1504. [Epub ahead of print]11(8):
    Ferroptosis and Its Multifaceted Role in Cancer: Mechanisms and Therapeutic Approach.
    Heshu Chen, Chenyu Wang, Zemin Liu, Xinmiao He, Wenjie Tang, Liuqin He, Yanzhong Feng, Di Liu, Yulong Yin, Tiejun Li.
      Ferroptosis, a new type of non-apoptotic cell death modality, is different from other modes of cell death and has been primarily found in tumor cells. Previous studies have reported that ferroptosis can be triggered by specific modulators (e.g., drugs, nutrients, and iron chelators), leading to increased intracellular lipid reactive oxygen species (ROS) accumulation and iron overload. Recent reports have shown that ferroptosis at the cellular and organism levels can prevent an inflammatory storm and cancer development. Emerging evidence suggests potential mechanisms (e.g., system Xc-, glutathione peroxidase 4 (GPX4), lipid peroxidation, glutathione (GSH), and iron chelators) are involved in ferroptosis, which may mediate biological processes such as oxidative stress and iron overload to treat cancer. To date, there are at least three pathways that mediate ferroptosis in cancer cells: system Xc-/GSH/GPX4, FSP1/CoQ10/NAD(P)H, and ATG5/ATG7/NCOA4. Here, we summarize recent advances in the occurrence and development of ferroptosis in the context of cancer, the associations between ferroptosis and various modulators, and the potential mechanisms and therapeutic strategies targeting ferroptosis for the treatment of cancer.
    Keywords:  cancer; ferroptosis; iron; lipid peroxidation; oxidative stress
    DOI:  https://doi.org/10.3390/antiox11081504
  195. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2022 Aug 21. e1842
    Tumor microenvironment-regulating nanomedicine design to fight multi-drug resistant tumors.
    Qinqin Xu, Xinyue Lan, Huimin Lin, Qiye Xi, Manchun Wang, Xiaolong Quan, Guangyu Yao, Zhiqiang Yu, Yongxia Wang, Meng Yu.
      The tumor microenvironment (TME) is a very cunning system that enables tumor cells to escape death post-traditional antitumor treatments through the comprehensive effect of different factors, thereby leading to drug resistance. Deep insights into TME characteristics and tumor resistance encourage the construction of nanomedicines that can remodel the TME against drug resistance. Tremendous interest in combining TME-regulation measurement with traditional tumor treatment to fight multidrug-resistant tumors has been inspired by the increasing understanding of the role of TME reconstruction in improving the antitumor efficiency of drug-resistant tumor therapy. This review focuses on the underlying relationships between specific TME characteristics (such as hypoxia, acidity, immunity, microorganisms, and metabolism) and drug resistance in tumor treatments. The exciting antitumor activities strengthened by TME regulation are also discussed in-depth, providing solutions from the perspective of nanomedicine design. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.
    Keywords:  TME reconstruction; drug-resistance; hypoxia; nanomedicine; tumor microenvironment
    DOI:  https://doi.org/10.1002/wnan.1842
  196. Biomacromolecules. 2022 Aug 25.
    Oxidative Stress Amplifying Polyprodrug Micelles as Drug Carriers for Combination Anticancer Therapy.
    Yujin Lee, Nanhee Song, Nuri Kim, Manseok Yang, Gayoung Kwon, Hyejin Hyeon, Eunkyeong Jung, Seong-Cheol Park, Chunho Kim, Dongwon Lee.
      Cancer cells are more vulnerable to reactive oxygen species (ROS)-mediated oxidative stress than normal cells due to disturbed redox balance. It can be postulated that ROS-generating drug carriers exert anticancer actions, leading to combination anticancer therapy with drug payloads. Here, we report a ROS-generating polyprodrug of cinnamaldehyde (CA) that not only serves as a drug carrier but also synergizes with drug payloads. The polyprodrug of CA (pCA) incorporates ROS-generating CA in the backbone of an amphiphilic polymer through an acid-cleavable acetal linkage. pCA could self-assemble with tumor-targeting lipopeptide (DSPE-PEG-RGD) and encapsulate doxorubicin (DOX) to form T-pCAD micelles. At acidic pH, T-pCAD micelles release both CA and DOX to exert synergistic anticancer actions. Animal studies using mouse xenograft models revealed that T-pCAD micelles accumulate in tumors preferentially and suppress the tumor growth significantly. Based on the oxidative stress amplification and acid-responsiveness, ROS-generating pCAD micelles hold tremendous potential as drug carriers for combination anticancer therapy.
    DOI:  https://doi.org/10.1021/acs.biomac.2c00700
  197. Front Nutr. 2022 ;9 964273
    Hypertension of liver-yang hyperactivity syndrome induced by a high salt diet by altering components of the gut microbiota associated with the glutamate/GABA-glutamine cycle.
    Tao Zheng, Yi Wu, Mai-Jiao Peng, Nen-Qun Xiao, Zhou-Jin Tan, Tao Yang.
      The gut microbiota and metabolites are closely related to hypertension; however, the changes in the composition of the gut microbiome and metabolites linking a high salt diet to elevated blood pressure are not established. In this study, traditional Chinese medicine (TCM) syndrome of hypertension caused by high salt had been diagnosed and the pathogenesis of hypertension was explored from the perspective of intestinal microecology. Rats in a high salt diet-induced hypertension group (CG) and normal group (CZ) were compared by 16S rRNA gene full-length sequencing and liquid chromatography and mass spectrometry to identify differences in the bacterial community structure, metabolites, and metabolic pathways. Hypertension induced by a high salt diet belongs to liver-Yang hyperactivity syndrome. Alpha and beta diversity as well as the composition of microbiota from the phylum to species levels differed substantially between the CG and CZ groups. In an analysis of differential metabolites in the intestines, a high salt diet mainly affected the metabolism of amino acids and their derivatives; in particular, γ-aminobutyric acid (GABA) was down-regulated and glutamic acid and its derivatives were up-regulated under a high salt diet. Based on a KEGG analysis, high salt intake mainly altered pathways related to GABA and the glutamate/glutamine metabolism, such as the GABAergic synapse pathway and glutamatergic synapse pathway. The correlation analysis of differential gut microbes and differential metabolites suggested that a high salt diet promoted hypertension via the inhibition of Clostridiaceae_1 growth and alterations in the GABA metabolic pathway, leading to increased blood pressure. These findings suggest that a high salt diet induces hypertension of liver-Yang hyperactivity syndrome by mediating the microbiota associated with the glutamate/GABA-glutamine metabolic cycle via the gut-brain axis.
    Keywords:  glutamate/GABA-glutamine cycle; gut microbiota; high salt diet; hypertension; liver-yang hyperactivity syndrome; metabolite
    DOI:  https://doi.org/10.3389/fnut.2022.964273
  198. Polymers (Basel). 2022 Aug 09. pii: 3248. [Epub ahead of print]14(16):
    Punicalagin-Loaded Alginate/Chitosan-Gallol Hydrogels for Efficient Wound Repair and Hemostasis.
    Jaewon Ju, Jungwoo Kim, Yeonsun Choi, Subin Jin, Sumin Kim, Donghee Son, Mikyung Shin.
      For recently devised wound-healing materials, a variety of acute application systems with sustainable therapeutic effects on wound sites have been suggested. For example, hydrogel-type healing agents with porous structures and high drug encapsulation efficiencies have been developed for wound repair. However, challenges remain about the poor mechanical and adhesive properties of hydrogels. Herein, we propose a punicalagin (PC)-containing wound-healing hydrogel in adhesive form that is mechanically stable and has sustainable wound-healing therapeutic efficiency. The APC hydrogel, composed of alginate (ALG), PC, and chitosan-gallol (CHI-G), exhibits significant mechanical and self-healing properties, thus indicating that PC increases cross-linking in ALG/CHI-G as macromolecule. The PC-containing mechanically enhanced hydrogel demonstrates high tissue adhesiveness. Sustainable PC release for 192 h, which indicates high therapeutic effect of the released PC, and great blood compatibility are evaluated based on rapid blood coagulation and minimal hemolysis. The cytocompatibility and wound-healing abilities of the PC-containing APC hydrogel are greater than those of the non-PC hydrogel, as verified by cell compatibility and wound scratch assays. These results indicate that a suitable concentration of PC-containing hydrogel with sustainable moisture condition and PC release may inspire further polyphenol-agent-containing hydrogels as wound-healing agents with structural stability and therapeutic efficiency.
    Keywords:  adhesive hydrogel; hemostasis; polyphenol; wound-healing material
    DOI:  https://doi.org/10.3390/polym14163248
  199. Pharmaceutics. 2022 Aug 15. pii: 1703. [Epub ahead of print]14(8):
    Herb Polysaccharide-Based Drug Delivery System: Fabrication, Properties, and Applications for Immunotherapy.
    Yubiao Cao, Zhuowen Chen, Liangliang Sun, Yameng Lin, Ye Yang, Xiuming Cui, Chengxiao Wang.
      Herb polysaccharides (HPS) have been studied extensively for their healthcare applications. Though the toxicity was not fully clarified, HPS were widely accepted for their biodegradability and biocompatibility. In addition, as carbohydrate polymers with a unique chemical composition, molecular weight, and functional group profile, HPS can be conjugated, cross-linked, and functionally modified. Thus, they are great candidates for the fabrication of drug delivery systems (DDS). HPS-based DDS (HPS-DDS) can bypass phagocytosis by the reticuloendothelial system, prevent the degradation of biomolecules, and increase the bioavailability of small molecules, thus exerting therapeutic effects. In this review, we focus on the application of HPS as components of immunoregulatory DDS. We summarize the principles governing the fabrication of HPS-DDS, including nanoparticles, micelles, liposomes, microemulsions, hydrogels, and microneedles. In addition, we discuss the role of HPS in DDS for immunotherapy. This comprehensive review provides valuable insights that could guide the design of effective HPS-DDS.
    Keywords:  application; drug delivery system; herb polysaccharides; immune regulation; structure modification
    DOI:  https://doi.org/10.3390/pharmaceutics14081703
  200. Nutrients. 2022 Aug 18. pii: 3402. [Epub ahead of print]14(16):
    Dietary Supplement Use among Older Cancer Survivors: Socio-Demographic Associations, Supplement Types, Reasons for Use, and Cost.
    Harleen Kaur, Teri Hoenemeyer, Kelsey B Parrish, Wendy Demark-Wahnefried.
      Most Americans take dietary supplements (DSs) and use is even higher among cancer survivors. This secondary analysis seeks to identify types, reasons, and costs of supplements used by 367 older cancer survivors enrolled in the Harvest for Health vegetable gardening trial and evaluate associations between supplement intake and medical/socio-demographic factors. Descriptive statistics were used to identify supplement type and reasons for use. Average market price was used to estimate cost. Fifty-nine percent of the sample reported supplement use. Female (OR 2.11, 95% CI 1.35-3.30), non-Hispanic White (OR 1.77, 95% CI 1.05-3.0), and breast and gynecological survivors (OR 1.57, 1.03-2.38) were significantly more likely to report DS use compared to males, minorities, and survivors of other cancers. Use of vitamins (39%), multivitamins (23%), and minerals (12%) were the most prevalent. Commonly reported reasons for supplement use were to improve general health (47%) or treat medical conditions (39%) and cancer-related symptoms (12%). DSs daily costs ranged from USD 0.02 to 19.81, with a mean of USD 1.28 ± 1.74, a median of USD 0.78, and a mode of USD 0.34. DS use is prevalent among older cancer survivors, with overall health reported as the leading reason for use. Out-of-pocket recurrent costs can be substantial and underscore the need to promote a nutrient-rich diet whenever possible in this vulnerable population.
    Keywords:  aging; cancer survivors; supplements; vitamins
    DOI:  https://doi.org/10.3390/nu14163402
  201. Cell Mol Biol (Noisy-le-grand). 2022 Mar 31. 68(3): 34-42
    Preparation and characterization of chloridazon-loaded alginate/chitosan nanocapsules.
    Sajjad Babaei, Danial Kahrizi, Iraj Nosratti, Naser Karimi, Elham Arkan, M B Tahir.
      In addition to the detrimental environmental effects of herbicides, including the pollution of soil, atmosphere, groundwater aquifers and run-off water, the lack of caution and direct or indirect exposure to these products can cause short-term and long-term human health effects. However, nanotechnology, with its many applications, can be very helpful in improving agriculture and reducing the side effects of chemicals used in agriculture. Nano-encapsulation of chemicals used in agriculture is one of the strategies to improve precision agriculture. Nano-encapsulated herbicides are controlled membrane systems in which the active ingredient is coated with semi-permeable membranes, which may be organic or inorganic polymers. In our study, chloridazon herbicide was selected as the active ingredient for Nano-encapsulation. Like many other agricultural herbicides, the major problem with this herbicide is environmental pollution and its adverse health effects. The ionic gelation method was used to synthesize nanocapsules consisting of alginate and chitosan for chloridazon encapsulation. Alginate-chitosan nanoparticles were prepared in a two-step process involving the ionotropic pre-gelation of an alginate core and then the formation of a chitosan polyelectrolyte complex. The alginate-chitosan nanocapsules containing chloridazon were synthesized at a size of 253 nm with a polydispersity index (PDI) of 0.266 and a zeta potential of -1.43 mV. The loading capacity and entrapment efficiency of these nanocapsules were 14% and 57%, respectively. The study of chloridazon release from formulated alginate-chitosan nanocapsules was performed using dialysis tube testing and UV spectroscopy. The results of our study showed controlled release of chloridazon from loaded alginate-chitosan nanocapsules. In general, alginate-chitosan nanocapsules as a Nano-carrier, have the potential to become a commercial formulation for chloridazon encapsulation. On the other hand, controlled release and increasing the duration of action of chloridazon, along with reducing the required dose, is promising in reducing the adverse health and environmental effects caused by chloridazon and improving precision agriculture.
    DOI:  https://doi.org/10.14715/cmb/2022.68.3.5
  202. Colloids Surf B Biointerfaces. 2022 Aug 17. pii: S0927-7765(22)00464-7. [Epub ahead of print]218 112781
    Glycyrrhetinic acid proliposomes mediated by mannosylated ligand: Preparation, physicochemical characterization, environmental stability and bioactivity evaluation.
    Jing Chen, Yuan Lin, Min Wu, Chuangnan Li, Kaijie Cen, Fujin Liu, Yazhi Liao, Xiaoqing Zhou, Jucai Xu, Yi Cheng.
