bims-kracam Biomed News
on K-Ras in cancer metabolism
Issue of 2022–07–10
95 papers selected by
Yasmin Elkabani, Egyptian Foundation for Research and Community Development
  1. Cancer metabolism control by natural products: Pyruvate kinase M2 targeting therapeutics.
  2. A prodrug hydrogel with tumor microenvironment and near-infrared light dual-responsive action for synergistic cancer immunotherapy.
  3. Zinc-curcumin based complexes in health and diseases: An approach in chemopreventive and therapeutic improvement.
  4. [Progresses on active targeting liposome drug delivery systems for tumor therapy].
  5. Targeting necroptosis as an alternative strategy in tumor treatment: From drugs to nanoparticles.
  6. Recent advances on nanoparticle-based photothermal therapy for breast cancer.
  7. Facile Synthesis of Fe3O4@Au/PPy-DOX Nanoplatform with Enhanced Glutathione Depletion and Controllable Drug Delivery for Enhanced Cancer Therapeutic Efficacy.
  8. Natural flavonoids in the prevention and treatment of lung cancer: A pharmacological aspect.
  9. Dysregulated metabolism: A friend-to-foe skewer of macrophages.
  10. Oxidative Stress and Redox-Dependent Signaling in Prostate Cancer.
  11. Review on the Therapeutic Potential of Curcumin and its Derivatives on Glioma Biology.
  12. Natural bioactive compounds: a potential therapeutic strategy to sensitize bladder cancer to cisplatin treatment?
  13. Chitosan-modified nanocarriers as carriers for anticancer drug delivery: Promises and hurdles.
  14. pH-Responsive Hydrogel Beads Based on Alginate, κ-Carrageenan and Poloxamer for Enhanced Curcumin, Natural Bioactive Compound, Encapsulation and Controlled Release Efficiency.
  15. pH-stable polymersome as nanocarrier for post-loaded rose bengal in photodynamic therapy.
  16. Simultaneous chemotherapy/sonodynamic therapy of the melanoma cancer cells using a gold-paclitaxel nanostructure.
  17. Multifunctional active ingredient-based delivery systems for skincare formulations: A review.
  18. Co-Targeting Tumor Angiogenesis and Immunosuppressive Tumor Microenvironment: A Perspective in Ethnopharmacology.
  19. The place of a ketogenic diet in the treatment of resistant epilepsy: a comprehensive review.
  20. Flavonoids Targeting the mTOR Signaling Cascades in Cancer: A Potential Crosstalk in Anti-Breast Cancer Therapy.
  21. Redox-sensitive doxorubicin liposome: a formulation approach for targeted tumor therapy.
  22. Review of the Effects and Mechanism of Curcumin in the Treatment of Inflammatory Bowel Disease.
  23. Nanoencapsulation of Tea Catechins for Enhancing Skin Absorption and Therapeutic Efficacy.
  24. Role of HIF-1α/ERRα in Enhancing Cancer Cell Metabolism and Promoting Resistance of Endometrial Cancer Cells to Pyroptosis.
  25. Plant-Based and Ketogenic Diets As Diverging Paths to Address Cancer: A Review.
  26. Global metabolic alterations in colorectal cancer cells during irinotecan-induced DNA replication stress.
  27. Fullerenes for the treatment of cancer: an emerging tool.
  28. Role of Ginseng, Quercetin, and Tea in Enhancing Chemotherapeutic Efficacy of Colorectal Cancer.
  29. Trabectedin suppresses escape from therapy-induced senescence in tumor cells by interfering with glutamine metabolism.
  30. A Poly (Caprolactone)-Cellulose Nanocomposite Hydrogel for Transdermal Delivery of Hydrocortisone in Treating Psoriasis Vulgaris.
  31. Design and structural regulation of AIE photosensitizers for imaging-guided photodynamic anti-tumor application.
  32. Glioblastoma and Methionine Addiction.
  33. An update on dual targeting strategy for cancer treatment.
  34. Exercise in cancer prevention and anticancer therapy: Efficacy, molecular mechanisms and clinical information.
  35. Pharmacological Properties of 4', 5, 7-Trihydroxyflavone (Apigenin) and Its Impact on Cell Signaling Pathways.
  36. Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer's Disease.
  37. Pharmaceutical Nanoemulsion System: A Strategy to Enhance the Bioavailability of Drugs.
  38. Benefits and limitations of nanomedicine treatment of brain cancers and age-dependent neurodegenerative disorders.
  39. Computation Screening of Multi-Target Antidiabetic Properties of Phytochemicals in Common Edible Mediterranean Plants.
  40. Nanotherapeutic treatment of the invasive glioblastoma tumor microenvironment.
  41. Current Advancements in Antitumor Properties and Mechanisms of Medicinal Components in Edible Mushrooms.
  42. Molecular Basis Underlying the Therapeutic Potential of Vitamin D for the Treatment of Depression and Anxiety.
  43. An in situ hydrogel-mediated chemo-immunometabolic cancer therapy.
  44. Reactive oxygen species activated by mitochondria-specific camptothecin prodrug for enhanced chemotherapy.
  45. Nanoparticles in chemotherapy: characteristics, design strategies, mechanism of internalization and intracellular degradation
  46. DNA Base Pairing-Inspired Supramolecular Nanodrug Camouflaged by Cancer-Cell Membrane for Osteosarcoma Treatment.
  47. Research on the Construction of Bispecific-Targeted Sustained-Release Drug-Delivery Microspheres and Their Function in Treatment of Hepatocellular Carcinoma.
