bims-kracam Biomed News
on K-Ras in cancer metabolism
Issue of 2022‒10‒16
121 papers selected by
Yasmin Elkabani, Egyptian Foundation for Research and Community Development
  1. Ginsenosides in cancer: A focus on the regulation of cell metabolism.
  2. Therapeutic Drug-Induced Metabolic Reprogramming in Glioblastoma.
  3. Advances in Dietary Phenolic Compounds to Improve Chemosensitivity of Anticancer Drugs.
  4. Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies.
  5. Polyphenols as Potent Epigenetics Agents for Cancer.
  6. Resveratrol in cancer therapy; from stimulation of genomic stability to adjuvant cancer therapy; A comprehensive review.
  7. Chitosan on the surface of nanoparticles for enhanced drug delivery: A comprehensive review.
  8. From iron chelation to overload as a therapeutic strategy to induce ferroptosis in hematologic malignancies.
  9. The ketogenic diet could improve the efficacy of curcumin and Oldenlandia diffusa extract in the treatment of gastric cancer by increasing miR340 expression and apoptosis mediated by autophagy, oxidative stress, and angiogenesis.
  10. Ferritin-hijacking Nanoparticles Spatiotemporally Directing Endogenous Ferroptosis for Synergistic Anticancer Therapy.
  11. Photodynamic therapy in breast cancer treatment.
  12. Current status and future perspective of sonodynamic therapy for cancer.
  13. The "Sweet Spot" of Targeting Tumor Metabolism in Ovarian Cancers.
  14. Nanogels as Potential Delivery Vehicles in Improving the Therapeutic Efficacy of Phytopharmaceuticals.
  15. Chitosan Nanoparticles: A Versatile Platform for Biomedical Applications.
  16. The dynamicity of mutant KRAS β2 strand modulates its downstream activation and predicts anticancer KRAS inhibition.
  17. Flavonoids in vegetables: improvement of dietary flavonoids by metabolic engineering to promote health.
  18. Recent Advances in Natural Product-Based Hybrids as Anti-Cancer Agents.
  19. Glutathione peroxidase 2 overexpression promotes malignant progression and cisplatin resistance of KRAS‑mutated lung cancer cells.
  20. Topical Advances in Mucoadhesive Ocular Drug Delivery System.
  21. Pharmacokinetic of berberine, the main constituent of Berberis vulgaris L.: A comprehensive review.
  22. Tumor microenvironment and redox dual stimuli-responsive polymeric nanoparticles for the effective cisplatin-based cancer chemotherapy.
  23. Polyphenol-Rich Ginger (Zingiber officinale) for Iron Deficiency Anaemia and Other Clinical Entities Associated with Altered Iron Metabolism.
  24. Critical Review on Nutritional, Bioactive, and Medicinal Potential of Spices and Herbs and Their Application in Food Fortification and Nanotechnology.
  25. Recent findings on the role of wild-type and mutant p53 in cancer development and therapy.
  26. Mentha: Nutritional and Health Attributes to Treat Various Ailments Including Cardiovascular Diseases.
  27. Effect of Ketogenic Diets on Body Composition and Metabolic Parameters of Cancer Patients: A Systematic Review and Meta-Analysis.
  28. Tumor-targeting oxidative stress nanoamplifiers as anticancer nanomedicine with immunostimulating activity.
  29. Evolutionary View on Lactate-Dependent Mechanisms of Maintaining Cancer Cell Stemness and Reprimitivization.
  30. Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention.
  31. Curcumin encapsulation in self-assembled nanoparticles based on amphiphilic palmitic acid-grafted-quaternized chitosan with enhanced cytotoxic, antimicrobial and antioxidant properties.
  32. Potential of Kalanchoe pinnata as a Cancer Treatment Adjuvant and an Epigenetic Regulator.
  33. Nanoparticles Loaded with Platinum Drugs for Colorectal Cancer Therapy.
  34. Crataegus pinnatifida: A botanical, ethnopharmacological, phytochemical, and pharmacological overview.
  35. Recent Reports on Polysaccharide-Based Materials for Drug Delivery.
  36. A technical note on emerging combination approach involved in the onconanotherapeutics.
  37. Nanoenzyme-chitosan hydrogel complex with cascade catalytic and self-reinforced antibacterial performance for accelerated healing of diabetic wounds.
  38. Monoamine Oxidase Inhibitors Prevent Glucose-Dependent Energy Production, Proliferation and Migration of Bladder Carcinoma Cells.
  39. Selected polyphenolic compounds and their use as a supportive therapy in metabolic syndrome.
  40. Enhanced Antioxidant and Anti-Inflammatory Effects of Self-Nano and Microemulsifying Drug Delivery Systems Containing Curcumin.
  41. Ferroptosis: A new strategy for traditional Chinese medicine treatment of stroke.
  42. Antitumor effects of Chinese herbal medicine compounds and their nano-formulations on regulating the immune system microenvironment.
  43. Porphyrin Centered Paclitaxel Tetrameric Prodrug Nanoassembliesas Tumor-Selective Theranostics for Synergized Breast Cancer Therapy.
  44. New Insights into Dietary Pterostilbene: Sources, Metabolism, and Health Promotion Effects.
  45. Repurposing of Benzimidazole Anthelmintic Drugs as Cancer Therapeutics.
  46. Inhibition of Glycogen Metabolism Induces Reactive Oxygen Species-Dependent Cytotoxicity in Anaplastic Thyroid Cancer in Female Mice.
  47. Post-Remedial Oxygen Supply: A New Perspective on Photodynamic Therapy to Suppress Tumor Metastasis.
  48. Liposomes encapsulating methylene blue and acridine orange: An approach for phototherapy of skin cancer.
  49. Hydrogels as promising carriers for the delivery of food bioactive ingredients.
  50. Polydopamine encapsulated new indocyanine green theranostic nanoparticles for enhanced photothermal therapy in cervical cancer HeLa cells.
  51. Curcumin-loaded hydroxypropyl-β-cyclodextrin inclusion complex with enhanced dissolution and oral bioavailability for epilepsy treatment.
  52. The Problem of Vitamin D Scarcity: Cultural and Genetic Solutions by Indigenous Arctic and Tropical Peoples.
  53. Resveratrol-loaded α-lactalbumin-chitosan nanoparticle-encapsulated high internal phase Pickering emulsion for curcumin protection and its in vitro digestion profile.
  54. Recent progress in nitric oxide-generating nanomedicine for cancer therapy.
  55. Effect of TP53 deficiency and KRAS signaling on the bioenergetics of colon cancer cells in response to different substrates: A single cell study.
  56. Polyphenols in Metabolic Diseases.
  57. Curcumin and Diclofenac Therapeutic Efficacy Enhancement Applying Transdermal Hydrogel Polymer Films, Based on Carrageenan, Alginate and Poloxamer.
  58. Evaluating Cannabis sativa L.'s neuroprotection potential: From bench to bedside.
  59. Hepatocellular carcinoma stage: an almost loss of fatty acid metabolism and gain of glucose metabolic pathways dysregulation.
  60. Suicide gene delivery system mediated by ultrasound targeted microbubble destruction: A promising strategy for cancer therapy.
  61. Using omics approaches to dissect the therapeutic effects of Chinese herbal medicines on gastrointestinal cancers.
  62. Andrographolide, a natural anti-inflammatory agent: An Update.
  63. The Warburg effect in osteoporosis: Cellular signaling and epigenetic regulation of energy metabolic events to targeting the osteocalcin for phenotypic alteration.
  64. Biomimetic Targeted Theranostic Nanoparticles for Breast Cancer Treatment.
  65. Sesame (Sesamum indicum L.): A Comprehensive Review of Nutritional Value, Phytochemical Composition, Health Benefits, Development of Food, and Industrial Applications.
  66. Engineered Mesoporous Silica-Based Core-Shell Nanoarchitectures for Synergistic Chemo-Photodynamic Therapies.
  67. Oxidative Stress and Autophagy Mediate Anti-Cancer Properties of Cannabis Derivatives in Human Oral Cancer Cells.
  68. A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells.
  69. Fast dissolving oral films: An approach to co-load and deliver the atorvastatin and ezetimibe for better therapeutic response.
  70. Curcumin Sustained Release with a Hybrid Chitosan-Silk Fibroin Nanofiber Containing Silver Nanoparticles as a Novel Highly Efficient Antibacterial Wound Dressing.
  71. Development, Evaluation, Pharmacokinetic and Biodistribution Estimation of Resveratrol Loaded Solid Lipid Nanoparticles for Prostate Cancer Targeting.
  72. Evaluation of the Anti-Cancer Potential of Rosa damascena Mill. Callus Extracts against the Human Colorectal Adenocarcinoma Cell Line.
  73. Intracellular pH-Regulating Nanoparticles to Improve Anticancer Drug Efficacy for Cancer Treatment.
  74. A mitochondria-targeted nano-platform for pancreatic cancer therapy.
  75. Molecular Mechanistic Pathways Targeted by Natural Compounds in the Prevention and Treatment of Diabetic Kidney Disease.
  76. Polydatin: Pharmacological Mechanisms, Therapeutic Targets, Biological Activities, and Health Benefits.
  77. Efficacy of Metformin as Adjuvant Therapy in Metastatic Breast Cancer Treatment.
  78. Gold Nanoparticle-Incorporated Chitosan Nanogels as a Theranostic Nanoplatform for CT Imaging and Tumour Chemotherapy.
  79. L-Cysteine Modified Chitosan Nanoparticles and Carbon-Based Nanostructures for the Intranasal Delivery of Galantamine.
  80. Photodynamic therapy for prostate cancer: Recent advances, challenges and opportunities.
  81. Advancements of Prussian blue-based nanoplatforms in biomedical fields: Progress and perspectives.
  82. Breast Cancer Metastatic Dormancy and Relapse: An enigma of microenvironment(s).
  83. Physicochemical aspects of the tumour microenvironment as drivers of vasculogenic mimicry.
  84. Nanomaterial-Based Drug Delivery Systems: A New Weapon for Cancer Immunotherapy.
  85. Self-Amplified Chain-Shattering Cinnamaldehyde-Based Poly(thioacetal) Boosts Cancer Chemo-Immunotherapy.
  86. Carbohydrate and sleep: An evaluation of putative mechanisms.
  87. Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy.
  88. Delivery of curcumin by shellac encapsulation: Stability, bioaccessibility, freeze-dried redispersibility, and solubilization.
  89. Amphotericin B-Loaded Plant-Inspired Polyphenol Nanoparticles Enhance Its Antifungal Activity and Biocompatibility.
  90. A review of protein-phenolic acid interaction: reaction mechanisms and applications.
  91. Supramolecular Tools to Improve Wound Healing and Antioxidant Properties of Abietic Acid: Biocompatible Microemulsions and Emulgels.
  92. Definition, Assessment, and Management of Vitamin D Inadequacy: Suggestions, Recommendations, and Warnings from the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS).
  93. Is Melatonin the "Next Vitamin D"?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements.
  94. A Comprehensive Review on Beneficial Effects of Catechins on Secondary Mitochondrial Diseases.
  95. Formulation, Characterisation and Evaluation of the Antihypertensive Peptides, Isoleucine-Proline-Proline and Leucine-Lysine-Proline in Chitosan Nanoparticles Coated with Zein for Oral Drug Delivery.
  96. Advances in Preclinical/Clinical Glioblastoma Treatment: Can Nanoparticles Be of Help?
  97. Ferroptosis and its emerging role in esophageal cancer.
  98. Lactate-Lactylation Hands between Metabolic Reprogramming and Immunosuppression.
  99. The effect of insulin-loaded gold and carboxymethyl chitosan nanoparticles on gene expression of glucokinase and pyruvate kinase in rats with diabetes type 1.
  100. Phytochemistry, Biological and Pharmacological Activities of the Anacyclus pyrethrum (L.) Lag: A Systematic Review.
  101. Feeding the Brain: Effect of Nutrients on Cognition, Synaptic Function, and AMPA Receptors.
  102. Metabolic Reprogramming in Tumor Endothelial Cells.
  103. Polygonum capitatum, the Hmong Medicinal Flora: A Comprehensive Review of Its Phytochemical, Pharmacological and Pharmacokinetic Characteristics.
  104. Recent advances in oral delivery of bioactive molecules: Focus on prebiotic carbohydrates as vehicle matrices.
  105. Applications of Focused Ultrasound for the Treatment of Glioblastoma: A New Frontier.
  106. Targeting hypoxia-inducible factor-1alpha: A new strategy for triple-negative breast cancer therapy.
  107. The role of iron nanoparticles on anaerobic digestion: mechanisms, limitations, and perspectives.
  108. A vicious circle in breast cancer: The interplay between inflammation, reactive oxygen species, and microRNAs.
  109. The development of a novel antioxidant-based antiemetic drug to improve quality of life during anticancer therapy.
  110. Mitochondrial transporter expression patterns distinguish tumor from normal tissue and identify cancer subtypes with different survival and metabolism.
  111. Nutrition and Microbiome Interactions in Human Cancer.
  112. The design of multi-responsive nanohydrogel networks of chitosan for controlled drug delivery.
  113. Lipid nanocapsules enhance the transdermal delivery of drugs regardless of their physico-chemical properties.
  114. The Good, the Bad and the New about Uric Acid in Cancer.
  115. Selenium: An Antioxidant with a Critical Role in Anti-Aging.
  116. The interferon-inducible protein viperin controls cancer metabolic reprogramming to enhance cancer progression.
  117. Nutraceuticals and COVID-19: A mechanistic approach toward attenuating the disease complications.
  118. Multifunctional chitosan ferrogels for targeted cancer therapy by on-demand magnetically triggered drug delivery and hyperthermia.
  119. Thermosensitive Liposomal Nanoplatform Based on Metal-Free Phthalocyanine with Copper(II)-Regulated Photoactivities.
  120. VITAMIN D LEVEL AND ITS RELATIONSHIP WITH CANCER STAGE IN PATIENTS WITH DIFFERENTIATED THYROID CARCINOMA.
  121. A hydrogel-fiber-hydrogel composite scaffold based on silk fibroin with the dual-delivery of oxygen and quercetin.
  1. Biomed Pharmacother. 2022 Oct 10. pii: S0753-3322(22)01145-3. [Epub ahead of print]156 113756
    Ginsenosides in cancer: A focus on the regulation of cell metabolism.
    Wang Yao, Yunfeng Guan.
      Metabolic alterations play a key role in promoting tumor initiation and progression, leading to extensive tumor heterogeneity and adaptability. Thus, targeting abnormal metabolic processes is a promising novel approach for cancer treatment. Numerous pharmacological studies have indicated that many traditional Chinese medicines possess remarkable antitumor activities. Ginsenosides, the main bioactive ingredients of Panax and other types of ginseng, exert beneficial antitumor effects, in addition to the anti-inflammation, anti-oxidant, and anti-fatigue effects. Recently, considerable attention has been paid to the regulation of cancer cell metabolism by ginsenosides. Here, we summarize the structural characteristics and classification of ginsenosides, their antitumor mechanisms, recent progress and the achievements of ginsenoside research in modulating cancer cell metabolism, including the diverse metabolic processes and their regulatory processes, as well as the opportunities and challenges of strategies targeting metabolic vulnerabilities. This review provides novel perspectives on the potential applications of ginsenosides that exert antitumor effects by reshaping cancer metabolism.
    Keywords:  Antitumor activity; Cancer; Cell metabolism; Ginsenosides; Mechanism
    DOI:  https://doi.org/10.1016/j.biopha.2022.113756
  2. Cells. 2022 Sep 22. pii: 2956. [Epub ahead of print]11(19):
    Therapeutic Drug-Induced Metabolic Reprogramming in Glioblastoma.
    Trang T T Nguyen, Enyuan Shang, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D Siegelin.
      Glioblastoma WHO IV (GBM), the most common primary brain tumor in adults, is a heterogenous malignancy that displays a reprogrammed metabolism with various fuel sources at its disposal. Tumor cells primarily appear to consume glucose to entertain their anabolic and catabolic metabolism. While less effective for energy production, aerobic glycolysis (Warburg effect) is an effective means to drive biosynthesis of critical molecules required for relentless growth and resistance to cell death. Targeting the Warburg effect may be an effective venue for cancer treatment. However, past and recent evidence highlight that this approach may be limited in scope because GBM cells possess metabolic plasticity that allows them to harness other substrates, which include but are not limited to, fatty acids, amino acids, lactate, and acetate. Here, we review recent key findings in the literature that highlight that GBM cells substantially reprogram their metabolism upon therapy. These studies suggest that blocking glycolysis will yield a concomitant reactivation of oxidative energy pathways and most dominantly beta-oxidation of fatty acids.
    Keywords:  TCA cycle; glioblastoma; glycolysis; metabolism; oxidative phosphorylation (OXPHOS)
    DOI:  https://doi.org/10.3390/cells11192956
  3. Cancers (Basel). 2022 Sep 21. pii: 4573. [Epub ahead of print]14(19):
    Advances in Dietary Phenolic Compounds to Improve Chemosensitivity of Anticancer Drugs.
    Abdelhakim Bouyahya, Nasreddine El Omari, Saad Bakrim, Naoufal El Hachlafi, Abdelaali Balahbib, Polrat Wilairatana, Mohammad S Mubarak.
      Despite the significant advances and mechanistic understanding of tumor processes, therapeutic agents against different types of cancer still have a high rate of recurrence associated with the development of resistance by tumor cells. This chemoresistance involves several mechanisms, including the programming of glucose metabolism, mitochondrial damage, and lysosome dysfunction. However, combining several anticancer agents can decrease resistance and increase therapeutic efficacy. Furthermore, this treatment can improve the effectiveness of chemotherapy. This work focuses on the recent advances in using natural bioactive molecules derived from phenolic compounds isolated from medicinal plants to sensitize cancer cells towards chemotherapeutic agents and their application in combination with conventional anticancer drugs. Dietary phenolic compounds such as resveratrol, gallic acid, caffeic acid, rosmarinic acid, sinapic acid, and curcumin exhibit remarkable anticancer activities through sub-cellular, cellular, and molecular mechanisms. These compounds have recently revealed their capacity to increase the sensitivity of different human cancers to the used chemotherapeutic drugs. Moreover, they can increase the effectiveness and improve the therapeutic index of some used chemotherapeutic agents. The involved mechanisms are complex and stochastic, and involve different signaling pathways in cancer checkpoints, including reactive oxygen species signaling pathways in mitochondria, autophagy-related pathways, proteasome oncogene degradation, and epigenetic perturbations.
    Keywords:  cancer; chemotherapy; combination treatment; dietary phenolic compounds; drugs resistance; drugs sensibilization
    DOI:  https://doi.org/10.3390/cancers14194573
  4. Cancers (Basel). 2022 Sep 21. pii: 4568. [Epub ahead of print]14(19):
    Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies.
    Yi Zhang, Qiong Li, Zhao Huang, Bowen Li, Edouard C Nice, Canhua Huang, Liuya Wei, Bingwen Zou.
      Reprogramming of glucose metabolism provides sufficient energy and raw materials for the proliferation, metastasis, and immune escape of cancer cells, which is enabled by glucose metabolism-related enzymes that are abundantly expressed in a broad range of cancers. Therefore, targeting glucose metabolism enzymes has emerged as a promising strategy for anticancer drug development. Although several glucose metabolism modulators have been approved for cancer treatment in recent years, some limitations exist, such as a short half-life, poor solubility, and numerous adverse effects. With the rapid development of medicinal chemicals, more advanced and effective glucose metabolism enzyme-targeted anticancer drugs have been developed. Additionally, several studies have found that some natural products can suppress cancer progression by regulating glucose metabolism enzymes. In this review, we summarize the mechanisms underlying the reprogramming of glucose metabolism and present enzymes that could serve as therapeutic targets. In addition, we systematically review the existing drugs targeting glucose metabolism enzymes, including small-molecule modulators and natural products. Finally, the opportunities and challenges for glucose metabolism enzyme-targeted anticancer drugs are also discussed. In conclusion, combining glucose metabolism modulators with conventional anticancer drugs may be a promising cancer treatment strategy.
    Keywords:  glucose metabolism enzymes; glycolysis; malignant tumor; targeted therapy
    DOI:  https://doi.org/10.3390/cancers14194568
  5. Int J Mol Sci. 2022 Oct 03. pii: 11712. [Epub ahead of print]23(19):
    Polyphenols as Potent Epigenetics Agents for Cancer.
    Peramaiyan Rajendran, Salaheldin Abdelraouf Abdelsalam, Kaviyarasi Renu, Vishnupriya Veeraraghavan, Rebai Ben Ammar, Emad A Ahmed.
      Human diseases such as cancer can be caused by aberrant epigenetic regulation. Polyphenols play a major role in mammalian epigenome regulation through mechanisms and proteins that remodel chromatin. In fruits, seeds, and vegetables, as well as food supplements, polyphenols are found. Compounds such as these ones are powerful anticancer agents and antioxidants. Gallic acid, kaempferol, curcumin, quercetin, and resveratrol, among others, have potent anti-tumor effects by helping reverse epigenetic changes associated with oncogene activation and tumor suppressor gene inactivation. The role dietary polyphenols plays in restoring epigenetic alterations in cancer cells with a particular focus on DNA methylation and histone modifications was summarized. We also discussed how these natural compounds modulate gene expression at the epigenetic level and described their molecular targets in cancer. It highlights the potential of polyphenols as an alternative therapeutic approach in cancer since they modulate epigenetic activity.
    Keywords:  cancer; epigenetics; polyphenol
    DOI:  https://doi.org/10.3390/ijms231911712
  6. Curr Top Med Chem. 2022 Oct 14.
    Resveratrol in cancer therapy; from stimulation of genomic stability to adjuvant cancer therapy; A comprehensive review.
    Peyman Amini, Reza Moazamiyanfar, Mohammad Sedigh Dakkali, Ali Khani, Emad Jafarzadeh, Kave Mouludi, Ehsan Khodamoradi, Ramin Johari, Shahram Taeb, Masoud Najafi.
      Cancer therapy through anticancer drugs and radiotherapy is associated with several side effects as well as tumor resistance to therapy. The genotoxic effects of chemotherapy and radiotherapy may lead to genomic instability and increased risk of second cancers. Furthermore, some responses in the tumor may induce the exhaustion of antitumor immunity and increase the resistance of cancer cells to therapy. Administration of low-toxicity adjuvants to protect normal tissues and improve therapy efficacy is an intriguing strategy. Several studies have focused on natural-derived agents for improving the antitumor efficiency of radiotherapy, chemotherapy, and novel anticancer drugs such as immunotherapy and targeted cancer therapy. Resveratrol is a naturally occurring substance with intriguing antioxidant, cardioprotective, anti-diabetes, and antitumor properties. Resveratrol has been demonstrated to modulate tumor resistance and mitigate normal tissue toxicity following exposure to various drugs and ionizing radiation. Compelling data suggest that resveratrol may be an appealing adjuvant in combination with various anticancer modalities. Although the natural form of resveratrol has some limitations, such as low absorption in the intestine and low bioavailability, several experiments have demonstrated that using certain carriers, such as nanoparticles, can increase the therapeutic efficacy of resveratrol in preclinical studies. This review highlights various effects of resveratrol that may be useful for cancer therapy. Consequently, we describe how resveratrol can protect normal tissue from genomic instability. In addition, the various mechanisms by which resveratrol exerts its antitumor effects are addressed. Moreover, the outcomes of combination therapy with resveratrol and other anticancer agents are reviewed.
    Keywords:  Cancer; Chemotherapy; Genomic Instability; Radiotherapy; Resveratrol
    DOI:  https://doi.org/10.2174/1568026623666221014152759
  7. J Control Release. 2022 Oct 11. pii: S0168-3659(22)00675-7. [Epub ahead of print]351 923-940
    Chitosan on the surface of nanoparticles for enhanced drug delivery: A comprehensive review.
    Mohammed H Elkomy, Adel A Ali, Hussein M Eid.
      The ability of chitosan (CTS) to promote mucoadhesion, trigger positive/negative surface interactions, and open tight junctions has inspired researchers to coat lipid-based and polymeric-based nanoparticles with CTS in an attempt to reach new heights in the delivery of drugs and nutraceuticals across different routes. This article discusses literature relevant to the pharmaceutical and biomedical area published in the last 10 years on nanoparticles overlaid with CTS. Herein, we addressed the technical aspects of the coating procedure by adding CTS solution to nanoparticles that have already been produced or during the production phase. Besides, we reviewed the applications of CTS coated nanoparticles as drug delivery systems in the oral and non-oral routes of administrations. Special attention was paid to the physicochemical and biological benefits of the CTS coating, such as improving physicochemical stability, enhancing cell and tissue interactions, controlled drug release, and augmentation of active substance bioavailability and efficacy. Moreover, this review projects the current standing and future prospects of the delivery system. The future calls for more investigations on therapeutic proteins, genes and vaccines as potential cargos. Extensive studies on the merits of integrating CTS with hydropolymer-synthesized nanoparticles and using longer-chain and chemically-modified variants of CTS are also warranted.
    Keywords:  Chitosan; Coating; Liposomes; Nanostructured lipid carriers; Poly-lactic-co-glycolic acid; Solid lipid nanoparticles
    DOI:  https://doi.org/10.1016/j.jconrel.2022.10.005
  8. Hematology. 2022 Dec;27(1): 1163-1170
    From iron chelation to overload as a therapeutic strategy to induce ferroptosis in hematologic malignancies.
    Jiaojiao Li, Wei Zhang.
      OBJECTIVES: Ferroptosis is an iron-dependent, non-apoptotic mode of cell death characterized by excessive accumulation of reactive oxygen species (ROS). It plays an important role in the occurrence, development and treatment of various cancers, but little is known regarding the role of ferroptosis in hematologic malignancies. This review elaborates the regulatory mechanism of ferroptosis and the treatment opportunities for targeting ferroptosis in hematologic malignancies.METHODS: A systematic literature review through PubMed was conducted to summarize the published evidence on the therapeutic potential of targeting ferroptosis in hematological malignant tumors. Literature sources published in English were searched, using the terms ferroptosis, leukemia, myelodysplastic syndrome, lymphoma and multiple myeloma.
    RESULTS: More and more small molecules have been found to induce ferroptosis in hematologic malignancies through targeted iron metabolism and lipid peroxidation, and some ferroptosis inducers have been proved to have synergistic effect with other chemotherapeutic drugs.
    CONCLUSION: This paper discusses the significance of ferroptosis in hematologic malignancies and provides a new way for the treatment of hematologic malignancies, and more experimental studies should be conducted in future.
    Keywords:  Ferroptosis; Ferroptosis-inducing agents; hematological malignancies; iron; iron chelation; iron overload; lipid Peroxidation; reactive oxygen species (ROS)
    DOI:  https://doi.org/10.1080/16078454.2022.2132362
  9. J Food Biochem. 2022 Oct 11. e14407
    The ketogenic diet could improve the efficacy of curcumin and Oldenlandia diffusa extract in the treatment of gastric cancer by increasing miR340 expression and apoptosis mediated by autophagy, oxidative stress, and angiogenesis.
    Qiuju Xiao, Bo Deng, Abolfazl Akbari, Qisheng Liu, Bisheng Zhu.
      The pathogenesis of gastric cancer is a multistage process that involves glucose metabolism, inflammation, oxidative damage, angiogenesis, autophagy, and apoptosis. Moreover, microRNA-340 (miR340) also plays a vital role in tumorigenesis and the biology of gastric cancer as an epigenetic factor. It seems that the use of ketogenic diets (KDs) and plant extracts that have antitumor, anti-inflammatory, and antioxidant properties can be good treatment options to cure gastric cancer. The aim of this study was to investigate the role of miR-340 on pathways involved in the pathogenesis of gastric cancer and the improving effects of the KD, Oldenlandia diffusa extract (ODE), and curcumin in the animal model of gastric cancer. One hundred and ten male Wistar rats were divided into control and treatment groups. The expression of miR-340 along with genes involved in inflammation, oxidative damage, angiogenesis, and apoptosis were assessed. The results showed that the KD and different doses of curcumin and ODE in a dose-dependent behavior could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue of rats with cancer. In addition, there was no significant difference between cancer groups receiving ODE and curcumin. These results also showed that consumption of KD could significantly increase the efficacy of ODE and curcumin which may be due to increasing miR-340 expression. The results of this study suggested well that the KD along with conventional therapies in traditional medicine can be a useful solution for the prevention and treatment of gastric cancer. PRACTICAL APPLICATIONS: Gastric cancer is the third leading cause of cancer death, and genetic and epigenetic factors, including miR-340, are involved in its pathogenesis. However, the use of ketogenic diets (KDs) and plant products such as curcumin and Oldenlandia diffusa extract (ODE) can play an effective role in inhibiting tumorigenesis in some cancers. Our results showed that the KD and different doses of curcumin and ODE could induce apoptosis and the expression of the Akt/mTORC1 pathway and inhibit inflammation, oxidative damage, and angiogenesis in the gastric tissue. Moreover, the KD could significantly increase the efficacy of ODE and curcumin which may be due to an increase in miR-340 expression. These findings provide novel perceptions about the mechanisms of the KD, curcumin, and ODE to cure gastric cancer. It suggested that the KD as adjunctive therapy along with conventional therapies in traditional medicine could be considered a useful solution to prevent and treat gastric cancer.