      Glycyrrhetinic acid is a bioactive compound extracted from licorice that exhibits inhibition effect on various cancers. However, its hydrophobicity results in low bioavailability that limits application. We aim to overcome this barrier, the present research was performed to prepare glycyrrhetinic acid proliposomes mediated mannosylated ligand (mannose-diester lauric diacid-cholesterol, MDC) and to evaluate its physicochemical characterizations, environmental stability and bioactivity. In preliminary optimization studies of glycyrrhetinic acid proliposomes mediated MDC (MDC-GA-PL), four optimum operating parameters, cryoprotectant of glucose and mannitol, the mixed cryoprotectant ratio (glucose/mannitol) of 1:1, a cryoprotectant/egg phosphatidylcholine mass ratio of 10/1, and -60 ℃ pre-freezing temperature, were obtained after investigation. Under the optimum lyophilization conditions, MDC-GA-PL was freeze-dried and reconstituted proliposomes were characterized. These proliposomes showed that MDC-GA-PL were well-dispersible spherical particles with an average particle size of 120.80 nm, a polydispersity index about 0.095, a zeta potential of -33.15 mV, encapsulation efficiency of 85.9% and drug loading of 6.38%. In vitro drug release study showed that glycyrrhetinic acid release of MDC-GA-PL conforms to the Higuchi release model. In addition, these proliposomes were stable during six months at 4 ℃. Moreover, acute toxicity assay revealed no substantial safety concern for MDC-GA-PL. Finally, in vitro bioactivity of proliposomes was evaluated. Cytotoxicity effect and apoptosis efficiency of MDC-GA-PL by HepG2 cells was significantly higher than that of glycyrrhetinic acid proliposomes without MDC, demonstrating that MDC has a desirable effect on liver target. Overall, we have reason to believe that MDC-GA-PL would be a promising target delivery to improve therapeutic against hepatic diseases.
    Keywords:  Bioactivity evaluation; Glycyrrhetinic acid proliposomes; Lyophilization; Mannosylated ligand; Stability assay
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112781
  203. Environ Toxicol. 2022 Aug 27.
    The toxicity mechanism of glabridin in prostate cancer cells is involved in reactive oxygen species-dependent PI3K/Akt pathway: Integrated utilization of bioinformatic analysis and in vitro test validation.
    Fengyan Zhang, Fufang Wang, Wenjie Li, Liping Liang, Xicheng Sang.
      Glabridin is a prenylated isoflavonoid with considerable anticancer property. Reactive oxygen species (ROS) have evolved as regulators of many cellular signaling pathways in prostate cancer (PC). However, the role of ROS signaling in the anticancer activity of glabridin has not been investigated. Here, we attempted to evaluate the effect of glabridin on PC and the involvement of ROS signaling. Intracellular ROS and mitochondrial ROS (mitoROS) production in PC cell lines, DU-145 and LNCaP, were measured by H2DCFDA and MitoSOX Red staining, respectively. MTT assay was used to analyze the cellular viability. EdU staining assay was conducted to analyze the cell proliferation. To analyze apoptotic rate, TUNEL assay was performed. Caspase-3 activity was detected to reflect cell apoptosis. Western blot was carried out to detect the expression levels of Akt and p-Akt. We found that intracellular ROS and mitoROS levels were dose-dependently upregulated after glabridin treatment in both DU-145 and LNCaP cells, which was reversed by the treatment of ROS inhibitor, N-acetyl-L-cysteine (NAC). Glabridin inhibited the cell viability and reduced the number of EdU-positive DU-145 and LNCaP cells, which were respectively proved by MTT assay and EdU staining assay. Glabridin promoted cell death with increased apoptotic rate and caspase-3 activity in DU-145 and LNCaP cells. The effects of glabridin on cell proliferation and apoptosis were reversed by NAC. Moreover, glabridin suppressed the ratio of p-Akt/Akt, while NAC mitigated the decreased p-Akt/Akt ratio. In addition, the effects of glabridin on cell proliferation and apoptosis were also attenuated by Akt activator, SC79. Collectively, our results demonstrated that glabridin suppressed proliferation and induced apoptosis in PC cells via regulating ROS-mediated PI3K/Akt pathway. These findings suggested that glabridin might hold a promising prospective as a therapeutic agent against PC.
    Keywords:  Akt; ROS; glabridin; prostate cancer
    DOI:  https://doi.org/10.1002/tox.23649
  204. Neurosci Lett. 2022 Aug 23. pii: S0304-3940(22)00416-5. [Epub ahead of print] 136855
    Cannabidiol attenuates hypersensitivity and oxidative stress after traumatic spinal cord injury in rats.
    Verónica Baron-Flores, Araceli Diaz-Ruiz, Jorge Manzanares, Camilo Rios, Masha Burelo, Gustavo Jardon-Guadarrama, María de Los Ángeles Martínez-Cárdenas, Alfonso Mata-Bermudez.
      Neuropathic pain (NP) arises as a direct consequence of traumatic spinal cord injury (SCI), which leads to devastating consequences for people suffering from this condition since no specific treatment has been defined. One relevant mechanism in generating painful stimuli involves the direct participation of reactive oxygen species (ROS) at the cellular and subcellular levels. Cannabidiol (CBD) is one of the two most crucial cannabinoid components of the cannabis plant and has been proposed as a potential treatment for NP. Its antioxidant, neuroprotective and anti-inflammatory properties have been documented. However, there is insufficient evidence regarding CBD as treatment of NP induced by SCI or the mechanisms that underlie this effect. In this study, we evaluated the antinociceptive effect of CBD as an acute treatment after the nociceptive behaviors characteristic of NP were established (hypersensitivity threshold and hypersensitivity response). Furthermore, the participation of oxidative stress was determined by lipid peroxidation (LP) and glutathione concentration (GSH) in female Wistar rats with SCI. Acute treatment with CBD (2.5-20 mg/kg, i.p.) decreased nociceptive behaviors in a dose-dependent manner, decreased LP, and increased GSH concentration in injured tissue 15 days after injury. The findings of this study suggest that the antinociceptive effect induced by CBD is regulated by reducing oxidative stress by decreasing the LP and increasing the concentration of antioxidant (GSH) defenses.
    Keywords:  Cannabidiol; Hypersensitivity response; Hypersensitivity threshold; Neuropathic pain; Oxidative Stress; Spinal cord injury
    DOI:  https://doi.org/10.1016/j.neulet.2022.136855
  205. Crit Rev Food Sci Nutr. 2022 Aug 23. 1-24
    Virgin coconut oil: A comprehensive review of antioxidant activity and mechanisms contributed by phenolic compounds.
    Yu-Qing Zeng, Jin-Tao He, Bo-Yong Hu, Wen Li, Jing Deng, Qin-Lu Lin, Yong Fang.
      Virgin coconut oil (VCO) is obtained by processing mature coconut cores with mechanical or natural methods. In recent years, VCO has been widely used in the food, pharmaceutical, and cosmetic industries because of its excellent functional activities. VCO has biological functions such as antioxidant, anti-inflammatory, antibacterial, and antiviral, and also has potential therapeutic effects on many chronic degenerative diseases. Among these functions, the antioxidant is the most basic and important function, which is mainly determined by phenolic compounds and medium-chain fatty acids (MCFAs). This review aims to elucidate the antioxidant functions of each phenolic compound in VCO, and discuss the antioxidant mechanisms of VCO in terms of the role of phenolic compounds with fat, intestinal microorganisms, and various organs. Besides, the composition of VCO and its application in various industries are summarized, and the biological functions of VCO are generalized, which should lay a foundation for further research on the antioxidant activity of VCO and provide a theoretical basis for the development of food additives with antioxidant activity.
    Keywords:  Virgin coconut oil; antioxidant; mechanism; phenolic compounds
    DOI:  https://doi.org/10.1080/10408398.2022.2113361
  206. Food Funct. 2022 Aug 24.
    Antioxidant and pro-oxidant phytochemicals in ultrasound and microwave assisted extracts from hop cones: a statistical modelling approach.
    Ileana Ramazzina, Valentina Macchioni, Katya Carbone.
      The present study investigated the relationships between different green extracts from hop cones (HGEs) and their cytoprotective/cytotoxic effects on human cultured colonocytes, using a multivariate statistical approach. HGEs were obtained by ultrasound (US) and microwave (MW) assisted extraction, using food grade solvents (ethanol and ethanol : water = 50 : 50 mixture). Their chemical fingerprinting showed the presence of 21 bioactive compounds belonging to the classes of polyphenols, prenylcalcones and floroacylglucinols, which were more abundant in MW ethanolic extracts. All the extracts, except for the US hydroalcoholic one, exerted a cytotoxic effect in a dose-dependent manner. HGEs did not alter the cellular redox status at low doses, while at the highest concentrations considered they displayed a pro-oxidant or antioxidant activity. Chemometric analysis revealed the compounds most correlated with cellular toxicity and/or ROS production and that the differences observed in Caco2 cells could be adequately explained by 2D statistical models including inhibitor-promoting agent pairs.
    DOI:  https://doi.org/10.1039/d2fo02020c
  207. Recent Pat Biotechnol. 2022 Aug 20.
    Bioactive polysaccharides from microalgae: A close look at the biomedical applications.
    Mariany C Depra, Rosangela R Dias, Mariana M Maroneze, Tatiele C Nascimento, Ihana A Severo, Leila Q Zepka, Eduardo Jacob-Lopes.
      There is a current tendency towards bioactive natural products that can be used in different areas such as food, pharmaceutical, and biomedical. In the last decades, the polysaccharides have attracted an increasing interest because of the potent nontoxic effects, therapeutic properties, and the diversified range of applications. Polysaccharides are complex and heterogeneous macromolecules, constituted of different monosaccharides, and in some cases of glucuronic acid and sulphate groups. Polysaccharides with biological activity can be derived from plants, animals and microorganisms, especially microalgae. Microalgae are considered one of most promising source of these compounds that have already proved to have several important biological properties. In this sense, our objective is to elucidate the use of bioactive polysaccharides from microalgae in biomedical applications, emphasizing the biological activity of these compounds. Furthermore, the microalgal biomass production systems and polysaccharides extraction methods were presented and discussed.
    Keywords:  Algae; bioactive compounds; biological activity; exopolysaccharides.; natural products; sulphated polysaccharides
    DOI:  https://doi.org/10.2174/1872208316666220820092643
  208. Biomed Opt Express. 2022 Jul 01. 13(7): 3939-3953
    Hybrid laser activated phycocyanin/capecitabine treatment of cancerous MCF7 cells.
    Sahar Jahdi Abdollahi, Parviz Parvin, Sara Mayahi, Solaleh Seyedi, Parnian Mohsenian, Fatemeh Ramezani.
      Laser-induced fluorescence is recently used as an efficient technique in cancer diagnosis and non-invasive treatment. Here, the synergic therapeutical efficacies of the Capecitabine (CAP) chemodrug, photosensitive Phycocyanin (PC) and graphene oxide (GO) under laser irradiation were investigated. The therapeutical efficacies of diverse concentrations of CAP (0.001-10 mg/ml) and PC (0.5-10 mg/ml) alone and with laser irradiation on human breast adenocarcinoma (MCF-7) cells were examined. The interactional effects of 100 mW SHG Nd:YAG laser at 532nm and GaAs laser at 808 nm ranging power of 150 mW- 2.2W were considered. The contribution of graphene oxide (GO) in biocompatible concentrations of 2.5-20 ng/ml and thermal characteristics of laser exposure at 808 nm on GO + fluorophores have been studied. The effects of the bare and laser-excited CAP + PC on cell mortality have been obtained. Despite the laser irradiation could not hold up the cell proliferation in the absence of drug interaction considerably; however, the viability of the treated cells (by a combination of fluorophores) under laser exposure at 808 nm was significantly reduced. The laser at 532 nm excited the fluorescent PC in (CAP + PC) to trigger the photodynamic processes via oxygen generation. Through the in-vitro experiments of laser-induced fluorescence (LIF) spectroscopy of PC + CAP, the PC/CAP concentrations of the maximum fluorescence signal and spectral shifts have been characterized. The synergic effects of the laser exposures and (CAP + PC) treatment at different concentrations were confirmed. It has been shown here that the laser activation of (CAP + PC) can induce the mortality of the malignant cells by reducing the chemotherapeutic dose of CAP to avoid its non-desirable side effects and by approaching the minimally invasive treatment. Elevation of the laser intensity/exposure time could contribute to the therapeutic efficacy. Survival of the treated cells with a combination of GO and fluorophores could be reduced under laser exposure at 808 nm compared to the same combination therapy in the absence of GO. This survey could benefit the forthcoming clinical protocols based on laser spectroscopy for in-situ imaging/diagnosis/treatment of adenocarcinoma utilizing PC + CAP + GO.
    DOI:  https://doi.org/10.1364/BOE.459737
  209. Pharmaceuticals (Basel). 2022 Jul 29. pii: 944. [Epub ahead of print]15(8):
    The Role of Myrrh Metabolites in Cancer, Inflammation, and Wound Healing: Prospects for a Multi-Targeted Drug Therapy.
    Rasha Saad Suliman, Sahar Saleh Alghamdi, Rizwan Ali, Dimah Aljatli, Norah Abdulaziz Aljammaz, Sarah Huwaizi, Rania Suliman, Khawla Mohammed Kahtani, Ghadeer M Albadrani, Tlili Barhoumi, Abdulelah Altolayyan, Ishrat Rahman.
      BACKGROUND: Myrrh extract is a well-known medicinal plant with significant therapeutic benefits attributed to the activity of its diverse metabolites. It has promising activity against cancer and inflammatory diseases, and could serve as a potential therapeutic alternative since most therapeutic agents have severe side effects that impair quality of life.METHOD: The current study identified the active metabolites from the myrrh resin methanolic extract. Then, the extracts were tested for in vitro anti-inflammatory and anti-cancer activity using cancer cell lines and Tamm-Horsfall Protein 1 (Thp-1)-like macrophage cell lines. Furthermore, using an in vivo rat model, the extracts' anti-inflammatory and wound-healing activity was investigated. In addition, in silico predictions of the myrrh constituents highlighted the pharmacokinetic properties, molecular targets, and safety profile, including cytochrome P 450 (CYP) inhibition and organ toxicity.
    RESULTS: Nine secondary metabolites were identified, and computational predictions suggested a good absorption profile, anticancer, anti-inflammatory, and wound-healing effects. The myrrh extract had moderate cytotoxic activity against both HL60 and K562 leukemia cell lines and the KAIMRC1 breast cancer cell line. Myrrh caused a dose-dependent effect on macrophages to increase the reactive oxygen species (ROS) levels, promote their polarization to classically activated macrophages (M1) and alternatively activated macrophages (M2) phenotypes, and consequently induce apoptosis, highlighting its ability to modulate macrophage function, which could potentially aid in several desired therapeutic processes, including the resolution of inflammation, and autophagy which is an important aspect to consider in cancer treatment. The topical application of myrrh improved wound healing, with no delayed inflammatory response, and promoted complete re-epithelization of the skin, similar to the positive control. In conclusion, we provide evidence for the methanolic extract of myrrh having cytotoxic activity against cancer cells and anti-inflammatory wound-healing properties, which may be attributed to its role in modulating macrophage function. Furthermore, we suggest the active constituents responsible for these properties, which warrants further studies focusing on the precise roles of the active metabolites.