  48. The Critical Role of Ferroptosis in Hepatocellular Carcinoma.
  49. Surface-mediated high antioxidant and anti-inflammatory effects of astaxanthin-loaded ultrathin graphene oxide film that inhibits the overproduction of intracellular reactive oxygen species.
  50. Enzyme-activated prodrugs and their release mechanisms for the treatment of cancer.
  51. Anthocyanins as Key Phytochemicals Acting for the Prevention of Metabolic Diseases: An Overview.
  52. Nanoencapsulation of Ru(p-cymene) Complex Bearing Ginger-based Natural Product into Liposomal Nanoformulation to Improve Its Cellular Uptake and Antiproliferative Activity.
  53. Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review.
  54. Safety and Toxicity Implications of Multifunctional Drug Delivery Nanocarriers on Reproductive Systems In Vitro and In Vivo.
  55. Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation.
  56. Tissue Engineering and Photodynamic Therapy: A New Frontier of Science for Clinical Application -An Up-To-Date Review.
  57. Drug delivery based on chitosan, β-cyclodextrin and sodium carboxymethyl cellulose as well as nanocarriers for advanced leukemia treatment.
  58. Examination of Combined Treatment of Ginsenoside Rg3 and 5-Fluorouracil in Lung Adenocarcinoma Cells.
  59. Human Growth Hormone Fragment 176-191 Peptide Enhances the Toxicity of Doxorubicin-Loaded Chitosan Nanoparticles Against MCF-7 Breast Cancer Cells.
  60. Preparation, physical characterization, pharmacokinetics and anti-hyperglycemic activity of esculetin-loaded mixed micelles.
  61. Antitumor Effect of Glandora rosmarinifolia (Boraginaceae) Essential Oil through Inhibition of the Activity of the Topo II Enzyme in Acute Myeloid Leukemia.
  62. Lipid metabolism in tumor microenvironment: novel therapeutic targets.
  63. A Co-Encapsulation of Coenzyme Q10 and Curcumin in Liposomes Coated with Chitosan (Q10-Cur-Lip-Chi) with Enhanced Solubility and Stability for Good Release Performance and Antioxidative Activity.
  64. Metformin Can Enhance the Inhibitory Effect of Olaparib in Bladder Cancer Cells.
  65. Ziziphus nummularia: A Comprehensive Review of Its Phytochemical Constituents and Pharmacological Properties.
  66. Nutritional Values of Minikiwi Fruit (Actinidia arguta) after Storage: Comparison between DCA New Technology and ULO and CA.
  67. Naringenin: A potential flavonoid phytochemical for cancer therapy.
  68. Approaches to Improve Macromolecule and Nanoparticle Accumulation in the Tumor Microenvironment by the Enhanced Permeability and Retention Effect.
  69. Multifunctional hemoporfin-Cu9S8-MnO2 for magnetic resonance imaging-guided catalytically-assisted photothermal-sonodynamic therapies.
  70. Green nanoparticles as multifunctional nanomedicines: Insights into anti-inflammatory effects, growth signaling and apoptosis mechanism in cancer.
  71. N6-methyladenosine modification and metabolic reprogramming of digestive system malignancies.
  72. Paradigm Shift in Phytochemicals Research: Evolution from Antioxidant Capacity to Anti-Inflammatory Effect and to Roles in Gut Health and Metabolic Syndrome.
  73. Trends in iron oxide nanoparticles: a nano-platform for theranostic application in breast cancer.
  74. Novel Iron Oxide Nanoparticles Induce Ferroptosis in a Panel of Cancer Cell Lines.
  75. Formulation development and evaluation of transdermal emulgel using Aloevera extract and natural penetration enhancers.
  76. Nanocarrier based Drug Delivery to Brain: Interventions of Surface Modification.
  77. Optimum inhibition of MCF-7 breast cancer cells by efficient targeting of the macropinocytosis using optimized paclitaxel-loaded nanoparticles.
  78. Food-Grade Microencapsulation Systems to Improve Protection of the Epigallocatechin Gallate.
  79. Role of Drug Delivery System in Improving the Bioavailability of Resveratrol.
  80. Temperature-Responsive Polysaccharide Microparticles Containing Nanoparticles: Release of Multiple Cationic/Anionic Compounds.
  81. An injectable, self-healing carboxymethylated chitosan hydrogel with mild photothermal stimulation for wound healing.
  82. Origanum syriacum Phytochemistry and Pharmacological Properties: A Comprehensive Review.
  83. Vascularized nanocomposite hydrogel mechanically reinforced by polyelectrolyte-modified nanoparticles.
  84. Lipid-Head-Polymer-Tail Chimeric Vesicles.
  85. Hypolipidemic Activity of Olive Oil-Based Nanostructured Lipid Carrier Containing Atorvastatin.
  86. Preparation, Characterization and In Vitro Evaluation of Eudragit S100-Coated Bile Salt-Containing Liposomes for Oral Colonic Delivery of Budesonide.
  87. The Polyphenolic Profile and Antioxidant Activity of Five Vegetal Extracts with Hepatoprotective Potential.
  88. Self-Assembled ATP-Responsive DNA Nanohydrogel for Specifically Activated Fluorescence Imaging and Chemotherapy in Cancer Cells.