    Keywords:   Oldenlandia diffusa ; curcumin; gastric cancer; ketogenic diet; miR340
    DOI:  https://doi.org/10.1111/jfbc.14407
  10. Adv Mater. 2022 Oct 10. e2207174
    Ferritin-hijacking Nanoparticles Spatiotemporally Directing Endogenous Ferroptosis for Synergistic Anticancer Therapy.
    Luwen Zhu, Yuchan You, Minxia Zhu, Yanling Song, Jucong Zhang, Jiahao Hu, Xinyi Xu, Xiaoling Xu, Yongzhong Du, Jiansong Ji.
      Existing ferroptosis as an iron-dependent form of regulated cell death primarily relies on importing exogenous iron. However, the excessive employment of toxic materials may cause potential adverse effects on human health. Herein, we fabricated a ferritin-hijacking nanoparticle (Ce6-PEG-HKN15 ) by conjugating the ferritin-homing peptide HKN15 with the photosensitizer chlorin e6 (Ce6) for endogenous ferroptosis without introducing Fenton-reactive metals. Once internalized, the designed Ce6-PEG-HKN15 NPs could specifically accumulate around ferritin. With laser irradiation, the activated Ce6 in nanoparticles potently generated reactive oxygen species (ROS) surrounding ferritin. Abundant ROS not only help to destroy the iron storage protein and activate endogenous ferroptosis but also directly kill tumor cells. In turn, the released iron partially interacted with intracellular excess H2 O2 to produce O2 , thereby enhancing photodynamic therapy (PDT) and further amplifying oxidative stress. Overall, this work highlights the possibility of endogenous ferroptosis via spatiotemporally destroying ferritin, offering a paradigm for synergistic ferroptosis-photodynamic antitumor therapy. This article is protected by copyright. All rights reserved.
    Keywords:  endogenous ferroptosis; ferritin; nanosystem; photodynamic therapy; synergistic therapy
    DOI:  https://doi.org/10.1002/adma.202207174
  11. J Appl Biomed. 2022 Oct;20(3): 98-105
    Photodynamic therapy in breast cancer treatment.
    Joanna Gustalik, David Aebisher, Dorota Bartusik-Aebisher.
      Breast cancer is a serious public problem in modern society. Photodynamic therapy (PDT) is increasingly used in modern medicine. Currently, PDT is an innovative method of treating breast cancer. Irreversible damage to neoplastic tissues is associated with the use of physicochemical processes. Generating cytotoxic reactive oxygen species [singlet oxygen (1O2)] is leading to tumor cell death. At the same time, valuable information can be extracted from breast cancer cells. Photogenerated 1O2 is the major factor responsible for cell necrosis during PDT. 1O2 can react rapidly intracellularly with all organic substances. The use of photodynamic therapy on tissues in vitro creates conditions for testing various types of solutions and implementing them in in vivo treatment. This article is a review of recent advances in PDT for treatment of breast cancer. PDT is a novel cancer diagnostic and cancer treatment therapy. Therefore, an understanding of the possibility to generate a toxic form of 1O2 is necessary. The knowledge gained from the basics of PDT in vitro can be useful in biomedical applications in vivo. The current literature mentions PDT in the treatment of cancers located very deep within the human body. Therefore, the development of agents used to deliver 1O2 to the deep cancerous tissue is a new challenge which can have an efficient impact on this discipline. This review covers the literature between 2000-2022.
    Keywords:  Breast cancer tissues; Intracellular; Photodynamic therapy; Reactive oxygen species; Treatment
    DOI:  https://doi.org/10.32725/jab.2022.013
  12. J Med Ultrason (2001). 2022 Oct 12.
    Current status and future perspective of sonodynamic therapy for cancer.
    Atsushi Sofuni, Takao Itoi.
      There is a tremendous need for prevention and effective treatment of cancer due to the associated morbidity and mortality. In this study, we introduce sonodynamic therapy (SDT), which is expected to be a new cancer treatment modality. SDT is a promising option for minimally invasive treatment of solid tumors and comprises three different components: sonosensitizers, ultrasound, and molecular oxygen. These components are harmless individually, but in combination they generate cytotoxic reactive oxygen species (ROS). We will explore the molecular mechanism by which SDT kills cancer cells, the class of sonosensitizers, drug delivery methods, and in vitro and in vivo studies. At the same time, we will highlight clinical applications for cancer treatment. The progress of SDT research suggests that it has the potential to become an advanced field of cancer treatment in clinical application. In this article, we will focus on the mechanism of action of SDT and its application to cancer treatment, and explain key factors to aid in developing strategies for future SDT development.
    Keywords:  Minimally invasive cancer therapy; Sonodynamic therapy; Sonosensitizers; Ultrasound
    DOI:  https://doi.org/10.1007/s10396-022-01263-x
  13. Cancers (Basel). 2022 Sep 27. pii: 4696. [Epub ahead of print]14(19):
    The "Sweet Spot" of Targeting Tumor Metabolism in Ovarian Cancers.
    Katelyn Tondo-Steele, Karen McLean.
      The objective of this review is to explore the metabolomic environment of epithelial ovarian cancer that contributes to chemoresistance and to use this knowledge to identify possible targets for therapeutic intervention. The Warburg effect describes increased glucose uptake and lactate production in cancer cells. In ovarian cancer, we require a better understanding of how cancer cells reprogram their glycogen metabolism to overcome their nutrient deficient environment and become chemoresistant. Glucose metabolism in ovarian cancer cells has been proposed to be influenced by altered fatty acid metabolism, oxidative phosphorylation, and acidification of the tumor microenvironment. We investigate several markers of altered metabolism in ovarian cancer including hypoxia-induced factor 1, VEGF, leptin, insulin-like growth factors, and glucose transporters. We also discuss the signaling pathways involved with these biomarkers including PI3K/AKT/mTOR, JAK/STAT and OXPHOS. This review outlines potential metabolic targets to overcome chemoresistance in ovarian cancer. Continued research of the metabolic changes in ovarian cancer is needed to identify and target these alterations to improve treatment approaches.
    Keywords:  PI3K/AKT/mTOR; fatty acid oxidation; glucose; glycolysis; insulin; leptin; metabolism; metabolomics; ovarian cancer; oxidative phosphorylation
    DOI:  https://doi.org/10.3390/cancers14194696
  14. Polymers (Basel). 2022 Oct 03. pii: 4141. [Epub ahead of print]14(19):
    Nanogels as Potential Delivery Vehicles in Improving the Therapeutic Efficacy of Phytopharmaceuticals.
    Murtada Taha, Nabil A Alhakamy, Shadab Md, Mohammad Zaki Ahmad, Md Rizwanullah, Sana Fatima, Naveed Ahmed, Faisal M Alyazedi, Shahid Karim, Javed Ahmad.
      Nanogel is a promising drug delivery approach to improve the pharmacokinetics and pharmacodynamic prospect of phytopharmaceuticals. In the present review, phytopharmaceuticals with astonishing therapeutic utilities are being explored. However, their in vivo delivery is challenging, owing to poor biopharmaceutical attributes that impact their drug release profile, skin penetration, and the reach of optimal therapeutic concentrations to the target site. Nanogel and its advanced version in the form of nanoemulgel (oil-in-water nanoemulsion integrated gel matrix) offer better therapeutic prospects than other conventional counterparts for improving the biopharmaceutical attributes and thus therapeutic efficacy of phytopharmaceuticals. Nanoemulgel-loaded phytopharmaceuticals could substantially improve permeation behavior across skin barriers, subsequently enhancing the delivery and therapeutic effectiveness of the bioactive compound. Furthermore, the thixotropic characteristics of polymeric hydrogel utilized in the fabrication of nanogel/nanoemulgel-based drug delivery systems have also imparted improvements in the biopharmaceutical attributes of loaded phytopharmaceuticals. This formulation approach is about to be rife in the coming decades. Thus, the current review throws light on the recent studies demonstrating the role of nanogels in enhancing the delivery of bioactive compounds for treating various disease conditions and the challenges faced in their clinical translation.
    Keywords:  biopharmaceutical attributes; nanoemulgel; nanogels; phytopharmaceuticals; skin permeation; therapeutic efficacy; thixotropy
    DOI:  https://doi.org/10.3390/polym14194141
  15. Materials (Basel). 2022 Sep 20. pii: 6521. [Epub ahead of print]15(19):
    Chitosan Nanoparticles: A Versatile Platform for Biomedical Applications.
    Showkeen Muzamil Bashir, Gulzar Ahmed Rather, Ana Patrício, Zulfiqar Haq, Amir Amin Sheikh, Mohd Zahoor Ul Haq Shah, Hemant Singh, Azmat Alam Khan, Sofi Imtiyaz, Sheikh Bilal Ahmad, Showket Nabi, Rabia Rakhshan, Saqib Hassan, Pedro Fonte.
      Chitosan is a biodegradable and biocompatible natural polymer that has been extensively explored in recent decades. The Food and Drug Administration has approved chitosan for wound treatment and nutritional use. Furthermore, chitosan has paved the way for advancements in different biomedical applications including as a nanocarrier and tissue-engineering scaffold. Its antibacterial, antioxidant, and haemostatic properties make it an excellent option for wound dressings. Because of its hydrophilic nature, chitosan is an ideal starting material for biocompatible and biodegradable hydrogels. To suit specific application demands, chitosan can be combined with fillers, such as hydroxyapatite, to modify the mechanical characteristics of pH-sensitive hydrogels. Furthermore, the cationic characteristics of chitosan have made it a popular choice for gene delivery and cancer therapy. Thus, the use of chitosan nanoparticles in developing novel drug delivery systems has received special attention. This review aims to provide an overview of chitosan-based nanoparticles, focusing on their versatile properties and different applications in biomedical sciences and engineering.
    Keywords:  chemotherapy; drug delivery; gene therapy; nanocarrier; target therapy; tissue engineering
    DOI:  https://doi.org/10.3390/ma15196521
  16. Life Sci. 2022 Oct 10. pii: S0024-3205(22)00753-6. [Epub ahead of print] 121053
    The dynamicity of mutant KRAS β2 strand modulates its downstream activation and predicts anticancer KRAS inhibition.
    Jeiran Pashapour Anousheh, Abolfazl Barzegar, Mohammad Saeid Hejazi, Elnaz Mehdizadeh Aghdam.
      AIM: Oncogenic mutations involving KRAS are human cancer's most common driving force. We aimed to determine specific conformational features of the active KRAS regarding downstream signaling activation, especially in mutant forms of KRAS.MAIN METHODS: We applied Molecular Dynamics (MD) simulations in triplicate and post-MD analytical methods on the KRAS and its G12 mutant structures. In addition, clustering, umbrella sampling, and principal component analysis were conducted to improve the significant conformations related to the activity of the KRAS variants. The results were generally represented as the probability of the conformations regarding different structural aspects, including β2-strand length, main residual distances, and critical residue interactions.
    KEY FINDINGS: Our results showed that the KRAS β2-strand length was a convenient structural criterion to show the KRAS activity. Accordingly, the active conformations of KRAS were the most probable to have 9-10 residue numbers of β2-strand. Based on this observation, it was also shown that the GDP forms of KRAS G12 mutants could be in the active mode because of increased β2-strand length. Moreover, the distance between the E37 and A59 residues differed in relation to β2-β3 sheet length and can be considered another KRAS activity indicator. Interestingly, β2-strand length could also predict the KRAS activity in the presence of a direct mutant KRAS inhibitor.
    SIGNIFICANCE: As a result, our observations provide a new mechanism regarding the high efficacy of direct inhibition of KRAS-GDP in cancer therapy. In addition, designing and screening the mutant KRAS inhibitors can be more achievable using the β2-strand length probability.
    Keywords:  Beta-sheet; Downstream signaling; KRAS; MD simulation; Protein structure
    DOI:  https://doi.org/10.1016/j.lfs.2022.121053
  17. Crit Rev Food Sci Nutr. 2022 Oct 11. 1-15
    Flavonoids in vegetables: improvement of dietary flavonoids by metabolic engineering to promote health.
    Han Tao, Linying Li, Yuqing He, Xueying Zhang, Yao Zhao, Qiaomei Wang, Gaojie Hong.
      Flavonoids are the most abundant polyphenols in plants, and have antioxidant effects as well as other bioactivities (e.g., anti-inflammatory, anti-cancer, anti-allergic, and neuroprotective effects). Vegetables are rich in flavonoids and are indispensable in our daily diet. Moreover, the vegetables as chassis for producing natural products would emerge as a promising means for cost-effective and sustainable production of flavonoids. Understanding the metabolic engineering of flavonoids in vegetables allows us to improve their nutrient composition. In this review, a comprehensive overview of flavonoids in vegetables, including the characterized types and distribution, health-promoting effects, associated metabolic pathways, and applied metabolic engineering are provided. We also introduce breakthroughs in multi-omics approaches that pertain to the elucidation of flavonoids metabolism in vegetables, as well as prospective and potential genome-editing technologies. Based on the varied composition and content of flavonoids among vegetables, dietary suggestions are further provided for human health.
    Keywords:  Antioxidants; flavonoids; metabolic engineering; vegetables
    DOI:  https://doi.org/10.1080/10408398.2022.2131726
  18. Molecules. 2022 Oct 06. pii: 6632. [Epub ahead of print]27(19):
    Recent Advances in Natural Product-Based Hybrids as Anti-Cancer Agents.
    Eleni Sflakidou, George Leonidis, Eirini Foroglou, Christos Siokatas, Vasiliki Sarli.
      Cancer is one of the top leading causes of death worldwide. It is a heterogenous disease characterized by unregulated cell proliferation and invasiveness of abnormal cells. For the treatment of cancer, natural products have been widely used as a source of therapeutic ingredients since ancient times. Although natural compounds and their derivatives have demonstrated strong antitumor activity in many types of cancer, their poor pharmacokinetic properties, low cell selectivity, limited bioavailability and restricted efficacy against drug-resistant cancer cells hinder their wide clinical application. Conjugation of natural products with other bioactive molecules has given rise to a new field in drug discovery resulting to the development of novel, bifunctional and more potent drugs for cancer therapy to overcome the current drawbacks. This review discusses multiple categories of such bifunctional conjugates and highlights recent trends and advances in the development of natural product hybrids. Among them, ADCs, PDCs, ApDCs, PROTACs and AUTOTACs represent emerging therapeutic agents against cancer.
    Keywords:  AUTOTAC; PROTAC; antibody–drug conjugate; aptamer–drug conjugate; folate hybrid; hybrid; natural product; peptide–drug conjugate; steroidal hybrid
    DOI:  https://doi.org/10.3390/molecules27196632
  19. Oncol Rep. 2022 Dec;pii: 207. [Epub ahead of print]48(6):
    Glutathione peroxidase 2 overexpression promotes malignant progression and cisplatin resistance of KRAS‑mutated lung cancer cells.
    Mei Wang, Xu Chen, Guang Fu, Mingjian Ge.
      Kirsten rat sarcoma viral oncogene homolog (KRAS) aberrations frequently occur in patients with lung cancer. Oncogenic KRAS is characterized by excessive reactive oxygen species (ROS) accumulation, thus, ROS detoxification may contribute to KRAS‑driven lung tumorigenesis. In the present study, the influence of glutathione peroxidase 2 (GPX2) on malignant progression and cisplatin resistance of KRAS‑driven lung cancer was explored. The RNA sequencing data from TCGA lung cancer samples and GEO database were downloaded and analyzed. The effects of GPX2 on KRAS‑driven lung tumorigenesis were evaluated by western blotting, cell viability assay, soft agar assay, Transwell assay, tumor xenograft model, flow cytometry, BrdU incorporation assay, transcriptome RNA sequencing, luciferase reporter assay and RNA immunoprecipitation. In the present study, GPX2 was upregulated in patients with non‑small cell lung carcinoma (NSCLC), and positively correlated with poor overall survival. Ectopic GPX2 expression facilitated malignant progression of KRASG12C‑transformed BEAS‑2B cells. Moreover, GPX2 overexpression promoted growth, migration, invasion, tumor xenograft growth and cisplatin resistance of KRAS‑mutated NSCLC cells, while GPX2 knockdown exhibited the opposite effects. GPX2 overexpression reduced ROS accumulation and increased matrix metalloproteinase‑1 (MMP1) expression in KRAS‑mutated NSCLC cells. In addition, GPX2 was directly targeted by miR‑325‑3p, while MMP1 knockdown or miR‑325‑3p overexpression partially abrogated the effects of GPX2 in NSCLC cells. In conclusion, the results indicated that GPX2 facilitated malignant progression and cisplatin resistance of KRAS‑driven lung cancer, and inhibition of GPX2 may be a feasible strategy for lung cancer treatment, particularly in patients with active KRAS mutations.
    Keywords:  Kirsten rat sarcoma viral oncogene homolog; cisplatin resistance; glutathione peroxidase 2; non‑small cell lung carcinoma; reactive oxygen species
    DOI:  https://doi.org/10.3892/or.2022.8422
  20. Curr Drug Deliv. 2022 Oct 10.
    Topical Advances in Mucoadhesive Ocular Drug Delivery System.
    Koushal Billowria, Navjot K Sandhu, Baljinder Singh.
      The current article mainly highlights the mucoadhesive drug delivery with merits like the prolonged holding timeat the action site and also provides a controlled rate of drug release for improved therapeutic outcomes. Moreover, mucosal delivery can eliminate problems of the conventional oral route, such as first pass metabolism as well as acid degradation. However, the eye has unique anatomy and physiology that can cause hindrance and challenges in comparison to the other organs of the body. Additionally, conventional delivery vehicles like solutions, suspensions, and ointments have many demerits such as rapid precorneal clearance, subject variability, drainage, and uncontrolled releasefrom the dosage form. Therefore, novel pharmaceutical ophthalmic formulationslike gels, nanosuspensions, nano-particles, liposomes, microemulsions, iontophoretic dosage forms, and ocusertswere tried and tested in the past few years for ophthalmic delivery. These novel delivery products provideenhanced solubility and bioavailability in a controlled manner to overcome conventional demerits. Here in this review, we have summarized the improvement of drug studies thatare currently underway for eye drug carriers along with stages and important aspects of novel drug delivery to the eye.
    Keywords:  Mucoadhesive; bioavailability; in-situ gel; iontophoresis; liposome; microemulsion.; nanoparticle; nanosuspension; ocular insert
    DOI:  https://doi.org/10.2174/1567201819666221010122413
  21. Phytother Res. 2022 Oct 11.
    Pharmacokinetic of berberine, the main constituent of Berberis vulgaris L.: A comprehensive review.
    Arian Khoshandam, Mohsen Imenshahidi, Hossein Hosseinzadeh.
      Barberry (Berberis vulgaris L.) is a medicinal plant and its main constituent is an isoquinoline alkaloid named berberine that has multiple pharmacological effects such as antioxidant, anti-microbial, antiinflammatory, anticancer, anti-diabetes, anti-dyslipidemia, and anti-obesity. However, it has restricted clinical uses due to its very poor solubility and bioavailability (less than 1%). It undergoes demethylenation, reduction, and cleavage of the dioxymethylene group in the first phase of metabolism. Its phase two reactions include glucuronidation, sulfation, and methylation. The liver is the main site for berberine distribution. Berberine could excrete in feces, urine, and bile. Fecal excretion of berberine (11-23%) is higher than urinary and biliary excretion routes. However, a major berberine metabolite is excreted in urine greater than in feces. Concomitant administration of berberine with other drugs such as metformin, cyclosporine A, digoxin, etc. may result in important interactions. Thus, in this review, we gathered and dissected any related animal and human research articles regarding the pharmacokinetic parameters of berberine including bioavailability, metabolism, distribution, excretion, and drug-drug interactions. Also, we discussed and gathered various animal and human studies regarding the developed products of berberine with better bioavailability and consequently, better therapeutic effects.
    Keywords:  Berberis vulgaris; berberine; bioavailability; distribution; excretion; metabolism; pharmacokinetics
    DOI:  https://doi.org/10.1002/ptr.7589
  22. Nanotechnology. 2022 Oct 11.
    Tumor microenvironment and redox dual stimuli-responsive polymeric nanoparticles for the effective cisplatin-based cancer chemotherapy.
    Yi-Yang Jia, Meng-Lei Huan, Wei Wang, Zhou-Yan Jia, Yu-Hang Wan, Si-Yuan Zhou, Bang-Le Zhang.
      The serious side effects of cisplatin hindered its clinical application and the nanotechnology might be the potential strategy to address the limitation. However, rapid clearance in the blood circulation and ineffective controlled drug release from nanocarriers hamper the therapeutic efficacy of the nano-delivery system. We constructed a tumor microenvironment and redox dual stimuli-responsive nano-delivery system PEG-c-(BPEI-SS-Pt) by cross-linking the disulfide-containing polymeric conjugate BPEI-SS-Pt with the dialdehyde group-modified PEG2000 via Schiff base. After optimized the cross-linking time, 72 h was selected to get the nano-delivery system. 1H NMR and drug release assays showed that under the acidic tumor microenvironment (pH6.5-6.8), the Schiff base can be broken and detached the PEG cross-linked outer shells, displaying the capability to release the drugs with a sequential pH- and redox-responsive manner. Moreover, PEG-c-(BPEI-SS-Pt) showed more effective anti-tumor therapeutic efficacy in vivo with no significant side effects when compared with the drug of cisplatin used in the clinic. This strategy highlights a promising platform with the dual stimuli-responsive profile to achieve better therapeutic efficacy and minor side effects for platinum-based chemotherapy.
    Keywords:  Chemotherapy; Cisplatin; Polymeric conjugate; Polymeric nanoparticles; Stimuli-responsive delivery system
    DOI:  https://doi.org/10.1088/1361-6528/ac990e
  23. Molecules. 2022 Sep 28. pii: 6417. [Epub ahead of print]27(19):
    Polyphenol-Rich Ginger (Zingiber officinale) for Iron Deficiency Anaemia and Other Clinical Entities Associated with Altered Iron Metabolism.
    Soo Liang Ooi, Sok Cheon Pak, Ron Campbell, Arumugam Manoharan.
      Ginger (Zingiber officinale) is rich in natural polyphenols and may potentially complement oral iron therapy in treating and preventing iron deficiency anaemia (IDA). This narrative review explores the benefits of ginger for IDA and other clinical entities associated with altered iron metabolism. Through in vivo, in vitro, and limited human studies, ginger supplementation was shown to enhance iron absorption and thus increase oral iron therapy's efficacy. It also reduces oxidative stress and inflammation and thus protects against excess free iron. Ginger's bioactive polyphenols are prebiotics to the gut microbiota, promoting gut health and reducing the unwanted side effects of iron tablets. Moreover, ginger polyphenols can enhance the effectiveness of erythropoiesis. In the case of iron overload due to comorbidities from chronic inflammatory disorders, ginger can potentially reverse the adverse impacts and restore iron balance. Ginger can also be used to synthesise nanoparticles sustainably to develop newer and more effective oral iron products and functional ingredients for IDA treatment and prevention. Further research is still needed to explore the applications of ginger polyphenols in iron balance and anaemic conditions. Specifically, long-term, well-designed, controlled trials are required to validate the effectiveness of ginger as an adjuvant treatment for IDA.
    Keywords:  blood disorder; haemoglobin; natural product; nutraceutical; nutritional disease; phenolic compounds
    DOI:  https://doi.org/10.3390/molecules27196417
  24. Appl Biochem Biotechnol. 2022 Oct 11.
    Critical Review on Nutritional, Bioactive, and Medicinal Potential of Spices and Herbs and Their Application in Food Fortification and Nanotechnology.
    Debopriya Mandal, Tanmay Sarkar, Runu Chakraborty.
      Medicinal or herbal spices are grown in tropical moist evergreen forestland, surrounding most of the tropical and subtropical regions of Eastern Himalayas in India (Sikkim, Darjeeling regions), Bhutan, Nepal, Pakistan, Iran, Afghanistan, a few Central Asian countries, Middle East, USA, Europe, South East Asia, Japan, Malaysia, and Indonesia. According to the cultivation region surrounded, economic value, and vogue, these spices can be classified into major, minor, and colored tropical spices. In total, 24 tropical spices and herbs (cardamom, black jeera, fennel, poppy, coriander, fenugreek, bay leaves, clove, chili, cassia bark, black pepper, nutmeg, black mustard, turmeric, saffron, star anise, onion, dill, asafoetida, celery, allspice, kokum, greater galangal, and sweet flag) are described in this review. These spices show many pharmacological activities like anti-inflammatory, antimicrobial, anti-diabetic, anti-obesity, cardiovascular, gastrointestinal, central nervous system, and antioxidant activities. Numerous bioactive compounds are present in these selected spices, such as 1,8-cineole, monoterpene hydrocarbons, γ-terpinene, cuminaldehyde, trans-anethole, fenchone, estragole, benzylisoquinoline alkaloids, eugenol, cinnamaldehyde, piperine, linalool, malabaricone C, safrole, myristicin, elemicin, sinigrin, curcumin, bidemethoxycurcumin, dimethoxycurcumin, crocin, picrocrocin, quercetin, quercetin 4'-O-β-glucoside, apiol, carvone, limonene, α-phellandrene, galactomannan, rosmarinic acid, limonene, capsaicinoids, eugenol, garcinol, and α-asarone. Other than that, various spices are used to synthesize different types of metal-based and polymer-based nanoparticles like zinc oxide, gold, silver, selenium, silica, and chitosan nanoparticles which provide beneficial health effects such as antioxidant, anti-carcinogenic, anti-diabetic, enzyme retardation effect, and antimicrobial activity. The nanoparticles can also be used in environmental pollution management like dye decolorization and in chemical industries to enhance the rate of reaction by the use of catalytic activity of the nanoparticles. The nutritional value, phytochemical properties, health advantages, and both traditional and modern applications of these spices, along with their functions in food fortification, have been thoroughly discussed in this review.
    Keywords:  Antimicrobial; Bio-prospecting; Essential oil; Ethnobotany; Nanoparticles; Phytochemicals
    DOI:  https://doi.org/10.1007/s12010-022-04132-y
  25. Front Mol Biosci. 2022 ;9 903075
    Recent findings on the role of wild-type and mutant p53 in cancer development and therapy.
    Mehregan Babamohamadi, Esmaeil Babaei, Burhan Ahmed Salih, Mahshid Babamohammadi, Hewa Jalal Azeez, Goran Othman.
      The p53 protein is a tumor suppressor encoded by the TP53 gene and consists of 393 amino acids with four main functional domains. This protein responds to various cellular stresses to regulate the expression of target genes, thereby causing DNA repair, cell cycle arrest, apoptosis, metabolic changes, and aging. Mutations in the TP53 gene and the functions of the wild-type p53 protein (wtp53) have been linked to various human cancers. Eight TP53 gene mutations are located in codons, constituting 28% of all p53 mutations. The p53 can be used as a biomarker for tumor progression and an excellent target for designing cancer treatment strategies. In wild-type p53-carrying cancers, abnormal signaling of the p53 pathway usually occurs due to other unusual settings, such as high MDM2 expression. These differences between cancer cell p53 and normal cells have made p53 one of the most important targets for cancer treatment. In this review, we have dealt with various issues, such as the relative contribution of wild-type p53 loss of function, including transactivation-dependent and transactivation-independent activities in oncogenic processes and their role in cancer development. We also discuss the role of p53 in the process of ferroptosis and its targeting in cancer treatment. Finally, we focus on p53-related drug delivery systems and investigate the challenges and solutions.
    Keywords:  MDM2; accumulation of p53; erastin; mTOR; mutant p53; therapeutic-approaches; wild-type p53
    DOI:  https://doi.org/10.3389/fmolb.2022.903075
  26. Molecules. 2022 Oct 09. pii: 6728. [Epub ahead of print]27(19):
    Mentha: Nutritional and Health Attributes to Treat Various Ailments Including Cardiovascular Diseases.
    Saddam Saqib, Fazal Ullah, Muhammad Naeem, Muhammad Younas, Asma Ayaz, Sajid Ali, Wajid Zaman.