    Keywords:  ADME 7; breast cancer 6; computational activity predictions 3; in vivo anti-inflammatory 2; leukemia 5; myrrh resin methanolic extract 1; natural products 4; target prediction 8
    DOI:  https://doi.org/10.3390/ph15080944
  210. J Ethnopharmacol. 2022 Aug 18. pii: S0378-8741(22)00689-4. [Epub ahead of print]298 115650
    A comprehensive review on ethnopharmacological, phytochemical, pharmacological and toxicological evaluation, and quality control of Pinellia ternata (Thunb.) Breit.
    Jing Bai, Jianbo Qi, Li Yang, Zhengtao Wang, Rui Wang, Yanhong Shi.
      ETHNOPHARMACOLOGICAL RELEVANCE: Pinellia ternata tuber (PTT), the dried tuber of Pinellia ternata (Thunb.) Breit., has a long history of use in traditional Chinese medicine for drying dampness, resolving phlegm, down-bearing counterflow to check vomiting and dissipating masses. Modern pharmacology studies have revealed that PTT has diverse pharmacological effects such as antitussive and expectorant, anti-emetic, anti-tumor, and anti-inflammatory effect, etc. AIM OF THE REVIEW: This review aims to provide a critical and comprehensive evaluation on ethnopharmacological uses, chemical constituents, pharmacological and toxicological effects, analytical methods and quality control of PTT, which would provide scientific evidence for exploring future therapeutic, and formulating quality and safety criteria of PTT.MATERIALS AND METHODS: Pertinent information was systematically collected from several electronic scientific databases including Web of Science, Science Direct, PubMed, Elsevier, Wiley Online Library and China national knowledge infrastructure (CNKI), as well as the classic Chinese medical books.
    RESULTS: PTT is reported to be widely used traditionally for the treatment of cough, vomiting, infection, and inflammatory diseases in many southeast Asian countries. Phytochemical studies have revealed the presence of a total of 233 compounds belonging to alkaloids, nucleosides, organic acids, polysaccharides, volatile oils, amino acids, proteins, starches, etc. The extracts and components of PTT have possessed diverse pharmacological activities, such as antitussive, antiemetic, antitumor, antibacterial, and sedative-hypnotic activities. Raw P. ternata tuber (RPTT) with a pungent taste causes acrid irritation of the oral and laryngopharynx mucosa when taken by mistake, while its toxicity and side effects of RPTT can be dramatically reduced with proper processing. Three kinds of processed P. ternata tuber with different processing methods are available and traded in market, as well as applied in clinical treatments. Additionally, although raw or processed PTT have been recorded in several mainstream pharmacopoeias such as Chinese Pharmacopoeia, Japanese Pharmacopoeia, and Korean Pharmacopoeia, the quality items and requirements varies a lot. Therefore, a unified international standard of raw and processed PTT is urgent need to be done.
    CONCLUSIONS: The ethnopharmacological, phytochemical, pharmacological and toxicological and quality evaluation of PTT were highlighted in this review, which provides potential reference information to future investigate and commercially explore for pharmaceutical applications. Nevertheless, an efficient method for chemical profiling is still unavailable to find potent bioactive markers for quality control, and then comprehensive pharmacological effects and mechanisms and toxicological evaluation of PTT require further detailed research to ensure their quality and safety.
    Keywords:  Ethnopharmacological uses; Pharmacological applications; Phytochemicals; Pinellia ternata tuber; Quality evaluation; Toxicology
    DOI:  https://doi.org/10.1016/j.jep.2022.115650
  211. Oxid Med Cell Longev. 2022 ;2022 1366957
    Lysionotin Induces Ferroptosis to Suppress Development of Colorectal Cancer via Promoting Nrf2 Degradation.
    Zhuo Gao, Junnan Jiang, Lijian Hou, Fujian Ji.
      Extensive use of substances derived from natural sources has been documented in the treatment of colorectal cancer (CRC). Lysionotin (Lys) is a flavonoid present in the flowers and leaves of Gesneriaceae family plants. Despite its various pharmacological properties, which include neuroprotective, pro, antimalarial, and anticancer effects, the therapeutic advantages of Lys for CRC remain uncertain. In this present study, we demonstrated that Lys treatment successfully inhibited cell proliferation, migration, and invasion in HCT116 and SW480 CRC cells in vitro. Intriguingly, significant ferroptosis and reactive oxygen species (ROS) accumulation in CRC cells were induced by Lys treatment, whereas antagonism of ferroptosis by Liproxstatin-1 (Lip1) pretreatment retarded the anti-CRC effects of Lys. In addition, Lys reduced the amount of Nrf2 protein in CRC cells by increasing the rate at which it is degraded. Overexpression of Nrf2 rescued Lys reduced ferroptosis, suggesting the Nrf2 signaling is a crucial determinant of whether Lys induces ferroptosis in CRC cells. We also revealed that Lys suppressed tumor growth in vivo without obvious adverse effects on the main organs of mice. In conclusion, our results discovered that Lys treatment induced ferroptosis to exert antitumor effects in HCT116 and SW480 CRC cells by modulating Nrf2 signaling, providing a potential therapeutic approach for the prevention of colorectal cancer.
    DOI:  https://doi.org/10.1155/2022/1366957
  212. Integr Cancer Ther. 2022 Jan-Dec;21:21 15347354221117776
    Combined Effects of Tanshinone IIA and an Autophagy Inhibitor on the Apoptosis of Leukemia Cells via p53, Apoptosis-Related Proteins and Oxidative Stress Pathways.
    Ying-Chyi Song, Cheng-Chieh Kuo, Chuan-Teng Liu, Tsai-Chen Wu, Yi-Ting Kuo, Hung-Rong Yen.
      BACKGROUND: Acute myeloid leukemia (AML) is a kind of hematopoietic malignancy with limited response and acquired resistance to therapy. Inducing apoptosis and inhibiting autophagy in tumor cells is a combinational strategy for the development of anticancer therapeutics. Tanshinone IIA (TAIIA) is one of the major ingredients in Salvia miltiorrhiza, which is the most prescribed herb for the treatment of AML in Taiwan. Therefore, this study aimed to delineate the anticancer effects of TAIIA and its effect when combined with an autophagy inhibitor to treat AML.METHODS: The anticancer effects of a combination of TAIIA and the autophagy inhibitor 3-methladenine (3MA) on the human monocytic leukemia cell line THP-1 were explored. The apoptosis and cell cycle of the leukemia cells were examined by Annexin V and propidium iodide staining and analyzed by flow cytometry. The oxidative stress level was determined by a malondialdehyde (MDA) colorimetric assay, nitric oxide colorimetric assay and glutathione peroxidase (GPx) colorimetric assay. The expression of apoptosis-related proteins was determined by western blotting.
    RESULTS: TAIIA treatment significantly induced apoptosis via increased p53, Bax/Bcl, PARP, and caspase-3 signals and oxidative stress by enhancing MDA and nitrate/nitrite production and reducing GPx activity in THP-1 cells in a dose-dependent and time-dependent manner. The combination of the autophagy inhibitor 3MA enhanced TAIIA-induced apoptosis via the p53, Bax/Bcl, PARP, caspase-3, and oxidative stress pathways in THP-1 cells.
    CONCLUSION: The results suggest that TAIIA and autophagy inhibitors have combined effects on the apoptosis of leukemia cells, thus representing a novel and effective combination with the potential for application as a clinical therapy for AML.
    Keywords:  acute myeloid leukemia (AML); apoptosis; autophagy; oxidative stress; tanshinone IIA; traditional Chinese medicine
    DOI:  https://doi.org/10.1177/15347354221117776
  213. Nutrients. 2022 Aug 17. pii: 3367. [Epub ahead of print]14(16):
    Nootropics as Cognitive Enhancers: Types, Dosage and Side Effects of Smart Drugs.
    Matěj Malík, Pavel Tlustoš.
      Nootropics, also known as "smart drugs" are a diverse group of medicinal substances whose action improves human thinking, learning, and memory, especially in cases where these functions are impaired. This review provides an up-to-date overview of the potential effectiveness and importance of nootropics. Based on their nature and their effects, this heterogeneous group of drugs has been divided into four subgroups: classical nootropic compounds, substances increasing brain metabolism, cholinergic, and plants and their extracts with nootropic effects. Each subgroup of nootropics contains several main representatives, and for each one, its uses, indications, experimental treatments, dosage, and possible side effects and contraindications are discussed. For the nootropic plant extracts, there is also a brief description of each plant representative, its occurrence, history, and chemical composition of the medicinal part. Lastly, specific recommendations regarding the use of nootropics by both ill and healthy individuals are summarized.
    Keywords:  Panax ginseng; Paullinia cupana; antioxidant activity; ayurvedic; brain injury; learning; memory; nootropics; piracetam; smart drugs
    DOI:  https://doi.org/10.3390/nu14163367
  214. Mar Drugs. 2022 Jul 28. pii: 487. [Epub ahead of print]20(8):
    Microalgae Photo-Protectants and Related Bio-Carriers Loaded with Bioactive Entities for Skin Applications-An Insight of Microalgae Biotechnology.
    Berenice Santiesteban-Romero, Manuel Martínez-Ruiz, Juan Eduardo Sosa-Hernández, Roberto Parra-Saldívar, Hafiz M N Iqbal.
      Microalgae are photosynthetic organisms known for producing valuable metabolites under different conditions such as extreme temperatures, high salinity, osmotic pressure, and ultraviolet radiation. In recent years, these metabolites have become a trend due to their versatility in applications such as pharmaceuticals, cosmetics, and others. They have even been proposed as an alternative source of bioactive metabolites to avoid the harmful effects on the environment produced by active compounds such as oxybenzone in commercials sunscreens. One of the most studied applications is the use of microalgae for skin care and topical use as cosmeceuticals. With the increasing demand for more environmentally friendly products in cosmetics, microalgae have been further explored in relation to this application. It has been shown that some microalgae are resistant to UV rays due to certain compounds such as mycosporine-like amino acids, sporopollenin, scytonemin, and others. These compounds have different mechanisms of action to mitigate UV damage induced. Still, they all have been proven to confer UV tolerance to microalgae with an absorbance spectrum like the one in conventional sunscreens. This review focuses on the use of these microalgae compounds obtained by UV stimulation and takes advantage of their natural UV-resistant characteristics to potentially apply them as an alternative for UV protection products.
    Keywords:  MAAs; bio-carriers; biomedical application; microalgae; photo protectants; scytonemin; sporopollenin
    DOI:  https://doi.org/10.3390/md20080487
  215. Cancers (Basel). 2022 Aug 19. pii: 4011. [Epub ahead of print]14(16):
    Bisphenols A and S Alter the Bioenergetics and Behaviours of Normal Urothelial and Bladder Cancer Cells.
    Ève Pellerin, Félix-Antoine Pellerin, Stéphane Chabaud, Frédéric Pouliot, Stéphane Bolduc, Martin Pelletier.
      Bisphenol A (BPA) and bisphenol S (BPS) are used in the production of plastics. These endocrine disruptors can be released into the environment and food, resulting in the continuous exposure of humans to bisphenols (BPs). The bladder urothelium is chronically exposed to BPA and BPS due to their presence in human urine samples. BPA and BPS exposure has been linked to cancer progression, especially for hormone-dependent cancers. However, the bladder is not recognized as a hormone-dependent tissue. Still, the presence of hormone receptors on the urothelium and their role in bladder cancer initiation and progression suggest that BPs could impact bladder cancer development. The effects of chronic exposure to BPA and BPS for 72 h on the bioenergetics (glycolysis and mitochondrial respiration), proliferation and migration of normal urothelial cells and non-invasive and invasive bladder cancer cells were evaluated. The results demonstrate that chronic exposure to BPs decreased urothelial cells' energy metabolism and properties while increasing them for bladder cancer cells. These findings suggest that exposure to BPA and BPS could promote bladder cancer development with a potential clinical impact on bladder cancer progression. Further studies using 3D models would help to understand the clinical consequences of this exposure.
    Keywords:  bisphenol A; bisphenol S; bladder cancer; energy metabolism; migration; proliferation
    DOI:  https://doi.org/10.3390/cancers14164011
  216. Gels. 2022 Aug 09. pii: 494. [Epub ahead of print]8(8):
    Chitosan Grafted Poly (Ethylene Glycol) Methyl Ether Acrylate Particulate Hydrogels for Drug Delivery Applications.
    Corina-Lenuța Logigan, Christelle Delaite, Crina-Elena Tiron, Cristian Peptu, Marcel Popa, Cătălina Anișoara Peptu.
      Chitosan (CS) crosslinking has been thoroughly investigated, but the chemical reactions leading to submicronic hydrogel formulations pose problems due to various physical/chemical interactions that limit chitosan processability. The current study employs the chemical modification of chitosan by Michael addition of poly (ethylene glycol) methyl ether acrylate (PEGA) to the amine groups to further prepare chitosan particulate hydrogels (CPH). Thus, modified CS is subjected to a double crosslinking, ionic and covalent, in water/oil emulsion. The studied process parameters are polymer concentration, stirring speed, and quantity of ionic crosslinker. The CPH were structurally and morphologically characterized through infrared spectroscopy, scanning electron microscopy, light scattering granulometry, and zeta potential, showing that modified CS allows better control of dimensional properties and morphology as compared with neat CS. Swelling properties were studied in acidic and neutral pH conditions, showing that pH-dependent behavior was maintained after grafting and double crosslinking. The applicability of the prepared materials was further tested for drug loading and in vitro delivery of levofloxacin (LEV), showing excellent capacity. CPH were found to be cyto- and hemocompatible demonstrating their potential for effective use as a controlled release system for different biomedical applications.
    Keywords:  biomedical applications; chitosan particulate hydrogels; double crosslinking; levofloxacin; poly (ethylene glycol) methyl ether acrylate
    DOI:  https://doi.org/10.3390/gels8080494
  217. Int J Mol Sci. 2022 Aug 20. pii: 9404. [Epub ahead of print]23(16):
    Functionalized Platinum Nanoparticles with Biomedical Applications.
    Sagrario Yadira Gutiérrez de la Rosa, Ramiro Muñiz Diaz, Paola Trinidad Villalobos Gutiérrez, Rita Patakfalvi, Óscar Gutiérrez Coronado.
      Functionalized platinum nanoparticles have been of considerable interest in recent research due to their properties and applications, among which they stand out as therapeutic agents. The functionalization of the surfaces of nanoparticles can overcome the limits of medicine by increasing selectivity and thereby reducing the side effects of conventional drugs. With the constant development of nanotechnology in the biomedical field, functionalized platinum nanoparticles have been used to diagnose and treat diseases such as cancer and infections caused by pathogens. This review reports on physical, chemical, and biological methods of obtaining platinum nanoparticles and the advantages and disadvantages of their synthesis. Additionally, applications in the biomedical field that can be utilized once the surfaces of nanoparticles have been functionalized with different bioactive molecules are discussed, among which antibodies, biodegradable polymers, and biomolecules stand out.
    Keywords:  biomedical applications; functionalized nanoparticles; nanomedicine; platinum nanoparticles
    DOI:  https://doi.org/10.3390/ijms23169404
  218. Toxicon. 2022 Aug 20. pii: S0041-0101(22)00241-0. [Epub ahead of print]217 131-142
    Anticancer potential and toxicity of the genus Handroanthus Mattos (Bignoniaceae): A systematic review.