  89. Photodynamic therapy to a primary cancer of the peripheral lung: Case report.
  90. Assessment of nano lipid carrier loaded transdermal patch of rizatriptan benzoate.
  91. The Promise of Targeting Hypoxia to Improve Cancer Immunotherapy: Mirage or Reality?
  92. A Combined Cyanine/Carbomer Gel Enhanced Photodynamic Antimicrobial Activity and Wound Healing.
  93. Dietary Therapy in Prevention of Cardiovascular Disease (CVD)-Tradition or Modernity? A Review of the Latest Approaches to Nutrition in CVD.
  94. Carvacrol as a prospective regulator of cancer targets/signalling pathways.
  95. Elaborately engineering of a dual-drug co-assembled nanomedicine for boosting immunogenic cell death and enhancing triple negative breast cancer treatment.
  1. Phytother Res. 2022 Jul 06.
    Cancer metabolism control by natural products: Pyruvate kinase M2 targeting therapeutics.
    Ali H El-Far, Soad K Al Jaouni, Xiaotao Li, Junjiang Fu.
      Glycolysis is the primary source of energy for cancer growth and metastasis. The shift in metabolism from mitochondrial oxidative phosphorylation to aerobic glycolysis is called the Warburg effect. Cancer progression due to aerobic glycolysis is often associated with the activation of oncogenes or the loss of tumor suppressors. Therefore, inhibition of glycolysis is one of the effective strategies in cancer control. Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme overexpressed in breast, prostate, lung, colorectal, and liver cancers. Here, we discuss published studies regarding PKM2 inhibitors from natural products that are promising drug candidates for cancer therapy. We have highlighted the potential of natural PKM2 inhibitors for various cancer types. Moreover, we encourage researchers to evaluate the combinational effects between natural and synthetic PKM2 inhibitors. Also, further high-quality studies are needed to firmly establish the clinical efficacy of natural products.
    Keywords:  PKM2 inhibitors; glycolysis; natural products; pyruvate kinase M2 (PKM2)
    DOI:  https://doi.org/10.1002/ptr.7534
  2. Acta Biomater. 2022 Jun 30. pii: S1742-7061(22)00380-4. [Epub ahead of print]
    A prodrug hydrogel with tumor microenvironment and near-infrared light dual-responsive action for synergistic cancer immunotherapy.
    Mengbin Ding, Yongliang Fan, Yicheng Lv, Jiansheng Liu, Ningyue Yu, Deping Kong, Haitao Sun, Jingchao Li.
      Immunotherapy has been used for cancer treatment, while it faces the common dilemmas of low therapeutic efficacy and serious immunotoxicity. In this study, we report the construction of a tumor microenvironment and near-infrared (NIR) light dual-responsive prodrug hydrogel for cancer synergistic immunotherapy in a more effective and safe manner. Such prodrug hydrogels were in-situ formed via calcium-induced gelation of alginate solution containing protoporphyrin IX (PpIX)-modified iron oxide (Fe3O4) nanoparticles and programmed death ligand 1 antibody (aPD-L1) prodrug nanoparticles crosslinked by reactive oxygen species (ROS)-responsive linkers. PpIX served as a photosensitizer to produce singlet oxygen (1O2) under NIR laser irradiation for photodynamic therapy (PDT), and Fe3O4 nanoparticles mediated chemodynamic therapy (CDT) to generate hydroxyl radical (·OH) via Fenton reaction in the tumor microenvironment. In view of the cumulative actions of PDT and CDT, amplified ROS was generated to not only induce immunogenic cell death (ICD), but also destroy ROS-responsive linkers to achieve on-demand release of aPD-L1 from prodrug nanoparticles. Boosted antitumor immunity was elicited in tumor-bearing mice due to the aPD-L1-mediated immune checkpoint blocking. As a result, the prodrug hydrogel-based synergistic immunotherapy could almost treat bilateral tumors and prevent lung and liver metastasis using 4T1 tumor mouse models. This study thus offers a dual-responsive prodrug hydrogel platform for precision cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Via calcium-induced gelation of alginate, we constructed a prodrug hydrogel with tumor microenvironment and near-infrared light dual-responsive action for synergistic cancer immunotherapy. Such hydrogels can achieve on-demand release of aPD-L1 upon photoactivation in the tumor microenvironment. Through mediating photodynamic and chemodynamic therapy, the prodrug hydrogels can induce enhanced immunogenic cell death and synergistically improve the efficacy of aPD-L1-mediated immune checkpoint blocking. The prodrug hydrogel-based synergistic therapy almost deracinates the primary and distant tumors, and prevents lung and liver metastasis in tumor mouse models.
    Keywords:  Chemodynamic therapy; Hydrogels; Immunotherapy; Photodynamic therapy; Prodrugs
    DOI:  https://doi.org/10.1016/j.actbio.2022.06.041
  3. J Trace Elem Med Biol. 2022 Jun 20. pii: S0946-672X(22)00103-1. [Epub ahead of print]73 127023
    Zinc-curcumin based complexes in health and diseases: An approach in chemopreventive and therapeutic improvement.
    Sahdeo Prasad, Rajiv Lall.