      A poor diet, resulting in malnutrition, is a critical challenge that leads to a variety of metabolic disorders, including obesity, diabetes, and cardiovascular diseases. Mentha species are famous as therapeutic herbs and have long served as herbal medicine. Recently, the demand for its products, such as herbal drugs, medicines, and natural herbal formulations, has increased significantly. However, the available literature lacks a thorough overview of Mentha phytochemicals' effects for reducing malnutritional risks against cardiovascular diseases. In this context, we aimed to review the recent advances of Mentha phytochemicals and future challenges for reducing malnutritional risks in cardiovascular patients. Current studies indicated that Mentha species phytochemicals possess unique antimicrobial, antidiabetic, cytotoxic, and antioxidant potential, which can be used as herbal medicine directly or indirectly (such as food ingredients) and are effective in controlling and curing cardiovascular diseases. The presence of aromatic and flavor compounds of Mentha species greatly enhance the nutritional values of the food. Further interdisciplinary investigations are pivotal to explore main volatile compounds, synergistic actions of phytochemicals, organoleptic effects, and stability of Mentha sp. phytochemicals.
    Keywords:  antidiabetic; cytotoxic; herbal medicine; organoleptic; phytoconstituents
    DOI:  https://doi.org/10.3390/molecules27196728
  27. Nutrients. 2022 Oct 08. pii: 4192. [Epub ahead of print]14(19):
    Effect of Ketogenic Diets on Body Composition and Metabolic Parameters of Cancer Patients: A Systematic Review and Meta-Analysis.
    Haobin Zhao, Han Jin, Junfang Xian, Zhifu Zhang, Junling Shi, Xiaosu Bai.
      A ketogenic diet characterized by high fat and low carbohydrate can drive the body to produce a large number of ketone bodies, altering human metabolism. Unlike normal cells, tumor cells have difficulty in consuming ketone bodies. Therefore, the application of ketogenic diets in cancer therapy is gaining attention. However, the effect of ketogenic diets on body parameters of cancer patients is not well established. This meta-analysis aimed to summarize the effects of ketogenic diets on cancer patients in earlier controlled trials. PubMed, Embase, and Cochrane Library were searched for clinical trials that enrolled cancer patients who received ketogenic diets intervention. Ten controlled trials were included in this meta-analysis. Data were extracted and checked by three authors independently. Pooled effect sizes revealed a significant effect of ketogenic diets on body weight (SMD -1.83, 95% CI -2.30 to -1.35; p < 0.00001) and fat mass (SMD -1.52, 95% CI -1.92 to -1.07; p < 0.00001). No significant effect on blood glucose, insulin, or lipid profile except triglycerides was found in the analysis. It had no effect on liver and kidney function except that GGT were decreased a little. There were no significant changes in IGF-1 and TNF-α related to tumor growth. Mental health improvement of cancer patients was supported by several trials. Taken together, findings in this study confirmed that the ketogenic diet was a safe approach for cancer patients reducing body weight and fat mass. In addition, cancer treatment-related indicators changed insignificantly. Ketogenic diets may be beneficial to the quality of life of cancer patients. However, intervention duration in most studies is shorter than 6 months, and the effect of a long-term ketogenic diet is still required further validation. More trials with a larger sample size are necessary to give a more conclusive result; PROSPERO registration number: CRD42021277559.
    Keywords:  body composition; cancer patients; food function; ketogenic diets; metabolic parameters; nutrition
    DOI:  https://doi.org/10.3390/nu14194192
  28. Biomater Sci. 2022 Oct 12.
    Tumor-targeting oxidative stress nanoamplifiers as anticancer nanomedicine with immunostimulating activity.
    Nanhee Song, Miran Park, Nuri Kim, Yujin Lee, Eunkyeong Jung, Dongwon Lee.
      Compared to normal cells, cancer cells are more susceptible to insults of prooxidants that generate ROS (reactive oxygen species) or scavenge antioxidants such as glutathione (GSH). Cancer cells undergo immunogenic cell death (ICD) by elevated oxidative stress. Herein, we report rationally designed F-ssPBCA nanoparticles as a tumor-targeting prooxidant, which generates ROS and scavenges GSH simultaneously to cooperatively amplify oxidative stress, leading to ICD. Prooxidant F-ssPBCA nanoparticles are composed of a disulfide-bridged GSH scavenging dimeric prodrug (ssPB) that self-assembles to form nanoconstructs and encapsulates ROS-generating BCA (benzoyloxy cinnamaldehyde). F-ssPBCA nanoparticles significantly elevate oxidative stress to kill cancer cells and also evoke ICD featured by the release of CRT (calreticulin), HMGB-1 (high mobility group box-1), and adenosine triphosphate (ATP). Animal studies revealed that F-ssPBCA nanoparticles accumulate in tumors preferentially and suppress tumor growth effectively. The results of this study demonstrate that prooxidant-mediated oxidative stress elevation is a highly effective strategy to kill cancer cells selectively and even evoke abundant ICD. We anticipate that oxidative stress amplifying F-ssPBCA nanoparticles hold tremendous translational potential as a tumor targeted ICD-inducing anticancer nanomedicine.
    DOI:  https://doi.org/10.1039/d2bm00601d
  29. Cancers (Basel). 2022 Sep 20. pii: 4552. [Epub ahead of print]14(19):
    Evolutionary View on Lactate-Dependent Mechanisms of Maintaining Cancer Cell Stemness and Reprimitivization.
    Petr V Shegay, Anastasia A Zabolotneva, Olga P Shatova, Aleksandr V Shestopalov, Andrei D Kaprin.
      The role of lactic acid (lactate) in cell metabolism has been significantly revised in recent decades. Initially, lactic acid was attributed to the role of a toxic end-product of metabolism, with its accumulation in the cell and extracellular space leading to acidosis, muscle pain, and other adverse effects. However, it has now become obvious that lactate is not only a universal fuel molecule and the main substrate for gluconeogenesis but also one of the most ancient metabolites, with a signaling function that has a wide range of regulatory activity. The Warburg effect, described 100 years ago (the intensification of glycolysis associated with high lactate production), which is characteristic of many malignant tumors, confirms the key role of lactate not only in physiological conditions but also in pathologies. The study of lactate's role in the malignant transformation becomes more relevant in the light of the "atavistic theory of carcinogenesis," which suggests that tumor cells return to a more primitive hereditary phenotype during microevolution. In this review, we attempt to summarize the accumulated knowledge about the functions of lactate in cell metabolism and its role in the process of carcinogenesis and to consider the possible evolutionary significance of the Warburg effect.
    Keywords:  carcinogenesis; evolutionary oncology; glycolysis; lactate; lactic acid; malignant tumors
    DOI:  https://doi.org/10.3390/cancers14194552
  30. Cell Prolif. 2022 Oct 13. e13346
    Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention.
    Shuangfeng Li, Shuangshuang Yin, Hui Ding, Yingying Shao, Shiyue Zhou, Weiling Pu, Lifeng Han, Tao Wang, Haiyang Yu.
      BACKGROUND: Liver cancer is one of the common malignancies. The dysregulation of metabolism is a driver of accelerated tumourigenesis. Metabolic changes are well documented to maintain tumour growth, proliferation and survival. Recently, a variety of polyphenols have been shown to have a crucial role both in liver disease prevention and metabolism regulation.METHODS: We conducted a literature search and combined recent data with systematic analysis to comprehensively describe the molecular mechanisms that link polyphenols to metabolic regulation and their contribution in liver protection and liver cancer prevention.
    RESULTS: Targeting metabolic dysregulation in organisms prevents and resists the development of liver cancer, which has important implications for identifying new therapeutic strategies for the management and treatment of cancer. Polyphenols are a class of complex compounds composed of multiple phenolic hydroxyl groups and are the main active ingredients of many natural plants. They mediate a broad spectrum of biological and pharmacological functions containing complex lipid metabolism, glucose metabolism, iron metabolism, intestinal flora imbalance, as well as the direct interaction of their metabolites with key cell-signalling proteins. A large number of studies have found that polyphenols affect the metabolism of organisms by interfering with a variety of intracellular signals, thereby protecting the liver and reducing the risk of liver cancer.
    CONCLUSION: This review systematically illustrates that various polyphenols, including resveratrol, chlorogenic acid, caffeic acid, dihydromyricetin, quercetin, catechins, curcumin, etc., improve metabolic disorders through direct or indirect pathways to protect the liver and fight liver cancer.
    DOI:  https://doi.org/10.1111/cpr.13346
  31. Int J Biol Macromol. 2022 Oct 11. pii: S0141-8130(22)02305-4. [Epub ahead of print]
    Curcumin encapsulation in self-assembled nanoparticles based on amphiphilic palmitic acid-grafted-quaternized chitosan with enhanced cytotoxic, antimicrobial and antioxidant properties.
    Yinzhuo Xie, Xiaochen Gong, Zheng Jin, Wei Xu, Kai Zhao.
      The practical application of curcumin (CUR) is greatly limited due to its instability, high hydrophobicity, low bioavailability, and inability to cross the mucosal barrier of gastrointestinal tract. To overcome these disadvantages, several delivery systems have been explored to formulate CUR for oral administration. Nanoparticles (NPs) can significantly enhance oral absorption, bioavailability and therapeutic efficacy of drug, however, NPs are limited by the gastrointestinal degradation, mucosal and epithelial barriers. A novel amphiphilic quaternary ammonium chitosan (N-2-HACC) based NP delivery carrier was prepared using palmitic acid (PA) to encapsulate CUR. Palmitoyl chitosan (PA-N-2-HACC) was characterized including FT-IR, 1H NMR, TGA, and CAC. The particle size of PA-N-2-HACC NPs and PA-N-2-HACC NPs loaded with CUR (CUR@PA-N-2-HACC NPs) was 231.6 ± 9.24 nm and 264.5 ± 4.31 nm. The encapsulation efficiency and loading capacity of CUR@PA-N-2-HACC NPs was 75.43 ± 1.25 % and 6.81 ± 0.16 %. CUR@PA-N-2-HACC NPs exhibited sustained and controlled release. Compared with the CUR, minimum inhibitory concentration of the CUR@PA-N-2-HACC NPs against Escherichia coli, Staphylococcus aureus and Candida albicans was reduced by 4.2 times, 1.6 times and 4.6 times, respectively. Moreover, the antioxidant activity of CUR@PA-N-2-HACC NPs was dose-dependent and higher than that of free. The PA-N-2-HACC NPs show little toxicity and are a promising delivery system for encapsulating hydrophobic drugs.
    Keywords:  Curcumin; Delivery system; Palmitic acid; Quaternized chitosan; Sustained release
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.10.064
  32. Molecules. 2022 Sep 29. pii: 6425. [Epub ahead of print]27(19):
    Potential of Kalanchoe pinnata as a Cancer Treatment Adjuvant and an Epigenetic Regulator.
    Marta Elena Hernández-Caballero, José Alfredo Sierra-Ramírez, Ricardo Villalobos-Valencia, Emmanuel Seseña-Méndez.
      Cancer is a global public health problem that is related to different environmental and lifestyle factors. Although the combination of screening, prevention, and treatment of cancer has resulted in increased patient survival, conventional treatments sometimes have therapeutic limitations such as resistance to drugs or severe side effects. Oriental culture includes herbal medicine as a complementary therapy in combination with chemotherapy or radiotherapy. This study aimed to identify the bioactive ingredients in Kalanchoe pinnata, a succulent herb with ethnomedical applications for several diseases, including cancer, and reveal its anticancer mechanisms through a molecular approach. The herb contains gallic acid, caffeic acid, coumaric acid, quercetin, quercitrin, isorhamnetin, kaempferol, bersaldegenin, bryophyllin a, bryophyllin c, bryophynol, bryophyllol and bryophollone, stigmasterol, campesterol, and other elements. Its phytochemicals participate in the regulation of proliferation, apoptosis, cell migration, angiogenesis, metastasis, oxidative stress, and autophagy. They have the potential to act as epigenetic drugs by reverting the acquired epigenetic changes associated with tumor resistance to therapy-such as the promoter methylation of suppressor genes, inhibition of DNMT1 and DNMT3b activity, and HDAC regulation-through methylation, thereby regulating the expression of genes involved in the PI3K/Akt/mTOR, Nrf2/Keap1, MEK/ERK, and Wnt/β-catenin pathways. All of the data support the use of K. pinnata as an adjuvant in cancer treatment.
    Keywords:  Kalanchoe pinnata; adjuvant agent; antitumor activity; phytochemicals
    DOI:  https://doi.org/10.3390/molecules27196425
  33. Int J Mol Sci. 2022 Sep 24. pii: 11261. [Epub ahead of print]23(19):
    Nanoparticles Loaded with Platinum Drugs for Colorectal Cancer Therapy.
    Buhle Buyana, Tobeka Naki, Sibusiso Alven, Blessing Atim Aderibigbe.
      Colorectal cancer is a common cancer in both men and women. Numerous studies on the therapeutic effectiveness of nanoparticles against colorectal cancer have been reported. Platinum treatments as well as other medications comprising of nanoparticles have been utilized. Drug resistance restricts the use of platinum medicines, despite their considerable efficacy against a variety of cancers. This review reports clinically licensed platinum medicines (cisplatin, carboplatin, and oxaliplatin) combined with various nanoparticles that have been evaluated for their therapeutic efficacy in the treatment of colorectal cancer, including their mechanism of action, resistance, and limitations.
    Keywords:  anticancer drugs; colon; colorectal cancer; nanoparticles; platinum; rectum
    DOI:  https://doi.org/10.3390/ijms231911261
  34. J Ethnopharmacol. 2022 Oct 10. pii: S0378-8741(22)00858-3. [Epub ahead of print] 115819
    Crataegus pinnatifida: A botanical, ethnopharmacological, phytochemical, and pharmacological overview.
    Ruiyu Li, Fei Luan, Yunyan Zhao, Mengyao Wu, Yang Lu, Chengtian Tao, Lv Zhu, Chi Zhang, Li Wan.
      ETHNOPHARMACOLOGICAL RELEVANCE: Crataegus pinnatifida belongs to the Rosaceae family and extensively distribute in North China, Europe, and North America. Its usage was first described in "Xinxiu Ben Cao." The dried fruits of Crataegus pinnatifida Bunge or Crataegus pinnatifida var. major N. E. Br., also known as "Shanzha," is a famous medicine and food homology herb with a long history of medicinal usage in China. C. pinnatifida has the functions for digestive promotion, cardiovascular protection, and lipid reduction. It was traditionally used to treat indigestion, cardiodynia, thoracalgia, hernia, postpartum blood stagnation, and hemafecia. In recent years, C. pinnatifida has attracted worldwide attention as an important medicinal and economical crop due to its multiple and excellent health-promoting effects on cardiovascular, nervous, digestive, endocrine systems, and morbigenous microorganisms of the human body due to its medicinal and nutritional values.AIM OF THE REVIEW: The current review aims to provide a comprehensive analysis of the geographical distribution, traditional usage, phytochemical components, pharmacological actions, clinical settings, and toxicities of C. pinnatifida. Moreover, the connection between the claimed biological activities and the traditional usage, along with the future perspectives for ongoing research on this plant, were also critically summarized.
    MATERIALS AND METHODS: We collected the published literature on C. pinnatifida using a variety of scientific databases, including Web of Science, ScienceDirect, PubMed, Wiley, Springer, Taylor & Francis, ACS Publications, Google Scholar, Baidu Scholar, CNKI, The Plant List Database, and other literature sources (Ph.D. and MSc dissertations) from 2012 to 2022.
    RESULTS: In the last decade, over 250 phytochemical compounds containing lignans, phenylpropanoids, flavonoids, triterpenoids, and their glycosides, as well as other compounds, have been isolated and characterized from different parts, including the fruit, leaves, and seeds of C. pinnatifida. Among these compounds, flavonoids and triterpenoids were major bioactive components of C. pinnatifida. They exhibited a broad spectrum of pharmacological actions with low toxicity in vitro and in vivo, such as cardiovascular protection, neuroprotection, anti-inflammatory, antioxidant, antibacterial, antiviral, anti-diabetes, anti-cancer, anti-mutagenic, anti-osteoporosis, anti-aging, anti-obesity, and hepatoprotection and other actions.
    CONCLUSION: A long history of traditional uses and abundant pharmacochemical and pharmacological investigations have demonstrated that C. pinnatifida is an important medicine and food homology herb, which displays outstanding therapeutic potential, especially in the digestive system and cardiovascular disease. Nevertheless, the current studies on the active ingredients or crude extracts of C. pinnatifida and the possible mechanism of action are unclear. More evidence-based scientific studies are required to verify the traditional uses of C. pinnatifida. Furthermore, more efforts must be paid to selecting index components for quality control research and toxicity and safety studies of C. pinnatifida.
    Keywords:  Cardiovascular protection; Clinical trials; Crataegus pinnatifida; Neuroprotection; Phytochemistry; Traditional usage
    DOI:  https://doi.org/10.1016/j.jep.2022.115819
  35. Polymers (Basel). 2022 Oct 06. pii: 4189. [Epub ahead of print]14(19):
    Recent Reports on Polysaccharide-Based Materials for Drug Delivery.
    Joanna Kurczewska.
      Polysaccharides constitute one of the most important families of biopolymers. Natural polysaccharide-based drug delivery systems are of constant interest to the scientific community due to their unique properties: biocompatibility, non-toxicity, biodegradability, and high availability. These promising biomaterials protect sensitive active agents and provide their controlled release in targeted sites. The application of natural polysaccharides as drug delivery systems is also intensively developed by Polish scientists. The present review focuses on case studies from the last few years authored or co-authored by research centers in Poland. A particular emphasis was placed on the diversity of the formulations in terms of the active substance carried, the drug delivery route, the composition of the material, and its preparation method.
    Keywords:  alginate; cellulose; chitosan; dextran; drug delivery; hyaluronic acid; pectin; polysaccharide; starch
    DOI:  https://doi.org/10.3390/polym14194189
  36. Drug Deliv. 2022 Dec;29(1): 3197-3212
    A technical note on emerging combination approach involved in the onconanotherapeutics.
    Mohammad Kashif Iqubal, Harsimran Kaur, Shadab Md, Nabil A Alhakamy, Ashif Iqubal, Javed Ali, Sanjula Baboota.
      Cancer is the second cause of mortality worldwide, and the currently available conventional treatment approach is associated with serious side effects and poor clinical outcomes. Based on the outcome of the exploratory preclinical and clinical studies, it was found that therapeutic response increases multiple folds when anticancer drugs are used in combination. However, the conventional combination of anticancer drugs was associated with various limitations such as increased cost of treatment, systemic toxicity, drug resistance, and reduced pharmacokinetic attributes. Hence, attempts were made to formulate nanocarrier fabricated combinatorial drugs (NFCDs) to effectively manage and treat cancer. This approach offers several advantages, such as improved stability, lower drug exposure, targeted drug delivery, low side effects, and improved clinical outcome. Hence, in this review, first time, we have discussed the recent advancement and various types of nano carrier-based combinatorial drug delivery systems in a different type of cancer and highlighted the personalized combinatorial theranostic medicine as a futuristic anticancer treatment approach.
    Keywords:  Chemotherapy; dual-drug combination; immunotherapy; nanotechnology; personalized medicine
    DOI:  https://doi.org/10.1080/10717544.2022.2132018
  37. Nanoscale. 2022 Oct 11.
    Nanoenzyme-chitosan hydrogel complex with cascade catalytic and self-reinforced antibacterial performance for accelerated healing of diabetic wounds.
    Zhiguo Li, Xiaotong Fan, Zheng Luo, Xian Jun Loh, Yedong Ma, Enyi Ye, Yun-Long Wu, Chaobin He, Zibiao Li.
      The significant disability and fatality rate of diabetes chronic wounds necessitates the development of efficient diabetic wound healing techniques. The present oxygen treatments for wound healing is restricted by issues such as poor penetration, inadequate supply, and absorption difficulties as well as tanglesome diabetic wound microenvironment issues such as hyperglycemia, excessive reactive oxygen species (ROS), and hypoxia. Herein, we designed a multifunctional glucose oxidase (GOx) and catalase (CAT) nanoenzyme-chitosan (GCNC) hydrogel complex to improve the microenvironment of diabetic wounds and provide continuous oxygen delivery for efficient wound healing. By simultaneously forming the GOx-CAT nanoenzyme (GCNE) composite, the GCNC hydrogel complex could effectively reduce glucose and ROS (H2O2) concentrations in diabetic wounds through cascade catalytic reactions and achieve continuous oxygen supply, which promoted cell proliferation, migration, and angiogenesis, thereby accelerating diabetic wound healing. In addition, the byproduct gluconic acid produced by the cascade reaction can activate the amino group of chitosan to reinforce the antibacterial performance and prevent microbial infection. This multifunctional GCNC hydrogel complex with continuous oxygen supply, self-reinforcing antibacterial properties, and byproduct-free features provides a general strategy for repairing the extensive tissue damage in diabetes.
    DOI:  https://doi.org/10.1039/d2nr04171e
  38. Int J Mol Sci. 2022 Oct 04. pii: 11747. [Epub ahead of print]23(19):
    Monoamine Oxidase Inhibitors Prevent Glucose-Dependent Energy Production, Proliferation and Migration of Bladder Carcinoma Cells.
    Jessica Resta, Yohan Santin, Mathieu Roumiguié, Elodie Riant, Alexandre Lucas, Bettina Couderc, Claudia Binda, Philippe Lluel, Angelo Parini, Jeanne Mialet-Perez.
      Bladder cancer is the 10th most common cancer in the world and has a high risk of recurrence and metastasis. In order to sustain high energetic needs, cancer cells undergo complex metabolic adaptations, such as a switch toward aerobic glycolysis, that can be exploited therapeutically. Reactive oxygen species (ROS) act as key regulators of cancer metabolic reprogramming and tumorigenesis, but the sources of ROS remain unidentified. Monoamine oxidases (MAOs) are mitochondrial enzymes that generate H2O2 during the breakdown of catecholamines and serotonin. These enzymes are particularly important in neurological disorders, but recently, a new link between MAOs and cancer has been uncovered, involving their production of ROS. At present, the putative role of MAOs in bladder cancer has never been evaluated. We observed that human urothelial tumor explants and the bladder cancer cell line AY27 expressed both MAO-A and MAO-B isoforms. Selective inhibition of MAO-A or MAO-B limited mitochondrial ROS accumulation, cell cycle progression and proliferation of bladder cancer cells, while only MAO-A inhibition prevented cell motility. To test whether ROS contributed to MAO-induced tumorigenesis, we used a mutated form of MAO-A which was unable to produce H2O2. Adenoviral transduction of the WT MAO-A stimulated the proliferation and migration of AY27 cells while the Lys305Met MAO-A mutant was inactive. This was consistent with the fact that the antioxidant Trolox strongly impaired proliferation and cell cycle progression. Most interestingly, AY27 cells were highly dependent on glucose metabolism to sustain their growth, and MAO inhibitors potently reduced glycolysis and oxidative phosphorylation, due to pyruvate depletion. Accordingly, MAO inhibitors decreased the expression of proteins involved in glucose transport (GLUT1) and transformation (HK2). In conclusion, urothelial cancer cells are characterized by a metabolic shift toward glucose-dependent metabolism, which is important for cell growth and is under the regulation of MAO-dependent oxidative stress.
    Keywords:  cancer; glucose transport; glycolysis; monoamine oxidases; oxidative stress; tumorigenesis
    DOI:  https://doi.org/10.3390/ijms231911747
  39. Ceska Slov Farm. 2022 ;71(4): 137-141
    Selected polyphenolic compounds and their use as a supportive therapy in metabolic syndrome.
    Jan Soukop, Rostislav Večeřa.
      Metabolic syndrome is diagnosed mainly in people of economically developed parts of the world and it affects 20-25% of the adult population worldwide. Nowadays, it is also more frequently diagnosed in children and adolescents. In addition to standard treatment that often involves polypharmacotherapy, and thus increases risk of side effects caused by drugdrug interactions, it is appropriate to look for alternative tools to support the treatment of metabolic syndrome components. Natural polyphenolic compounds, usually present in the so-called functional foods, are suitable candidates for that matter, due to the bioactivity and beneficial effects on the human body. Quercetin, troxerutin, diosmin, hesperidin or silybin are among the currently studied and used natural polyphenolic compounds with a positive effect on aspects of the metabolic syndrome. In addition to their antioxidant and anti-inflammatory effects, these compounds have other positive properties that very often outweigh their side effects whilst their usage in the pharmacotherapy.
    Keywords:  NAFLD; diosmin; metabolic syndrome; polyphenolic compounds; quercetin; silymarin; troxerutin
  40. Molecules. 2022 Oct 06. pii: 6652. [Epub ahead of print]27(19):
    Enhanced Antioxidant and Anti-Inflammatory Effects of Self-Nano and Microemulsifying Drug Delivery Systems Containing Curcumin.
    Liza Józsa, Gábor Vasvári, Dávid Sinka, Dániel Nemes, Zoltan Ujhelyi, Miklós Vecsernyés, Judit Váradi, Ferenc Fenyvesi, István Lekli, Alexandra Gyöngyösi, Ildikó Bácskay, Pálma Fehér.
      Turmeric has been used for decades for its antioxidant and anti-inflammatory effect, which is due to an active ingredient isolated from the plant, called curcumin. However, the extremely poor water-solubility of curcumin often limits the bioavailability of the drug. The aim of our experimental work was to improve the solubility and thus bioavailability of curcumin by developing self-nano/microemulsifying drug delivery systems (SN/MEDDS). Labrasol and Cremophor RH 40 as nonionic surfactants, Transcutol P as co-surfactant and isopropyl myristate as the oily phase were used during the formulation. The average droplet size of SN/MEDDS containing curcumin was between 32 and 405 nm. It was found that the higher oil content resulted in larger particle size. The drug loading efficiency was between 93.11% and 99.12% and all formulations were thermodynamically stable. The curcumin release was studied at pH 6.8, and the release efficiency ranged between 57.3% and 80.9% after 180 min. The results of the MTT cytotoxicity assay on human keratinocyte cells (HaCaT) and colorectal adenocarcinoma cells (Caco-2) showed that the curcumin-containing preparations were non-cytotoxic at 5 w/v%. According to the results of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide dismutase (SOD) assays, SNEDDS showed significantly higher antioxidant activity. The anti-inflammatory effect of the SN/MEDDS was screened by enzyme-linked immunosorbent assay (ELISA). SNEDDS formulated with Labrasol as surfactant, reduced tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels below 60% at a concentration of 10 w/w%. Our results verified the promising use of SN/MEDDS for the delivery of curcumin. This study demonstrates that the SN/MEDDS could be promising alternatives for the formulation of poorly soluble lipophilic compounds with low bioavailability.
    Keywords:  anti-inflammatory effect; antioxidant effect; curcumin; drug delivery; self-emulsifying systems
    DOI:  https://doi.org/10.3390/molecules27196652
  41. Biomed Pharmacother. 2022 Oct 10. pii: S0753-3322(22)01195-7. [Epub ahead of print]156 113806
    Ferroptosis: A new strategy for traditional Chinese medicine treatment of stroke.
    Yuan Lou, Maoqiang Ma, Yanan Jiang, Haoqun Xu, Zu Gao, Lin Gao, Yuan Wang.
      Stroke is a serious threat to human survival and health due to its high morbidity and mortality. The pathological mechanism of stroke is complex and involves various regulated cell death (RCD) modalities such as autophagy, apoptosis and necroptosis. ferroptosis, a novel form of RCD characterised by iron-dependent accumulation of lipid peroxides and reactive oxygen radicals, has been found to be closely associated with the prognosis and outcome of stroke. At the same time, ferroptosis is also associated with other forms of RCD with varying degrees of crosstalk. Traditional Chinese medicine(TCM), with its multi-component, multi-pathway and multi-target action characteristics, has unique advantages and good prospects for application in stroke prevention and treatment. Using ferroptosis and its crosstalk with other forms of RCD as an entry point, we review the research on TCM with anti-stroke effects discovered in the past 10 years, with a view to providing reference for further scientific development and application of anti-stroke therapeutic drugs.
    Keywords:  Crosstalk; Ferroptosis; Regulated cell death; Stroke; Traditional Chinese medicine
    DOI:  https://doi.org/10.1016/j.biopha.2022.113806
  42. Front Oncol. 2022 ;12 949332
    Antitumor effects of Chinese herbal medicine compounds and their nano-formulations on regulating the immune system microenvironment.
    Kexiang Sun, Linguangjin Wu, Shuyun Wang, Wanli Deng.