    José Jailson Lima Bezerra, Isabella Johanes, Anderson Angel Vieira Pinheiro.
      The genus Handroanthus Mattos (Bignoniaceae) is widely used for the treatment of cancer in traditional medicine in Brazil and other South American countries. The anticancer potential of species of this genus has been reported in the literature, indicating that their chemical compounds may be effective against different tumor cell lines. In this perspective, the present study aimed to conduct a systematic review of ethnobotanical, pharmacological, phytochemical and toxicological information on Handroanthus species related to cancer treatment. Searches were conducted in the Google Scholar, PubMed®, ScienceDirect® and SciELO databases. A total of 78 articles published in the last thirty-two years (1990-2022) were eligible and included in the review. According to the scientific documents analyzed, five species of Handroanthus are widely used for the treatment of cancer in the traditional medicine of Brazil and other South American countries, including Bolivia and Argentina. The bark (88%) is the main part used in traditional preparations. Extracts and fractions from Handroanthus showed cytotoxicity against the following tumor cell lines: HL-60, MDA-MB-435, MDA-MB-231, MCF-7, HT-29, HCT-8, HCT-116, HEp-2, HepG2, CACO-2, SF-295, NCI-H292, NCI-H460, HeLa, and OVCAR-8. β-Lapachone, a naphthoquinone isolated from some species of this genus, is the most investigated compound for anticancer potential and has proved effective against some lung cancer cell lines (CL1-1, CL1-5 and A549). Results related to toxicological studies were not conclusive, considering that some extracts and compounds isolated from plants of this genus may present some degree of toxicity depending on the time of use and the concentration/dose used. Thus, despite the promising effects against various cancer cell lines, caution is needed when making use of these products.
    Keywords:  Antitumor; Cytotoxicity; Ethnopharmacology; Medicinal plants; Naphthoquinones; Tabebuia
    DOI:  https://doi.org/10.1016/j.toxicon.2022.08.007
  219. Inflammopharmacology. 2022 Aug 21.
    The effect of statin therapy in combination with ezetimibe on circulating C-reactive protein levels: a systematic review and meta-analysis of randomized controlled trials.
    Seyyed Mostafa Arabi, Mahla Chambari, Mahsa Malek-Ahmadi, Leila Sadat Bahrami, Vahid Hadi, Manfredi Rizzo, Amirhossein Sahebkar.
      BACKGROUND: Previous studies have reported that statin or ezetimibe therapy has an anti-inflammatory effect. However, the results of individual studies on the effect of statin therapy in combination with ezetimibe on C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) levels have not been clear. Therefore, the present systematic review and meta-analysis were conducted on randomized clinical trials (RCTs) to evaluate the effect of statin therapy in combination with ezetimibe on CRP and hs-CRP levels.METHODS: A literature search was carried out on the MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases up to February 2022 to find eligible studies. The pooled effect sizes were considered for weighted mean difference (WMD) and 95% confidence intervals (CI) for CRP and hs-CRP, and it was also determined as standardized weighted mean difference (SMD) for overall CRP. For all variables, a random-effects model was used.
    RESULTS: Of the 57 studies included in the systematic review, 53 were used for meta-analysis. Statin therapy in combination with ezetimibe significantly reduced the serum levels of hs-CRP (WMD - 0.2 mg/l; 95% CI - 0.4, - 0.1, P ˂ 0.001) and overall CRP (SMD - 0.16 mg/l; 95% CI - 0.2, - 0.07, P ˂ 0.001). Nevertheless, CRP levels were not significantly changed by combination therapy. A significant association was observed between the serum low-density lipoprotein cholesterol (LDL-C) changes and hs-CRP levels, which can justify the source of heterogeneity.
    CONCLUSIONS: The current study showed that statin therapy in combination with ezetimibe could be effective in reducing the levels of hs-CRP and overall CRP.
    Keywords:  Atherosclerosis; CRP; Inflammation; Statins
    DOI:  https://doi.org/10.1007/s10787-022-01053-4
  220. J Agric Food Chem. 2022 Aug 25.
    Dietary Polyphenols Alleviate Autoimmune Liver Disease by Mediating the Intestinal Microenvironment: Challenges and Hopes.
    Zhen Cheng, Yuehua Wang, Bin Li.
      Autoimmune liver disease is a chronic liver disease caused by an overactive immune response in the liver that imposes a significant health and economic cost on society. Due to the side effects of existing medicinal medications, there is a trend toward seeking natural bioactive compounds as dietary supplements. Currently, dietary polyphenols have been proven to have the ability to mediate gut-liver immunity and control autoimmune liver disease through modulating the intestinal microenvironment. Based on the preceding, this Review covers the many forms of autoimmune liver illnesses, their pathophysiology, and the modulatory effects of polyphenols on immune disorders. Finally, we focus on how polyphenols interact with the intestinal milieu to improve autoimmune liver disease. In conclusion, we suggest that dietary polyphenols have the potential as gut-targeted modulators for the prevention and treatment of autoimmune liver disease and highlight new perspectives and critical issues for future pharmacological applications.
    Keywords:  autoimmune liver disease; dietary polyphenols; gut−liver axis; intestinal environment; liver; microbiome
    DOI:  https://doi.org/10.1021/acs.jafc.2c02654
  221. Sci Rep. 2022 Aug 23. 12(1): 14362
    Characterization of anti-proliferative and anti-oxidant effects of nano-sized vesicles from Brassica oleracea L. (Broccoli).
    Md Niamat Hossain, Vincenzo De Leo, Rosanna Tamborra, Onofrio Laselva, Chiara Ingrosso, Valeria Daniello, Lucia Catucci, Ilario Losito, Francesco Sollitto, Domenico Loizzi, Massimo Conese, Sante Di Gioia.
      In this in vitro study, we test our hypothesis that Broccoli-derived vesicles (BDVs), combining the anti-oxidant properties of their components and the advantages of their structure, can influence the metabolic activity of different cancer cell lines. BDVs were isolated from homogenized fresh broccoli (Brassica oleracea L.) using a sucrose gradient ultracentrifugation method and were characterized in terms of physical properties, such as particle size, morphology, and surface charge by transmission electron microscopy (TEM) and laser doppler electrophoresis (LDE). Glucosinolates content was assessed by RPLC-ESI-MS analysis. Three different human cancer cell lines (colorectal adenocarcinoma Caco-2, lung adenocarcinoma NCI-H441 and neuroblastoma SHSY5Y) were evaluated for metabolic activity by the MTT assay, uptake by fluorescence and confocal microscopy, and anti-oxidant activity by a fluorimetric assay detecting intracellular reactive oxygen species (ROS). Three bands were obtained with average size measured by TEM based size distribution analysis of 52 nm (Band 1), 70 nm (Band 2), and 82 nm (Band 3). Glucobrassicin, glucoraphanin and neoglucobrassicin were found mostly concentrated in Band 1. BDVs affected the metabolic activity of different cancer cell lines in a dose dependent manner compared with untreated cells. Overall, Band 2 and 3 were more toxic than Band 1 irrespective of the cell lines. BDVs were taken up by cells in a dose- and time-dependent manner. Pre-incubation of cells with BDVs resulted in a significant decrease in ROS production in Caco-2 and NCI-H441 stimulated with hydrogen peroxide and SHSY5Y treated with 6-hydroxydopamine, with all three Bands. Our findings open to the possibility to find a novel "green" approach for cancer treatment, focused on using vesicles from broccoli, although a more in-depth characterization of bioactive molecules is warranted.
    DOI:  https://doi.org/10.1038/s41598-022-17899-1
  222. Evid Based Complement Alternat Med. 2022 ;2022 4931556
    Ethnomedicinal Use, Phytochemistry, and Other Potential Application of Aquatic and Semiaquatic Medicinal Plants.
    Ashish Kumar Arya, Medha Durgapal, Arachna Bachheti, Deepti, Kamal Kant Joshi, Yilma H Gonfa, Rakesh Kumar Bachheti, Azamal Husen.
      Medicinal plants have been treating various ailments and diseases since ancient times. Aquatic and semiaquatic medicinal plants play an essential role in human welfare to fulfill their daily needs. They have shown biological, pharmacological, nutraceutical, and commercial applications. This review aims to collect and update all recent information on ethnomedicinal, phytochemistry, pharmacological activities, and nanoparticle synthesis and their uses in aquatic and semiaquatic medicinal plants. Original research papers, review papers, short communications, and book chapters on aquatic and semiaquatic plants have been retrieved from PubMed, Web of Science, Scopus, and Google Scholar. Keywords, ethnomedicinal studies, phytochemistry, pharmacological activities, and nanoparticle synthesis from aquatic and semiaquatic medicinal plants are used for the search. Different aquatic and semiaquatic medicinal plants belonging to the families Acanthaceae, Alismataceae, Amaranthaceae, Apiaceae, Araceae, Asteraceae, Boraginaceae, Ceratophyllaceae, Cyperaceae, Fabaceae, Hydrocharitaceae, Lythraceae, Marsileaceae, Menyanthaceae, Nelumbonaceae, Nymphaeaceae, Onagraceae, Plantaginaceae, Poaceae, Polygonaceae, Pontederiaceae, Primulaceae, Scrophulariaceae, and Zingiberaceae have been studied. They are rich in alkaloids, flavonoids, terpenoids, phenolics, saponins, tannins, dietary fiber, glycosidic derivatives, carbohydrates, and proteins. These phytochemicals have been used for their antimicrobial, antioxidant, hepatoprotective, sedative, anticonvulsant, cytotoxic, antiparasitic, and antidiabetic activities. Besides this, various parts of the plants are used as dietary supplements and green nanoparticle synthesis. These plants are also known for their commercial value and are used as an ingredient in some pharmaceutical industries.
    DOI:  https://doi.org/10.1155/2022/4931556
  223. Mar Drugs. 2022 Jul 27. pii: 482. [Epub ahead of print]20(8):
    Heteronemin and Tetrac Induce Anti-Proliferation by Blocking EGFR-Mediated Signaling in Colorectal Cancer Cells.
    Sukanya Unson, Tung-Cheng Chang, Yung-Ning Yang, Shwu-Huey Wang, Chi-Hung Huang, Dana R Crawford, Haw-Ming Huang, Zi-Lin Li, Hung-Yun Lin, Jacqueline Whang-Peng, Kuan Wang, Paul J Davis, Wen-Shan Li.
      Overexpressed EGFR and mutant K-Ras play vital roles in therapeutic resistance in colorectal cancer patients. To search for an effective therapeutic protocol is an urgent task. A secondary metabolite in the sponge Hippospongia sp., Heteronemin, has been shown to induce anti-proliferation in several types of cancers. A thyroxine-deaminated analogue, tetrac, binds to integrin αvβ3 to induce anti-proliferation in different cancers. Heteronemin- and in combination with tetrac-induced antiproliferative effects were evaluated. Tetrac enhanced heteronemin-induced anti-proliferation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC). Heteronemin and tetrac arrested cell cycle in different phases. Combined treatment increased the cell accumulation in sub-G1 and S phases. The combined treatment also induced the inactivation of EGFR signaling and downregulated the phosphorylated ERK1/2 protein in both cell lines. Heteronemin and the combination showed the downregulation of the phosphorylated and total PI3K protein in HT-29 cells (KRAS WT CRC). Results by NanoString technology and RT-qPCR revealed that heteronemin and combined treatment suppressed the expression of EGFR and downstream genes in HCT-116 cells (KRAS MT CRC). Heteronemin or combined treatment downregulated genes associated with cancer progression and decreased cell motility. Heteronemin or the combined treatment suppressed PD-L1 expression in both cancer cell lines. However, only tetrac and the combined treatment inhibited PD-L1 protein accumulation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC), respectively. In summary, heteronemin induced anti-proliferation in colorectal cancer cells by blocking the EGFR-dependent signal transduction pathway. The combined treatment further enhanced the anti-proliferative effect via PD-L1 suppression. It can be an alternative strategy to suppress mutant KRAS resistance for anti-EGFR therapy.
    Keywords:  EGFR signaling; KRAS; colorectal cancer; heteronemin; tetrac
    DOI:  https://doi.org/10.3390/md20080482
  224. Pharmaceutics. 2022 Aug 16. pii: 1711. [Epub ahead of print]14(8):
    A β-Sitosterol Encapsulated Biocompatible Alginate/Chitosan Polymer Nanocomposite for the Treatment of Breast Cancer.
    Obaid Afzal, Md Habban Akhter, Irfan Ahmad, Khursheed Muzammil, Adam Dawria, Mohammad Zeyaullah, Abdulmalik S A Altamimi, Habibullah Khalilullah, Shehla Nasar Mir Najib Ullah, Mohammad Akhlaquer Rahman, Abuzer Ali, Naiyer Shahzad, Mariusz Jaremko, Abdul-Hamid Emwas, Ibrahim Abdel Aziz Ibrahim.
      β-sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of β-sitosterol including lowering low-density lipoprotein and cholesterol levels, scavenging free radicals in the body, and interestingly, treating and preventing cancer. This study focuses on synthesizing and characterizing β-sitosterol encapsulated Alginate/Chitosan nanoparticles (β-sito-Alg/Ch/NPs) and evaluating their effectiveness in breast cancer treatment and their pharmacokinetic profile in vivo. The synthesized NPs, which incurred a mean size of 25 ± 1 nm, were extensively characterized in vitro for various parameters including surface charge and morphology. The NPs were further analyzed using DSC, FT-IR, thermogravimetry and X-ray diffraction studies. The release of β-sito from NPs was carried out in a bio-relevant medium of pH 7.4 and pH 5.5 and samples were drawn off and analyzed under time frames of 0, 8, 16, 32, 64, 48, 80, and 96 h, and the best kinetic release model was developed after fitting drug release data into different kinetic models. The metabolic activity of MCF-7 cells treated with the prepared formulation was assessed. The radical scavenging potential of β-sito-Alg/Ch/NPs was also studied. The pharmacokinetic parameters including Cmax, Tmax, half-life (t1/2), and bioavailability were measured for β-sito-Alg/Ch/NPs as compared to β-sito-suspension. The β-sito-Alg/Ch/NPs stability was assessed at biological pH 7.4. The % drug release in PBS of pH 7.4 reportedly has shown 41 ± 6% vs. 11 ± 1% from β-sito-Alg/Ch/NPs and β-sito-suspension. In acidic pH 5.5 mimicking the tumor microenvironment has shown 75 ± 9% vs. 12 ± 4% drug release from β-sito-Alg/Ch/NPs and β-sito-suspension. When compared to the β-sito-suspension, the β-sito-Alg/Ch/NPs demonstrated greater cytotoxicity (p &lt; 0.05) and ~3.41-fold higher oral bioavailability. Interestingly, this work demonstrated that β-sito-Alg/Ch/NPs showed higher cytotoxicity due to improved bioavailability and antioxidant potential compared to the β-sito-suspension.