      Curcumin, a polyphenolic compound isolated from turmeric rhizome, displays antioxidant, anti-inflammatory, anticancer, anti-microbial, antiviral, antidiabetic, neuroprotective, immune boosting and other chemopreventive and therapeutic properties. However, the efficacy of curcumin is confined due to its aqueous insolubility, instability, low intestinal absorption, poor bioavailability, and systemic elimination. Therefore, to overcome these issues and enhance pharmacological activities of curcumin, a complex of curcumin with metals such as zinc have been synthesized. Curcumin acts as a ligand and forms a stable complex with zinc. In this review, the improved protective, and therapeutic activities of zinc-curcumin complexes are discussed. Zinc-curcumin conjugates have exhibited enhanced antioxidant, anti-inflammatory, anticancer, antimicrobial and antidiabetic properties. Zinc-curcumin complexes have also displayed hepatoprotective, gastroprotective, neuroprotective, cardioprotective and osteogenesis efficacy. These protective and therapeutic efficacies of zinc-curcumin conjugates were associated with modulation of multiple molecular mechanisms including decreased inflammatory cytokines, increased antioxidant enzymes, quenched free radicals, decreased blood glucose levels, decreased insulin resistance, induced apoptosis markers, and restored function of tumor suppressor protein p53 in cancer cells. Overall, applications of zinc-curcumin complex could be a new approach against various diseases and could also be helpful in improvement of health.
    Keywords:  Antioxidant; Chronic diseases; Curcumin; Inflammation; Protective and therapeutic; Zinc
    DOI:  https://doi.org/10.1016/j.jtemb.2022.127023
  4. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2022 Jun 25. 39(3): 633-638
    [Progresses on active targeting liposome drug delivery systems for tumor therapy].
    Manyu Zhang, Chenxi Lou, Aoneng Cao.
      Liposome is an ideal drug carrier with many advantages such as excellent biocompatibility, non-immunogenicity, and easy functionalization, and has been used for the clinical treatment of many diseases including tumors. For the treatment of tumors, liposome has some passive targeting capability, but the passive targeting effect alone is very limited in improving the drug enrichment in tumor tissues, and active targeting is an effective strategy to improve the drug enrichment. Therefore, active targeting liposome drug-carriers have been extensively studied for decades. In this paper, we review the research progresses on active targeting liposome drug-carriers based on the specific binding of the carriers to the surface of tumor cells, and summarize the opportunities, challenges and future prospects in this field.
    Keywords:  Active targeting; Liposome; Tumor therapy
    DOI:  https://doi.org/10.7507/1001-5515.202110067
  5. J Control Release. 2022 Jul 03. pii: S0168-3659(22)00402-3. [Epub ahead of print]
    Targeting necroptosis as an alternative strategy in tumor treatment: From drugs to nanoparticles.
    Xinlong Zang, Jinxiao Song, Yanfeng Li, Yantao Han.
      Over last decades, most antitumor therapeutic strategies have focused on apoptosis, however, apoptosis resistance and immunological silence usually led to treatment failure. In this sense, triggering other programmed cell death such as necroptosis may achieve a better therapeutic efficacy and has gained widespread attentions in tumor therapy. Studies in this field have identified several types of necroptosis modulators and highlighted the therapeutic potential of necroptotic cell death in cancer. Nanoparticles further provide possibilities to improve therapeutic outcomes as an efficient drug delivery system, facilitating tumor targeting and controlled cargo release. Furthermore, some nanoparticles themselves can trigger/promote programmed necrosis through hyperthermia, ultrasound and autophagy blockage. These investigations have entered necroptosis for consideration as a promising strategy for tumor therapy, though numerous challenges remain and clinical applications are still distant. In this review, we would briefly introduce molecular mechanism and characteristics of necroptosis, and then summarize recent progress of programmed necrosis and their inducers in tumor therapy. Furthermore, the antitumor strategies that take advantages of nanoparticles to induce necroptosis are also discussed.
    Keywords:  Nanoparticles; Necroptotic cell death; Necroptotic inducers; Tumor immunity
    DOI:  https://doi.org/10.1016/j.jconrel.2022.06.060
  6. J Control Release. 2022 Jul 01. pii: S0168-3659(22)00392-3. [Epub ahead of print]
    Recent advances on nanoparticle-based photothermal therapy for breast cancer.
    Sania Ghobadi Alamdari, Mohammad Amini, Nazila Jalilzadeh, Behzad Baradaran, Reza Mohammadzadeh, Ahad Mokhtarzadeh, Fatemeh Oroojalian.
      Breast cancer is one of the most common cancers among women that is associated with high mortality. Conventional treatments including surgery, radiotherapy, and chemotherapy, which are not effective enough and have disadvantages such as toxicity and damage to healthy cells. Photothermal therapy (PTT) of cancer cells has been took great attention by researchers in recent years due to the use of light radiation and heat generation at the tumor site, which thermal ablation is considered a minimally invasive method for the treatment of breast cancer. Nanotechnology has opened up a new perspective in the treatment of breast cancer using PTT method. Through NIR light absorption, researchers applied various nanostructures because of their specific nature of penetrating and targeting tumor tissue, increasing the effectiveness of PTT, and combining it with other treatments. If PTT is used with common cancer treatments, it can dramatically increase the effectiveness of treatment and reduce the side effects of other methods. PTT performance can also be improved by hybridizing at least two different nanomaterials. Nanoparticles that intensely absorb light and increase the efficiency of converting light into heat can specifically kill tumors through hyperthermia of cancer cells. One of the main reasons that have increased the efficiency of nanoparticles in PTT is their permeability and durability effect and they can accumulate in tumor tissue. Targeted PTT can be provided by incorporating specific ligands to target receptors expressed on the surface of cancer cells on nanoparticles. These nanoparticles can specifically target cancer cells by maintaining the surface area and increasing penetration. In this study, we briefly introduce the performance of light therapy, application of metal nanoparticles, polymer nanoparticles, carbon nanoparticles, and hybrid nanoparticles for use in PTT of breast cancer.