      Traditional Chinese medicine (TCM), including herbal medicine, acupuncture and meditation, has a wide range of applications in China. In recent years, herbal compounding and active ingredients have been used to control tumor growth, reduce suffering, improve quality of life, and prolong the life span of cancer patients. To reduce side effects, herbal medicine can be used in conjunction with radiotherapy and chemotherapy or can be used as an adjuvant to strengthen the immune effect of anticancer vaccines. In particular, in the immunosuppressed tumor microenvironment, herbal medicine can have antitumor effects by stimulating the immune response. This paper reviews the advances in research on antitumor immunomodulation in Chinese herbal medicine, including the regulation of the innate immune system, which includes macrophages, MDSCs, and natural killer cells, and the adaptive immune system, which includes CD4+ T cells, CD8+ T cells, and regulatory T cells (Tregs), to influence tumor-associated inflammation. In addition, a combination of active ingredients of herbal medicine and modern nanotechnology alter the tumor immune microenvironment. In recent years, immunological antitumor therapy in TCM has been applied on a reasonably large scale both nationally and internationally, and there is potential for further clinical expansion. Investigation of immune modulation mechanisms in Chinese herbal medicine will provide novel perspectives of how herbal medicine controls tumor growth and metastasis, which will contribute to the evolution of tumor research.Methodology: Experimental research between the years of 2012-2022, meta-analysis and reviews for the period 2002-2022 found on the Databases including PubMed, Embase, and the Cochrane database were used. The inclusion criteria were experimental research literature addressing the anti-tumor immunological effects of active ingredients and nanoparticles in Chinese herbal medicine. Exclusion criteria were articles that addressed Chinese herbal medicine and nano-formulations without discussing anti-tumor immunological effects in innate, adaptive immune cells, MDSCs, and nuclear factors.
    Keywords:  TCM; nano-formulation; oncology; traditional Chinese medicine; tumor immune microenvironment
    DOI:  https://doi.org/10.3389/fonc.2022.949332
  43. Adv Healthc Mater. 2022 Oct 12. e2202024
    Porphyrin Centered Paclitaxel Tetrameric Prodrug Nanoassembliesas Tumor-Selective Theranostics for Synergized Breast Cancer Therapy.
    Xiaodong Ma, Pengfei Wang, Qiwei Wu, Junnian Zhou, Dongqing Wang, Deependra Yadav, Hongbo Zhang, Yuezhou Zhang.
      Although undergo decades of development, nanoparticulate drug delivery vehicles for efficient cancer therapy remain a challenge, confined by low drug loading, instability, and poor cancer tissue selectivity. Self-assembled prodrug, the combination of prodrug strategy and the self-assembly merits, represents a special chemical entity which spontaneously organized into supramolecular composites with defined architecture, therefore also provides a strategy to develop new medications. Paclitaxel (PTX) is still among the most generally prescribed chemotherapeutics in oncology but restricted by poor solubility and unpleasant patients' compliance. Although photodynamic therapy (PDT), with its noninvasive features and barely developed drug resistance, signifies an alternative tool to suppress life-threatening cancer, sole use hardly fulfills its potential. To this end, we synthesized a reduction-activatable heterotetrameric prodrug that centred on the photosensitizer sensitizer 5,10,5,20-Tetrakis(4-hydroxyphenyl)-porphine(THPP), then branched four PTX through redox sensitive disulfide linker, then formulated into self-assembled nanoparticles (NPs) for tumor imaging and combined chemo- and photodynamic therapy. Coating the NPs with amphiphilic polymer distearylphosphatidylethanolamine-polyethylene glycol-arginine-glycine-aspartate (DSPE-PEG-RGD) offered high stability and enabled cancer tissue targeting. The as-prepared NPs enlighten disease cells and revealed more potent cytotoxicity comparing to PTX and THPP alone. Besides, the NPs selectively accumulated into tumor and synergistically inhibited tumor proliferation with reduced side effects in mice. This article is protected by copyright. All rights reserved.
    Keywords:  Nanoassemblies; Synergized Therapy; Tetrameric Prodrug; Theranostics
    DOI:  https://doi.org/10.1002/adhm.202202024
  44. Molecules. 2022 Sep 25. pii: 6316. [Epub ahead of print]27(19):
    New Insights into Dietary Pterostilbene: Sources, Metabolism, and Health Promotion Effects.
    Sanjushree Nagarajan, Sundhar Mohandas, Kumar Ganesan, Baojun Xu, Kunka Mohanram Ramkumar.
      Pterostilbene (PTS), a compound most abundantly found in blueberries, is a natural analog of resveratrol. Several plant species, such as peanuts and grapes, produce PTS. While resveratrol has been extensively studied for its antioxidant properties, recent evidence also points out the diverse therapeutic potential of PTS. Several studies have identified the robust pharmacodynamic features of PTS, including better intestinal absorption and elevated hepatic stability than resveratrol. Indeed, due to its higher bioavailability paired with reduced toxicity compared to other stilbenes, PTS has become an attractive drug candidate for the treatment of several disease conditions, including diabetes, cancer, cardiovascular disease, neurodegenerative disorders, and aging. This review article provides an extensive summary of the nutraceutical potential of PTS in various disease conditions while discussing the crucial mechanistic pathways implicated. In particular, we share insights from our studies about the Nrf2-mediated effect of PTS in diabetes and associated complications. Moreover, we elucidate the important sources of PTS and discuss in detail its pharmacokinetics and the range of formulations and routes of administration used across experimental studies and human clinical trials. Furthermore, this review also summarizes the strategies successfully used to improve dietary availability and the bio-accessibility of PTS.
    Keywords:  Nrf2; antioxidant; bioavailability; cancer; diabetes; pterostilbene; resveratrol
    DOI:  https://doi.org/10.3390/molecules27196316
  45. Cancers (Basel). 2022 Sep 22. pii: 4601. [Epub ahead of print]14(19):
    Repurposing of Benzimidazole Anthelmintic Drugs as Cancer Therapeutics.
    Bomi Song, Eun Young Park, Kwang Joon Kim, Sung Hwan Ki.
      Benzimidazoles have shown significant promise for repurposing as a cancer therapy. The aims of this review are to investigate the possibilities and limitations of the anti-cancer effects of benzimidazole anthelmintics and to suggest ways to overcome these limitations. This review included studies on the anti-cancer effects of 11 benzimidazoles. Largely divided into three parts, i.e., preclinical anti-cancer effects, clinical anti-cancer effects, and pharmacokinetic properties, we examine the characteristics of each benzimidazole and attempt to elucidate its key properties. Although many studies have demonstrated the anti-cancer effects of benzimidazoles, there is limited evidence regarding their effects in clinical settings. This might be because the clinical trials conducted using benzimidazoles failed to restrict their participants with specific criteria including cancer entities, cancer stages, and genetic characteristics of the participants. In addition, these drugs have limitations including low bioavailability, which results in insufficient plasma concentration levels. Additional studies on whole anti-cancer pathways and development strategies, including formulations, could result significant enhancements of the anti-cancer effects of benzimidazoles in clinical situations.
    Keywords:  anthelmintic drugs; benzimidazole; cancer therapy; repurposing
    DOI:  https://doi.org/10.3390/cancers14194601
  46. Endocrinology. 2022 Oct 14. pii: bqac169. [Epub ahead of print]
    Inhibition of Glycogen Metabolism Induces Reactive Oxygen Species-Dependent Cytotoxicity in Anaplastic Thyroid Cancer in Female Mice.
    Cole D Davidson, Jennifer A Tomczak, Eyal Amiel, Frances E Carr.
      Anaplastic thyroid cancer (ATC) is one of the most lethal solid tumors, yet there are no effective, long-lasting treatments for ATC patients. Most tumors, including tumors of the endocrine system, exhibit an increased consumption of glucose to fuel cancer progression, and some cancers meet this high glucose requirement by metabolizing glycogen. Our goal was to determine if ATC cells metabolize glycogen and if this could be exploited for treatment. We detected glycogen synthase and glycogen phosphorylase (PYG) isoforms in normal thyroid and thyroid cancer cell lines and patient-derived biopsy samples. Inhibition of PYG using CP-91,149 induced apoptosis in ATC cells but not normal thyroid cells. CP-91,149 decreased NADPH levels and induced reactive oxygen species accumulation. CP-91,149 severely blunted ATC tumor growth in vivo. Our work establishes glycogen metabolism as a novel metabolic process in thyroid cells that presents a unique, oncogenic target that could offer an improved clinical outcome.
    Keywords:  149; Anaplastic thyroid cancer; CP-91; cancer metabolism; glycogen; reactive oxygen species; sorafenib
    DOI:  https://doi.org/10.1210/endocr/bqac169
  47. Nano Lett. 2022 Oct 11.
    Post-Remedial Oxygen Supply: A New Perspective on Photodynamic Therapy to Suppress Tumor Metastasis.
    Chaoqiang Qiao, Zuo Yang, Xuelan Liu, Ruili Zhang, Yuqiong Xia, Lexuan Wang, Zhuang Chen, Qian Jia, Ruhao Wang, Yang Yang, Zhongliang Wang.
      Photodynamic therapy (PDT) holds great promise in tumor therapy due to high safety, efficacy, and specificity. However, the risk of increased metastasis in hypoxic tumors after oxygen-dependent PDT remains underestimated. Here, we propose a post-PDT oxygen supply (POS) strategy to reduce the risk of metastasis. Herein, biocompatible and tumor-targeting Ce6@BSA and PFC@BSA nanoparticles were constructed for PDT and POS in a 4T1-orthotropic breast cancer model. PDT with Ce6@BSA nanoparticles increased tumor metastasis via the HIF-1α signaling pathway, whereas POS significantly reduced the PDT-triggered metastasis by blocking this pathway. Furthermore, POS, with clinical protocols and an FDA-approved photosensitizer (hypericin), and oxygen inhalation reduced PDT-induced metastasis. Our study findings indicate that PDT may increase the risk of tumor metastasis and that POS may solve this problem. POS can reduce the metastasis resulting not only from PDT but also from other oxygen-dependent treatments such as radiotherapy and sonodynamic therapy.
    Keywords:  Hypoxia induced factors; Metastasis; Photodynamic therapy; Postoxygen supply
    DOI:  https://doi.org/10.1021/acs.nanolett.2c02983
  48. Colloids Surf B Biointerfaces. 2022 Oct 04. pii: S0927-7765(22)00585-9. [Epub ahead of print]220 112901
    Liposomes encapsulating methylene blue and acridine orange: An approach for phototherapy of skin cancer.
    Thais P Pivetta, Quirina Ferreira, Tânia Vieira, Jorge C Silva, Sandra Simões, Paulo A Ribeiro, Maria Raposo.
      Photodynamic therapy uses photosensitizer molecules for the photo-mediated treatment of several diseases such as cancer and skin disorders. However, most of the photosensitizer molecules present problems such as aggregation and low solubility in physiological environments which hinders the treatment efficacy. To overcome these problems, the development of stable liposomes loading photosensitizing molecules as delivery systems can be explored as promising alternatives to enhance cellular uptake and the therapy's efficacy. In this work, liposomes composed by different lipids with or without surfactants were characterized for the encapsulation of photosensitizer molecules such as Methylene Blue (MB) and Acridine Orange (AO). Liposomes were produced by the thin-film hydration method followed by extrusion to reduce particle size and were characterized by Dynamic Light Scattering and Atomic Force Microscopy. Encapsulation efficiency was evaluated as well as the release profile of these molecules from the liposome systems. Cytotoxicity and phototoxicity studies were performed on keratinocytes with and without carcinoma. Results showed that liposome's stability depends on the composition of lipids regardless of the presence of surfactants. Most stable liposomes were those with cholesterol plus the surfactants Span® 80 or sodium cholate that were able to provide higher stability for the liposomes considering the MB and AO encapsulation. Encapsulation efficiency (EE) studies revealed that AO had greater affinity for the vesicles presenting high EE (>98%) while for MB the encapsulation was, in general, moderate (between 63% and 86%). Greater phototoxicity was observed for MET1 squamous cell carcinoma (SCC) cells treated with AO liposomes, achieving similar half-maximal inhibition concentration (IC50) as for the free drug. Finally, two different possible approaches were found, namely, MB-liposomes with potential as a cytotoxic agent for cancer cells; and AO liposomes with a great phototoxicity potential at very low concentrations.
    Keywords:  Acridine orange; Liposomes; Methylene blue; Photodynamic therapy; Photosensitizers
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112901
  49. Front Nutr. 2022 ;9 1006520
    Hydrogels as promising carriers for the delivery of food bioactive ingredients.
    Min Li, Xiaoqian He, Ran Zhao, Qixin Shi, Yingqun Nian, Bing Hu.
      The burden of public health challenges associated with the western dietary and living style is growing. Nutraceuticals have been paid increasing attentions due to their effects in promotion of health. However, in the gastrointestinal (GI) tract, the nutraceuticals suffer from not only the harsh acidic environment of the stomach and a variety of digestive enzymes, but also the antibacterial activity of intestinal bile salts and the action of protease from the gut microbiota. The amount of the nutraceuticals arriving at the sites in GI tract for absorption or exerting the bioactivities is always unfortunately limited, which puts forward high requirements for protection of nutraceuticals in a certain high contents during oral consumption. Hydrogels are three-dimensional polymeric porous networks formed by the cross-linking of polymer chains, which can hold huge amounts of water. Compared with other carries with the size in microscopic scale such as nanoparticle and microcapsules, hydrogels could be considered to be more suitable delivery systems in food due to their macroscopic bulk properties, adjustable viscoelasticity and large spatial structure for embedding nutraceuticals. Regarding to the applications in food, natural polymer-based hydrogels are commonly safe and popular due to their source with the appealing characteristics of affordability, biodegradability and biocompatibility. Although chemical crosslinking has been widely utilized in preparation of hydrogels, it prefers the physical crosslinking in the researches in food. The reasonable design for the structure of natural polymeric hydrogels is essential for seeking the favorable functionalities to apply in the delivery system, and it could be possible to obtain the enhanced adhesive property, acid stability, resistant to bile salt, and the controlled release behavior. The hydrogels prepared with proteins, polysaccharides or the mix of them to deliver the functional ingredients, mainly the phenolic components, vitamins, probiotics are discussed to obtain inspiration for the wide applications in delivery systems. Further efforts might be made in the in situ formation of hydrogels in GI tract through the interaction among food polymers and small-molecular ingredients, elevation of the loading contents of nutraceuticals in hydrogels, development of stomach adhesive hydrogels as well as targeting modification of gut microbiota by the hydrogels.
    Keywords:  acidic stability; adhesive; bioactive ingredients; controlled release; crosslinking; hydrogels; natural polymers
    DOI:  https://doi.org/10.3389/fnut.2022.1006520
  50. Front Bioeng Biotechnol. 2022 ;10 984166
    Polydopamine encapsulated new indocyanine green theranostic nanoparticles for enhanced photothermal therapy in cervical cancer HeLa cells.
    Huimin Fan, Ting Yan, Shuang Chen, Zhong Du, Gulinigaer Alimu, Lijun Zhu, Rong Ma, Xiaohui Tang, Youqiang Heng, Nuernisha Alifu, Xueliang Zhang.
      Photothermal therapy (PTT) has attracted extensive attention in cancer treatment due to its non-invasiveness, high efficiency, and repeatability in recent years. Photothermal agents (PTAs) are the key factor for PTT. Recently, although an increasing number of PTAs have been developed, there is still a great demand for optimized photothermal nanoparticles (NPs) with low toxicity, bio-safety and stability. Herein, new indocyanine green (IR820) with near-infrared (NIR:700-1,700 nm) fluorescence emission was selected as a photothermal agent (PTA). To enhance the PTT property, IR820 was encapsulated with another kind of PTA, polydopamine (PDA) under alkaline conditions. Furthermore, to improve the biocompatibility of the NPs, methoxy polyethylene glycol amine (mPEG-NH2) was modified via a Michael addition to form a novel kind of IR820@PDA@PEG NPs. After detailed characterization and analysis, the obtained IR820@PDA@PEG NPs showed a spherical shape with an average diameter of ∼159.6 nm. Meanwhile, the formed IR820@PDA@PEG NPs exhibited better photostability and lower cytotoxicity than free IR820 molecules. The photothermal performance of IR820@PDA@PEG NPs was further analyzed in vitro, and the temperature of IR820@PDA@PEG NPs (100 μg/ml) reached 54.8°C under 793 nm laser irradiation. Afterwards, the cellular uptake of IR820@PDA@PEG NPs was evaluated via confocal laser scanning fluorescence microscopic imaging. Then, PTT experiments on HeLa cells demonstrated that IR820@PDA@PEG NPs can hyperthermal ablate cancer cells (∼49.1%) under 793 nm laser irradiation. Therefore, IR820@PDA@PEG NPs would be a promising PTA for the treatment of cervical cancer HeLa cells.
    Keywords:  cervical cancer; nanoparticles; new indocyanine green; photothermal therapy; polydopamine
    DOI:  https://doi.org/10.3389/fbioe.2022.984166
  51. Xenobiotica. 2022 Oct 13. 1-35
    Curcumin-loaded hydroxypropyl-β-cyclodextrin inclusion complex with enhanced dissolution and oral bioavailability for epilepsy treatment.
    Yao Zeng, Yalan Lv, Mengyun Hu, Feng Guo, Chunbo Zhang.
      Curcumin, the main bioactive component of turmeric, has a wild range of beneficial effects on central nervous diseases, including anti-Alzheimer's disease, antioxidant stress, and anti-inflammation. Currently, it has been demonstrated the anti-epileptic potential. However, curcumin has poor water solubility, high sensitivity to light and heat, and low absorption, which results in low bioavailability and greatly limits the clinical application of curcumin, as well as the elusive effects in anti-epileptic treatment.This study aimed to develop a curcumin hydroxypropyl-β-cyclodextrin inclusion complex (CUR-HP-β-CD) to improve its bioavailability and facilitate its potential development as an anti-epileptic drug. The CUR-HP-β-CD was generated by the solvent evaporation method, which has efficient entrapment, high solubility, and facilitated bioavailability and brain distribution.The solubility of the CUR-HP-β-CD was 63.5, 60.1, and 52.9 times that of the unformulated curcumin in H2O, HCl (pH 1.2), and PBS (pH 6.8), respectively. The bioavailability of CUR-HP-β-CD is improved 2.8 times and 38.7 folds higher brain concentrations. Moreover, the therapeutic anti-epileptic effects of CUR-HP-β-CD were much more effective in pentylenetetrazol (PTZ)-induced zebrafish and mouse models.This study showed a simple and reproducible strategy to effectively improve the bioavailability and therapeutic effects of curcumin, which could be potentially used in epilepsy treatment.
    Keywords:  Bioavailability; Curcumin; Epilepsy; Inclusion complex
    DOI:  https://doi.org/10.1080/00498254.2022.2136044
  52. Nutrients. 2022 Sep 30. pii: 4071. [Epub ahead of print]14(19):
    The Problem of Vitamin D Scarcity: Cultural and Genetic Solutions by Indigenous Arctic and Tropical Peoples.
    Peter Frost.
      Vitamin D metabolism differs among human populations because our species has adapted to different natural and cultural environments. Two environments are particularly difficult for the production of vitamin D by the skin: the Arctic, where the skin receives little solar UVB over the year; and the Tropics, where the skin is highly melanized and blocks UVB. In both cases, natural selection has favored the survival of those individuals who use vitamin D more efficiently or have some kind of workaround that ensures sufficient uptake of calcium and other essential minerals from food passing through the intestines. Vitamin D scarcity has either cultural or genetic solutions. Cultural solutions include consumption of meat in a raw or boiled state and extended breastfeeding of children. Genetic solutions include higher uptake of calcium from the intestines, higher rate of conversion of vitamin D to its most active form, stronger binding of vitamin D to carrier proteins in the bloodstream, and greater use of alternative metabolic pathways for calcium uptake. Because their bodies use vitamin D more sparingly, indigenous Arctic and Tropical peoples can be misdiagnosed with vitamin D deficiency and wrongly prescribed dietary supplements that may push their vitamin D level over the threshold of toxicity.
    Keywords:  Arctic; Inuit; Samoyed; Sámi; Tropics; UVB; culture; genetics; vitamin D
    DOI:  https://doi.org/10.3390/nu14194071
  53. Food Chem X. 2022 Oct 30. 15 100433
    Resveratrol-loaded α-lactalbumin-chitosan nanoparticle-encapsulated high internal phase Pickering emulsion for curcumin protection and its in vitro digestion profile.
    Yuting Fan, Dixue Luo, Jiang Yi.
      The use of antioxidant-loaded protein-polysaccharide nanoparticle in stabilizing and delivering curcumin with high internal phase Pickering emulsions is comparatively scarce. Resveratrol (RES)-loaded α-lactalbumin (ALA)-chitosan (CHI) particles were fabricated and used for curcumin-loaded high internal phase Pickering emulsions (HIPPEs) stabilization and delivery. CLSM illustrated that RES-ALA-CHI nanoparticles were effectively adsorbed on oil/water (O/W) interface and a gel-like structure was formed surrounding oil droplets. All HIPPEs exhibited excellent physical stability. CUR retention was 75.4 % for HIPPEs with RES-ALA-CHI colloidal particles, which was appreciably higher than that with ALA-CHI colloidal particles (63.9 %) after 30 days storage. Compared to bulk medium-chain triglyceride (MCT), both lipolysis extent and curcumin (CUR) bioaccessibility were pronouncedly enhanced with HIPPEs-based delivery systems. But both HIPPEs (51.4 % and 43.7 %) exhibited lower extent of lipolysis than conventional emulsions (90.4 %). The occurrence of RES significantly restrained the lipolysis. These results demonstrated that HIPPEs could be excellent delivery systems for delivering lipophilic curcumin.
    Keywords:  Chitosan; Colloidal particles; Curcumin; HIPPEs; Resveratrol; a-Lactalbumin
    DOI:  https://doi.org/10.1016/j.fochx.2022.100433
  54. J Control Release. 2022 Oct 10. pii: S0168-3659(22)00682-4. [Epub ahead of print]
    Recent progress in nitric oxide-generating nanomedicine for cancer therapy.
    Yuce Li, Been Yoon, Anup Dey, Nguyen Van Quy, Jae Hyung Park.
      Nitric oxide (NO) is an endogenous, multipotent biological signaling molecule that participates in several physiological processes. Recently, exogenous supplementation of tumor tissues with NO has emerged as a potential anticancer therapy. In particular, it induces synergistic effects with other conventional therapies (such as chemo-, radio-, and photodynamic therapies) by regulating the activity of P-glycoprotein, acting as a vascular relaxant to relieve tumor hypoxia, and participating in the metabolism of reactive oxygen species. However, NO is highly reactive, and its half-life is relatively short after generation. Meanwhile, NO-induced anticancer activity is dose-dependent. Therefore, the targeted delivery of NO to the tumor is required for better therapeutic effects. In the past decade, NO-generating nanomedicines (NONs), which enable sustained and specific NO release in tumor tissues, have been developed for enhanced cancer therapy. This review describes the recent efforts and preclinical achievements in the development of NON-based cancer therapies. The chemical structures employed in the fabrication of NONs are summarized, and the strategies involved in NON-based cancer therapies are elaborated.
    Keywords:  Nitric oxide; P-glycoprotein; cancer therapy; nanomedicine; peroxynitrite; vasodilation
    DOI:  https://doi.org/10.1016/j.jconrel.2022.10.012
  55. Front Cell Dev Biol. 2022 ;10 893677
    Effect of TP53 deficiency and KRAS signaling on the bioenergetics of colon cancer cells in response to different substrates: A single cell study.
    James Kealey, Heiko Düssmann, Irene Llorente-Folch, Natalia Niewidok, Manuela Salvucci, Jochen H M Prehn, Beatrice D'Orsi.
      Metabolic reprogramming is a hallmark of cancer. Somatic mutations in genes involved in oncogenic signaling pathways, including KRAS and TP53, rewire the metabolic machinery in cancer cells. We here set out to determine, at the single cell level, metabolic signatures in human colon cancer cells engineered to express combinations of activating KRAS gene mutations and TP53 gene deletions. Specifically, we explored how somatic mutations in these genes and substrate availability (lactate, glucose, substrate deprivation) from the extracellular microenvironment affect bioenergetic parameters, including cellular ATP, NADH and mitochondrial membrane potential dynamics. Employing cytosolic and mitochondrial FRET-based ATP probes, fluorescent NADH sensors, and the membrane-permeant cationic fluorescent probe TMRM in HCT-116 cells as a model system, we observed that TP53 deletion and KRAS mutations drive a shift in metabolic signatures enabling lactate to become an efficient metabolite to replenish both ATP and NADH following nutrient deprivation. Intriguingly, cytosolic, mitochondrial and overall cellular ATP measurements revealed that, in WT KRAS cells, TP53 deficiency leads to an enhanced ATP production in the presence of extracellular lactate and glucose, and to the greatest increase in ATP following a starvation period. On the other hand, oncogenic KRAS in TP53-deficient cells reversed the alterations in cellular ATP levels. Moreover, cell population measurements of mitochondrial and glycolytic metabolism using a Seahorse analyzer demonstrated that WT KRAS TP53-silenced cells display an increase of the basal respiration and tightly-coupled mitochondria, in the presence of glucose as substrate, compared to TP53 competent cells. Furthermore, cells possessing oncogenic KRAS, independently of TP53 status, showed less pronounced mitochondrial membrane potential changes in response to metabolic nutrients. Furthermore, analysis of cytosolic and mitochondrial NADH levels revealed that the simultaneous presence of TP53 deletion and oncogenic KRAS showed the most pronounced alteration in cytosolic and mitochondrial NADH during metabolic stress. In conclusion, our findings demonstrate how activating KRAS mutation and loss of TP53 remodel cancer metabolism and lead to alterations in bioenergetics under metabolic stress conditions by modulating cellular ATP production, NADH oxidation, mitochondrial respiration and function.
    Keywords:  Cancer Metabolism; OxPhos; bioenergetics; colorectal cancer; metabolic stress
    DOI:  https://doi.org/10.3389/fcell.2022.893677
  56. Molecules. 2022 Sep 23. pii: 6280. [Epub ahead of print]27(19):
    Polyphenols in Metabolic Diseases.
    Amin Gasmi, Pavan Kumar Mujawdiya, Sadaf Noor, Roman Lysiuk, Roman Darmohray, Salva Piscopo, Larysa Lenchyk, Halyna Antonyak, Kateryna Dehtiarova, Mariia Shanaida, Alexandr Polishchuk, Volodymyr Shanaida, Massimiliano Peana, Geir Bjørklund.
      Polyphenols (PPs) are a large group of phytochemicals containing phenolic rings with two or more hydroxyl groups. They possess powerful antioxidant properties, multiple therapeutic effects, and possible health benefits in vivo and in vitro, as well as reported clinical studies. Considering their free-radical scavenging and anti-inflammatory properties, these substances can be used to treat different kinds of conditions associated with metabolic disorders. Many symptoms of metabolic syndrome (MtS), including obesity, dyslipidemia, atherosclerosis, elevated blood sugar, accelerating aging, liver intoxication, hypertension, as well as cancer and neurodegenerative disorders, are substantially relieved by dietary PPs. The present study explores the bioprotective properties and associated underlying mechanisms of PPs. A detailed understanding of these natural compounds will open up new opportunities for producing unique natural PP-rich dietary and medicinal plans, ultimately affirming their health benefits.
    Keywords:  bioprotective property; metabolic syndrome; natural sources; phenolic compounds; therapeutic effect
    DOI:  https://doi.org/10.3390/molecules27196280
  57. Polymers (Basel). 2022 Sep 29. pii: 4091. [Epub ahead of print]14(19):
    Curcumin and Diclofenac Therapeutic Efficacy Enhancement Applying Transdermal Hydrogel Polymer Films, Based on Carrageenan, Alginate and Poloxamer.
    Katarina S Postolović, Milan D Antonijević, Biljana Ljujić, Slavko Radenković, Marina Miletić Kovačević, Zoltan Hiezl, Svetlana Pavlović, Ivana Radojević, Zorka Stanić.
      Films based on carrageenan, alginate and poloxamer 407 have been formulated with the main aim to apply prepared formulations in wound healing process. The formulated films were loaded with diclofenac, an anti-inflammatory drug, as well as diclofenac and curcumin, as multipurpose drug, in order to enhance encapsulation and achieve controlled release of these low-bioavailability compounds. The obtained data demonstrated improved drug bioavailability (encapsulation efficiency higher than 90%), with high, cumulative in vitro release percentages (90.10% for diclofenac, 89.85% for curcumin and 95.61% for diclofenac in mixture-incorporated films). The results obtained using theoretical models suggested that curcumin establishes stronger, primarily dispersion interactions with carrier, in comparison with diclofenac. Curcumin and diclofenac-loaded films showed great antibacterial activity against Gram-positive bacteria strains (Bacillus subtilis and Staphylococcus aureus, inhibition zone 16.67 and 13.67 mm, respectively), and in vitro and in vivo studies indicated that curcumin- and diclofenac-incorporated polymer films have great potential, as a new transdermal dressing, to heal wounds, because diclofenac can target the inflammatory phase and reduce pain, whereas curcumin can enhance and promote the wound healing process.