    Keywords:  alginate; breast cancer; chitosan; nanoparticle; phytosterol; β–sitosterol
    DOI:  https://doi.org/10.3390/pharmaceutics14081711
  225. Nanoscale. 2022 Aug 24.
    Bio-polymeric transferrin-targeted temozolomide nanoparticles in gel for synergistic post-surgical GBM therapy.
    Puja Sandbhor, Jayant S Goda, Bhabani Mohanty, Pradip Chaudhari, Shilpee Dutt, Rinti Banerjee.
      Spatiotemporal targeting of anti-glioma drugs remains a pressing issue in glioblastoma (GBM) treatment. We challenge this issue by developing a minimally invasive in situ implantable hydrogel implant comprising transferrin-targeted temozolomide-miltefosine nanovesicles in the surgically resected GBM cavity (tumour bed). Injection of the "nanovesicle in hydrogel system" in orthotopic GBM-bearing mice improved drug penetration into the peri-cavitary region (∼4.5 mm in depth) with the potential to act as a bridge therapy in the immediate postoperative period, before the initiation of adjuvant radiotherapy. The controlled and sustained release of temozolomide over a month in the surgical cavity eradicated the microscopic GBM cells present within the tumour bed, thereby augmenting the efficacy of adjuvant therapy. The drug (temozolomide and miltefosine) combination was tolerable and efficiently inhibited tumour growth, causing significant prolongation of the survival of tumour-bearing mice compared to that with the free drug. Direct implantation at the target site in the brain resulted in spatiotemporal anti-glioma activity with minimal extracranial and systemic distribution. Nanovesicle in flexible hydrogel systems can be used as potential platforms for the post-surgical management of GBM before initiating adjuvant radiation therapy.
    DOI:  https://doi.org/10.1039/d2nr00171c
  226. Photodiagnosis Photodyn Ther. 2022 Aug 23. pii: S1572-1000(22)00368-4. [Epub ahead of print] 103082
    The role of autophagy in the treatment of colon cancer by chlorin e6 photodynamic therapy combined with Oxaliplatin.
    Mengyu Luo, Jiayin Ji, Kaizhen Yang, Hongxia Li, Ling Kang.
      BACKGROUND: Photodynamic therapy is a tumour treatment method that has emerged in recent years. Its mechanism mainly induces apoptosis, autophagy, and other ways to cause tumour cell death. Therefore, this study aims to evaluate the therapeutic effect of chlorine e6 photodynamic therapy (Ce6-PDT) combined with oxaliplatin (L-OHP) in colon cancer and to investigate the role of autophagy in L-OHP treatment and Ce6-PDT combined with L-OHP in colon cancer.METHODS: CCK-8 assay, Scratch wound healing assay, and Western Blot (WB) were used to identify drug-resistant colon cancer cell line SW620/L-OHP. Annexin V/FITC assay, laser confocal double immunofluorescence staining method and WB were employed to investigate the apoptosis and autophagy changes in Ce6-PDT combined with L-OHP.
    RESULTS: Drug resistance cells SW620/L-OHP were developed under the continuous multi-generation of L-OHP treatment, and the expression of ATP-binding cassette subfamily B member 1 (ABCB1) and ATG5 proteins were increased. The results of immunofluorescence showed that LC3B accumulated in SW620 cells and SW620/L-OHP cells under the treatment of L-OHP. The WB results indicated that LC3B and ATG5 protein expression was increasing in SW620 cells and SW620/L-OHP cells. Inhibition of L-OHP-induced autophagy reduces SW620 cells and SW620/L-OHP cells' viability while increasing apoptosis and the Pro Caspase-3 protein expression. The combination of Ce6-PDT and L-OHP decreased the cell viability, the cell migration ability, the Bcl-2 protein expression, and increased the apoptosis rate, Pro Caspase-3 protein expression in SW620 cells.
    CONCLUSIONS: L-OHP can cause SW620 cells drug resistance. Autophagy plays a protective role in the L-OHP treatment of SW620 cells and SW620/L-OHP cells, and inhibition of autophagy can increase the efficacy of L-OHP. Ce6-PDT combined with L-OHP can further improve the tumour's therapeutic effect, and autophagy inhibition can improve the efficacy of combined therapy.
    Keywords:  Colorectal cancer; Drug resistance; L-OHP; autophagy; photodynamic therapy
    DOI:  https://doi.org/10.1016/j.pdpdt.2022.103082
  227. Front Oncol. 2022 ;12 947479
    Mitochondria dysfunction in circulating tumor cells.
    Chiara Agnoletto, Stefano Volinia.
      Circulating tumor cells (CTCs) represent a subset of heterogeneous cells, which, once released from a tumor site, have the potential to give rise to metastasis in secondary sites. Recent research focused on the attempt to detect and characterize these rare cells in the circulation, and advancements in defining their molecular profile have been reported in diverse tumor species, with potential implications for clinical applications. Of note, metabolic alterations, involving mitochondria, have been implicated in the metastatic process, as key determinants in the transition of tumor cells to a mesenchymal or stemness-like phenotype, in drug resistance, and in induction of apoptosis. This review aimed to briefly analyse the most recent knowledge relative to mitochondria dysfunction in CTCs, and to envision implications of altered mitochondria in CTCs for a potential utility in clinics.
    Keywords:  CTC; ROS; drug resistance; invasiveness; mitochondria
    DOI:  https://doi.org/10.3389/fonc.2022.947479
  228. Foods. 2022 Aug 10. pii: 2404. [Epub ahead of print]11(16):
    Effect of Thermal Treatment on the Physicochemical, Ultrastructural, and Antioxidant Characteristics of Euryale ferox Seeds and Flour.
    Qin Li, Hong-Tao Li, Yi-Peng Bai, Ke-Rui Zhu, Ping-Hsiu Huang.
      Euryale ferox seeds (EFS) were less gelatinized, preventing the release of nutrients and functional compounds, resulting in limited applications in meals and the food industry. Nutraceutical importance of EFS includes starch, protein, lipids, 20 amino acids, minerals, and vitamins (C, E, and beta carotene). This study aimed to evaluate the effect of three different thermal treatments on EFS's physicochemical and nutritional properties and expected to improve its applicability. The results showed that the bulk density, thousand-grain weight, and hardness of thermal treated EFS were significantly decreased (p &lt; 0.05), whereas the maximum decrease was observed in the industrial infrared heating-assisted fluidized bed (IHFH) treatment. Meanwhile, there were more crevices, fissures, and heightened porous structures in EFS between the pericarp and episperm and the endosperm after heat treatment, which facilitated grinding and water absorption. Notably, EFS's water and oil absorption capacities increased significantly (p &lt; 0.05) with microwave and IHFH treatments. EFS ground's solubility into powder was increased significantly with thermal treatment (p &lt; 0.05). Furthermore, the functional properties of TPC, TFC, DPPH radical scavenging activity, and reducing power were significantly increased (p &lt; 0.05). In general, the changes in the physicochemical properties of EFS and increased bioactivity were caused by microwave and IHFH treatments. Hence, it might improve the food value of EFS while providing valuable information to researchers and food manufacturers.
    Keywords:  Euryale ferox seed; antioxidant; bioactive components; coarse grain; gelatinized; microwave; physicochemical; roasted
    DOI:  https://doi.org/10.3390/foods11162404
  229. Int J Mol Sci. 2022 Aug 15. pii: 9134. [Epub ahead of print]23(16):
    Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice.
    Chun-Jung Chen, Chih-Cheng Wu, Cheng-Yi Chang, Jian-Ri Li, Yen-Chuan Ou, Wen-Ying Chen, Su-Lan Liao, Jiaan-Der Wang.
      Metformin may offer benefits to certain cancer populations experiencing metabolic abnormalities. To extend the anticancer studies of metformin, a tumor model was established through the implantation of murine Lewis Lung Carcinoma (LLC) cells to Normal Diet (ND)-fed and High-Fat Diet (HFD)-fed C57BL/6 mice. The HFD-fed mice displayed metabolic and pro-inflammatory alterations together with accompanying aggressive tumor growth. Metformin mitigated tumor growth in HFD-fed mice, paralleled by reductions in circulating glucose, insulin, soluble P-selectin, TGF-β1 and High Mobility Group Box-1 (HMGB1), as well as tumor expression of cell proliferation, aerobic glycolysis, glutaminolysis, platelets and neutrophils molecules. The suppressive effects of metformin on cell proliferation, migration and oncogenic signaling molecules were confirmed in cell study. Moreover, tumor-bearing HFD-fed mice had higher contents of circulating and tumor immunopositivity of Neutrophil Extracellular Traps (NETs)-associated molecules, with a suppressive effect from metformin. Data taken from neutrophil studies confirmed the inhibitory effect that metformin has on NET formation induced by HMGB1. Furthermore, HMGB1 was identified as a promoting molecule to boost the transition process towards NETs. The current study shows that metabolic, pro-inflammatory and NET alterations appear to play roles in the obesity-driven aggressiveness of cancer, while also representing candidate targets for anticancer potential of metformin.
    Keywords:  metabolism; metformin; neutrophil extracellular traps; neutrophils; obesity; salignancy
    DOI:  https://doi.org/10.3390/ijms23169134
  230. Pharmaceuticals (Basel). 2022 Aug 19. pii: 1023. [Epub ahead of print]15(8):
    Chitosan-Based Scaffolds for Facilitated Endogenous Bone Re-Generation.
    Yao Zhao, Sinuo Zhao, Zhengxin Ma, Chunmei Ding, Jingdi Chen, Jianshu Li.
      Facilitated endogenous tissue engineering, as a facile and effective strategy, is emerging for use in bone tissue regeneration. However, the development of bioactive scaffolds with excellent osteo-inductivity to recruit endogenous stem cells homing and differentiation towards lesion areas remains an urgent problem. Chitosan (CS), with versatile qualities including good biocompatibility, biodegradability, and tunable physicochemical and biological properties is undergoing vigorously development in the field of bone repair. Based on this, the review focus on recent advances in chitosan-based scaffolds for facilitated endogenous bone regeneration. Initially, we introduced and compared the facilitated endogenous tissue engineering with traditional tissue engineering. Subsequently, the various CS-based bone repair scaffolds and their fabrication methods were briefly explored. Furthermore, the functional design of CS-based scaffolds in bone endogenous regeneration including biomolecular loading, inorganic nanomaterials hybridization, and physical stimulation was highlighted and discussed. Finally, the major challenges and further research directions of CS-based scaffolds were also elaborated. We hope that this review will provide valuable reference for further bone repair research in the future.
    Keywords:  bioactive scaffold; bone repair; chitosan; facilitated endogenous tissue engineering; functional design
    DOI:  https://doi.org/10.3390/ph15081023
  231. Molecules. 2022 Aug 11. pii: 5128. [Epub ahead of print]27(16):
    Traditional Use, Phytochemical Profiles and Pharmacological Properties of Artemisia Genus from Central Asia.
    Aliya Nurlybekova, Aidana Kudaibergen, Aizhan Kazymbetova, Magzhan Amangeldi, Aizhamal Baiseitova, Meirambek Ospanov, Haji Akber Aisa, Yang Ye, Mohamed Ali Ibrahim, Janar Jenis.
      The flora of Kazakhstan is characterized by its wide variety of different types of medicinal plants, many of which can be used on an industrial scale. The Traditional Kazakh Medicine (TKM) was developed during centuries based on the six elements of ancient Kazakh theory, associating different fields such as pharmacology, anatomy, pathology, immunology and food nursing as well as disease prevention. The endemic Artemisia L. species are potential sources of unique and new natural products and new chemical structures, displaying diverse bioactivities and leading to the development of safe and effective phytomedicines against prevailing diseases in Kazakhstan and the Central Asia region. This review provides an overview of Artemisia species from Central Asia, particularly traditional uses in folk medicine and the recent numerous phytochemical and pharmacological studies. The review is done by the methods of literature searches in well-known scientific websites (Scifinder and Pubmed) and data collection in university libraries. Furthermore, our aim is to search for promising and potentially active Artemisia species candidates, encouraging us to analyze Protein Tyrosine Phosphatase 1B (PTP1B), α-glucosidase and bacterial neuraminidase (BNA) inhibition as well as the antioxidant potentials of Artemisia plant extracts, in which endemic species have not been explored for their secondary metabolites and biological activities so far. The main result of the study was that, for the first time, the species Artemisia scopiformis Ledeb. Artemisia albicerata Krasch., Artemisia transiliensis Poljakov, Artemisia schrenkiana Ledeb., Artemisia nitrosa Weber and Artemisia albida Willd. ex Ledeb. due to their special metabolites, showed a high potential for α-glucosidase, PTP1B and BNA inhibition, which is associated with diabetes, obesity and bacterial infections. In addition, we revealed that the methanol extracts of Artemisia were a potent source of polyphenolic compounds. The total polyphenolic contents of Artemisia extracts were correlated with antioxidant potential and varied according to plant origin, the solvent of extraction and the analytical method used. Consequently, oxidative stress caused by reactive oxygen species (ROS) may be managed by the dietary intake of current Artemisia species. The antioxidant potentials of the species A. schrenkiana, A. scopaeformis, A. transiliensis and Artemisia scoparia Waldst. & Kitam. were also promising. In conclusion, the examination of details between different Artemisia species in our research has shown that plant materials are good as an antioxidant and eznyme inhibitory functional natural source.
    Keywords:  Artemisia genus; BNA; Kazakhstan; PTP1B; TKM; antioxidant; essential oils; flavonoids; sequiterpene lactone; α-glucosidase
    DOI:  https://doi.org/10.3390/molecules27165128
  232. Fish Shellfish Immunol. 2022 Aug 22. pii: S1050-4648(22)00517-4. [Epub ahead of print]
    Modulatory role of dietary curcumin and resveratrol on growth performance, serum immunity responses, mucus enzymes activity, antioxidant capacity and serum and mucus biochemicals in the common carp, Cyprinus carpio exposed to abamectin.
    Martina Kurnia Rohmah, Omar Dheyauldeen Salahdin, Reena Gupta, Khursheed Muzammil, Maytham T Qasim, Zahraa Haleem Al-Qaim, Nada Fadhil Abbas, Mohammed Abed Jawad, Ghulam Yasin, Yasser Fakri Mustafa, Aadel Heidary, Safoura Abarghouei.