    Keywords:  Breast cancer; Photothermal therapy; carbon nanoparticles; hybrid nanoparticles; metal nanoparticles; polymer nanoparticles
    DOI:  https://doi.org/10.1016/j.jconrel.2022.06.050
  7. Molecules. 2022 Jun 22. pii: 4003. [Epub ahead of print]27(13):
    Facile Synthesis of Fe3O4@Au/PPy-DOX Nanoplatform with Enhanced Glutathione Depletion and Controllable Drug Delivery for Enhanced Cancer Therapeutic Efficacy.
    Chunxia Qi, Wanni Wang, Peisan Wang, Hanlong Cheng, Xueyan Wang, Baoyou Gong, Anjian Xie, Yuhua Shen.
      The complex physiological environment and inherent self-healing function of tumors make it difficult to eliminate malignant tumors by single therapy. In order to enhance the efficacy of antitumor therapy, it is significant and challenging to realize multi-mode combination therapy by utilizing/improving the adverse factors of the tumor microenvironment (TME). In this study, a novel Fe3O4@Au/PPy nanoplatform loaded with a chemotherapy drug (DOX) and responsive to TME, near-infrared (NIR) laser and magnetic field was designed for the combination enhancement of eliminating the tumor. The Fe2+ released at the low pH in TME can react with endogenous H2O2 to induce toxic hydroxyl radicals (·OH) for chemodynamic therapy (CDT). At the same time, the generated Fe3+ could deplete overexpressed glutathione (GSH) at the tumor site to prevent reactive oxygen species (ROS) from being restored while producing Fe2+ for CDT. The designed Fe3O4@Au/PPy nanoplatform had high photothermal (PT) conversion efficiency and photodynamic therapy (PDT) performance under NIR light excitation, which can promote CDT efficiency and produce more toxic ROS. To maximize the cancer-killing efficiency, the nanoplatform can be successfully loaded with the chemotherapeutic drug DOX, which can be efficiently released under NIR excitation and induction of slight acidity at the tumor site. In addition, the nanoplatform also possessed high saturation magnetization (20 emu/g), indicating a potential magnetic targeting function. In vivo and in vitro results identified that the Fe3O4@Au/PPy-DOX nanoplatform had good biocompatibility and magnetic-targeted synergetic CDT/PDT/PTT/chemotherapy antitumor effects, which were much better than those of the corresponding mono/bi/tri-therapies. This work provides a new approach for designing intelligent TME-mediated nanoplatforms for synergistically enhancing tumor therapy.
    Keywords:  DOX; Fe3O4@Au/PPy nanoplatform; glutathione-depleting; multimodal cancer therapy; tumor microenvironment
    DOI:  https://doi.org/10.3390/molecules27134003
  8. Comb Chem High Throughput Screen. 2022 Jul 01.
    Natural flavonoids in the prevention and treatment of lung cancer: A pharmacological aspect.
    Rajat Nath, Chandrima Das, Sibashish Kityania, Deepa Nath, Subrata Das, Manabendra Dutta Choudhury, Jayanta Kumar Patra, Anupam Das Talukdar.
      Deadly disease cancer has many types, among them, lung cancer is responsible for the highest number of cancer mortality. Existing therapies as well as drugs for treating lung cancer are not good enough and often associated with innumerable side effects and toxicities. For these reasons, researchers have been working on developing novel anti-cancer medicines from plant and other natural sources that have a high safety profile. Natural flavonoids are a polyphenolic group of phytochemicals extracted from plants and other plant-derived compounds. Natural flavonoids are gaining popularity day by day due to their unique and priceless medicinal properties including anticancer properties. Several researchers have already declared that flavonoids possess the ability to treat different cancers and lung cancer. The bioactivity of natural flavonoids is mainly due to their structural diversity. Natural flavonoids fight lung cancer by regulating redox homeostasis, upregulating apoptosis, pro-apoptotic factors, and survival genes, arresting cell cycle progression, autophagy, reducing cell proliferation and invasiveness, maintaining inflammation response, downregulating anti-apoptotic factors, and targeting lung cancer signaling pathways. Flavonoids can act alone or synergistically with other agents to treat lung cancer. Due to these reasons, it is possible to use natural flavonoids as pharmaceutical leads to prevent and treat lung cancer.
    Keywords:  Cancer; Flavonoids; Lung Cancer; Natural Products; pharmacology.
    DOI:  https://doi.org/10.2174/1386207325666220701121537
  9. Int Rev Immunol. 2022 Jul 06. 1-17
    Dysregulated metabolism: A friend-to-foe skewer of macrophages.
    Keywan Mortezaee, Jamal Majidpoor.