    Keywords:  biopolymers; carrageenan/alginate/poloxamer; curcumin; diclofenac; films; wound healing
    DOI:  https://doi.org/10.3390/polym14194091
  58. Phytomedicine. 2022 Dec;pii: S0944-7113(22)00574-8. [Epub ahead of print]107 154485
    Evaluating Cannabis sativa L.'s neuroprotection potential: From bench to bedside.
    John Staton Laws, Scott D Smid.
      BACKGROUND: Neurodegenerative diseases and dementia pose a global health challenge in an aging population, exemplified by the increasing incidence and prevalence of its most common form, Alzheimer's disease. Although several approved treatments exist for Alzheimer's disease, they only afford transient symptomatic improvements and are not considered disease-modifying. The psychoactive properties of Cannabis sativa L. have been recognized for thousands of years and now with burgeoning access to medicinal formulations globally, research has turned to re-evaluate cannabis and its myriad phytochemicals as a potential treatment and adjunctive agent for neurodegenerative diseases.PURPOSE: This review evaluated the neuroprotective potential of C. sativa's active constituents for potential therapeutic use in dementia and Alzheimer's disease, based on published studies demonstrating efficacy in experimental preclinical settings associated with neurodegeneration.
    STUDY DESIGN: Relevant information on the neuroprotective potential of the C. sativa's phytoconstituents in preclinical studies (in vitro, in vivo) were included. The collated information on C. sativa's component bioactivity was organized for therapeutic applications against neurodegenerative diseases.
    METHODS: The therapeutic use of C. sativa related to Alzheimer's disease relative to known phytocannabinoids and other phytochemical constituents were derived from online databases, including PubMed, Elsevier, The Plant List (TPL, www.theplantlist.org), Science Direct, as well as relevant information on the known pharmacological actions of the listed phytochemicals.
    RESULTS: Numerous C. sativa -prevalent phytochemicals were evidenced in the body of literature as having efficacy in the treatment of neurodegenerative conditions exemplified by Alzheimer's disease. Several phytocannabinoids, terpenes and select flavonoids demonstrated neuroprotection through a myriad of cellular and molecular pathways, including cannabinoid receptor-mediated, antioxidant and direct anti-aggregatory actions against the pathological toxic hallmark protein in Alzheimer's disease, amyloid β.
    CONCLUSIONS: These findings provide strong evidence for a role of cannabis constituents, individually or in combination, as potential neuroprotectants timely to the emergent use of medicinal cannabis as a novel treatment for neurodegenerative diseases. Future randomized and controlled clinical studies are required to substantiate the bioactivities of phytocannabinoids and terpenes and their likely synergies.
    Keywords:  Alzheimer's disease; Cannabinoids; Cannabis sativa L; Dementia; Neuroprotection
    DOI:  https://doi.org/10.1016/j.phymed.2022.154485
  59. Med Oncol. 2022 Oct 08. 39(12): 247
    Hepatocellular carcinoma stage: an almost loss of fatty acid metabolism and gain of glucose metabolic pathways dysregulation.
    Karthik Balakrishnan.
      Cancer cells rewire the metabolic processes beneficial for cancer cell proliferation, survival, and their progression. In this study, metabolic processes related to glucose, glutamine, and fatty acid metabolism signatures were collected from the molecular signatures database and investigated in the context of energy metabolic pathways through available genome-wide expression profiles of liver cancer cohorts by gene sets-based pathway activation scoring analysis. The outcomes of this study portray that the fatty acid metabolism, transport, and its storage related signatures are highly expressed across early stages of liver tumors and on the contrary, the gene sets related to glucose transport and glucose metabolism are prominently activated in the hepatocellular carcinoma (HCC) stage. Based on the results, these metabolic pathways are clearly dysregulated across specific stages of carcinogenesis. The identified dimorphic metabolic pathway dysregulation patterns are further reconfirmed by examining corresponding metabolic pathway genes expression patterns across various stages encompassing profiles. Recurrence is the primary concern in the carcinogenesis of liver tumors due to liver tissues regeneration. Hence, to further explore these dysregulation effects on recurrent cirrhosis and recurrent HCC sample containing profile GSE20140 was examined and interestingly, this result also reiterated these differential metabolic pathways dysregulation. In addition, a recently established metabolome profile for the massive panel of cancer cell-lines, including liver cancer cell-lines, was used for further exploration. These findings also reassured those differential metabolites abundance of the fatty acid and glucose metabolic pathways enlighten those dimorphic metabolic pathways dysregulation. Moreover, ROC curves of fatty acid metabolic pathway genes such as acetyl-CoA carboxylase (ACACB), acyl-CoA dehydrogenase long chain (ACADL), and acyl-CoA dehydrogenase medium chain (ACADM) as well as glucose metabolic pathway genes such as phosphoglycerate kinase (PGK1), pyruvate dehydrogenase (PDHA1), pyruvate dehydrogenase kinase (PDK1) demonstrated greater sensitivity and specificity in the corresponding stage-specific tumors with significant p-values (p < 0.05). Furthermore, overall survival (OS) and recurrence-free survival (RFS) studies also reconfirmed that the rate-limiting genes expression of fatty acid and glucose metabolic pathways reveal better and poor survival in HCC patient cohorts, respectively. In conclusion, all these results clearly show that metabolic rewiring and the existence of two diverse metabolic pathways dysregulation involving fatty acid and glucose metabolism across the stages of liver tumors have been identified. These findings might be useful for developing therapeutic target treatments in stage-specific tumors.
    Keywords:  Fatty acid metabolism; Glucose metabolism; Hepatocellular carcinoma; Liver cancer
    DOI:  https://doi.org/10.1007/s12032-022-01839-0
  60. Hum Gene Ther. 2022 Oct 10.
    Suicide gene delivery system mediated by ultrasound targeted microbubble destruction: A promising strategy for cancer therapy.
    Tong Wu, Chi Huang, Yiran Yao, Zhaolin Du, Zhijun Liu.
      The treatment of malignant tumors has always been one of the challenges that have plagued researchers and clinicians. The ideal status in cancer treatment is to eliminate tumor cells while avoiding damage to normal tissues. Different approaches have been investigated to achieve such a goal, and suicide gene therapy has emerged as a novel mode of cancer treatment. This approach involves the delivery of genes encoding enzymes that activate non-toxic prodrugs into cytotoxic metabolites that cause the death of transfected cancer cells. Despite promising results obtained both in vitro and in vivo, this innovative approach has long been stalled in the clinic due to the lack of a suitable delivery system to introduce the suicide gene into cancer cells. Ultrasound-targeted microbubble destruction (UTMD) represents a valuable non-viral vector system for site-specific and noninvasive gene therapy. Ultrasound promotes intracellular uptake of therapeutic agents by increasing vascular and cell membrane permeability, especially in the presence of microbubbles. In this scenario, the true potential of suicide genes can be translated into clinically valuable treatments for patients. This review provides background information on suicide gene therapy and UTMD technology, summarizes the current state of knowledge about UTMD-mediated suicide gene delivery in cancer treatment, and presents an outlook on its future development.
    DOI:  https://doi.org/10.1089/hum.2022.152
  61. Front Pharmacol. 2022 ;13 884822
    Using omics approaches to dissect the therapeutic effects of Chinese herbal medicines on gastrointestinal cancers.
    Si-Yi Li, Wei-Jia Wang, Qiu-Yue Li, Peng-Hui Yang, Xin-Long Li, Yan Yan, Yong Yuan, Yi-Bin Feng, Ming Hong.
      Chinese herbal medicines offer a rich source of anti-cancer drugs. Differences between the pharmacology of Chinese herbal medicines and modern synthetic chemicals hinder the development of drugs derived from herbal products. To address this challenge, novel omics approaches including transcriptomics, proteomics, genomics, metabolomics, and microbiomics have been applied to dissect the pharmacological benefits of Chinese herbal medicines in cancer treatments. Numerous Chinese herbal medicines have shown potential anti-tumor effects on different gastrointestinal (GI) cancers while eliminating the side effects associated with conventional cancer therapies. The present study aimed to provide an overview of recent research focusing on Chinese herbal medicines in GI cancer treatment, based on omics approaches. This review also illustrates the potential utility of omics approaches in herbal-derived drug discovery. Omics approaches can precisely and efficiently reveal the key molecular targets and intracellular interaction networks of Chinese herbal medicines in GI cancer treatment. This study summarizes the application of different omics-based approaches in investigating the effects and mechanisms of Chinese herbal medicines in GI cancers. Future research directions are also proposed for this area of study.
    Keywords:  Chinese herbal medicines; gastrointestinal cancers; omics; review; side effects
    DOI:  https://doi.org/10.3389/fphar.2022.884822
  62. Front Pharmacol. 2022 ;13 920435
    Andrographolide, a natural anti-inflammatory agent: An Update.
    Xiaohong Li, Weichen Yuan, Jibiao Wu, Jianhua Zhen, Qihui Sun, Minmin Yu.
      Botanicals have attracted much attention in the field of anti-inflammatory due to their good pharmacological activity and efficacy. Andrographis paniculata is a natural plant ingredient that is widely used around the world. Andrographolide is the main active ingredient derived from Andrographis paniculata, which has a good effect on the treatment of inflammatory diseases. This article reviews the application, anti-inflammatory mechanism and molecular targets of andrographolide in different inflammatory diseases, including respiratory, digestive, immune, nervous, cardiovascular, skeletal, and tumor system diseases. And describe its toxicity and explain its safety. Studies have shown that andrographolide can be used to treat inflammatory lesions of various systemic diseases. In particular, it acts on many inflammation-related signalling pathways. The future direction of andrographolide research is also introduced, as is the recent research that indicates its potential clinical application as an anti-inflammatory agent.
    Keywords:  andrographolide; anti-inflammation; immunomodulation; inflammatory diseases; review
    DOI:  https://doi.org/10.3389/fphar.2022.920435
  63. Cell Signal. 2022 Oct 05. pii: S0898-6568(22)00250-9. [Epub ahead of print]100 110488
    The Warburg effect in osteoporosis: Cellular signaling and epigenetic regulation of energy metabolic events to targeting the osteocalcin for phenotypic alteration.
    Chithravel Vadivalagan, Anand Krishnan, Siang-Jyun Chen, You-Cheng Hseu, Sathish Muthu, Rajib Dhar, Alaa A A Aljabali, Murtaza M Tambuwala.
      Osteoporosis is a silent disease of skeletal morphology that induces fragility and fracture risk in aged persons irrespective of gender. Juvenile secondary osteoporosis is rare and is influenced by familial genetic abnormalities. Despite the currently available therapeutic options, more-acute treatments are in need. Women suffer from osteoporosis after menopause, which is characterized by a decline in the secretion of sex hormones in the later phase of life. Several studies in the past two decades emphasized hormone-related pathways to combat osteoporosis. Some studies partially examined energy-related pathways, but achieving a more vivid picture of metabolism and bone remodeling in terms of the Warburg phenomenon is still warranted. Each cell requires sufficient energy for cellular propagation and growth; in particular, osteoporosis is an energy-dependent mechanism affected by a decreased cellular mass of the bone morphology. Energy utilization is the actual propagation of such diseases, and narrowing down these criteria will hopefully provide clues to formulate better therapeutic strategies. Oxidative glycolysis is a particular type of energy metabolic pathway in cancer cells that influences cellular proliferation. Therefore, the prospect of utilizing collective glucose metabolism by inducing the Warburg effect may improve cell propagation. The benefits of utilizing the energy from the Warburg effect may be a difficult task. However, it seems to improve their effectiveness in the osteoblast phenotype by connecting the selected pathways such as WNT, Notch, AKT, and Insulin signaling by targeting osteocalcin resulting in phenotypic alteration. Osteocalcin directs ATP utilization through the sclerostin SOST gene in the bone microenvironment. Thus, selective activation of ATP production involved in osteoblast maturation remains a prime strategy to fight osteoporosis.
    Keywords:  ATP production; Alternative therapy; Glucose metabolism; Glycolysis; Osteoblast; Osteoporosis; Warburg effect
    DOI:  https://doi.org/10.1016/j.cellsig.2022.110488
  64. Molecules. 2022 Oct 01. pii: 6473. [Epub ahead of print]27(19):
    Biomimetic Targeted Theranostic Nanoparticles for Breast Cancer Treatment.
    Suphalak Khamruang Marshall, Pavimol Angsantikul, Zhiqing Pang, Norased Nasongkla, Rusnah Syahila Duali Hussen, Soracha D Thamphiwatana.
      The development of biomimetic drug delivery systems for biomedical applications has attracted significant research attention. As the use of cell membrane as a surface coating has shown to be a promising platform for several disease treatments. Cell-membrane-coated nanoparticles exhibit enhanced immunocompatibility and prolonged circulation time. Herein, human red blood cell (RBC) membrane-cloaked nanoparticles with enhanced targeting functionality were designed as a targeted nanotheranostic against cancer. Naturally, derived human RBC membrane modified with targeting ligands coated onto polymeric nanoparticle cores containing both chemotherapy and imaging agent. Using epithelial cell adhesion molecule (EpCAM)-positive MCF-7 breast cancer cells as a disease model, the nature-inspired targeted theranostic human red blood cell membrane-coated polymeric nanoparticles (TT-RBC-NPs) platform was capable of not only specifically binding to targeted cancer cells, effectively delivering doxorubicin (DOX), but also visualizing the targeted cancer cells. The TT-RBC-NPs achieved an extended-release profile, with the majority of the drug release occurring within 5 days. The TT-RBC-NPs enabled enhanced cytotoxic efficacy against EpCAM positive MCF-7 breast cancer over the non-targeted NPs. Additionally, fluorescence images of the targeted cancer cells incubated with the TT-RBC-NPs visually indicated the increased cellular uptake of TT-RBC-NPs inside the breast cancer cells. Taken together, this TT-RBC-NP platform sets the foundation for the next-generation stealth theranostic platforms for systemic cargo delivery for treatment and diagnostic of cancer.
    Keywords:  biomimetic; cancer; nanomedicine; nanoparticles; theranostics
    DOI:  https://doi.org/10.3390/molecules27196473
  65. Nutrients. 2022 Sep 30. pii: 4079. [Epub ahead of print]14(19):
    Sesame (Sesamum indicum L.): A Comprehensive Review of Nutritional Value, Phytochemical Composition, Health Benefits, Development of Food, and Industrial Applications.
    Panpan Wei, Fenglan Zhao, Zhen Wang, Qibao Wang, Xiaoyun Chai, Guige Hou, Qingguo Meng.
      Sesame (Sesamum indicum L.), of the Pedaliaceae family, is one of the first oil crops used in humans. It is widely grown and has a mellow flavor and high nutritional value, making it very popular in the diet. Sesame seeds are rich in protein and lipids and have many health benefits. A number of in vitro and in vivo studies and clinical trials have found sesame seeds to be rich in lignan-like active ingredients. They have antioxidant, cholesterol reduction, blood lipid regulation, liver and kidney protection, cardiovascular system protection, anti-inflammatory, anti-tumor, and other effects, which have great benefits to human health. In addition, the aqueous extract of sesame has been shown to be safe for animals. As an important medicinal and edible homologous food, sesame is used in various aspects of daily life such as food, feed, and cosmetics. The health food applications of sesame are increasing. This paper reviews the progress of research on the nutritional value, chemical composition, pharmacological effects, and processing uses of sesame to support the further development of more functionalities of sesame.
    Keywords:  bioactivity; food use; nutritional value; phytochemical composition; sesame; sesamin
    DOI:  https://doi.org/10.3390/nu14194079
  66. Int J Mol Sci. 2022 Oct 01. pii: 11604. [Epub ahead of print]23(19):
    Engineered Mesoporous Silica-Based Core-Shell Nanoarchitectures for Synergistic Chemo-Photodynamic Therapies.
    Yue-Mei Gao, Shih-Han Chiu, Prabhakar Busa, Chen-Lun Liu, Ranjith Kumar Kankala, Chia-Hung Lee.
      Combinatorial therapies have garnered enormous interest from researchers in efficiently devastating malignant tumors through synergistic effects. To explore the combinatorial approach, multiple therapeutic agents are typically loaded in the delivery vehicles, controlling their release profiles and executing subsequent therapeutic purposes. Herein, we report the fabrication of core (silica)-shell (mesoporous silica nanoparticles, MSNs) architectures to deliver methylene blue (MB) and cupric doxorubicin (Dox) as model drugs for synergistic photodynamic therapy (PDT), chemotherapy, and chemodynamic therapy (CDT). MB, as the photosensitizer, is initially loaded and stabilized in the silica core for efficient singlet oxygen generation under light irradiation towards PDT. The most outside shell with imidazole silane-modified MSNs is immobilized with a chemotherapeutic agent of Dox molecules through the metal (Copper, Cu)-ligand coordination interactions, achieving the pH-sensitive release and triggering the production of intracellular hydrogen peroxide and subsequent Fenton-like reaction-assisted Cu-catalyzed free radicals for CDT. Further, the designed architectures are systematically characterized using various physicochemical characterization techniques and demonstrate the potent anti-cancer efficacy against skin melanoma. Together our results demonstrated that the MSNs-based core-shell nanoarchitectures have great potential as an effective strategy in synergistically ablating cancer through chemo-, chemodynamic, and photodynamic therapies.
    Keywords:  chemodynamic therapy; core-shell nanoarchitectures; mesoporous silica nanoparticles; photodynamic therapy
    DOI:  https://doi.org/10.3390/ijms231911604
  67. Cancers (Basel). 2022 Oct 08. pii: 4924. [Epub ahead of print]14(19):
    Oxidative Stress and Autophagy Mediate Anti-Cancer Properties of Cannabis Derivatives in Human Oral Cancer Cells.
    Lionel Loubaki, Mahmoud Rouabhia, Mohamed Al Zahrani, Abdullah Al Amri, Abdelhabib Semlali.
      Cannabinoids, the active components of cannabis exert palliative effects in cancer patients by preventing nausea, vomiting and pain as well as by stimulating appetite. Recent studies indicated that cannabinoids could be helpful in treating certain rare forms of cancer and other inflammatory diseases. The objective of this study was to investigate the cytotoxic effect of a cannabinoid mixture (CM) in oral cells. Thus, normal and cancer gingival cells were treated with different concentrations of CM to evaluate their proliferation by MTT assay, cytotoxicity by using LDH assay, colony formation with crystal violet and migration by the scratch method. In addition, apoptosis, autophagy, oxidative stress, antioxidant level, DNA damage and the mitochondrial membrane potential (ΔΨm) generated by proton pumps were measured by flow cytometry. Furthermore, deactivation of the key signaling pathways involved in cancer progression such as NF-κB, ERK1/2, p38, STAT1, STAT3, STAT5 was also evaluated by this technique. These outcomes indicate that CM, at a concentration higher than 0.1 µg/mL, provokes high cytotoxicity in Ca9-22 oral cancer cells but not in GMSM-K gingival normal cells. Apoptosis, autophagy, antioxidant levels and mitochondrial stress as well as DNA damage in oral cells were increased following exposure to low concentration (1 µg/mL). In addition, major signaling pathways that are involved such as MAPKase, STATs and NF-κB pathways were inhibited by CM as well as cell migration. Our results suggest that cannabinoids could potentially have a beneficial effect on oral cancer therapy.
    Keywords:  MAPK; STAT and NF-κB pathways; apoptosis; autophagy; cannabinoid mixture; oral cancer; oxidative stress
    DOI:  https://doi.org/10.3390/cancers14194924
  68. Int J Mol Sci. 2022 Oct 04. pii: 11746. [Epub ahead of print]23(19):
    A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells.
    Partha Biswas, Dipta Dey, Polash Kumar Biswas, Tanjim Ishraq Rahaman, Shuvo Saha, Anwar Parvez, Dhrubo Ahmed Khan, Nusrat Jahan Lily, Konka Saha, Md Sohel, Mohammad Mehedi Hasan, Salauddin Al Azad, Shabana Bibi, Md Nazmul Hasan, Mohammed Rahmatullah, Jaemoo Chun, Md Ataur Rahman, Bonglee Kim.
      Reactive oxygen species (ROS) induce carcinogenesis by causing genetic mutations, activating oncogenes, and increasing oxidative stress, all of which affect cell proliferation, survival, and apoptosis. When compared to normal cells, cancer cells have higher levels of ROS, and they are responsible for the maintenance of the cancer phenotype; this unique feature in cancer cells may, therefore, be exploited for targeted therapy. Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors. Adaptive stress responses may be induced by persistent ROS stress, allowing cancer cells to survive with high levels of ROS while maintaining cellular viability. However, large amounts of ROS make cancer cells extremely susceptible to quercetin, one of the most available dietary flavonoids. Because of the molecular and metabolic distinctions between malignant and normal cells, targeting ROS metabolism might help overcome medication resistance and achieve therapeutic selectivity while having little or no effect on normal cells. The powerful bioactivity and modulatory role of quercetin has prompted extensive research into the chemical, which has identified a number of pathways that potentially work together to prevent cancer, alongside, QC has a great number of evidences to use as a therapeutic agent in cancer stem cells. This current study has broadly demonstrated the function-mechanistic relationship of quercetin and how it regulates ROS generation to kill cancer and cancer stem cells. Here, we have revealed the regulation and production of ROS in normal cells and cancer cells with a certain signaling mechanism. We demonstrated the specific molecular mechanisms of quercetin including MAPK/ERK1/2, p53, JAK/STAT and TRAIL, AMPKα1/ASK1/p38, RAGE/PI3K/AKT/mTOR axis, HMGB1 and NF-κB, Nrf2-induced signaling pathways and certain cell cycle arrest in cancer cell death, and how they regulate the specific cancer signaling pathways as long-searched cancer therapeutics.
    Keywords:  REDOX imbalance; ROS; cancer stem cells; carcinogenesis; malignant cells; quercetin
    DOI:  https://doi.org/10.3390/ijms231911746
  69. Pak J Pharm Sci. 2022 Jul;35(4(Special)): 1229-1239
    Fast dissolving oral films: An approach to co-load and deliver the atorvastatin and ezetimibe for better therapeutic response.
    Meshal Alshamrani, Iqra Mubeen, Muhammad Hashir Iqbal, Muhammad Farooq, Muhammad Zaman, Mueen Ahmad Chaudhry, Omer Salman Qureshi, Muhammad Hammad Butt, Ahmad Salawi, Muhammad Rizwan Khan, Yosif Almoshari.
      Atherosclerotic patients suffering with acute coronary disease are lying at high risk. This life-threatening problem can be curtailed by using statins e.g., ezetimibe (EZT), atorvastatin calcium (ATC). In this study, co-loaded Fast Dissolving oral films (FDOFs), of ATC-EZT with HPMC E5 prepared by solvent evaporation method. Prepared FDOFs were evaluated for physicochemical, thermal and mechanical properties. In-vivo animal studies were performed on albino rats against diet induced hyperlipidemia. Prepared FDOFs have rapid DT; 27sec, TDT >2min and in-vitro drug release 97% in a min. In DSC, FTIR and XRD analysis, prepared films were chemically compatible and no chemical interaction of drugs and excipient was found. In kinetic modeling, it was observed their EZT exhibited lowest R2 value for zero order kinetic and best fit model was first order kinetic (n, 0.9823). The korsmeyer peppas model films (n, 0.016) indicate fickian type drug diffusion. The groups treated with marketed suspension of drug and FODPs were compared with normal group and high fats diet group. Study reviled that combination FDOPs of both ATC/EZT significantly reduce hyperlipemia as compared to high fat diet group. It can be concluded that ATC and EZT encapsulated in FODFs provide instant drug release and better therapeutic outcomes.
  70. Nanomaterials (Basel). 2022 Sep 29. pii: 3426. [Epub ahead of print]12(19):
    Curcumin Sustained Release with a Hybrid Chitosan-Silk Fibroin Nanofiber Containing Silver Nanoparticles as a Novel Highly Efficient Antibacterial Wound Dressing.
    Parisa Heydari Foroushani, Erfan Rahmani, Iran Alemzadeh, Manouchehr Vossoughi, Mehrab Pourmadadi, Abbas Rahdar, Ana M Díez-Pascual.
      Drug loading in electrospun nanofibers has gained a lot of attention as a novel method for direct drug release in an injury site to accelerate wound healing. The present study deals with the fabrication of silk fibroin (SF)-chitosan (CS)-silver (Ag)-curcumin (CUR) nanofibers using the electrospinning method, which facilitates the pH-responsive release of CUR, accelerates wound healing, and improves mechanical properties. Response surface methodology (RSM) was used to investigate the effect of the solution parameters on the nanofiber diameter and morphology. The nanofibers were characterized via Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), zeta potential, and Dynamic Light Scattering (DLS). CS concentration plays a crucial role in the physical and mechanical properties of the nanofibers. Drug loading and entrapment efficiencies improved from 13 to 44% and 43 to 82%, respectively, after the incorporation of Ag nanoparticles. The application of CS hydrogel enabled a pH-responsive release of CUR under acid conditions. The Minimum Inhibitory Concentration (MIC) assay on E. coli and S. aureus bacteria showed that nanofibers with lower CS concentration cause stronger inhibitory effects on bacterial growth. The nanofibers do not have any toxic effect on cell culture, as revealed by in vitro wound healing test on NIH 3T3 fibroblasts.
    Keywords:  biomedical engineering; chitosan; curcumin; drug delivery; electrospinning; healthcare; silk fibroin; silver nanoparticles; wound dressing
    DOI:  https://doi.org/10.3390/nano12193426
  71. J Microencapsul. 2022 Oct 12. 1-25
    Development, Evaluation, Pharmacokinetic and Biodistribution Estimation of Resveratrol Loaded Solid Lipid Nanoparticles for Prostate Cancer Targeting.
    Alok Nath Sharma, Prabhat Kumar Upadhyay, Hitesh Kumar Dewangan.
      BACKGROUND AND AIM: The study was to extend systemic circulation and biological half-life (t1/2) of Trans-resveratrol (RSV) using solid lipid nanoparticles (RSV-SLN) to improve its anti-cancer potential.METHODS: RSV-SLN was prepared by solvent emulsification evaporation technique and proceeded for evaluation like particle size, PDI, zeta potential, in-vitro release, in-vitro cytotoxicity, cellular internalization, haemolysis and erythrocyte membrane integrity, platelet aggregation and pharmacokinetic studies in rats. Moreover, cancer cells accumulation of RSV-SLN also needs to be evaluated for proving their targeting ability.
    RESULT: Prepared SLN showed 126.85 ± 12.09 nm particle size, -24.23 ± 3.27 mV Zeta potential and 74.67 ± 4.76%. release at 48 hrs and haemocompatible. The cellular internalization image showed the SLN reach in a cytoplasm and nucleus of PC3 prostate cells. RSV-SLN exhibited high t1/2 (8.22 ± 1.36 hrs) and 7.19 ± 0.69 hrs MRT (Mean residence time) and lower clearance i.e. 286.42 ± 13.64 mL/min/kg. The bio-distribution of RSV-SLN was found to be extremely high in prostate cells and accumulate 7.56 times greater than that of RSV solution.
    CONCLUSION: The developed RSV-SLN can be applied as potential carrier for delivery of drug of chemotherapeutics at an extend systemic circulation and targeting efficiency at tumor site.
    Keywords:  Resveratrol; prolonging systemic circulation; prostate; solid lipid nanoparticles; targeting
    DOI:  https://doi.org/10.1080/02652048.2022.2135785
  72. Molecules. 2022 Sep 22. pii: 6241. [Epub ahead of print]27(19):
    Evaluation of the Anti-Cancer Potential of Rosa damascena Mill. Callus Extracts against the Human Colorectal Adenocarcinoma Cell Line.
    Hadeer Darwish, Sarah Alharthi, Radwa A Mehanna, Samar S Ibrahim, Mustafa A Fawzy, Saqer S Alotaibi, Sarah M Albogami, Bander Albogami, Sedky H A Hassan, Ahmed Noureldeen.