      In this study, we investigate the potentials of dietary curcumin and resveratrol on blood biochemistry, immune responses and resistance to the toxicity of the pesticide, abamectin. 540 common carps (30.78 ± 0.17 g) were randomly distributed into 18 tanks (30 fish per tank), as six experimental groups (T1: non-supplemented and on-exposed fish, T2: 300 mg/kg curcumin, T3: 300 mg/kg resveratrol, T4: 12.5% LC50 of abamectin, T5: 300 mg/kg curcumin +12.5% LC50 of abamectin, T6: 300 mg/kg resveratrol + 12.5% LC50 of abamectin). Use of 300 mg/kg resveratrol in the diet of non-abamectin exposed fish improved the growth performance (P < 0.05), while such effects were not observed for curcumin (P > 0.05). There were no differences in the final weight (FW), feed conversion ratio (FCR) and weight gain (WG) between control and fish of the treatments, resveratrol + abamectin and curcumin + abamectin (P < 0.05). The immune components in blood [lysozyme, complement activity, Total immunoglobulin (total Ig), protease, myeloperoxidase (MPO), nitro-blue-tetrazolium (NBT), peroxidase, albumin] and mucus [acid phosphatase (ACP), alkaline phosphatase (ALP), esterase, antiprotease)] and antioxidant enzymes [(superoxide dismutase (SOD), glutathione peroxidase (GPx)] exhibited various change patterns compared to the control group, however, these components were almost all higher in fish supplemented with curcumin and resveratrol in an abamectin-free medium than in control and other groups (P < 0.05). In most cases, the levels of immune and antioxidant components in the control did not show significant difference with the treatments, resveratrol + abamectin and curcumin + abamectin (P > 0.05). Abamectin induced oxidative stress in fish, as the malondialdehyde (MDA) levels significantly increased in the exposed fish compared to non-exposed groups (P < 0.05). It appears that neither curcumin nor resveratrol were as effective in preventing oxidative stress, because MDA levels were higher in exposed fish (abamectin, curcumin + abamectin, resveratrol + abamectin) than in control and non-exposed individuals (P < 0.05). Curcumin and resveratrol also showed protective effects on liver, since the levels of liver metabolic enzymes [aspartate transaminase (AST), ALP, lactate dehydrogenase (LDH)] were lower in the supplemented fish in a abamectin-free medium than in control (P < 0.05). Curcumin and resveratrol also mitigated the stress responses in the exposed fish, as cortisol and glucose levels showed significant decreases in the supplemented fish (P < 0.05). In conclusion, this study revealed that abamectin can depress the growth and immunity in the common carp. Although, both resveratrol and curcumin were mitigated the toxic effects of abamectin, it seems that resveratrol be more effective than curcumin.
    Keywords:  Curcumin; Fish; Growth; Immunity; Pesticide; Resveratrol
    DOI:  https://doi.org/10.1016/j.fsi.2022.08.042
  233. J Control Release. 2022 Aug 18. pii: S0168-3659(22)00536-3. [Epub ahead of print]
    Oral administration of sodium bicarbonate can enhance the therapeutic outcome of Doxil® via neutralizing the acidic tumor microenvironment.
    Hidenori Ando, Ai Ikeda, Maho Tagami, Nana Cristina Amorim Matsuo, Taro Shimizu, Yu Ishima, Kiyoshi Eshima, Tatsuhiro Ishida.
      The pH of the tumor microenvironment in solid tumors is reported to be more acidic than that of normal tissues. The pH is controlled by over-expression of several transporters that are associated with the progression, angiogenesis, and metastasis of solid tumors. Antitumor effects of weak-base anticancer agents, such as doxorubicin (DXR), could be reduced in an acidic environment because of increases in the ionized form of the drug under these conditions, reducing its membrane penetrability. In our previous studies, we demonstrated that oral administration of sodium bicarbonate (NaHCO3) can neutralize the acidic tumor microenvironment and enhance the effects of small molecule anticancer drugs. However, it is not known whether or not increasing the tumor pH by oral administration of NaHCO3 leads to enhanced antitumor effects of lipidic nanoparticle formulations of weak-base anticancer drugs, such as Doxil®. In this study, we investigated the antitumor efficacy of Doxil® in combination with oral administration of NaHCO3 in a Colon26 tumor-bearing mouse model. NaHCO3 clearly enhanced the tumor-growth inhibitory effect of Doxil® without exacerbating any systemic side effects. In vitro studies indicated that high levels of DXR were internalized into cells at neutral pH. These studies demonstrate that the neutralization of acidic tumor microenvironment by an oral administration of NaHCO3 could be a promising approach to enhance the therapeutic outcomes of Doxil®.
    Keywords:  Acidic tumor microenvironment; Doxil®; Sodium bicarbonate (NaHCO(3)); Tumor neutralization
    DOI:  https://doi.org/10.1016/j.jconrel.2022.08.031
  234. Cell Metab. 2022 Aug 15. pii: S1550-4131(22)00313-8. [Epub ahead of print]
    Warburg-like metabolic transformation underlies neuronal degeneration in sporadic Alzheimer's disease.
    Larissa Traxler, Joseph R Herdy, Davide Stefanoni, Sophie Eichhorner, Silvia Pelucchi, Attila Szücs, Alice Santagostino, Yongsung Kim, Ravi K Agarwal, Johannes C M Schlachetzki, Christopher K Glass, Jessica Lagerwall, Douglas Galasko, Fred H Gage, Angelo D'Alessandro, Jerome Mertens.
      The drivers of sporadic Alzheimer's disease (AD) remain incompletely understood. Utilizing directly converted induced neurons (iNs) from AD-patient-derived fibroblasts, we identified a metabolic switch to aerobic glycolysis in AD iNs. Pathological isoform switching of the glycolytic enzyme pyruvate kinase M (PKM) toward the cancer-associated PKM2 isoform conferred metabolic and transcriptional changes in AD iNs. These alterations occurred via PKM2's lack of metabolic activity and via nuclear translocation and association with STAT3 and HIF1α to promote neuronal fate loss and vulnerability. Chemical modulation of PKM2 prevented nuclear translocation, restored a mature neuronal metabolism, reversed AD-specific gene expression changes, and re-activated neuronal resilience against cell death.
    Keywords:  Alzheimer's disease; WGCNA; Warburg effect; cancer; direct conversion; induced neurons; metabolomics; pyruvate kinase M; reprogramming
    DOI:  https://doi.org/10.1016/j.cmet.2022.07.014
  235. Colloids Surf B Biointerfaces. 2022 Aug 17. pii: S0927-7765(22)00454-4. [Epub ahead of print]218 112771
    Rational surface modification of gadolinium borate nanoparticles enhancing colloidal stability in physiological media for potential neutron capture therapy and magnetic resonance imaging.
    Yucai Zhang, Chengbo Qian, Daochang Li, Li Zhao.
      Colloidal stability of nanomaterials in physiological media is an indispensable property for their biomedical applications. However, gadolinium borate (GdBO3) nanoparticles that hold promise as a theranostic agent for neutron capture therapy (NCT) and magnetic resonance imaging (MRI) of cancer tend to precipitate in phosphate buffered saline (PBS) owing to formation of insoluble gadolinium phosphate. To address this issue, in this work 10B-enriched GdBO3 nanoparticles were prepared and coated with mesoporous silica (mSiO2) of ~ 40 nm in thickness and subsequently grafted with hydrophilic polyglycerol (PG). The resulting GdBO3 @mSiO2-PG nanoparticles showed excellent colloidal stability in PBS due to the protection of the mSiO2 coating as well as superior dispersibility because of the high hydrophilicity of the PG layer. In vitro experiments revealed that GdBO3 @mSiO2-PG possessed low cytotoxicity and could be taken up by cancer cells in a concentration-dependent manner. In vivo studies indicated that GdBO3 @mSiO2-PG can circulate in mouse body for a considerably long time without obvious acute toxicity. In addition, GdBO3 @mSiO2-PG also showed promise as a T1-weighted MRI contrast agent with a proton longitudinal relaxivity of 0.67 mM-1 s-1. Our results indicate that GdBO3 @mSiO2-PG with enhanced colloidal stability in physiological media could serve as a promising multifunctional agent for cancer theranostics.
    Keywords:  Cancer theranostics; Colloidal stability; Gadolinium borate nanoparticles; Physiological media; Surface modification
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112771
  236. Br J Biomed Sci. 2022 ;79 10382
    Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency.
    Patricia Karissa, Timothy Simpson, Simon P Dawson, Teck Yew Low, Sook Hui Tay, Fatimah Diana Amin Nordin, Shamsul Mohd Zain, Pey Yee Lee, Yuh-Fen Pung.
      Pyruvate dehydrogenase (PDH) deficiency is caused by a number of pathogenic variants and the most common are found in the PDHA1 gene. The PDHA1 gene encodes one of the subunits of the PDH enzyme found in a carbohydrate metabolism pathway involved in energy production. Pathogenic variants of PDHA1 gene usually impact the α-subunit of PDH causing energy reduction. It potentially leads to increased mortality in sufferers. Potential treatments for this disease include dichloroacetate and phenylbutyrate, previously used for other diseases such as cancer and maple syrup urine disease. However, not much is known about their efficacy in treating PDH deficiency. Effective treatment for PDH deficiency is crucial as carbohydrate is needed in a healthy diet and rice is the staple food for a large portion of the Asian population. This review analysed the efficacy of dichloroacetate and phenylbutyrate as potential treatments for PDH deficiency caused by PDHA1 pathogenic variants. Based on the findings of this review, dichloroacetate will have an effect on most PDHA1 pathogenic variant and can act as a temporary treatment to reduce the lactic acidosis, a common symptom of PDH deficiency. Phenylbutyrate can only be used on patients with certain pathogenic variants (p.P221L, p.R234G, p.G249R, p.R349C, p.R349H) on the PDH protein. It is hoped that the review would provide an insight into these treatments and improve the quality of lives for patients with PDH deficiency.
    Keywords:  E1a; PDHA1; inborn error of metabolism; lactic acidosis; mitochondrial disease
    DOI:  https://doi.org/10.3389/bjbs.2022.10382
  237. J Med Chem. 2022 Aug 26.
    Acriflavine, an Acridine Derivative for Biomedical Application: Current State of the Art.
    Kinga Piorecka, Jan Kurjata, Wlodzimierz A Stanczyk.
      Acriflavine (ACF) has been known for years as an antibacterial drug. The identification of key oncogenic mechanisms has brought, in recent years, a significant increase in studies on ACF as a multipurpose drug that would improve the prognosis for cancer patients. ACF interferes with the expression of the hypoxia inducible factor, thus acting on metastatic niches of tumors and significantly enhancing the effects of other anticancer therapies. It has been recognized as the most potent HIF-1 inhibitor out of the 336 drugs approved by the FDA. This work presents up-to-date knowledge about the mechanisms of action of ACF and its related prodrug systems in the context of anticancer and SARS-CoV-2 inhibitory properties. It explains the multitask nature of this drug and suggests mechanisms of ACF's action on the coronavirus. Other recent reports on ACF-based systems as potential antibacterial and antiviral drugs are also described.
    DOI:  https://doi.org/10.1021/acs.jmedchem.2c00573
  238. Horm Mol Biol Clin Investig. 2022 Aug 22.
    Anti-migratory effect of curcumin on A-549 lung cancer cells via epigenetic reprogramming of RECK/ matrix metalloproteinase axis.
    Shabnam Mostofi, Dariush Shanehbandi, Seyyed Ali Rahmani, Milad Asadi.
      OBJECTIVES: The aim of this study was to investigate the effects of curcumin on the viability, migration, and apoptosis of A549 lung cancer cells. Furthermore, RECK/MMPs axis as a probable regulator of cancer cell migration was assessed.METHODS: In this study, effect of curcumin on viability changes, cell migration, and percentage of apoptosis of A549 non-small cell lung carcinoma was examined. The methylation status of RECK gene was investigated using MS-HRM technique. Moreover, expression changes of genes involved in apoptosis and migration (including CASP3, CASP8, CASP9, BAX, BCL2, MMP9, MMP2, and RECK) were investigated by quantitative Real-Time PCR.
    RESULTS: The results of MTT assay showed that the cytotoxic effect of curcumin was in a dose dependent manner. Flow cytometry results demonstrated a significant increase in the percentage of apoptotic cells in curcumin treated group. In addition, curcumin inhibited migration rate in lung cancer cells. qRT-PCR revealed that expression of the candidate genes was in line with suppressed growth and migration. This could be due to, decreased methylation of the RECK gene promoter after curcumin treatment.
    CONCLUSIONS: Curcumin inhibited lung cancer cells through various molecular pathways. RECK/MMPs axis as a regulator of cancer cell migration was modulated after curcumin treatment and invasion of lung cancer cells was decreased.
    Keywords:   RECK gene; apoptosis; curcumin; lung cancer; matrix metalloproteinase; methylation; migration
    DOI:  https://doi.org/10.1515/hmbci-2021-0100
  239. Nanomaterials (Basel). 2022 Aug 17. pii: 2826. [Epub ahead of print]12(16):
    Recent Advances in Functionalized Nanoparticles in Cancer Theranostics.
    Sarkar Siddique, James C L Chow.
      Cancer theranostics is the combination of diagnosis and therapeutic approaches for cancer, which is essential in personalized cancer treatment. The aims of the theranostics application of nanoparticles in cancer detection and therapy are to reduce delays in treatment and hence improve patient care. Recently, it has been found that the functionalization of nanoparticles can improve the efficiency, performance, specificity and sensitivity of the structure, and increase stability in the body and acidic environment. Moreover, functionalized nanoparticles have been found to possess a remarkable theranostic ability and have revolutionized cancer treatment. Each cancer treatment modality, such as MRI-guided gene therapy, MRI-guided thermal therapy, magnetic hyperthermia treatment, MRI-guided chemotherapy, immunotherapy, photothermal and photodynamic therapy, has its strengths and weaknesses, and combining modalities allows for a better platform for improved cancer control. This is why cancer theranostics have been investigated thoroughly in recent years and enabled by functionalized nanoparticles. In this topical review, we look at the recent advances in cancer theranostics using functionalized nanoparticles. Through understanding and updating the development of nanoparticle-based cancer theranostics, we find out the future challenges and perspectives in this novel type of cancer treatment.
    Keywords:  MRI-guided therapy; biomedical imaging; cancer theranostics; cancer therapy; functionalized nanoparticles; molecular imaging
    DOI:  https://doi.org/10.3390/nano12162826
  240. Pharmaceutics. 2022 Aug 02. pii: 1618. [Epub ahead of print]14(8):
    Polyhydroxyalkanoate Decelerates the Release of Paclitaxel from Poly(lactic-co-glycolic acid) Nanoparticles.
    Si Yeong Lee, So Yun Kim, Sook Hee Ku, Eun Ji Park, Dong-Jin Jang, Sung Tae Kim, Seong-Bo Kim.
      Biodegradable nanoparticles (NPs) are preferred as drug carriers because of their effectiveness in encapsulating drugs, ability to control drug release, and low cytotoxicity. Although poly(lactide co-glycolide) (PLGA)-based NPs have been used for controlled release strategies, they have some disadvantages. This study describes an approach using biodegradable polyhydroxyalkanoate (PHA) to overcome these challenges. By varying the amount of PHA, NPs were successfully fabricated by a solvent evaporation method. The size range of the NPS ranged from 137.60 to 186.93 nm, and showed zero-order release kinetics of paclitaxel (PTX) for 7 h, and more sustained release profiles compared with NPs composed of PLGA alone. Increasing the amount of PHA improved the PTX loading efficiency of NPs. Overall, these findings suggest that PHA can be used for designing polymeric nanocarriers, which offer a potential strategy for the development of improved drug delivery systems for sustained and controlled release.