      Metabolic reprogramming is a hallmark of solid cancers. Macrophages as major constituents of immune system take important roles in regulation of tumorigenesis. Pro-tumor M2 macrophages preferentially use oxidative phosphorylation (OXPHOS) to meet their metabolic demands, while anti-tumor M1 macrophages use glycolysis as their dominant metabolic source. Dysregulation in metabolic systems is a driving force of skewing macrophages from M1 toward M2 phenotypical state. Hyperactive M1 macrophages, for instance, release metabolic products that are contributed to M2 macrophage polarization. Thus, metabolic remodeling through reinstating normalization in metabolic systems can be an effective tool in cancer therapy. The key focus of this review is over metabolic systems in macrophages and factors influencing their metabolic acquisition and reprogramming in cancer, as well as discussing bout strategies to adjust macrophage metabolism and reeducation toward M1-like phenotype.
    Keywords:  Tumor microenvironment (TME); glycolysis; hypoxia; hypoxia inducible factor (HIF); lactate; macrophage; metabolism; oxidative phosphorylation (OXPHOS)
    DOI:  https://doi.org/10.1080/08830185.2022.2095374
  10. Biochemistry (Mosc). 2022 May;87(5): 413-424
    Oxidative Stress and Redox-Dependent Signaling in Prostate Cancer.
    Elena V Kalinina, Ludmila A Gavriliuk, Vadim S Pokrovsky.
      Tumor emergence and progression is complicated by the dual role of reactive oxygen species (ROS). Low concentrations of ROS are essential for many intracellular metabolic processes and cell proliferation, while excessive ROS generation disrupts the mechanisms of cancer suppression, leading to the cell damage and death. A long-term imbalance in the ROS/antioxidant ratio and upregulation of the ROS generation due to the reduced efficacy of the antioxidant defense system cause chronic oxidative stress resulting in the damage of proteins, lipid, and DNA molecules and cancer development. Numerous data demonstrate that prostate cancer (the most common cancer in males) is associated with the development of oxidative stress. However, the reasons for the emergence of prostate cancer, as well as changes in the redox signaling and cellular redox homeostasis in this disease, are still poorly understood. The review examines the role of prooxidant and antioxidant enzyme systems, the imbalance in their activity leading to the oxidative stress development, changes in the key components of redox signaling, and the role of microRNAs in the modulation of redox status of cancer cells in prostate cancer.
    Keywords:  NF-κB; Nrf2; antioxidant and prooxidant enzymes; microRNA; oxidative stress; prostate cancer; redox-dependent signaling; transcription factors
    DOI:  https://doi.org/10.1134/S0006297922050030
  11. Neurochem Res. 2022 Jul 05.
    Review on the Therapeutic Potential of Curcumin and its Derivatives on Glioma Biology.
    Malihe Mohamadian, Seyed Sajad Ahmadi, Afsane Bahrami, Gordon A Ferns.
      Gliomas are common and aggressive brain tumors that carry a poor prognosis. The current multimodal therapeutic option for glioma includes surgery subsequently temozolomide chemotherapy and/or radiation; but gliomas are often associated with multidrug resistance, intensive adverse events, and tumor relapse. Thus, novel interventions that can enhance successful chemo-prevention and overcome therapeutic resistance are urgently needed. Phytochemicals have several biological properties with multi-target sites and relatively limited degrees of toxicity. Curcumin is a natural polyphenolic compound with several anti-tumor effects which potentially inhibit tumor growth, development, proliferation, invasion, dissemination, and angiogenesis in different human malignancies. Experimental model studies have demonstrated that curcumin attenuates glioma cell viability by G2/M cell cycle arrest, apoptosis, induction of autophagy, gene expression alteration, and disruption of multi-molecular pathways. Moreover, curcumin has been reported to re-sensitize cancer to chemotherapeutics as well as augment the effect of radiotherapy on glioma cells. In this review, we have provided an update on the in vitro and in vivo effects of curcumin-based therapy on gliomas. We have also discussed the use of curcumin in combination therapies, its effectiveness on drug-resistant cells, and new formulations of curcumin in the treatment of gliomas.
    Keywords:  Apoptosis; Brain tumor; PI3K; Temozolomide; Turmeric
    DOI:  https://doi.org/10.1007/s11064-022-03666-1
  12. Cancer Drug Resist. 2022 ;5(2): 339-343
    Natural bioactive compounds: a potential therapeutic strategy to sensitize bladder cancer to cisplatin treatment?
    Vicenç Ruiz de Porras.
      Bladder cancer (BC) is the tenth most common cancer, and its incidence is steadily rising worldwide, with the highest rates in developed countries. Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the standard therapy for patients with muscle-invasive bladder cancer. However, less than 50% of patients initially respond to this treatment and nearly all of them eventually develop resistance, which is an important barrier to long-term survival. Therefore, there is an urgent need to understand the mechanisms of cisplatin resistance in BC and develop ways to counteract them. Several preclinical studies have demonstrated that naturally derived bioactive compounds, such as phytochemicals and flavonoids, can enhance the antitumor activity of cisplatin, with minimal side effects, by targeting different pathways involved in cisplatin sensitivity and resistance. However, their poor bioavailability has been one of the main problems for their successful introduction into clinical practice. At present, however, many new formulations with greatly increased bioavailability are under study in several clinical trials with encouraging results.