      Chemotherapy is an aggressive form of chemical drug therapy aiming to destroy cancer cells. Adjuvant therapy may reduce hazards of chemotherapy and help in destroying these cells when obtained from natural products, such as medical plants. In this study, the potential therapeutic effect of Rosa damascena callus crude extract produced in vitamin-enhanced media is investigated on colorectal cancer cell line Caco-2. Two elicitors, i.e., L-ascorbic acid and citric acid at a concentration of 0.5 g/L were added to the callus induction medium. Callus extraction and the GC-MS analysis of methanolic crude extracts were also determined. Cytotoxicity, clonogenicity, proliferation and migration of Caco-2 colorectal cancer cells were investigated using MTT cytotoxicity, colony-forming, Ki-67 flow cytometry proliferation and Migration Scratch assays, respectively. Our results indicated that L-ascorbic acid treatment enhanced callus growth parameters and improved secondary metabolite contents. It showed the least IC50 value of 137 ug/mL compared to 237 ug/mL and 180 ug/mL in the citric acid-treated and control group. We can conclude that R. damascena callus elicited by L-ascorbic acid improved growth and secondary metabolite contents as well as having an efficient antiproliferative, anti-clonogenic and anti-migratory effect on Caco-2 cancer cells, thus, can be used as an adjuvant anti-cancer therapy.
    Keywords:  Rosa damascena; anti-cancer activity; bio-elicitors; callus induction; colorectal cancer cell line
    DOI:  https://doi.org/10.3390/molecules27196241
  73. Biomacromolecules. 2022 Oct 12.
    Intracellular pH-Regulating Nanoparticles to Improve Anticancer Drug Efficacy for Cancer Treatment.
    Taebum Lee, Kyoung Sub Kim, Kun Na.
      Here, we describe an intracellular pH-regulating nanoparticle (IPRN), coencapsulated with chemosensitizers and anticancer agents for effective and safe cancer treatment. IPRN contains a tubulysin derivative (TUB), a hydrophobic anticancer drug, and pantoprazole (PTZ), a hydrophilic proton-pump inhibitor. IPRN with a size of 62 nm has an anionic surface charge and is stable for at least two weeks under storage conditions, though PTZ and TUB encapsulated in IPRN showed different drug release patterns. PTZ was released before TUB, controlling the cancer's intracellular pH, maintaining a pH at which TUB can work well. The encapsulated PTZ increased the pH of endolysosomes and inhibited ion trapping, with TUB ionization, thereby exhibiting increased cytotoxicity compared with free TUB observed in various cancer cell lines, such as human liver adenocarcinoma, human glioblastoma, and human pancreatic carcinoma. IPRN exhibited a 1.9-fold improved tumor growth inhibitory effect in a human liver adenocarcinoma-bearing mouse model, while minimizing the hepatotoxicity of free TUB. Thus, nanomedicines that contain both a chemosensitizer and an anticancer agent, such as IPRN, are expected to be next-generation anticancer agents that reduce the side effects of anticancer drugs and increase the therapeutic effect.
    DOI:  https://doi.org/10.1021/acs.biomac.2c00952
  74. Front Chem. 2022 ;10 951434
    A mitochondria-targeted nano-platform for pancreatic cancer therapy.
    Xiaoke Tan, Xin Zhu, Duanjie Xu, Yanmei Shi, Zhenzhen Wang, Mingzhuo Cao, Kai Hu, Lingzhou Zhao, Junwei Zhao, Mingsan Miao, Huahui Zeng, Xiangxiang Wu.
      Liposome is a conventional drug delivery system which has been widely used in the pharmacy field. However, its applications are greatly restricted in clinical practice by the disadvantages of cholesterol and nonselective distribution. Herein, a novel platform for anti-tumor drug delivery was developed by incorporating an amphiphilic stachydrine-octadecane conjugate (SS) as the mitochondria-targeting molecule onto the triptolide-liposome surfaces (SS-TP LPs). The polyethylene glycol (PEG) and the suitable particle size (about 133 nm) of liposomes facilitated their stabilities, the long half-life in blood and the escape from the rapid elimination. The SS-TP LPs were internalized and accumulated into the mitochondria of cancer cells in a time-dependent manner, followed by triggering permeabilization of the mitochondrial outer membrane by inhibiting Bcl-2, and then further caused greater cancer cell death via releasing cytochrome C and initiating a cascade of caspase 3 reactions. In the Pan02 tumor-bearing mice, the SS-TP LPs showed significant efficacy in inhibiting tumor growth and reducing tumor size but synchronously exhibited specific mitochondria-targeting and much lower subacute toxicity compared with the free TP and TP LPs. Our study suggests that SS-TP LPs can be a promising anticancer drug delivery system for mitochondria-targeted therapy in pancreatic cancer.
    Keywords:  apoptosis; liposome; mitochondria; pancreatic cancer; stachydrine; triptolide
    DOI:  https://doi.org/10.3389/fchem.2022.951434
  75. Molecules. 2022 Sep 21. pii: 6221. [Epub ahead of print]27(19):
    Molecular Mechanistic Pathways Targeted by Natural Compounds in the Prevention and Treatment of Diabetic Kidney Disease.
    Kaixuan Zhou, Xue Zi, Jiayu Song, Qiulu Zhao, Jia Liu, Huiwei Bao, Lijing Li.
      Diabetic kidney disease (DKD) is one of the most common complications of diabetes, and its prevalence is still growing rapidly. However, the efficient therapies for this kidney disease are still limited. The pathogenesis of DKD involves glucotoxicity, lipotoxicity, inflammation, oxidative stress, and renal fibrosis. Glucotoxicity and lipotoxicity can cause oxidative stress, which can lead to inflammation and aggravate renal fibrosis. In this review, we have focused on in vitro and in vivo experiments to investigate the mechanistic pathways by which natural compounds exert their effects against the progression of DKD. The accumulated and collected data revealed that some natural compounds could regulate inflammation, oxidative stress, renal fibrosis, and activate autophagy, thereby protecting the kidney. The main pathways targeted by these reviewed compounds include the Nrf2 signaling pathway, NF-κB signaling pathway, TGF-β signaling pathway, NLRP3 inflammasome, autophagy, glycolipid metabolism and ER stress. This review presented an updated overview of the potential benefits of these natural compounds for the prevention and treatment of DKD progression, aimed to provide new potential therapeutic lead compounds and references for the innovative drug development and clinical treatment of DKD.
    Keywords:  diabetic kidney disease; inflammation; mechanism; natural compounds; oxidative stress; renal fibrosis
    DOI:  https://doi.org/10.3390/molecules27196221
  76. Molecules. 2022 Oct 01. pii: 6474. [Epub ahead of print]27(19):
    Polydatin: Pharmacological Mechanisms, Therapeutic Targets, Biological Activities, and Health Benefits.
    Ahmad Karami, Sajad Fakhri, Leila Kooshki, Haroon Khan.
      Polydatin is a natural potent stilbenoid polyphenol and a resveratrol derivative with improved bioavailability. Polydatin possesses potential biological activities predominantly through the modulation of pivotal signaling pathways involved in inflammation, oxidative stress, and apoptosis. Various imperative biological activities have been suggested for polydatin towards promising therapeutic effects, including anticancer, cardioprotective, anti-diabetic, gastroprotective, hepatoprotective, neuroprotective, anti-microbial, as well as health-promoting roles on the renal system, the respiratory system, rheumatoid diseases, the skeletal system, and women's health. In the present study, the therapeutic targets, biological activities, pharmacological mechanisms, and health benefits of polydatin are reviewed to provide new insights to researchers. The need to develop further clinical trials and novel delivery systems of polydatin is also considered to reveal new insights to researchers.
    Keywords:  health benefits; novel delivery system; pharmacological mechanism; polydatin; therapeutic target
    DOI:  https://doi.org/10.3390/molecules27196474
  77. J Clin Med. 2022 Sep 20. pii: 5505. [Epub ahead of print]11(19):
    Efficacy of Metformin as Adjuvant Therapy in Metastatic Breast Cancer Treatment.
    Nourhan M Essa, Heba F Salem, Marwa O Elgendy, A Gabr, Mervat M Omran, Nivin A Hassan, Hanaa M Tashkandi, Steve Harakeh, Marian S Boshra.
      BACKGROUND: Metformin has been reported to have an anti-tumorigenic impact against metastatic breast cancer (MBC) cells through several mechanisms. Its effect can be evaluated by using many variables such as the response rate (RR) as well as the progression-free survival (PFS).MATERIALS AND METHODS: A prospective study was conducted to investigate and estimate the metformin effect on MBC. About 107 subjects were included in the study and were divided into two groups: Group A included non-diabetic MBC patients treated with metformin in conjunction with chemotherapy and group B included those treated with chemotherapy alone. Both PFS and RR were used as a criteria to evaluate the treatment outcome. Associated adverse effects of metformin were also assessed.
    RESULTS: The average age of the participants in group A and group B was 50 vs. 47.5, respectively. No significant differences were detected between both cohorts concerning RR levels (regression disease (RD) 27.8% vs. 12.5%, stationary disease (SD) 44.4% vs. 41.7%, progression disease (PD) 27.8% vs. 45.8%, respectively, p = 0.074). Moreover, PFS showed no significant difference between both groups (p = 0.753). There was no significant correlation between metformin concentration and their adverse effects on the study participants.
    CONCLUSION: Metformin as an adjuvant therapy to MBC undergoing chemotherapy showed no significant survival benefit as determined by RR and PFS.
    Keywords:  metastatic breast cancer (MBC); metformin; non-diabetic patients
    DOI:  https://doi.org/10.3390/jcm11195505
  78. Int J Nanomedicine. 2022 ;17 4757-4772
    Gold Nanoparticle-Incorporated Chitosan Nanogels as a Theranostic Nanoplatform for CT Imaging and Tumour Chemotherapy.
    Zhe Liu, Dong Zhou, Xuan Yan, Lan Xiao, Pei Wang, Junchao Wei, Lan Liao.
      Purpose: The translation of nanocarrier-based theranostics into cancer treatment is limited by their poor cellular uptake, low drug-loading capacity, uncontrolled drug release, and insufficient imaging ability.Methods: In this study, novel hybrid nanogels were fabricated as theranostic nanocarriers by modifying chitosan (CTS)/tripolyphosphate (TPP) nanoparticles (NPs) with polyacrylic acid (PAA) and further conjugating cysteine-functionalized gold nanoparticles (AuNPs).
    Results: The resultant nanogels, referred to as CTS/TPP/PAA@AuNPs (CTPA), exhibited excellent colloidal stability and a high encapsulation rate of 87% for the cationic drug doxorubicin (DOX). In the tumour microenvironment, the acidic pH and overexpression of lysozyme triggered CTPA@DOX to degrade and emit smaller nanoblocks (30-40 nm), which sequentially released the drug in a tumour-responsive manner. Cellular uptake experiments demonstrated that CTPA facilitates the entry of DOX into the cytoplasm. Furthermore, as visualised through AuNP-mediated computed tomography (CT) imaging, CTPA@DOX enabled favourable accumulation in the tumour. Our in vitro and in vivo data demonstrated that CTPA enabled advanced tumour cell-targeting delivery of DOX, which showed greater anti-tumour activity and biosafety than free DOX.
    Conclusion: The natural polymer CTS was developed for degradable nanogels, which can precisely track drugs with high antitumour activity. Additionally, the surface adjustment strategy can be assembled to achieve cationic drug loading and high drug-loading capacity, controlled drug release, and sufficient imaging ability. Therefore, multifunctional CTPA enables efficient drug delivery and CT imaging, which is expected to provide a valuable strategy for designing advanced theranostic systems.
    Keywords:  computed tomography imaging; degradability; hybrid nanogel; theranostic nanomaterial
    DOI:  https://doi.org/10.2147/IJN.S375999
  79. Polymers (Basel). 2022 Sep 24. pii: 4004. [Epub ahead of print]14(19):
    L-Cysteine Modified Chitosan Nanoparticles and Carbon-Based Nanostructures for the Intranasal Delivery of Galantamine.
    Stavroula G Nanaki, Konstantinos Spyrou, Pelagia Veneti, Niki Karouta, Dimitrios Gournis, Turki N Baroud, Panagiotis Barmpalexis, Dimitrios N Bikiaris.
      The present study evaluates the use of thiolized chitosan conjugates (CS) in combination with two fundamental carbon nanoforms (carbon dots (CDs) and Hierarchical Porous Carbons (HPC)) for the preparation of intranasally (IN) administrated galantamine (GAL) nanoparticles (NPs). Initially, the modification of CS with L-cysteine (Cys) was performed, and the successful formation of a Cys-CS conjugates was verified via 1H-NMR, FTIR, and pXRD. The new Cys-CS conjugate showed a significant solubility enhancement in neutral and alkaline pH, improving CS's utility as a matrix-carrier for IN drug administration. In a further step, drug-loaded NPs were prepared via solid-oil-water double emulsification, and thoroughly analyzed by SEM, DLS, FTIR and pXRD. The results showed the formation of spherical NPs with a smooth surface, while the drug was amorphously dispersed within most of the prepared NPs, with the exemption of those systems contianing the CDs. Finally, in vitro dissolution release studies revealed that the prepared NPs could prolong GAL's release for up to 12 days. In sum, regarding the most promising system, the results of the present study clearly suggest that the preparation of NPs using both Cys-CS and CDs results in a more thermodynamically stable drug dispersion, while a zero-order release profile was achieved, which is essential to attain a stable in vivo pharmacokinetic behavior.
    Keywords:  L-cysteine; carbon dots; drug delivery; galantamine; modified chitosan; nanoparticles; porous carbon nanostructures
    DOI:  https://doi.org/10.3390/polym14194004
  80. Front Oncol. 2022 ;12 980239
    Photodynamic therapy for prostate cancer: Recent advances, challenges and opportunities.
    Qin Xue, Jingliang Zhang, Jianhua Jiao, Weijun Qin, Xiaojian Yang.
      Over the past two decades, there has been a tendency toward early diagnosis of prostate cancer due to raised awareness among the general public and professionals, as well as the promotion of prostate-specific antigen (PSA) screening. As a result, patients with prostate cancer are detected at an earlier stage. Due to the risks of urine incontinence, erectile dysfunction, etc., surgery is not advised because the tumor is so small at this early stage. Doctors typically only advise active surveillance. However, it will bring negative psychological effects on patients, such as anxiety. And there is a higher chance of cancer progression. Focal therapy has received increasing attention as an alternative option between active monitoring and radical therapy. Due to its minimally invasive, oncological safety, low toxicity, minimal effects on functional outcomes and support by level 1 evidence from the only RCT within the focal therapy literature, photodynamic treatment (PDT) holds significant promise as the focal therapy of choice over other modalities for men with localized prostate cancer. However, there are still numerous obstacles that prevent further advancement. The review that follows provides an overview of the preclinical and clinical published research on PDT for prostate cancer from 1999 to the present. It focuses on clinical applications of PDT and innovative techniques and technologies that address current problems, especially the use of nanoparticle photosensitizers in PDT of prostate cancer.
    Keywords:  clinical studies; nanoparticle photosensitizers; photodynamic therapy; photosensitizer; prostate cancer
    DOI:  https://doi.org/10.3389/fonc.2022.980239
  81. J Control Release. 2022 Oct 10. pii: S0168-3659(22)00677-0. [Epub ahead of print]351 752-778
    Advancements of Prussian blue-based nanoplatforms in biomedical fields: Progress and perspectives.
    Yanhui Wang, Zonghao Liang, Ziyang Liang, Wenfeng Lv, Min Chen, Yi Zhao.
      Prussian blue (PB) nanoparticles possess excellent physicochemical properties, including imaging features, robust photothermal conversion ability, catalytic activity, surface modifiability, effective drug loading, good stability, biocompatibility and biodegradability. With the advancement of nanotechnology, diverse PB-based nanoplatforms have been developed for biomedical applications. This review systematically summarized recent studies on PB-based nanoplatforms in the treatment of tumor (photothermal therapy, photodynamic therapy, chemotherapy, immunotherapy, theranostics, etc.), cardiovascular and cerebrovascular diseases (restenosis, atherosclerosis, thrombosis, ischemic stroke, etc.), bacterial infections (photothermal sterilization, biofilms disruption, etc.), and other inflammation-related diseases (liver injury, acute pancreatitis, inflammatory bowel disease, osteoarthritis, etc.). Finally, the existing challenges associated with current studies are discussed, and the future possible research and application directions for PB-based nanoplatforms are proposed, providing paradigms for subsequent development.
    Keywords:  Biomimetic enzyme; Diagnosis; Drug delivery; Prussian blue nanoparticles; Therapies
    DOI:  https://doi.org/10.1016/j.jconrel.2022.10.007
  82. Cancer Res. 2022 Oct 10. pii: CAN-22-1902. [Epub ahead of print]
    Breast Cancer Metastatic Dormancy and Relapse: An enigma of microenvironment(s).
    Islam E Elkholi, Andréane Lalonde, Morag Park, Jean-François Côté.
      Multiple factors act in concert to define the fate of disseminated tumor cells (DTCs) to enter dormancy or develop overt metastases. Here, we review these factors in the context of three stages of the metastatic cascade that impact DTCs. First, cells can be programmed within the primary tumor microenvironment to promote or inhibit dissemination, and the primary tumor can condition a premetastatic niche. Then, cancer cells from the primary tumor spread through hematogenous and lymphatic routes, and the primary tumor sends cues systematically to regulate the fate of DTCs. Finally, DTCs home to their metastatic site, where they are influenced by various organ-specific aspects of the new microenvironment. We discuss these factors in the context of breast cancer, where about one third of patients develop metastatic relapse. Finally, we discuss how the standard-of-care options for breast cancer might affect the fate of DTCs.
    DOI:  https://doi.org/10.1158/0008-5472.CAN-22-1902
  83. Cancer Metastasis Rev. 2022 Oct 13.
    Physicochemical aspects of the tumour microenvironment as drivers of vasculogenic mimicry.
    Elena Andreucci, Silvia Peppicelli, Jessica Ruzzolini, Francesca Bianchini, Lido Calorini.
      Tumour vascularisation is vital for cancer sustainment representing not only the main source of nutrients and oxygen supply but also an escape route for single or clustered cancer cells that, once detached from the primary mass, enter the blood circulation and disseminate to distant organs. Among the mechanisms identified to contribute to tumour vascularisation, vasculogenic mimicry (VM) is gaining increasing interest in the scientific community representing an intriguing target for cancer treatment. VM indeed associates with highly aggressive tumour phenotypes and strongly impairs patient outcomes. Differently from vessels of healthy tissues, tumour vasculature is extremely heterogeneous and tortuous, impeding efficient chemotherapy delivery, and at the meantime hyperpermeable and thus extremely accessible to metastasising cancer cells. Moreover, tumour vessel disorganisation creates a self-reinforcing vicious circle fuelling cancer malignancy and progression. Because of the inefficient oxygen delivery and metabolic waste removal from tumour vessels, many cells within the tumour mass indeed experience hypoxia and acidosis, now considered hallmarks of cancer. Being strong inducers of vascularisation, therapy resistance, inflammation and metastasis, hypoxia and acidosis create a permissive microenvironment for cancer progression and dissemination. Along with these considerations, we decided to focus our attention on the relationship between hypoxia/acidosis and VM. Indeed, besides tumour angiogenesis, VM is strongly influenced by both hypoxia and acidosis, which could potentiate each other and fuel this vicious circle. Thus, targeting hypoxia and acidosis may represent a potential target to treat VM to impair tumour perfusion and cancer cell sustainment.
    Keywords:  Extracellular acidosis; Hypoxia; Tumour microenvironment; Tumour progression; Vasculogenic mimicry
    DOI:  https://doi.org/10.1007/s10555-022-10067-x
  84. Int J Nanomedicine. 2022 ;17 4677-4696
    Nanomaterial-Based Drug Delivery Systems: A New Weapon for Cancer Immunotherapy.
    Zhengting Jiang, Wenjie Zhang, Jie Zhang, Tian Liu, Juan Xing, Huan Zhang, Dong Tang.
      Cancer immunotherapy, a major breakthrough in cancer treatment, has been successfully applied to treat a number of tumors. However, given the presence of factors in the tumor microenvironment (TME) that impede immunotherapy, only a small proportion of patients achieve a good clinical response. With the ability to increase permeability and cross biological barriers, nanomaterials have been successfully applied to deliver immunotherapeutic agents, thus realizing the anti-cancer therapeutic potential of therapeutic agents. This has driven a wave of research into systems for the delivery of immunotherapeutic agents, which has resulted in widespread interest in nanomaterial-based drug delivery systems. Nanomaterial-based drug delivery systems are able to overcome the challenges from TME and thus achieve good results in cancer immunotherapy. If it can make a breakthrough in improving biocompatibility and reducing cytotoxicity, it will be more widely used in clinical practice. Different types of nanomaterials may also have some subtle differences in enhancing cancer immunotherapy. Moreover, delivery systems made of nanomaterials loaded with drugs, such as cytotoxic drugs, cytokines, and adjuvants, could be used for cancer immunotherapy because they avoid the toxicity and side effects associated with these drugs, thereby enabling their reuse. Therefore, further insights into nanomaterial-based drug delivery systems will provide more effective treatment options for cancer patients.
    Keywords:  delivery system; drug repurposing; immunotherapy; nanomaterial; tumor microenvironment
    DOI:  https://doi.org/10.2147/IJN.S376216
  85. Acta Biomater. 2022 Oct 06. pii: S1742-7061(22)00638-9. [Epub ahead of print]
    Self-Amplified Chain-Shattering Cinnamaldehyde-Based Poly(thioacetal) Boosts Cancer Chemo-Immunotherapy.
    Qingyu Zong, Jisi Li, Xuan Xiao, Xiaojiao Du, Youyong Yuan.
      The selective activation of stimuli-responsive polymers in the tumor microenvironment is a great concern to achieve intelligent cancer therapy, but most of them show inadequate response due to insufficient endogenous triggering agents. Herein, we rationally designed a reactive oxygen species (ROS)-responsive cinnamaldehyde (CA)-based poly(thioacetal), consisting of ROS-responsive thioacetal (TA) and ROS-generating agent CA, with self-amplified chain-shattering polymer degradation. The mechanism of self-amplified chain-shattering is that endogenous ROS as a triggering agent facilitates chain cleavage of TA with the release of CA, which in turn produces more ROS through mitochondrial dysfunction, resulting in an exponential polymer degradation cascade. The polymer can be further modified with anticancer drug doxorubicin (DOX) for cooperative amplification of oxidative stress and immunogenic cell death (ICD) of tumor cells, thereby boosting the effect of chemo-immunotherapy. The self-amplified chain-shattering polymer designed in this work holds great promise in developing stimuli-responsive polymers for efficient drug delivery. STATEMENT OF SIGNIFICANCE: This study presented an approach to utilize self-amplified chain-shattering cinnamaldehyde-based poly (thioacetal) as a drug delivery system to restrain tumor growth and boost chemo-immunotherapy. The endogenous ROS as a triggering agent initiates the chain cleavage with the release of CA, which in turn produces ROS through mitochondria dysfunction, resulting in an exponential polymer degradation cascade and rapid drug release.
    Keywords:  Chain-shattering; Chemo-immunotherapy; Immunogenic cell death; ROS-responsive; Stimuli-responsive polymer
    DOI:  https://doi.org/10.1016/j.actbio.2022.09.066
  86. Front Nutr. 2022 ;9 933898
    Carbohydrate and sleep: An evaluation of putative mechanisms.
    David Benton, Anthony Bloxham, Chantelle Gaylor, Anthony Brennan, Hayley A Young.
      Sleep problems are extremely common in industrialized countries and the possibility that diet might be used to improve sleep has been considered. The topic has been reviewed many times, resulting in the frequent suggestion that carbohydrate increases the uptake of tryptophan by the brain, where it is metabolized into serotonin and melatonin, with the suggestion that this improves sleep. An alternative mechanism was proposed based on animal literature that has been largely ignored by those considering diet and sleep. The hypothesis was that, as in the hypothalamus there are glucose-sensing neurons associated with the sleep-wake cycle, we should consider the impact of carbohydrate-induced changes in the level of blood glucose. A meta-analysis found that after consuming a lower amount of carbohydrate, more time was spent in slow-wave sleep (SWS) and less in rapid-eye-movement sleep. As the credibility of alternative mechanisms has tended not to have been critically evaluated, they were considered by examining their biochemical, nutritional, and pharmacological plausibility. Although high carbohydrate consumption can increase the uptake of tryptophan by the brain, it only occurs with such low levels of protein that the mechanism is not relevant to a normal diet. After entering the brain tryptophan is converted to serotonin, a neurotransmitter known to influence so many different aspects of sleep and wakefulness, that it is not reasonable to expect a uniform improvement in sleep. Some serotonin is converted to melatonin, although the exogenous dose of melatonin needed to influence sleep cannot be credibly provided by the diet. This review was registered in the International Prospective Register of Systematic Reviews (CRD42020223560).
    Keywords:  carbohydrate; glucose-sensitive cells; melatonin; serotonin; sleep; sleep and energy homeostasis; tryptophan
    DOI:  https://doi.org/10.3389/fnut.2022.933898
  87. Int J Mol Sci. 2022 Oct 02. pii: 11662. [Epub ahead of print]23(19):
    Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy.
    Amanda J Stolarz, Bijay P Chhetri, Michael J Borrelli, Samir V Jenkins, Azemat Jamshidi-Parsian, Joshua H Phillips, Daniel Fologea, Jay Gandy, Robert J Griffin.
      Targeted delivery of drugs or other therapeutic agents through internal or external triggers has been used to control and accelerate the release from liposomal carriers in a number of studies, but relatively few utilize energy of therapeutic X-rays as a trigger. We have synthesized liposomes that are triggered by ionizing radiation (RTLs) to release their therapeutic payload. These liposomes are composed of natural egg phosphatidylethanolamine (PE), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-disteroyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-PEG-2000), and the mean size of the RTL was in the range of 114 to 133 nm, as measured by nanoparticle tracking analysis (NTA). The trigger mechanism is the organic halogen, chloral hydrate, which is known to generate free protons upon exposure to ionizing radiation. Once protons are liberated, a drop in internal pH of the liposome promotes destabilization of the lipid bilayer and escape of the liposomal contents. In proof of principle studies, we assessed RTL radiation-release of fluorescent tracers upon exposure to a low pH extracellular environment or exposure to X-ray irradiation. Biodistribution imaging before and after irradiation demonstrated a preferential uptake and release of the liposomes and their cargo at the site of local tumor irradiation. Finally, a potent metabolite of the commonly used chemotherapy irinotecan, SN-38, was loaded into RTL along with near infrared (NIR) fluorescent dyes for imaging studies and measuring tumor cell cytotoxicity alone or combined with radiation exposure, in vitro and in vivo. Fully loaded RTLs were found to increase tumor cell killing with radiation in vitro and enhance tumor growth delay in vivo after three IV injections combined with three, 5 Gy local tumor radiation exposures compared to either treatment modality alone.
    Keywords:  chemotherapy; drug delivery; liposome; radiation; tumor; tumor-targeted
    DOI:  https://doi.org/10.3390/ijms231911662
  88. Food Chem X. 2022 Oct 30. 15 100431
    Delivery of curcumin by shellac encapsulation: Stability, bioaccessibility, freeze-dried redispersibility, and solubilization.
    Yongkai Yuan, Shuaizhong Zhang, Mengjie Ma, Ying Xu, Dongfeng Wang.
      Curcumin is an active ingredient with multiple functions, however, its application is limited by its low stability, bioaccessibility, freeze-dried redispersibility, and solubilization. The work aims to improve the application of curcumin (Cur) by encapsulation. Shellac was the wall material inspired by its pH-dependent deprotonation and amphiphilic nature to form nanoparticles. The curcumin/shellac nanoparticles (S/Cur) exhibited a bright spot of high loading capacity (the maximum of higher than 70 %), while still having high encapsulation efficiency (the minimum of higher than 85 %). Transmission electron microscopy showed that S/Cur was a spherical structure. It exhibited good physical stability, including pH (4.0-8.0), ionic strength (NaCl, < 900 mM), thermo stability (80 ℃, 180 min), and storage stability (light and dark, 4 and 25 ℃, 20 days). Meanwhile, the chemical stability was increased by encapsulation. Furthermore, the bioaccessibility of Cur was improved to 75.95 %, which is attributed to the pH response of shellac. Additionally, S/Cur had freeze-dried redispersibility and solubilization, which is proportional to the mass ratio of shellac-to-Cur. The mechanism of S/Cur formation involved hydrophobic interaction and hydrogen bonds, and the nanoconfined Cur was amorphous.