    Keywords:  Poly(lactide co-glycolide); drug release; nanoparticle; paclitaxel; polyhydroxyalkanoate
    DOI:  https://doi.org/10.3390/pharmaceutics14081618
  241. Chin Med. 2022 Aug 26. 17(1): 100
    Propolis: An update on its chemistry and pharmacological applications.
    Rajib Hossain, Cristina Quispe, Rasel Ahmed Khan, Abu Saim Mohammad Saikat, Pranta Ray, Damira Ongalbek, Balakyz Yeskaliyeva, Divya Jain, Antonella Smeriglio, Domenico Trombetta, Roghayeh Kiani, Farzad Kobarfard, Naheed Mojgani, Parvaneh Saffarian, Seyed Abdulmajid Ayatollahi, Chandan Sarkar, Mohammad Torequl Islam, Dılhun Keriman, Arserim Uçar, Miquel Martorell, Antoni Sureda, Gianfranco Pintus, Monica Butnariu, Javad Sharifi-Rad, William C Cho.
      Propolis, a resinous substance produced by honeybees from various plant sources, has been used for thousands of years in traditional medicine for several purposes all over the world. The precise composition of propolis varies according to plant source, seasons harvesting, geography, type of bee flora, climate changes, and honeybee species at the site of collection. This apiary product has broad clinical applications such as antioxidant, anti-inflammatory, antimicrobial, anticancer, analgesic, antidepressant, and anxiolytic as well asimmunomodulatory effects. It is also well known from traditional uses in treating purulent disorders, improving the wound healing, and alleviating many of the related discomforts. Even if its use was already widespread since ancient times, after the First and Second World War, it has grown even more as well as the studies to identify its chemical and pharmacological features, allowing to discriminate the qualities of propolis in terms of the chemical profile and relative biological activity based on the geographic place of origin. Recently, several in vitro and in vivo studies have been carried out and new insights into the pharmaceutical prospects of this bee product in the management of different disorders, have been highlighted. Specifically, the available literature confirms the efficacy of propolis and its bioactive compounds in the reduction of cancer progression, inhibition of bacterial and viral infections as well as mitigation of parasitic-related symptoms, paving the way to the use of propolis as an alternative approach to improve the human health. However, a more conscious use of propolis in terms of standardized extracts as well as new clinical studies are needed to substantiate these health claims.
    Keywords:  Anti-inflammatory; Anticancer; Antioxidant; Bee glue; Bioactive compounds; Food preservative
    DOI:  https://doi.org/10.1186/s13020-022-00651-2
  242. Int J Mol Sci. 2022 Aug 13. pii: 9077. [Epub ahead of print]23(16):
    Experimental Evidence for the Anti-Metastatic Action of Ginsenoside Rg3: A Systematic Review.
    Hyeon-Muk Oh, Chong-Kwan Cho, Chang-Gue Son.
      Cancer metastasis is the leading cause of death in cancer patients. Due to the limitations of conventional cancer treatment, such as chemotherapy, there is a need for novel therapeutics to prevent metastasis. Ginsenoside Rg3, a major active component of Panax ginseng C.A. Meyer, inhibits tumor growth and has the potential to prevent tumor metastasis. Herein, we systematically reviewed the anti-metastatic effects of Rg3 from experimental studies. We searched for articles in three research databases, MEDLINE (PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) through March 2022. In total, 14 studies (eight animal and six in vitro) provide data on the anti-metastatic effects of Rg3 and the relevant mechanisms. The major anti-metastatic mechanisms of Rg3 involve cancer stemness, epithelial mesenchymal transition (EMT) behavior, and angiogenesis. Taken together, Rg3 would be one of the herbal resources in anti-metastatic drug developments through further well-designed investigations and clinical studies. Our review provides valuable reference data for Rg3-derived studies targeting tumor metastasis.
    Keywords:  cancer metastasis; ginsenoside Rg3; systematic review
    DOI:  https://doi.org/10.3390/ijms23169077
  243. Colloids Surf B Biointerfaces. 2022 Aug 09. pii: S0927-7765(22)00451-9. [Epub ahead of print]218 112768
    Laser-induced breakdown spectroscopy-guided synergistic phototherapy: A theranostic platform mediated by a single laser wavelength.
    Na An, Yao Zhang, Han Sheng Lu, Shuang Long Tang, Yan Gao, Xiao Hui Li, Chong Shen Guo.
      Currently, cancer theranostic studies have only focused on integrating existing medical imaging techniques with therapeutic modalities. Obviously, this strategy is not a real theranostic method, as diagnosis and therapy are based on different principles and require independent operation. Here, a cancer theranostic method was established by laser-induced breakdown spectroscopy (LIBS)-mediated synergistic photothermal/photodynamic therapy, which was activated by a single 1064-nm light for simultaneous tumor localization and treatment. PEGylated cobalt phosphate (CoP@PEG) nanoparticles (NPs) with strong near-infrared (NIR)-II absorbance, high photothermal conversion efficiency and a reactive oxygen species generation effect were fabricated, and they produced excellent antitumor outcomes under 1064-nm excitation, as evidenced by the substantial increase in HepG2 cell death in vitro and complete tumor elimination in vivo. Meanwhile, the diagnostic method of the LIBS imaging system used in the present study also uses 1064-nm light. The LIBS imaging system can provide fast, real-time analysis and imaging of elements and facilitate the localization of the tumor site by monitoring the distribution of CoP@PEG NPs for precise tumor treatment. We postulate that this theranostic platform will promote the development of further theranostic research.
    Keywords:  Laser-induced breakdown spectroscopy; Photodynamic therapy; Photothermal therapy; Theranostics
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112768
  244. Nutrients. 2022 Aug 18. pii: 3401. [Epub ahead of print]14(16):
    Role of Vitamin K in Selected Malignant Neoplasms in Women.
    Anna Markowska, Michał Antoszczak, Janina Markowska, Adam Huczyński.
      The main function of vitamin K in the human organism is its activity in the blood clotting cascade. Epidemiological studies suggest that reduced intake of vitamin K may contribute to an increased risk of geriatric diseases such as atherosclerosis, dementia, osteoporosis, and osteoarthritis. A growing number of studies also indicate that vitamin K may be involved not only in preventing the development of certain cancers but it may also support classical cancer chemotherapy. This review article summarizes the results of studies on the anticancer effects of vitamin K on selected female malignancies, i.e., breast, cervical, and ovarian cancer, published over the past 20 years. The promising effects of vitamin K on cancer cells observed so far indicate its great potential, but also the need for expansion of our knowledge in this area by conducting extensive research, including clinical trials.
    Keywords:  breast cancer; cervical cancer; ovarian cancer; vitamin K
    DOI:  https://doi.org/10.3390/nu14163401
  245. Polymers (Basel). 2022 Aug 18. pii: 3368. [Epub ahead of print]14(16):
    Intracranial In Situ Thermosensitive Hydrogel Delivery of Temozolomide Accomplished by PLGA-PEG-PLGA Triblock Copolymer Blending for GBM Treatment.
    Weinan Gu, Ranran Fan, Jingnan Quan, Yi Cheng, Shanshan Wang, Hui Zhang, Aiping Zheng, Shenghan Song.
      Glioblastoma (GBM) recurrence after surgical excision has grown to be a formidable obstacle to conquer. In this research, biodegradable thermosensitive triblock copolymer, poly(D, L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D, L-lactic acid-co-glycolic acid (PLGA-PEG-PLGA) was utilized as the drug delivery system, loading with micronized temozolomide(micro-TMZ) to form an in situ drug-gel depot inside the resection cavity. The rheology studies revealed the viscoelastic profile of hydrogel under various conditions. To examine the molecular characteristics that affect gelation temperature, 1H-NMR, inverse gated decoupling 13C-NMR, and GPC were utilized. Cryo-SEM and XRD were intended to disclose the appearance of the hydrogel and the micro-TMZ existence state. We worked out how to blend polymers to modify the gelation point (Tgel) and fit the correlation between Tgel and other dependent variables using linear regression. To simulate hydrogel dissolution in cerebrospinal fluid, a membraneless dissolution approach was used. In vitro, micro-TMZ@PLGA-PEG-PLGA hydrogel exhibited Korsmeyer-Peppas and zero-order release kinetics in response to varying drug loading, and in vivo, it suppressed GBM recurrence at an astoundingly high rate. Micro-TMZ@PLGA-PEG-PLGA demonstrates a safer and more effective form of chemotherapy than intraperitoneal TMZ injection, resulting in a spectacular survival rate (40%, n = 10) that is much more than intraperitoneal TMZ injection (22%, n = 9). By proving the viability and efficacy of micro-TMZ@PLGA-PEG-PLGA hydrogel, our research established a novel chemotherapeutic strategy for treating GBM recurrence.
    Keywords:  PLGA–PEG–PLGA; glioblastoma relapse; interstitial chemotherapy; polymer blending; temozolomide; thermosensitive; triblock copolymer
    DOI:  https://doi.org/10.3390/polym14163368
  246. Curr Res Pharmacol Drug Discov. 2022 ;3 100121
    Promising effects of emoxypine and its succinate derivative in the management of various diseases-with insights on recent patent applications.
    Dhruv Sanjay Gupta, Siddhi Bagwe Parab, Ginpreet Kaur.
      Emoxypine and its succinate derivative share a common hydroxypridine structure, which is similar to pyridoxine. These compounds have been utilized therapeutically and industrially, owing to the wide range of properties offered. This includes antihypoxic, neuroprotective and cardioprotective effects, along with pharmacokinetic benefits such as the ability to cross the blood brain barrier (BBB), owing to its relatively small size and low molecular weight. It was observed that emoxypine exhibited iron chelating property in vitro, indicating its usage as a promising therapeutic strategy in the management of neurodegenerative conditions such as Alzheimer's disease (AD), as well as hematologic disorders like thalassemia and hemochromatosis. In addition to this, it has been observed to exert a potent antioxidant effect, therefore, it may be considered for the amelioration of disorders resulting from free radical injury. Studies on its mechanism of action and implications on cellular and molecular levels would help to further the understanding of its benefits, as well as prospects for filing patents for novel applications. The primary focus of this review is to shed light on the broad spectrum of pharmacological properties offered by emoxypine and its succinate derivative, and to highlight the scope for an increased number of pre-clinical and clinical trials to assess its safety and efficacy. In addition to this, the highlights of this article include the recent patents filed and scope for novel applications of these agents.
    Keywords:  Acute kidney injury; Cerebroprotection; Iron overload; Mexidol; Mitochondrial dysfunction; Neuroinflammation
    DOI:  https://doi.org/10.1016/j.crphar.2022.100121
  247. Polymers (Basel). 2022 Aug 14. pii: 3307. [Epub ahead of print]14(16):
    The Potential of Pharmaceutical Hydrogels in the Formulation of Topical Administration Hormone Drugs.
    Aneta Ostróżka-Cieślik.
      Hormones have attracted considerable interest in recent years due to their potential use in treatment of many diseases. Their ability to have a multidirectional effect leads to searching for new and increasingly effective drugs and therapies. Limitations in formulating drug forms containing hormones are mainly due to their low enzymatic stability, short half-life and limited bioavailability. One of the solutions may be to develop a hydrogel as a potential hormone carrier, for epidermal and transdermal application. This review discusses the main research directions in developing this drug formulation. The factors determining the action of hormones as drugs are presented. An analysis of hydrogel substrates and permeation enhancers that have the potential to enhance the efficacy of hormones applied to the skin is reviewed.
    Keywords:  hormone; hydrogels; permeation enhancers; topical
    DOI:  https://doi.org/10.3390/polym14163307
  248. Biomed Res Int. 2022 ;2022 2188940
    Structural Modifications and Strategies for Native Starch for Applications in Advanced Drug Delivery.
    Pankaj Bhatt, Vipin Kumar, Richa Goel, Somesh Kumar Sharma, Shikha Kaushik, Shivani Sharma, Alankar Shrivastava, Mulugeta Tesema.
      Pharmaceutical excipients are compounds or substances other than API which are added to a dosage form, these excipients basically act as carriers, binders, bulk forming agents, colorants, and flavouring agents, and few excipients are even used to enhance the activity of active pharmaceutical ingredient (API) and various more properties. However, despite of these properties, there are problems with the synthetic excipients such as the possibility of causing toxicity, inflammation, autoimmune responses, lack of intrinsic bioactivity and biocompatibility, expensive procedures for synthesis, and water solubility. However, starch as an excipient can overcome all these problems in one go. It is inexpensive, there is no toxicity or immune response, and it is biocompatible in nature. It is very less used as an excipient because of its high digestibility and swelling index, high glycemic index, paste clarity, film-forming property, crystalline properties, etc. All these properties of starch can be altered by a few modification processes such as physical modification, genetic modification, and chemical modification, which can be used to reduce its digestibility and glycemic index of starch, improve its film-forming properties, and increase its paste clarity. Changes in some of the molecular bonds which improve its properties such as binding, crystalline structure, and retrogradation make starch perfect to be used as a pharmaceutical excipient. This research work provides the structural modifications of native starch which can be applicable in advanced drug delivery. The major contributions of the paper are advances in the modification of native starch molecules such as physically, chemically, enzymatically, and genetically traditional crop modification to yield a novel molecule with significant potential for use in the pharmaceutical industry for targeted drug delivery systems.
    DOI:  https://doi.org/10.1155/2022/2188940
  249. Foods. 2022 Aug 20. pii: 2518. [Epub ahead of print]11(16):
    Extracts of Common Vegetables Inhibit the Growth of Ovary Cancer Cells.
    Paulina Furdak, Natalia Pieńkowska, Grzegorz Bartosz, Izabela Sadowska-Bartosz.
      There is recent interest in a diet that can be recommended for patients suffering from cancer. In this respect, the effects were studied of the extracts of several common fruits, herbs and vegetables on the viability of two human ovary cancer cell lines (SKOV-3 and PEO1) in vitro. Normal human MRC-5 fibroblasts were used as a control cell line. The extracts of garlic, horseradish and curly kale as well as green and black tea were the most effective in lowering the viability of ovarian cancer cells, while not affecting the viability of MRC-5 fibroblasts. Except for garlic and horseradish, the cytotoxic effects of the extracts correlated with their polyphenol content. The examination of changes in the content of ATP and glutathione, in the level of reactive oxygen species, mitochondrial potential and mitochondrial mass did not show a consistent pattern, suggesting that various extracts may act via different mechanisms. Although the extracts' toxicity to cells in vitro is a first and direct suggestion concerning their possible anticancer effects in vivo, these results point to potential vegetable candidates to become diet components recommended for ovary cancer patients.
    Keywords:  PEO1; SKOV-3; curly kale; cytotoxicity; garlic; horseradish; ovary cancer; polyphenols; tea
    DOI:  https://doi.org/10.3390/foods11162518
  250. Acta Biomater. 2022 Aug 22. pii: S1742-7061(22)00503-7. [Epub ahead of print]
    Dynamic ginsenoside-sheltered nanocatalysts for safe ferroptosis-apoptosis combined therapy.