    Keywords:  Bladder cancer; bioavailability; chemoresistance; cisplatin; curcumin; muscle-invasive bladder cancer; natural products
    DOI:  https://doi.org/10.20517/cdr.2022.02
  13. Int J Biol Macromol. 2022 Jul 04. pii: S0141-8130(22)01414-3. [Epub ahead of print]
    Chitosan-modified nanocarriers as carriers for anticancer drug delivery: Promises and hurdles.
    Fahad Saad Alhodieb, Md Abul Barkat, Harshita Abul Barkat, Hazrina Ab Hadi, Muhammed Idrees Khan, Fauzia Ashfaq, Mohammad Akhlaquer Rahman, Mohd Zaheen Hassan.
      With the advent of drug delivery, various polymeric materials are being explored to fabricate numerous nanocarriers. Each polymer is associated with a few characteristics attributes which further facilitate its usage in drug delivery. One such polymer is chitosan (CS), which is extensively employed to deliver a variety of drugs to various targets, especially to cancer cells. The desired properties like biological origin, bio-adhesive, biocompatibility, the scope of chemical modification, biodegradability and controlled drug release make it a highly rough after polymer in pharmaceutical nanotechnology. The present review attempts to compile various chemical modifications on CS and showcase the outcomes of the derived nanocarriers, especially in cancer chemotherapy and drug delivery.
    Keywords:  Biocompatibility; Biodegradability; Chemotherapy; Chitin; Derivatives; Micelles; Nanoparticles; Nanotechnology
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.06.201
  14. Molecules. 2022 Jun 23. pii: 4045. [Epub ahead of print]27(13):
    pH-Responsive Hydrogel Beads Based on Alginate, κ-Carrageenan and Poloxamer for Enhanced Curcumin, Natural Bioactive Compound, Encapsulation and Controlled Release Efficiency.
    Katarina S Postolović, Milan D Antonijević, Biljana Ljujić, Marina Miletić Kovačević, Marina Gazdić Janković, Zorka D Stanić.
      Polyphenolic compounds are used for treating various diseases due to their antioxidant and anticancer properties. However, utilization of hydrophobic compounds is limited due to their low bioavailability. In order to achieve a greater application of hydrophobic bioactive compounds, hydrogel beads based on biopolymers can be used as carriers for their enhanced incorporation and controlled delivery. In this study, beads based on the biopolymers-κ-carrageenan, sodium alginate and poloxamer 407 were prepared for encapsulation of curcumin. The prepared beads were characterized using IR, SEM, TGA and DSC. The curcumin encapsulation efficiency in the developed beads was 95.74 ± 2.24%. The release kinetics of the curcumin was monitored in systems that simulate the oral delivery (pH 1.2 and 7.4) of curcumin. The drug release profiles of the prepared beads with curcumin indicated that the curcumin release was significantly increased compared with the dissolution of curcumin itself. The cumulative release of curcumin from the beads was achieved within 24 h, with a final release rate of 12.07% (gastric fluid) as well as 81.93% (intestinal fluid). Both the in vitro and in vivo studies showed that new hydrogel beads based on carbohydrates and poloxamer improved curcumin's bioavailability, and they can be used as powerful carriers for the oral delivery of different hydrophobic nutraceuticals.
    Keywords:  alginate; controlled release; curcumin; hydrogel beads; oral delivery; poloxamer; κ-carrageenan
    DOI:  https://doi.org/10.3390/molecules27134045
  15. Colloids Surf B Biointerfaces. 2022 Jun 27. pii: S0927-7765(22)00345-9. [Epub ahead of print]217 112662
    pH-stable polymersome as nanocarrier for post-loaded rose bengal in photodynamic therapy.
    K Sztandera, M Gorzkiewicz, X Wang, S Boye, D Appelhans, B Klajnert-Maculewicz.
      Photodynamic therapy is one of the best alternatives to chemo-, radio- or surgical therapy, as it is noninvasive and causes no severe side effects. The mechanism of photodynamic therapy involves activation of the drug (photosensitizer) with light of appropriate wavelength, which combined with molecular oxygen, leads to production of reactive oxygen species. This starts a cascade of reactions leading to cell death. Thus, the efficiency of this therapy is based mainly on the properties of a photosensitizer, including singlet oxygen yield and accumulation in the tumor area. Current research is aimed at applying nanosystems for the improvement of availability and photodynamic properties of photosensitizers. In order to improve the activity and increase photodynamic potential of rose bengal, one of the most promising drugs in anticancer photodynamic therapy, several drug delivery systems were developed. Among them, polymersomes represent a group of innovative polymeric vesicles mimicking membranous cell structures. Polymersomes are nanosystems made of amphiphilic block copolymers, possessing a spherical, liposome-like architecture. Within this study we present biophysical and in vitro biological characterization of this novel pH-stable nanosystem, which due to the improvement of singlet oxygen and reactive oxygen species (ROS) production by rose bengal is a good candidate for nanocarrier in photodynamic therapy.
    Keywords:  Photodynamic therapy; Polymersome; Rose bengal; Skin cancer
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112662
  16. Photodiagnosis Photodyn Ther. 2022 Jun 29. pii: S1572-1000(22)00277-0. [Epub ahead of print] 102991
    Simultaneous chemotherapy/sonodynamic therapy of the melanoma cancer cells using a gold-paclitaxel nanostructure.