    Keywords:  Curcumin; Encapsulation; Nanoparticles; Shellac
    DOI:  https://doi.org/10.1016/j.fochx.2022.100431
  89. ACS Appl Bio Mater. 2022 Oct 14.
    Amphotericin B-Loaded Plant-Inspired Polyphenol Nanoparticles Enhance Its Antifungal Activity and Biocompatibility.
    Suhair Sunoqrot, Amal G Al-Bakri, Lina Hasan Ibrahim, Neda'a Aldaken.
      Amphotericin B (AmB) is one of the first-line treatments for systemic fungal infections, yet it suffers from dose-limiting systemic toxicity and high cost of less toxic lipid-based formulations. Here, we report on a facile approach to synthesize an AmB-loaded nanomedicine by leveraging plant-inspired oxidative self-polymerization of the ubiquitous polyphenol quercetin (QCT). Polymerized QCT nanoparticles (pQCT NPs) were formed, loaded with AmB, and functionalized with poly(ethylene glycol) (PEG) to impart steric stability in a simple procedure that relied on mixing followed by dialysis. The AmB-loaded NPs (AmB@pQCT-PEG NPs) were characterized by a drug loading efficiency of more than 90%, a particle size of around 160 nm, a polydispersity index of 0.07, and a partially negative surface charge. AmB release from the NPs was sustained over several days and followed the Korsmeyer-Peppas model with a release exponent (n) value >0.85, denoting drug release by polymer relaxation and swelling. A hemolysis assay revealed the NPs to be highly biocompatible, with negligible hemolytic activity and 30-60% hemolysis after 1 and 24 h of incubation with erythrocytes, respectively, across a wide concentration range (6.25-100.00 μg/mL). Conversely, equivalent concentrations of free AmB caused 90-100% hemolysis within the same timeframe. Importantly, AmB@pQCT-PEG NPs outperformed free AmB in microbial susceptibility assays on Candida albicans, achieving a minimum inhibitory concentration of 62.5 ng/mL after 48 h of incubation, which was 2-fold lower than the free drug. Our results demonstrate that pQCT NPs may serve as a viable AmB delivery platform for the treatment of fungal infections and potentially other AmB-susceptible pathogens.
    Keywords:  amphotericin B; antifungal nanomedicine; plant polyphenols; quercetin
    DOI:  https://doi.org/10.1021/acsabm.2c00537
  90. Crit Rev Food Sci Nutr. 2022 Oct 12. 1-17
    A review of protein-phenolic acid interaction: reaction mechanisms and applications.
    Behzad Masoumi, Mahnaz Tabibiazar, Zahra Golchinfar, Mohammadamin Mohammadifar, Hamed Hamishehkar.
      Phenolic acids (PA) are types of phytochemicals with health benefits. The interaction between proteins and PAs can cause minor or extensive changes in the structure of proteins and subsequently affect various protein properties. This study investigates the protein/PA (PPA) interaction and its effects on the structural, physicochemical, and functional properties of the system. This work particularly focused on the ability of PAs as a subgroup of phenolic compounds (PC) on the modification of proteins. Different aspects including the influence of structure affinity relationship and molecular weight of PA on the protein interaction have been discussed in this review. The physicochemical properties of PPA change mainly due to the change of hydrophilic/hydrophobic parts and/or the formation of some covalent and non-covalent interactions. Furthermore, PPA interactions affecting functional properties were discussed in separate sections. Due to insufficient studies on the interaction of PPAs, understanding the mechanism and also the type of binding between protein and PA can help to develop a new generation of PPA. These systems seem to have good capabilities in the formulation of low-fat foods like high internal Phase Emulsions, drug delivery systems, hydrogel structures, multifunctional fibers or packaging films, and 3 D printing in the meat processing industry.
    Keywords:  Phenolic acid- protein interaction; Pickering emulsion; electrospinning; hydrogel; packaging films
    DOI:  https://doi.org/10.1080/10408398.2022.2132376
  91. Molecules. 2022 Sep 30. pii: 6447. [Epub ahead of print]27(19):
    Supramolecular Tools to Improve Wound Healing and Antioxidant Properties of Abietic Acid: Biocompatible Microemulsions and Emulgels.
    Alla Mirgorodskaya, Rushana Kushnazarova, Rais Pavlov, Farida Valeeva, Oksana Lenina, Kseniya Bushmeleva, Dmitry Kuryashov, Alexandra Vyshtakalyuk, Gulnara Gaynanova, Konstantin Petrov, Lucia Zakharova.
      Abietic acid, a naturally occurring fir resin compound, that exhibits anti-inflammatory and wound-healing properties, was formulated into biocompatible emulgels based on stable microemulsions with the addition of a carbamate-containing surfactant and Carbopol® 940 gel. Various microemulsion and emulgel formulations were tested for antioxidant and wound-healing properties. The chemiluminescence method has shown that all compositions containing abietic acid have a high antioxidant activity. Using Strat-M® skin-modelling membrane, it was found out that emulgels significantly prolong the release of abietic acid. On Wistar rats, it was shown that microemulsions and emulgels containing 0.5% wt. of abietic acid promote the rapid healing of an incised wound and twofold tissue reinforcement compared to the untreated group, as documented by tensiometric wound suture-rupture assay. The high healing-efficiency is associated with a combination of antibacterial activity of the formulation components and the anti-inflammatory action of abietic acid.
    Keywords:  abietic acid; antioxidant activity; drug delivery systems; emulgel; gelating polymer; microemulsion; surfactant; wound healing
    DOI:  https://doi.org/10.3390/molecules27196447
  92. Nutrients. 2022 Oct 06. pii: 4148. [Epub ahead of print]14(19):
    Definition, Assessment, and Management of Vitamin D Inadequacy: Suggestions, Recommendations, and Warnings from the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS).
    Francesco Bertoldo, Luisella Cianferotti, Marco Di Monaco, Alberto Falchetti, Angelo Fassio, Davide Gatti, Luigi Gennari, Sandro Giannini, Giuseppe Girasole, Stefano Gonnelli, Nazzarena Malavolta, Salvatore Minisola, Mario Pedrazzoni, Domenico Rendina, Maurizio Rossini, Iacopo Chiodini.
      In the recent years, both the prescriptions of serum 25(OH)D levels assay, and vitamin D supplementation are constantly increasing, as well as the costs to be incurred relating to these specific aspects. As in many other countries, the risk of vitamin D deficiency is particularly high in Italy, as recently confirmed by cohort studies in the general population as well as in patients with metabolic bone disorder. Results confirmed the North-South gradient of vitamin D levels described among European countries, despite the wide use of supplements. Although vitamin D supplementation is also recommended by the Italian Medicine Agency for patients at risk for fragility fracture or for initiating osteoporotic medication, the therapeutic gap for osteoporosis in Italy is very high. There is a consistent proportion of osteoporotic patients not receiving specific therapy for osteoporosis following a fragility fracture, with a poor adherence to the recommendations provided by national guidelines and position paper documents. The failure or inadequate supplementation with vitamin D in patients on antiresorptive or anabolic treatment for osteoporosis is thought to further amplify the problem and exposes patients to a high risk of re-fracture and mortality. Therefore, it is important that attention to its possible clinical consequences must be given. Thus, in light of new evidence from the literature, the SIOMMMS board felt the need to revise and update, by a GRADE/PICO system approach, its previous original recommendations about the definition, prevention, and treatment of vitamin D deficiency in adults, released in 2011. Several key points have been here addressed, such as the definition of the vitamin D status: normality values and optimal values; who are the subjects considered at risk of hypovitaminosis D; opportunity or not of performing the biochemical assessment of serum 25(OH)D levels in general population and in subjects at risk of hypovitaminosis D; the need or not to evaluate baseline serum 25(OH)D in candidate subjects for pharmacological treatment for osteoporosis; how and whether to supplement vitamin D subjects with hypovitaminosis D or candidates for pharmacological treatment with bone active agents, and the general population; how and whether to supplement vitamin D in chronic kidney disease and/or chronic liver diseases or under treatment with drugs interfering with hepatic metabolism; and finally, if vitamin D may have toxic effects in the subject in need of supplementation.
    Keywords:  bone fragility; bone metabolism; chronic diseases; osteoporosis; vitamin D
    DOI:  https://doi.org/10.3390/nu14194148
  93. Nutrients. 2022 Sep 22. pii: 3934. [Epub ahead of print]14(19):
    Is Melatonin the "Next Vitamin D"?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements.
    Deanna M Minich, Melanie Henning, Catherine Darley, Mona Fahoum, Corey B Schuler, James Frame.
      Melatonin has become a popular dietary supplement, most known as a chronobiotic, and for establishing healthy sleep. Research over the last decade into cancer, Alzheimer's disease, multiple sclerosis, fertility, PCOS, and many other conditions, combined with the COVID-19 pandemic, has led to greater awareness of melatonin because of its ability to act as a potent antioxidant, immune-active agent, and mitochondrial regulator. There are distinct similarities between melatonin and vitamin D in the depth and breadth of their impact on health. Both act as hormones, affect multiple systems through their immune-modulating, anti-inflammatory functions, are found in the skin, and are responsive to sunlight and darkness. In fact, there may be similarities between the widespread concern about vitamin D deficiency as a "sunlight deficiency" and reduced melatonin secretion as a result of "darkness deficiency" from overexposure to artificial blue light. The trend toward greater use of melatonin supplements has resulted in concern about its safety, especially higher doses, long-term use, and application in certain populations (e.g., children). This review aims to evaluate the recent data on melatonin's mechanisms, its clinical uses beyond sleep, safety concerns, and a thorough summary of therapeutic considerations concerning dietary supplementation, including the different formats available (animal, synthetic, and phytomelatonin), dosing, timing, contraindications, and nutrient combinations.
    Keywords:  antioxidant; blue light; chronobiotic; chrononutrition; circadian rhythm; darkness deficiency; melatonin; phytomelatonin; sleep; vitamin D
    DOI:  https://doi.org/10.3390/nu14193934
  94. Int J Mol Sci. 2022 Sep 30. pii: 11569. [Epub ahead of print]23(19):
    A Comprehensive Review on Beneficial Effects of Catechins on Secondary Mitochondrial Diseases.
    Baoyi Chen, Wenting Zhang, Chuyuan Lin, Lingyun Zhang.
      Mitochondria are the main sites for oxidative phosphorylation and synthesis of adenosine triphosphate in cells, and are known as cellular power factories. The phrase "secondary mitochondrial diseases" essentially refers to any abnormal mitochondrial function other than primary mitochondrial diseases, i.e., the process caused by the genes encoding the electron transport chain (ETC) proteins directly or impacting the production of the machinery needed for ETC. Mitochondrial diseases can cause adenosine triphosphate (ATP) synthesis disorder, an increase in oxygen free radicals, and intracellular redox imbalance. It can also induce apoptosis and, eventually, multi-system damage, which leads to neurodegenerative disease. The catechin compounds rich in tea have attracted much attention due to their effective antioxidant activity. Catechins, especially acetylated catechins such as epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), are able to protect mitochondria from reactive oxygen species. This review focuses on the role of catechins in regulating cell homeostasis, in which catechins act as a free radical scavenger and metal ion chelator, their protective mechanism on mitochondria, and the protective effect of catechins on mitochondrial deoxyribonucleic acid (DNA). This review highlights catechins and their effects on mitochondrial functional metabolic networks: regulating mitochondrial function and biogenesis, improving insulin resistance, regulating intracellular calcium homeostasis, and regulating epigenetic processes. Finally, the indirect beneficial effects of catechins on mitochondrial diseases are also illustrated by the warburg and the apoptosis effect. Some possible mechanisms are shown graphically. In addition, the bioavailability of catechins and peracetylated-catechins, free radical scavenging activity, mitochondrial activation ability of the high-molecular-weight polyphenol, and the mitochondrial activation factor were also discussed.
    Keywords:  biogenesis; calcium homeostasis; catechins; indirect beneficial; secondary mitochondrial diseases
    DOI:  https://doi.org/10.3390/ijms231911569
  95. Int J Mol Sci. 2022 Sep 22. pii: 11160. [Epub ahead of print]23(19):
    Formulation, Characterisation and Evaluation of the Antihypertensive Peptides, Isoleucine-Proline-Proline and Leucine-Lysine-Proline in Chitosan Nanoparticles Coated with Zein for Oral Drug Delivery.
    Minna Khalid Danish, John P Gleeson, David J Brayden, Hugh J Byrne, Jesus M Frías, Sinéad M Ryan.
      Isoleucine-Proline-Proline (IPP) and Leucine-Lysine-Proline (LKP) are food-derived tripeptides whose antihypertensive functions have been demonstrated in hypertensive rat models. However, peptides display low oral bioavailability due to poor intestinal epithelial permeability and instability. IPP and LKP were formulated into nanoparticles (NP) using chitosan (CL113) via ionotropic gelation and then coated with zein. Following addition of zein, a high encapsulation efficiency (EE) (&gt;80%) was obtained for the NP. In simulated gastric fluid (SGF), 20% cumulative release of the peptides was achieved after 2 h, whereas in simulated intestinal fluid (SIF), ~90% cumulative release was observed after 6 h. Higher colloidal stability (39-41 mV) was observed for the coated NP compared to uncoated ones (30-35 mV). In vitro cytotoxicity studies showed no reduction in cellular viability of human intestinal epithelial Caco-2 and HepG2 liver cells upon exposure to NP and NP components. Administration of NP encapsulating IPP and LKP by oral gavage to spontaneously hypertensive rats (SHR) attenuated systolic blood pressure (SBP) for 8 h. This suggests that the NP provide appropriate release to achieve prolonged hypotensive effects in vivo. In conclusion, chitosan-zein nanoparticles (CZ NP) have potential as oral delivery system for the encapsulation of IPP and LKP.
    Keywords:  Isoleucine-Proline-Proline (IPP); Leucine-Lysine-Proline (LKP); antihypertensive peptides; oral peptide delivery; zein
    DOI:  https://doi.org/10.3390/ijms231911160
  96. Cancers (Basel). 2022 Oct 10. pii: 4960. [Epub ahead of print]14(19):
    Advances in Preclinical/Clinical Glioblastoma Treatment: Can Nanoparticles Be of Help?
    Daniel Ruiz-Molina, Xiaoman Mao, Paula Alfonso-Triguero, Julia Lorenzo, Jordi Bruna, Victor J Yuste, Ana Paula Candiota, Fernando Novio.
      Glioblastoma multiforme (GB) is the most aggressive and frequent primary malignant tumor in the central nervous system (CNS), with unsatisfactory and challenging treatment nowadays. Current standard of care includes surgical resection followed by chemotherapy and radiotherapy. However, these treatments do not much improve the overall survival of GB patients, which is still below two years (the 5-year survival rate is below 7%). Despite various approaches having been followed to increase the release of anticancer drugs into the brain, few of them demonstrated a significant success, as the blood brain barrier (BBB) still restricts its uptake, thus limiting the therapeutic options. Therefore, enormous efforts are being devoted to the development of novel nanomedicines with the ability to cross the BBB and specifically target the cancer cells. In this context, the use of nanoparticles represents a promising non-invasive route, allowing to evade BBB and reducing systemic concentration of drugs and, hence, side effects. In this review, we revise with a critical view the different families of nanoparticles and approaches followed so far with this aim.
    Keywords:  BBB; brain cancer; drug delivery; glioblastoma; nanoparticles; preclinical model
    DOI:  https://doi.org/10.3390/cancers14194960
  97. Front Mol Biosci. 2022 ;9 1027912
    Ferroptosis and its emerging role in esophageal cancer.
    Rezeye Maimaitizunong, Kai Wang, Hui Li.
      The occurrence and development of tumors involve a series of life activities of cells, among which cell death has always been a crucial part in the research of tumor mechanisms and treatment methods. Ferroptosis is a non-apoptotic form of cell death, which is characterized by lipid peroxidation accumulation and further cell membrane rupture caused by excessive production of intracellular oxygen free radicals dependent on iron ions. Esophageal cancer is one of the common digestive tract tumors. Patients in the early stage are mainly treated with surgery, and the curative effect is awe-inspiring. However, surgery is far from enough for terminal patients, and it is the best choice to combine radiotherapy and chemotherapy before the operation or during the perioperative period. Although the treatment plan for patients with advanced esophageal cancer is constantly being optimized, we are disappointed at the still meager 5-year survival rate of patients and the poor quality of life. A series of complex problems, such as increased chemotherapy drug resistance and decreased radiotherapy sensitivity of esophageal cancer cells, are waiting for us to tackle. Perhaps ferroptosis can provide practical and feasible solutions and bring new hope to patients with advanced esophageal cancer. The occurrence of ferroptosis is related to the dysregulation of iron metabolism, lipid metabolism, and glutamate metabolism. Therefore, these dysregulated metabolic participant proteins and signaling pathways are essential entry points for using cellular ferroptosis to resist the occurrence and development of cancer cells. This review first introduced the main regulatory mechanisms of ferroptosis. It then summarized the current research status of ferroptosis in esophageal cancer, expecting to provide ideas for the research related to ferroptosis in esophageal cancer.
    Keywords:  antioxidant system; esophageal cancer; ferroptosis; lipid peroxidation; non-coding RNA
    DOI:  https://doi.org/10.3389/fmolb.2022.1027912
  98. Int J Mol Sci. 2022 Oct 08. pii: 11943. [Epub ahead of print]23(19):
    Lactate-Lactylation Hands between Metabolic Reprogramming and Immunosuppression.
    Lihua Chen, Lixiang Huang, Yu Gu, Wei Cang, Pengming Sun, Yang Xiang.
      Immune evasion and metabolic reprogramming are two fundamental hallmarks of cancer. Interestingly, lactate closely links them together. However, lactate has long been recognized as a metabolic waste product. Lactate and the acidification of the tumor microenvironment (TME) promote key carcinogenesis processes, including angiogenesis, invasion, metastasis, and immune escape. Notably, histone lysine lactylation (Kla) was identified as a novel post-modification (PTM), providing a new perspective on the mechanism by which lactate functions and providing a promising and potential therapy for tumors target. Further studies have confirmed that protein lactylation is essential for lactate to function; it involves important life activities such as glycolysis-related cell functions and macrophage polarization. This review systematically elucidates the role of lactate as an immunosuppressive molecule from the aspects of lactate metabolism and the effects of histone lysine or non-histone lactylation on immune cells; it provides new ideas for further understanding protein lactylation in elucidating lactate regulation of cell metabolism and immune function. We explored the possibility of targeting potential targets in lactate metabolism for cancer treatment. Finally, it is promising to propose a combined strategy inhibiting the glycolytic pathway and immunotherapy.
    Keywords:  immune evasion; immunotherapy; lactate; lactylation; metabolic reprogramming
    DOI:  https://doi.org/10.3390/ijms231911943
  99. J Food Biochem. 2022 Oct 11. e14447
    The effect of insulin-loaded gold and carboxymethyl chitosan nanoparticles on gene expression of glucokinase and pyruvate kinase in rats with diabetes type 1.
    Eman Mahmoud Shaaban, Doha Elsayed Ellakwa, Nesma Mohamed Elaraby, Khalda Sayed Amr, Ahmed Mahmoud Mohamadin.
      The goal of this study was to see how effective subcutaneous (SC) insulin is and two different types of oral insulin-loaded nanoparticles (INS) including carboxymethyl chitosan nanoparticles (CMCNPs) and gold nanoparticles (AuNPs) separately and compare their effects on glucokinase, pyruvate kinase gene expressions, and other parameters in diabetes type one male Wistar rats. Seven groups of ten male Wistar rats for each group were formed at random including four control groups (n = 10) and three treatment groups (n = 10). The control groups consisted of four control groups (10 rats for each) and three treatment groups (10 rats for each). Normal control rats were not given any treatment, as were diabetic rats that were not given any treatment, and diabetic rats that were given oral nanoparticles (CMCNPs and AuNPs). Diabetic rats were given subcutaneous insulin, oral insulin-loaded carboxymethyl chitosan nanoparticles (INS-CMCNPs), and oral insulin-loaded gold nanoparticles (INS-AuNPs). The rats were treated for the final 3 weeks of the experiment, which lasted 4 weeks. CMCNPs and AuNPs presented a promising effect on pyruvate kinase and Glucokinase gene expressions compared to subcutaneous insulin. We also discovered that conjugating insulin to CMCNPs and AuNPs protects them from the insulin-degrading enzyme, which offers managed bioavailability. Furthermore, we investigated the effects of CMCNPs and AuNPs on several parameters and discovered that both have a significant effect in vivo, which enables glucose level regulation, and improves patient organ activity for better glucose consumption. PRACTICAL APPLICATIONS: In this paper, we discussed the effect of oral INS-CMCNPs and INS-AuNPs, and compared their effects on Glucokinase and pyruvate kinase gene expressions and other biochemical parameters in diabetes type one male Wistar rats. On the other hand, we investigated the impact of oral INS and subcutaneous insulin separately on the same parameters and their effect on the histology of the liver and pancreas of diabetic rats. According to our research, as we discussed the different mechanisms of INS-CMCNPs and INS-AuNPs, they presented a promising effect compared to SC insulin. They can be used to keep oral insulin safe from the environment of the gastrointestinal system to overcome all the barriers, improve the therapeutic, and clinical outcomes of insulin by maintaining its desired concentration inside the body, ending the panic of the patient from receiving insulin by the SC injection by increasing his satisfaction with receiving accurate oral insulin doses.
    Keywords:  carboxymethyl chitosan nanoparticles; glucokinase; gold nanoparticles; insulin-loaded nanoparticles; pyruvate kinase
    DOI:  https://doi.org/10.1111/jfbc.14447
  100. Plants (Basel). 2022 Sep 30. pii: 2578. [Epub ahead of print]11(19):
    Phytochemistry, Biological and Pharmacological Activities of the Anacyclus pyrethrum (L.) Lag: A Systematic Review.
    Hanane Elazzouzi, Kamal Fadili, Ali Cherrat, Smail Amalich, Nadia Zekri, Hannou Zerkani, Imane Tagnaout, Christophe Hano, Jose M Lorenzo, Touria Zair.
      Anacyclus pyrethrum (L.) (Asteraceae) is an important annual medicinal herb and is widespread in Morocco and Algeria. Most of its parts are used in traditional medicine and the roots are the most important parts used. The present review gives an account of the updated information on its phytochemical and pharmacological properties. We have collected the essential characteristics and the different scientific data of the A. pyrethrum species, and reviewed its potential. It is seen from the literature that A. pyrethrum is a rich source of the phytochemical constituents such as alkaloids (pellitorin) and n-alkylamides. This species also contains pyrethrins, sesamin, traces of essential oils and a wide range of other chemical compounds. These active substances possess antimicrobial and anti-inflammatory activities. The plant has an antidiabetic, insecticidal and immunostimulatory effect, as well as an aphrodisiac and antioxidant potentials, and various other important medicinal properties. Many traditional uses are also reported in previous research such as for rheumatism, sciatica, colds, neuralgia and paralysis. This species is considered to be a sialagogue, and used in the treatment of stomach ailments, diseases of inflammation of the mouth, against cysts in the genital tract and to relieve toothaches. Thus, further research must be carried out in order to establish any relationship between the traditional uses, phytochemistry and toxicity. Moreover, A. pyrethrum is quite promising as a medicinal agent, so further clinical trials should be performed to prove its efficacy.
    Keywords:  Anacyclus pyrethrum; biological activity; medicinal plants; phytochemical; traditional medicine
    DOI:  https://doi.org/10.3390/plants11192578
  101. Nutrients. 2022 Oct 05. pii: 4137. [Epub ahead of print]14(19):
    Feeding the Brain: Effect of Nutrients on Cognition, Synaptic Function, and AMPA Receptors.
    Rut Fadó, Anna Molins, Rocío Rojas, Núria Casals.
      In recent decades, traditional eating habits have been replaced by a more globalized diet, rich in saturated fatty acids and simple sugars. Extensive evidence shows that these dietary factors contribute to cognitive health impairment as well as increase the incidence of metabolic diseases such as obesity and diabetes. However, how these nutrients modulate synaptic function and neuroplasticity is poorly understood. We review the Western, ketogenic, and paleolithic diets for their effects on cognition and correlations with synaptic changes, focusing mainly (but not exclusively) on animal model studies aimed at tracing molecular alterations that may contribute to impaired human cognition. We observe that memory and learning deficits mediated by high-fat/high-sugar diets, even over short exposure times, are associated with reduced arborization, widened synaptic cleft, narrowed post-synaptic zone, and decreased activity-dependent synaptic plasticity in the hippocampus, and also observe that these alterations correlate with deregulation of the AMPA-type glutamate ionotropic receptors (AMPARs) that are crucial to neuroplasticity. Furthermore, we explored which diet-mediated mechanisms modulate synaptic AMPARs and whether certain supplements or nutritional interventions could reverse deleterious effects, contributing to improved learning and memory in older people and patients with Alzheimer's disease.
    Keywords:  AMPARs; BDNF; cognition; diet; hippocampus; learning; memory; neurodegeneration; neuroplasticity; synaptic function
    DOI:  https://doi.org/10.3390/nu14194137
  102. Int J Mol Sci. 2022 Sep 21. pii: 11052. [Epub ahead of print]23(19):
    Metabolic Reprogramming in Tumor Endothelial Cells.
    Melissa García-Caballero, Liliana Sokol, Anne Cuypers, Peter Carmeliet.
      The dynamic crosstalk between the different components of the tumor microenvironment is critical to determine cancer progression, metastatic dissemination, tumor immunity, and therapeutic responses. Angiogenesis is critical for tumor growth, and abnormal blood vessels contribute to hypoxia and acidosis in the tumor microenvironment. In this hostile environment, cancer and stromal cells have the ability to alter their metabolism in order to support the high energetic demands and favor rapid tumor proliferation. Recent advances have shown that tumor endothelial cell metabolism is reprogrammed, and that targeting endothelial metabolic pathways impacts developmental and pathological vessel sprouting. Therefore, the use of metabolic antiangiogenic therapies to normalize the blood vasculature, in combination with immunotherapies, offers a clinical niche to treat cancer.
    Keywords:  metabolic reprogramming; tumor angiogenesis; tumor endothelial cell metabolism; tumor microenvironment
    DOI:  https://doi.org/10.3390/ijms231911052
  103. Molecules. 2022 Sep 28. pii: 6407. [Epub ahead of print]27(19):
    Polygonum capitatum, the Hmong Medicinal Flora: A Comprehensive Review of Its Phytochemical, Pharmacological and Pharmacokinetic Characteristics.
    Yan Lin, Lei He, Xing-Jun Chen, Xu Zhang, Xue-Long Yan, Bo Tu, Zhu Zeng, Ming-Hui He.
      Polygonum capitatum, known as "Tou Hua Liao" (Chinese name), is a crucial source of Hmong medicinal plants that has benefited human health for a long time. This folk-medicinal plant is widely distributed in the south-west of China for the treatment of various urologic disorders including urinary tract infections, pyelonephritis, and urinary calculus. The purpose of this paper was to provide a systematic and comprehensive overview of the traditional usages, botany, phytochemistry, pharmacology, pharmacokinetics and clinical applications of this flora. Up until the end of 2022, at least 91 compounds had been reported from P. capitatum, mainly covering the classes of flavonoids, lignanoids, phenols and other components. The compounds and extracts isolated from P. capitatum exhibit a wide range of pharmacological activities, such as anti-inflammatory, antioxidant, antimicrobial, anticancer, analgesic, hypothermic, diuretic and other pharmacological effects. Qualitative and quantitative chemical analyses were also covered. Furthermore, the possible development trends and perspectives for future research on this medicinal plant were also discussed.
    Keywords:  Polygonum capitatum; chemical analysis; flavonoids; pharmacological activities
    DOI:  https://doi.org/10.3390/molecules27196407
  104. Carbohydr Polym. 2022 Dec 15. pii: S0144-8617(22)00979-1. [Epub ahead of print]298 120074
    Recent advances in oral delivery of bioactive molecules: Focus on prebiotic carbohydrates as vehicle matrices.
    Seid Reza Falsafi, Sneh Punia Bangar, Vandana Chaudhary, Elham Hosseini, Zeinab Mokhtari, Asli Can Karaca, Mahesh Kumar Samota, Deepanyeta Goswami, Veda Krishnan, Gholamreza Askari, Hadis Rostamabadi.
      Controlled oral delivery of bioactive molecules remains a promising platform for the food and biomedical realm. Nonetheless, there are many bottlenecks to the efficient oral bioactive delivery that necessitates the development of advanced approaches. In recent years, prebiotic carbohydrates have drawn surging interest for targeted bioactive delivery due to their potential of multi-stimuli release mechanisms. Harnessing prebiotic-based vehicles confers novel possibilities for intact oral bioactive delivery, improving their bioavailability and efficacy. This critical review updates state of the art on progresses in oral delivery of natural active agents via prebiotic carbohydrates. We offer the latest advances concerning prebiotic-based vehicles (i.e., pH/time-dependent systems, enzyme-sensitive polymers, and colonic microbiota-dependent vehicles), emphasizing their key attributes to attaining controlled/targeted bioactive delivery to the intended locus. Finally, we discuss safety considerations, challenges, and future perspectives toward advances in the field.