    Xiaoxiong Zhao, Jicheng Wu, Danjing Guo, Shen Hu, Xiang Chen, Liangjie Hong, Junmei Wang, Jugang Ma, Yangkang Jiang, Tianye Niu, Fenglin Miao, Wengang Li, Ben Wang, Xinhua Chen, Yujun Song.
      Chemodynamic therapy (CDT)-activated apoptosis is a potential anticancer strategy. However, CDT encounters a bottleneck in clinical translation due to its serious side effects and low efficacy. Here, we first reveal that surface engineering of ginsenoside Rg3 dramatically alters the organ distribution and tumor enrichment of systematically administered nanocatalysts using the orthotopic pancreatic tumor model while avoiding toxicity and increasing efficacy in vivo to address the key and universal toxicity problems encountered in nanomedicine. Compared with nanocatalysts alone, Rg3-sheltered dynamic nanocatalysts form hydrophilic nanoclusters, prolonging their circulation lifespan in the blood, protecting the internal nanocatalysts from leakage while allowing their specific release at the tumor site. Moreover, the nanoclusters provide a drug-loading platform for Rg3 so that more Rg3 reaches the tumor site to achieve obvious synergistic effect with nanocatalysts. Rg3-sheltered dynamic nanocatalysts can simultaneously activate ferroptosis and apoptosis to significantly improve anticancer efficacy. Systematic administration of ginsenoside Rg3-sheltered nanocatalysts inhibited 86.6% of tumor growth without toxicity and prolonged the survival time of mice. This study provides a promising approach of nanomedicine with high biosafety and a new outlook for catalytic ferroptosis-apoptosis combined antitumor therapies. STATEMENT OF SIGNIFICANCE: : Chemodynamic therapy (CDT) has limited clinical efficacy in cancer. In this study, we developed Rg3-sheltered dynamic nanocatalysts, which could simultaneously activate ferroptosis based on CDT-activated apoptosis, and ultimately form a combined therapy of ferroptosis-apoptosis to kill tumors. Studies have shown that the nanocatalysts after Rg3 surface engineering dramatically alters the pharmacokinetics and organ distribution of the nanocatalysts after being systematically administered, resulting in avoiding the toxicity of the nanocatalysts. Nanocatalysts also act as a drug-loading platform, guiding more Rg3 into the tumor site. This study emphasizes that nanocatalysts after Rg3 surface engineering improve the safety and effectiveness of ferroptosis-apoptosis combined therapy, providing an effective idea for clinical practices.
    Keywords:  combined anticancer; ferroptosis; mitochondria; nanocatalysts; nanomedicine
    DOI:  https://doi.org/10.1016/j.actbio.2022.08.026
  251. Pharm Nanotechnol. 2022 Aug 27.
    β-Artemether and Lumefantrine Dual Drug Loaded Lipid Nanoparticles: Physicochemical Characterization, Pharmacokinetic Evaluation and Biodistribution Study.
    Kashif Shakeel, Farhan Jalees Ahmad, Ranjit Kumar Harwansh, Mohammad Akhlaquer Rahman.
      BACKGROUND: β-artemether (BAT) and lumefantrine (LFT) combination therapies are well recognized for the treatment of malaria. However, the current conventional formulations have several drawbacks.OBJECTIVE: The study aims to develop novel lipid nanoparticles (LNP) for efficient delivery of BAT and LFT.
    METHODS: The LNP were prepared by solvent injection method and optimized by the Box-Behnken experimental design to achieve the desired particle size, maximum entrapment efficiency (EE), and percentage drug release. BAT and LFT in rat plasma were estimated by liquid chromatographytandem mass spectrometry (LC-MS/MS).
    RESULTS: Freeze-dried LNP comprised of 78.74% (w/w) lipid, 15.74% (w/w) surfactant, 3.93% (w/w) co-surfactant and 1.57% mannitol with respect to the total inactive components. Mean particle size and zeta potential were found to be 140.22 ± 1.36 nm and -35.23 mv, respectively. EE was 80.60 ± 3.85% for BAT and 69.64 ± 2.63% for LFT. The optimized formulation exhibited a biphasic release profile in phosphate buffer (pH 7.2). In vivo study revealed an increased bioavailability of BAT and LFT from dual drug loaded LNP compared to the pure drug solution. Moreover, the tissue distribution study confirmed the high uptake of both the drugs in the liver and spleen.
    CONCLUSION: The study demonstrated the potential use of the developed formulation for oral administration in the treatment of malaria.
    Keywords:  Malaria; bioavailability; lumefantrine; pharmacokinetic; solubility; stability; β-artemether
    DOI:  https://doi.org/10.2174/2211738510666220428133532
  252. Ultrason Sonochem. 2022 Aug 18. pii: S1350-4177(22)00223-1. [Epub ahead of print]89 106127
    Optimization of ultrasound-assisted extraction of bioactive compounds from coffee pulp using propylene glycol as a solvent and their antioxidant activities.
    Hla Myo, Nuntawat Khat-Udomkiri.
      In the cosmetic and pharmaceutical industries, it has been increasingly popular to use alternative solvents in the extraction of bioactive compounds from plants. Coffee pulp, a by-product of coffee production, contains different phenolic compounds with antioxidant properties. The effects of polyols, amplitude, extraction time, solvent concentration, and liquid-solid ratio on total phenolic content (TPC) using ultrasound-assisted extraction (UAE) were examined by single-factor studies. Three main factors that impact TPC were selected to optimize the extraction conditions for total phenolic content (TPC), total flavonoid content (TFC), total tannin content (TTC), and their antioxidant activities using the Box-Behnken design. Different extraction methods were compared, the bioactive compounds were identified and quantified by liquid chromatography triple quadrupole mass spectrometer (LC-QQQ), and the cytotoxicity and cellular antioxidant activities of the extract were studied. According to the response model, the optimal conditions for the extraction of antioxidants from coffee pulp were as follows: extraction time of 7.65 min, liquid-solid ratio of 22.22 mL/g, and solvent concentration of 46.71 %. Under optimized conditions, the values of TPC, TFC, TTC, 1,1-diphenyl-2-picryl-hydrazil (DPPH) radical scavenging assay, 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical scavenging assay, and Ferric reducing antioxidant power assay (FRAP) were 9.29 ± 0.02 mg GAE/g sample, 58.82 ± 1.38 mg QE/g sample, 8.69 ± 0.25 mg TAE/g sample, 7.56 ± 0.27 mg TEAC/g sample, 13.59 ± 0.25 mg TEAC/g sample, and 10.90 ± 0.24 mg FeSO4/g sample, respectively. Compared with other extraction conditions, UAE with propylene glycol extract (PG-UAE) was significantlyhigher in TPC, TFC, TTC, DPPH, ABTS, and FRAP response values than UAE with ethanol (EtOH-UAE), maceration with propylene glycol (PG-maceration), and maceration with ethanol (EtOH -maceration) (p < 0.05). Major bioactive compounds detected by LC-QQQ included chlorogenic acid, caffeine, and trigonelline. At higher concentrations starting from 5 mg/ml, PG-UAE extract showed higher cell viability than EtOH-UAE in both cytotoxicity and cellular antioxidant assays. The researcher expects that this new extraction technique developed in this work could produce a higher yield of bioactive compounds with higher biological activity. Therefore, they can be used as active ingredients in cosmetics (anti-aging products) and pharmaceutical applications (food supplements, treatment for oxidative stress-related diseases) with minimal use of chemicals and energy.
    Keywords:  Coffee by-products; Hydrogen peroxide-induced oxidative stress; Non-conventional extraction method; Phenolic compounds; Polyols; Response surface methodology
    DOI:  https://doi.org/10.1016/j.ultsonch.2022.106127
  253. Nutrients. 2022 Aug 10. pii: 3265. [Epub ahead of print]14(16):
    Antioxidant Effect of Coenzyme Q10 in the Prevention of Oxidative Stress in Arsenic-Treated CHO-K1 Cells and Possible Participation of Zinc as a Pro-Oxidant Agent.
    Saulo Victor E Silva, María Celeste Gallia, Jefferson Romáryo Duarte da Luz, Adriana Augusto de Rezende, Guillermina Azucena Bongiovanni, Gabriel Araujo-Silva, Maria das Graças Almeida.
      Oxidative stress is an imbalance between levels of reactive oxygen species (ROS) and antioxidant enzymes. Compounds with antioxidant properties, such as coenzyme Q10 (CoQ10), can reduce cellular imbalance caused by an increase in ROS. CoQ10 participates in modulating redox homeostasis due to its antioxidant activity and its preserving mitochondrial functions. Thus, the present study demonstrated the protective effects of CoQ10 against oxidative stress and cytotoxicity induced by arsenic (As). Antioxidant capacity, formation of hydroperoxides, generation of ROS, and the effect on cellular viability of CoQ10, were investigated to determine the protective effect of CoQ10 against As and pro-oxidant compounds, such as zinc. Cell viability assays showed that CoQ10 is cytoprotective under cellular stress conditions, with potent antioxidant activity, regardless of the concentration tested. Zn, when used at higher concentrations, can increase ROS and show a pro-oxidant effect causing cell damage. The cytotoxic effect observed for As, Zn, or the combination of both could be prevented by CoQ10, without any decrease in its activity at cellular levels when combined with Zn.
    Keywords:  Zinc; antioxidants; coenzyme Q10; free radical; oxidative stress
    DOI:  https://doi.org/10.3390/nu14163265
  254. Pharmacol Res. 2022 Aug 18. pii: S1043-6618(22)00353-X. [Epub ahead of print] 106408
    Autophagy-nutrient sensing pathways in diabetic complications.
    Urvi M Parmar, Manjiri P Jalgaonkar, Yogesh A Kulkarni, Manisha J Oza.
      The incidence of diabetes has been increasing in recent decades which is affecting the population of both, developed and developing countries. Diabetes is associated with micro and macrovascular complications which predominantly result from hyperglycemia and disrupted metabolic pathways. Persistent hyperglycemia leads to increased reactive oxygen species (ROS) generation, formation of misfolded and abnormal proteins, and disruption of normal cellular functioning. The inability to maintain metabolic homeostasis under excessive energy and nutrient input, which induces insulin resistance, is a crucial feature during the transition from obesity to diabetes. According to various study reports, redox alterations, intracellular stress and chronic inflammation responses have all been linked to dysregulated energy metabolism and insulin resistance. Autophagy has been considered a cleansing mechanism to prevent these anomalies and restore cellular homeostasis. However, disrupted autophagy has been linked to the pathogenesis of metabolic disorders such as obesity and diabetes. Recent studies have reported that the regulation of autophagy has a beneficial role against these conditions. When there is plenty of food, nutrient-sensing pathways activate anabolism and storage, but the shortage of food activates homeostatic mechanisms like autophagy, which mobilises internal stockpiles. These nutrient-sensing pathways are well conserved in eukaryotes and are involved in the regulation of autophagy which includes SIRT1, mTOR and AMPK. The current review focuses on the role of SIRT1, mTOR and AMPK in regulating autophagy and suggests autophagy along with these nutrient-sensing pathways as potential therapeutic targets in reducing the progression of various diabetic complications.
    Keywords:  AMPK; SIRT1; diabetic cardiomyopathy; diabetic nephropathy; diabetic neuropathy; diabetic retinopathy; mTOR
    DOI:  https://doi.org/10.1016/j.phrs.2022.106408
  255. Pharmaceuticals (Basel). 2022 Aug 11. pii: 987. [Epub ahead of print]15(8):
    Phytochemical Composition and Cytoprotective Properties of the Endemic Sideritis sipylea Boiss Greek Species: A Valorization Study.
    Silvia Di Giacomo, Antonella Di Sotto, Apostolis Angelis, Ester Percaccio, Annabella Vitalone, Marco Gullì, Alberto Macone, Evangelos Axiotis, Alexios Leandros Skaltsounis.
      Sideritis sipylea Boiss. (Fam. Lamiaceae) is an endemic plant of the North Aegean Islands (Greece), commonly known as ironwort. Traditionally, its aerial parts have been used to relieve several ailments, especially gastrointestinal disorders, however, with scant knowledge about the pharmacological basis. In the present study, an endemic S. sipylea Greek species from Lesvos Island has been characterized for phytochemical composition and biological activities, in order to give a possible scientific basis to its traditional use and to highlight a further nutraceutical interest as a source of bioactive phytochemicals and extracts. Three different fractions obtained from a methanolic extract of S. sipylea aerial parts by using ethyl acetate with 10 (S10), 20 (S20), and 50% (S50) methanol as fractionation solvents were phytochemically characterized. Moreover, their antioxidant power and cytoprotective activity in different human cell lines were evaluated. The phytochemical analysis highlighted the presence of flavonoids, iridoids, and phenolic acids in all the tested samples. Particularly, the S10 fraction mainly contained iridoids, while S20 and S50 lavandulifolioside and chlorogenic acid, respectively. The fractions also showed antioxidant properties, S10 and S20 being the most potent. When assessed in human cholangiocytes, they counteracted the cytotoxicity of the tBOOH pro-oxidant agent, by reducing ROS levels and affecting GSH antioxidant system. The present findings highlight a possible interest in S10 and S20 fractions from S. sipylea as sources of bioactive molecules and stimulate further studies in order to characterize their possible application for nutraceutical and pharmaceutical purposes.
    Keywords:  Greek medicinal plants; North Aegean; UPLC-HRMS/MS; advanced glycation end products; antioxidant activity; antiproliferative activity; chelating activity; mountain tea; oxidative stress; phenolics
    DOI:  https://doi.org/10.3390/ph15080987
  256. Nanomedicine (Lond). 2022 Aug 25.
    Antitumor applications of polyphenol-conjugated turnip mosaic virus-derived nanoparticles.
    Edith Velázquez-Lam, Jaime Tome-Amat, Carmen Segrelles, Carmen Yuste-Calvo, Sara Asensio, Jorge Peral, Fernando Ponz, Corina Lorz.
      Background: Filamentous plant virus-derived nanoparticles are biodegradable and noninfectious to humans. Their structure is also amenable to chemical modifications. They constitute an appealing material for biomedical applications including imaging and drug delivery. We had previously used turnip mosaic virus-derived nanoparticles (TuMV-NPs) to increase antibody-sensing in vivo, to prevent biofilm formation and to build biological nanoscaffolds. Materials & methods: We analyzed TuMV-NP biodistribution and tumor homing using in vivo imaging. We studied in vitro the interaction with human cancer cell lines and the antiproliferative effect of epigallocatechin gallate-functionalized TuMV-NPs. Results & conclusion: TuMV-NPs are efficiently internalized by human cells and show good tumor homing. The antiproliferative effect of epigallocatechin gallate-TuMV-NPs suggests that they could offer a potential anticancer therapy.
    Keywords:  antitumor applications; biodistribution; cancer cell lines; cancer therapy; epigallocatechin gallate; green tea; head and neck cancer; in vivo imaging; turnip mosaic virus; viral-derived nanoparticles
    DOI:  https://doi.org/10.2217/nnm-2022-0067
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