    Keywords:  Bioactive agents; Biopolymers; Delivery systems; Encapsulation; Prebiotics; Targeted release
    DOI:  https://doi.org/10.1016/j.carbpol.2022.120074
  105. Cancers (Basel). 2022 Oct 08. pii: 4920. [Epub ahead of print]14(19):
    Applications of Focused Ultrasound for the Treatment of Glioblastoma: A New Frontier.
    Andrew M Hersh, Meghana Bhimreddy, Carly Weber-Levine, Kelly Jiang, Safwan Alomari, Nicholas Theodore, Amir Manbachi, Betty M Tyler.
      Glioblastoma (GBM) is an aggressive primary astrocytoma associated with short overall survival. Treatment for GBM primarily consists of maximal safe surgical resection, radiation therapy, and chemotherapy using temozolomide. Nonetheless, recurrence and tumor progression is the norm, driven by tumor stem cell activity and a high mutational burden. Focused ultrasound (FUS) has shown promising results in preclinical and clinical trials for treatment of GBM and has received regulatory approval for the treatment of other neoplasms. Here, we review the range of applications for FUS in the treatment of GBM, which depend on parameters, including frequency, power, pulse duration, and duty cycle. Low-intensity FUS can be used to transiently open the blood-brain barrier (BBB), which restricts diffusion of most macromolecules and therapeutic agents into the brain. Under guidance from magnetic resonance imaging, the BBB can be targeted in a precise location to permit diffusion of molecules only at the vicinity of the tumor, preventing side effects to healthy tissue. BBB opening can also be used to improve detection of cell-free tumor DNA with liquid biopsies, allowing non-invasive diagnosis and identification of molecular mutations. High-intensity FUS can cause tumor ablation via a hyperthermic effect. Additionally, FUS can stimulate immunological attack of tumor cells, can activate sonosensitizers to exert cytotoxic effects on tumor tissue, and can sensitize tumors to radiation therapy. Finally, another mechanism under investigation, known as histotripsy, produces tumor ablation via acoustic cavitation rather than thermal effects.
    Keywords:  FUS; blood–brain barrier; focused ultrasound; glioblastoma; targeted therapy
    DOI:  https://doi.org/10.3390/cancers14194920
  106. Biomed Pharmacother. 2022 Oct 10. pii: S0753-3322(22)01250-1. [Epub ahead of print]156 113861
    Targeting hypoxia-inducible factor-1alpha: A new strategy for triple-negative breast cancer therapy.
    Qi Liu, Chengcheng Guan, Cui Liu, Huayao Li, Jibiao Wu, Changgang Sun.
      Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is highly aggressive and hypoxic compared with other subtypes. The role of hypoxia inducible factor 1α (HIF-1α) as a key hypoxic transcription factor in oncogenic processes has been extensively studied. Recently, it has been shown that HIF-1α regulates the complex biological processes of TNBC, such as glycolysis, angiogenesis, invasion and metastasis, breast cancer stem cells (BCSCs) enrichment, and immune escape, to promote TNBC survival and development through the activation of downstream target genes. In addition, inflammatory mediators, oxygen levels, noncoding RNAs, complex signaling regulatory networks, epigenetic regulators are involved in the upstream regulatory expression of HIF-1α. However, further studies are needed to determine the potential and future directions of targeting HIF-1α in TNBC. This article discusses the expression of the HIF-1α transcription factor in TNBC. We also explored the mechanism by which HIF-1α drives TNBC progression. The potential significance of targeting HIF-1α for immunotherapy, chemotherapy, anti-angiogenic therapy, and photodynamic therapy is discussed. The intrinsic mechanism, existing problems and future directions of targeting HIF-1α are also studied.
    Keywords:  Combination therapy; HIF-1α; Hypoxia; Signaling pathways; TNBC progression; Triple-negative breast cancer
    DOI:  https://doi.org/10.1016/j.biopha.2022.113861
  107. Environ Sci Pollut Res Int. 2022 Oct 11.
    The role of iron nanoparticles on anaerobic digestion: mechanisms, limitations, and perspectives.
    Nicolás Hoffmann, Paola Fincheira, Gonzalo Tortella, Olga Rubilar.
      Anaerobic digestion (AD) is the most widely used technology for organic matter treatment. However, multiple types of research have reported on improving the process because different operation inhibition factors and limitations affect the performance of AD process. Owing to the increasing use of iron-nanoparticles (Fe-NP) on AD, this review addresses the knowledge gaps and summarizes the finding from academic articles based on (i) the AD upgrading operations: limitations and upgrade techniques, (ii) Fe-NPs mechanisms on AD, (iii) Fe-NP effect on microbial communities associated to AD systems, and (iv) perspectives. The selected topics give the Fe-NP positive effects on the AD methane-production process in terms of gas production, effluent quality, and process optimization. The main results of this work indicate that (i) Fe-NP addition can be adapted among different feedstocks and complement other pretreatments, (ii) Fe-NP physicochemical characteristics enhance biogas production via direct interspecies electron transfer (DIET) mechanisms, and Fe-ion release due to their structure and their conductivity capability, and (iii) syntrophic bacteria and acetoclastic methanogens have been reported as the communities that better uptake Fe-NPs on their metabolisms. Finally, our research perspectives and gaps will be discussed to contribute to our knowledge of using Fe-NPs on AD systems.
    Keywords:  Anaerobic digestion; Biogas; Bioprocess; Iron nanoparticles; Microbial communities; Nanoparticle mechanisms
    DOI:  https://doi.org/10.1007/s11356-022-23302-3
  108. Front Oncol. 2022 ;12 980694
    A vicious circle in breast cancer: The interplay between inflammation, reactive oxygen species, and microRNAs.
    Valeria Villarreal-García, José Roberto Estupiñan-Jiménez, Pablo E Vivas-Mejía, Vianey Gonzalez-Villasana, José Manuel Vázquez-Guillén, Diana Reséndez-Pérez.
      Breast cancer (BC) is the most common cancer in women worldwide. This highly heterogeneous disease is molecularly stratified into luminal A, luminal B, HER2, triple-negative/basal-like, and normal-like subtypes. An important aspect in BC progression is the activation of inflammatory processes. The activation of CD8+/Th1, NK, and M1 tumor associated macrophages (TAMs), leads to tumor destruction. In contrast, an anti-inflammatory response mediated by CD4+/Th2 and M2 TAMs will favor tumor progression. Inflammation also stimulates the production of inflammatory mediators like reactive oxygen species (ROS). In chronic inflammation, ROS activates oxidative stress and endothelial dysfunction. In cancer, ROS plays a dual role with anti-tumorigenic and pro-tumorigenic effects in cell signaling pathways that control proliferation, survival, apoptosis, and inflammation. MicroRNAs (miRNAs), which are known to be involved in BC progression and inflammation, can be regulated by ROS. At the same time, miRNAs regulate the expression of genes modulating oxidative stress. In this review, we will discuss the interplay between inflammation, ROS, and miRNAs as anticancer and tumor promoter molecules in BC. A clear understanding of the role of miRNAs in the regulation of ROS production and inflammation, may lead to new opportunities for therapy in BC.
    Keywords:  breast cancer; inflammation; microRNAs; regulation; ros
    DOI:  https://doi.org/10.3389/fonc.2022.980694
  109. Biochem Biophys Rep. 2022 Dec;32 101363
    The development of a novel antioxidant-based antiemetic drug to improve quality of life during anticancer therapy.
    Hiroto Yanagawa, Yoshihisa Koyama, Yuki Kobayashi, Hikaru Kobayashi, Shoichi Shimada.
      Anticancer agents can effectively treat several types of cancers but are often limited in clinical settings due to various adverse effects. In particular, nausea and vomiting are serious side effects that markedly reduce the patients' quality of life. Accordingly, the development of novel antiemetic drugs that lack side effects is crucial, given that most conventional antiemetic drugs are known to possess side effects. In addition, reactive oxygen species generated by anticancer agents are involved in nausea and vomiting; hence, appropriate antioxidants might also be effective toward nausea and vomiting. Silicon (Si)-based agents can abundantly generate antioxidant hydrogen in the intestine. Therefore, we assessed whether Si-based agents could be effective against nausea associated with anticancer agents in cisplatin-injected mice. We observed numerous neurons expressing c-Fos protein, a neuronal activity marker, in the nausea-associated regions of the dorsal medulla (area postrema, nuclei of the solitary tract, and dorsal vagal nuclei) 24 h after cisplatin injection. Conversely, mice fed a diet containing 2.5% Si-based agents showed a reduction in c-Fos-positive neurons. These findings revealed that the Si-based agent alleviated cisplatin-induced nausea. Si-based agents demonstrate potent antioxidant effects by producing hydrogen, which has no known side effects and will be a safer antiemetic agent and greatly help improve the quality of life of patients undergoing anticancer drug treatment.
    Keywords:  Antioxidant; Cisplatin chemotherapy; Nausea and vomiting; Si-based agent
    DOI:  https://doi.org/10.1016/j.bbrep.2022.101363
  110. Sci Rep. 2022 Oct 11. 12(1): 17035
    Mitochondrial transporter expression patterns distinguish tumor from normal tissue and identify cancer subtypes with different survival and metabolism.
    Hartmut Wohlrab, Sabina Signoretti, Lucia E Rameh, Derrick K DeConti, Steen H Hansen.
      Transporters of the inner mitochondrial membrane are essential to metabolism. We demonstrate that metabolism as represented by expression of genes encoding SLC25 transporters differentiates human cancers. Tumor to normal tissue expression ratios for clear cell renal cell carcinoma, colon adenocarcinoma, lung adenocarcinoma and breast invasive carcinoma were found to be highly significant. Affinity propagation trained on SLC25 gene expression patterns from 19 human cancer types (6825 TCGA samples) and normal tissues (2322 GTEx samples) was used to generate clusters. They differentiate cancers from normal tissues. They also indicate cancer subtypes with survivals distinct from the total patient population of the cancer type. Probing the kidney, colon, lung, and breast cancer clusters, subtype pairs of cancers were identified with distinct prognoses and differing in expression of protein coding genes from among 2080 metabolic enzymes assayed. We demonstrate that SLC25 expression clusters facilitate the identification of the tissue-of-origin, essential to efficacy of most cancer therapies, of CUPs (cancer-unknown-primary) known to have poor prognoses. Different cancer types within a single cluster have similar metabolic patterns and this raises the possibility that such cancers may respond similarly to existing and new anti-cancer therapies.
    DOI:  https://doi.org/10.1038/s41598-022-21411-0
  111. J Acad Nutr Diet. 2022 Oct 05. pii: S2212-2672(22)01068-1. [Epub ahead of print]
    Nutrition and Microbiome Interactions in Human Cancer.
    Phillip J Daschner, Sharon Ross, Harold Seifried, Amit Kumar, Roberto Flores.
      Individual physiologic responses and cancer risk can vary widely to changes in dietary patterns and are driven by multiple host-specific factors (e.g., genetics, epigenetics, inflammatory and metabolic states, and the colonizing microbiome). Emerging evidence indicates that diet-induced microbiota alterations are key modulators of several host functions important to tumor etiology, progression, and response to cancer therapy. Thus, diet may potentially be used to target alterations of the microbiota as an effective means to improve outcomes across the cancer continuum (from cancer prevention to tumor development and progression, to effects on treatment and survivorship). This review will focus on recent examples of functional interactions between dietary components (nutrients and non-nutrients) and the gastrointestinal (GI) microbiome, which are two critical and malleable environmental variables in cancer risk that affect host immune, metabolic, and cell signaling functions and which may provide insights for novel cancer therapeutic and preventive strategies.
    Keywords:  Cancer; Cancer Etiology; Cancer Prevention; Microbiome; Nutrition
    DOI:  https://doi.org/10.1016/j.jand.2022.10.004
  112. Carbohydr Polym. 2022 Dec 15. pii: S0144-8617(22)01048-7. [Epub ahead of print]298 120143
    The design of multi-responsive nanohydrogel networks of chitosan for controlled drug delivery.
    Mohsen Omrani, M Reza Naimi-Jamal, Bahareh Farasati Far.
      High swelling hydrogel networks (HSHNs) are materials with the ability to high swelling and outstanding candidates for sustained drug delivery systems (DDSs). The present paper demonstrates three different chitosan nanohydrogel networks (CNHN I-III) prepared through covalent and non-covalent interactions. These hydrogels have a high swelling ratio (up to 38-fold their dry weight) in various conditions. Two types of these hydrogels (CNHN I and II), swelled rapidly in an acidic environment, were able to successfully load an extraordinary amount (up to 95 %) of a model drug doxorubicin hydrochloride (DOX.HCl) at a 1:1 ratio (wt./wt.). The CNHN III had substantial swelling in pH 7.4, with a loading capacity of 92 % 5-fluorouracil (5-FU) at a 1:1 ratio (wt./wt.). The CNHN I and II have been considered for systemic drug delivery, while the CNHN III is one of the best candidates for oral drug delivery.
    Keywords:  Covalent and non-covalent interactions; Ionic H-bond; Multi-responsive nanohydrogel networks; Oral drug delivery; Systemic drug delivery
    DOI:  https://doi.org/10.1016/j.carbpol.2022.120143
  113. Int J Pharm. 2022 Oct 06. pii: S0378-5173(22)00819-5. [Epub ahead of print] 122264
    Lipid nanocapsules enhance the transdermal delivery of drugs regardless of their physico-chemical properties.
    Aneta Kalvodová, Jarmila Zbytovská.
      The transdermal application of actives offers numerous advantages over other conventional routes. Namely, a stable level of drugs in the bloodstream and reduced side effects are the argument for topical administration. Unfortunately, the exceptional skin barrier and unsuitable physico-chemical properties of drugs are the limiting factors for the transdermal passage. It is possible to overcome this by incorporating the drug into nano-carriers to enhance its permeation through the skin barrier. For this purpose, we prepared lipid nanocapsules (LNCs) to modulate skin passage of three pharmaceutically important drugs - indomethacin (IND), diclofenac sodium (DF) and caffeine (CF). We present a stable system prepared by the phase inversion temperature method with particle size under 100 nm and PDI<0.1 with great encapsulation efficiency for indomethacin and diclofenac. By FTIR it was possible to confirm (for IND and DF) or disprove (in case of CF) the incorporation of a drug into the LNCs. By ex vivo permeation experiments on porcine skin, we confirmed the superior effect of the LNCs on the APIs skin passage. The drug permeated through the skin with higher intensity when delivered from LNCs compared to other standard formulations. We show that lipid nanocapsules play an important role in enhanced topical application of actives.
    Keywords:  Caffeine; Dermal and transdermal delivery; Diclofenac; Indomethacin; Lipid nanocapsules
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.122264
  114. Cancers (Basel). 2022 Oct 10. pii: 4959. [Epub ahead of print]14(19):
    The Good, the Bad and the New about Uric Acid in Cancer.
    Simone Allegrini, Mercedes Garcia-Gil, Rossana Pesi, Marcella Camici, Maria Grazia Tozzi.
      Uric acid is the final product of purine catabolism in man and apes. The serum concentration of uric acid is sex-, age- and diet-dependent and is maintained close to its maximal solubility, indicating that it plays some important role. Indeed, it has been demonstrated that, at physiological concentrations, uric acid is a powerful antioxidant, while at high intracellular concentrations, it is a pro-oxidant molecule. In this review, we describe the possible causes of uric acid accumulation or depletion and some of the metabolic and regulatory pathways it may impact. Particular attention has been given to fructose, which, because of the complex correlation between carbohydrate and nucleotide metabolism, causes uric acid accumulation. We also present recent results on the positive and negative effects played by uric acid in cancer and some new findings and hypotheses about the implication of this metabolite in a variety of signaling pathways, which can play a role in the pathogenesis of diseases such as metabolic syndrome, diabetes, and inflammation, thus favoring the development of cancer. The loss of uricase in Homo sapiens and great apes, although exposing these species to the potentially adverse effects of uric acid, appears to be associated with evolutionary advantages.
    Keywords:  AKT; AMPK; cancer; fructose; hyperuricemia; mTOR; oxidative stress; uric acid; uricase; xanthine oxidoreductase
    DOI:  https://doi.org/10.3390/cancers14194959
  115. Molecules. 2022 Oct 05. pii: 6613. [Epub ahead of print]27(19):
    Selenium: An Antioxidant with a Critical Role in Anti-Aging.
    Geir Bjørklund, Mariia Shanaida, Roman Lysiuk, Halyna Antonyak, Ivan Klishch, Volodymyr Shanaida, Massimiliano Peana.
      Aging is characterized by an imbalance between damage inflicted by reactive oxygen species (ROS) and the antioxidative defenses of the organism. As a significant nutritional factor, the trace element selenium (Se) may remodel gradual and spontaneous physiological changes caused by oxidative stress, potentially leading to disease prevention and healthy aging. Se is involved in improving antioxidant defense, immune functions, and metabolic homeostasis. An inadequate Se status may reduce human life expectancy by accelerating the aging process or increasing vulnerability to various disorders, including immunity dysfunction, and cancer risk. This review highlights the available studies on the effective role of Se in aging mechanisms and shows the potential clinical implications related to its consumption. The main sources of organic Se and the advantages of its nanoformulations were also discussed.
    Keywords:  antioxidant effect; chemoprevention; health benefit; human aging; immunoprotection; selenium
    DOI:  https://doi.org/10.3390/molecules27196613
  116. J Clin Invest. 2022 Oct 13. pii: e157302. [Epub ahead of print]
    The interferon-inducible protein viperin controls cancer metabolic reprogramming to enhance cancer progression.
    Kyung Mi Choi, Jeong Jin Kim, Jihye Yoo, Ku Sul Kim, Youngeun Gu, John Eom, Haengdueng Jeong, Kyungeun Kim, Ki Taek Nam, Young Soo Park, Joon-Yong Chung, Jun-Young Seo.
      Metabolic reprogramming is an important cancer hallmark. However, the mechanisms driving metabolic phenotypes of cancer cells are unclear. Here, we showed that the interferon (IFN)-inducible protein, viperin, drives metabolic alteration in cancer cells. Viperin was observed in various types of cancer and inversely correlated with the survival rate of patients with gastric, lung, breast, renal, pancreatic, or brain cancer. By generating viperin knockdown or stably expressing cancer cells, we showed that viperin, but not a mutant lacking its iron-sulfur cluster-binding motif, increased lipogenesis and glycolysis via inhibition of fatty acid β-oxidation in cancer cells. In the tumor microenvironment, deficiency of fatty acids and oxygen as well as production of IFNs upregulated viperin expression via the PI3K/AKT/mTOR/HIF-1α and JAK/STAT pathways. Moreover, viperin was primarily expressed in cancer stem-like cells (CSCs) and functioned to promote metabolic reprogramming and enhance CSC properties, thereby facilitating tumor growth in xenograft mouse models. Collectively, our data indicate that viperin-mediated metabolic alteration drives the metabolic phenotype and progression of cancer.
    Keywords:  Cancer; Fatty acid oxidation; Glucose metabolism; Metabolism; Oncology
    DOI:  https://doi.org/10.1172/JCI157302
  117. J Food Biochem. 2022 Oct 14. e14445
    Nutraceuticals and COVID-19: A mechanistic approach toward attenuating the disease complications.
    Keshav Raj Paudel, Vyoma Patel, Sukriti Vishwas, Saurabh Gupta, Sumit Sharma, Yinghan Chan, Niraj Kumar Jha, Jesus Shrestha, Mohammad Imran, Nisha Panth, Shakti Dhar Shukla, Saurav Kumar Jha, Hari Prasad Devkota, Majid Ebrahimi Warkiani, Sachin Kumar Singh, Md Khadem Ali, Gaurav Gupta, Dinesh Kumar Chellappan, Philip M Hansbro, Kamal Dua.
      Nutraceuticals have emerged as potential compounds to attenuate the COVID-19 complications. Precisely, these food additives strengthen the overall COVID treatment and enhance the immunity of a person. Such compounds have been used at a large scale, in almost every household due to their better affordability and easy access. Therefore, current research is focused on developing newer advanced formulations from potential drug candidates including nutraceuticals with desirable properties viz, affordability, ease of availability, ease of administration, stability under room temperature, and potentially longer shelf-lives. As such, various nutraceutical-based products such as compounds could be promising agents for effectively managing COVID-19 symptoms and complications. Most importantly, regular consumption of such nutraceuticals has been shown to boost the immune system and prevent viral infections. Nutraceuticals such as vitamins, amino acids, flavonoids like curcumin, and probiotics have been studied for their role in the prevention of COVID-19 symptoms such as fever, pain, malaise, and dry cough. In this review, we have critically reviewed the potential of various nutraceutical-based therapeutics for the management of COVID-19. We searched the information relevant to our topic from search engines such as PubMed and Scopus using COVID-19, nutraceuticals, probiotics, and vitamins as a keyword. Any scientific literature published in a language other than English was excluded. PRACTICAL APPLICATIONS: Nutraceuticals possess both nutritional values and medicinal properties. They can aid in the prevention and treatment of diseases, as well as promote physical health and the immune system, normalizing body functions, and improving longevity. Recently, nutraceuticals such as probiotics, vitamins, polyunsaturated fatty acids, trace minerals, and medicinal plants have attracted considerable attention and are widely regarded as potential alternatives to current therapeutic options for the effective management of various diseases, including COVID-19.
    Keywords:  COVID-19; nutraceuticals; probiotics; vitamins
    DOI:  https://doi.org/10.1111/jfbc.14445
  118. Biomater Adv. 2022 Oct 03. pii: S2772-9508(22)00414-9. [Epub ahead of print]142 213137
    Multifunctional chitosan ferrogels for targeted cancer therapy by on-demand magnetically triggered drug delivery and hyperthermia.
    N S Sumitha, Nidhi G Krishna, G S Sailaja.
      A facile method for the synthesis of chitosan ferrogels for magnetically triggered drug release and hyperthermia treatment is presented. The glyoxal crosslinked, dried ferrogels (magnetic bioaerogels) have been characterized by FTIR, XRD, TGA and VSM analyses and they possess unique characteristics such as high porosity, ultra-low density and superparamagnetism (Ms up to 56 emu g-1). In addition, they present high drug (Doxorubicin, DOX) loading efficiency (~40 %), tumor-specific pH-responsive swelling, excellent biodegradation, remotely switchable drug release and high magnetic hyperthermia potential (42 °C within 4 min). Almost complete degradation of the ferrogels occurs in 3 months under physiological conditions (pH = 7.4), while the tumor-specific microenvironment (pH = 5.6) accelerates the degradation rate, where it occurs in ~8 weeks. Furthermore, an enhancement in drug release (by 30 %) was observed in 60 min, when subjected to a magnetic field of 50 mT. Excellent biocompatibility and promising cell-material interactions have been exhibited by the ferrogels, substantiated by MTT assay, cytoskeleton staining and confocal imaging. The viability has been drastically reduced for DOX-loaded samples due to the action of the released drug; validating the efficacy of DOX loaded ferrogels. The system presented, therefore, holds multi-functionalities enabling smart cancer treatment.
    Keywords:  Chitosan; Doxorubicin; Ferrogel; Hyperthermia; Magnetically triggered drug release; Superparamagnetism
    DOI:  https://doi.org/10.1016/j.bioadv.2022.213137
  119. Chempluschem. 2022 Sep 16. 87(10): e202200113
    Thermosensitive Liposomal Nanoplatform Based on Metal-Free Phthalocyanine with Copper(II)-Regulated Photoactivities.
    Xin-Yue Ma, Wen Zhang, Rong-Bin Que, Chao Wang, Wen-Wen Shang, Yuan-Yuan Zhu, Bi-Yuan Zheng, Yu Chen, Mei-Rong Ke, Jian-Dong Huang.
      This work reports the development of a multifunctional thermosensitive liposomal nanoplatform (PcS4 @Lip-FA) based on a metal-free phthalocyanine modified with tetra-sulfonates (PcPS4 ), which exhibited photodynamic and photothermal activities simultaneously. Upon irradiation with a near infrared laser, thermosensitive PcS4 @Lip-FA could release PcS4 as a result of the local hyperthermia of PcS4 . Interestingly, PcS4 could easily chelate with Cu2+ , leading to the enhancement of photothermal activity and decrease of photodynamic activity. In addition, in vivo fluorescence imaging revealed that PcS4 @Lip-FA could selectively accumulate in tumor tissue of H22 tumor-bearing mice after tail vein injection, and exhibited a significant anticancer phototherapeutic effect, with a tumor inhibition rate of 83.5 %. Therefore, PcPS4 @Lip-FA has realized fluorescence imaging-guided combined cancer treatment, providing a promising multifunctional nanoplatform for cancer diagnostics and therapy.
    Keywords:  copper; liposomes; photodynamic therapy; photothermal therapy; phthalocyanines
    DOI:  https://doi.org/10.1002/cplu.202200113
  120. Acta Endocrinol (Buchar). 2022 Apr-Jun;18(2):18(2): 168-173
    VITAMIN D LEVEL AND ITS RELATIONSHIP WITH CANCER STAGE IN PATIENTS WITH DIFFERENTIATED THYROID CARCINOMA.
    A M Cocolos, S Vladoiu, A Caragheorgheopol, A M Ghemigian, D Ioachim, C Poiana.
      Background: Differentiated thyroid carcinoma (DTC) has witnessed an increase in incidence and although it is considered to have a slow grow potential and a 90% 10-year survival rate, local or distant metastases can be observed in 20%. It is essential to recognize other factors associated with malignancy and poor prognosis. Vitamin D and its deficiency has proven useful as a prognostic biomarker for many types of cancer, including thyroid cancer.Aim: Evaluate the relationship between vitamin D status in DTC and benign thyroid disorders patients and correlation between vitamin D and histopathological findings in DTC group.
    Methods: Study included 170 patients with confirmed DTC and 200 with benign thyroid pathology. Evaluation included 25-hydroxy vitamin D [25(OH)D], ultrasound and histopathologic features.
    Results: In DTC patients, mean value of vitamin D was significantly lower (17.86 ng/mL ± 9.31 DS versus 20.26 ng/mL ± 9.31 DS, p=0.029). Statistical analysis confirmed a negative correlation between vitamin D levels and tumor size (T) according to TNM classification (r=-0.176, p=0.02).
    Conclusions: Vitamin D level was significantly lower in the DTC group and 25(OH)D levels may be correlated with histopathology features like tumor size and aggressiveness according to TNM classification.
    Keywords:  TNM; differentiated thyroid cancer; pappillary thyroid cancer; vitamin D
    DOI:  https://doi.org/10.4183/aeb.2022.168
  121. Biotechnol Bioeng. 2022 Oct 12.
    A hydrogel-fiber-hydrogel composite scaffold based on silk fibroin with the dual-delivery of oxygen and quercetin.
    Mina Aleemardani, Atefeh Solouk, Somaye Akbari, Mohammad Moeini.
      Supplying sufficient oxygen within the scaffolds is one of the essential hindrances in tissue engineering that can be resolved by oxygen-generating biomaterials (OGBs). Two main issues related to OGBs are controlling the oxygenation and reactive oxygen species (ROS). To address these concerns, we developed a composite scaffold entailing three layers (hydrogel-electrospun fibers-hydrogel) with antioxidant and antibacterial properties. The fibers, the middle layer, reinforced the composite structure, enhancing the mechanical strength from 4.27±0.15 kPa to 8.27±0.25 kPa; also, this layer is made of calcium peroxide and silk fibroin through electrospinning, which enables oxygen delivery. The first and third layers are physical silk fibroin hydrogels to control oxygen release, containing quercetin, a non-enzymatic antioxidant. This composite scaffold resulted in almost more than 40 mmHg oxygen release at least for 13 days, and compared with similar studies is in a high range. Here, quercetin was used for the first time for an OGB to scavenge the possible ROS. Quercetin delivery not only led to antioxidant activity but also stabilized oxygen release and enhanced cell viability. Based on the given results, this composite scaffold can be introduced as a safe and controllable oxygen supplier, which is promising for tissue engineering applications, particularly for bone. This article is protected by copyright. All rights reserved.
    Keywords:  Calcium peroxide; Composite scaffolds.; Oxygen-generating biomaterials; Quercetin; Silk fibroin
    DOI:  https://doi.org/10.1002/bit.28259
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