    N Zahraie, G Perota, R Dehdari Vais, N Sattarahmady.
      Nanodrug delivery systems are novel strategies for tumor treatment since delivery of chemotherapy drugs such as paclitaxel (PTX) is associated with substantial challenges due to its poor aqueous solubility. In addition, sonodynamic therapy (SDT) is a promising new approach that can increase the uptake, accumulation, and dispersion of desirable amounts of the drugs by activating sonosensitizer and enhancing cell membrane permeability. Herein, gold-paclitaxel nanoparticles (Au-PTX NPs) were synthesized and characterized to evaluate the cytotoxicity toward C540 cancer cells in comparison of free PTX, AuNPs, and AuNPs+free PTX in the absence and presence of ultrasound radiation. Evidence shows that AuNPs have a median diameter size of 95.0±15.4, while the size of Au-PTX NPs is roughly 219.7±40.4 nm. Negative zeta-potential results indicate high stability and good dispersion of nanoparticles. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay results revealed that Au-PTX NPs increased the cytotoxicity compared to other treatment groups that ensure the great potential of AuNPs as a promising nano-carrier for PTX drug delivery. Moreover, the viability of C540 cells treated by Au-PTX NPs under ultrasound radiation was decreased significantly by generating more reactive oxygen species (ROS) upon STD, with representing synergism effects confirming the role of gold nanoparticles as an excellent sonosensitizer and the role of SDT as an adjunctive treatment method with chemotherapy.
    Keywords:  Chemotherapeutic drug; Drug delivery; Malignant melanoma; Nanogold; Sonodynamic therapy; Taxol
    DOI:  https://doi.org/10.1016/j.pdpdt.2022.102991
  17. Colloids Surf B Biointerfaces. 2022 Jun 30. pii: S0927-7765(22)00359-9. [Epub ahead of print]217 112676
    Multifunctional active ingredient-based delivery systems for skincare formulations: A review.
    Marie-Carole Kouassi, Michel Grisel, Ecaterina Gore.
      Nowadays, there is a growing demand for effective cosmetic skincare products that can address the specific skin problems of consumers. Delivery systems play an important role in the effective action of cosmetic skincare formulations. Delivery systems are attractive and smart technologies used as carriers for cosmetic ingredients, which are sensitive to various physical factors such as light, oxygen, pH and temperature. Delivery systems offer several advantages: transport and protection of sensitive active compounds, controlled and targeted release of active ingredients. Several delivery systems, varying in chemical composition, with adaptable physicochemical characteristics (size, morphology, zeta potential, structure) as well as great advantages as carriers, are developed and described in the literature. This article reviews the current cosmetic active ingredients used in skincare products due to their beneficial properties such as antioxidant, anti-aging, photo-protective, anti-inflammatory, anti-microbial, etc.). In addition, the main advantages of several classes of delivery systems (emulsions, lipid nanoparticles, polymeric particles) are described, as well as some recent approaches used to ensure their efficacy (long-term stability, controlled release of the active, skin penetration/permeation) are reviewed. Finally, new trends to be considered for the development of delivery systems and cosmetic formulations are discussed.
    Keywords:  Cosmetic actives; Delivery systems; Skin damage; Skincare formulations
    DOI:  https://doi.org/10.1016/j.colsurfb.2022.112676
  18. Front Pharmacol. 2022 ;13 886198
    Co-Targeting Tumor Angiogenesis and Immunosuppressive Tumor Microenvironment: A Perspective in Ethnopharmacology.
    Jianbo Zhou, Li Wang, Cheng Peng, Fu Peng.
      Tumor angiogenesis is one of the most important processes of cancer deterioration via nurturing an immunosuppressive tumor environment (TME). Targeting tumor angiogenesis has been widely accepted as a cancer intervention approach, which is also synergistically associated with immune therapy. However, drug resistance is the biggest challenge of anti-angiogenesis therapy, which affects the outcomes of anti-angiogeneic agents, and even combined with immunotherapy. Here, emerging targets and representative candidate molecules from ethnopharmacology (including traditional Chinese medicine, TCM) have been focused, and they have been proved to regulate tumor angiogenesis. Further investigations on derivatives and delivery systems of these molecules will provide a comprehensive landscape in preclinical studies. More importantly, the molecule library of ethnopharmacology meets the viability for targeting angiogenesis and TME simultaneously, which is attributed to the pleiotropy of pro-angiogenic factors (such as VEGF) toward cancer cells, endothelial cells, and immune cells. We primarily shed light on the potentiality of ethnopharmacology against tumor angiogenesis, particularly TCM. More research studies concerning the crosstalk between angiogenesis and TME remodeling from the perspective of botanical medicine are awaited.
    Keywords:  delivery system; immunosuppressive microenvironment; molecular intervention; targets; tumor angiogenesis
    DOI:  https://doi.org/10.3389/fphar.2022.886198
  19. Nutr Neurosci. 2022 Jul 05. 1-14
    The place of a ketogenic diet in the treatment of resistant epilepsy: a comprehensive review.
    Ebru Cicek, Nevin Sanlier.
       OBJECTIVE: The ketogenic diet (KD) is a high-fat, adequate-protein, and low-carb diet. Ketone bodies increase in the blood due to low carbohydrate content and high-fat content in the diet. The most important feature of the ketogenic diet is that it causes the production of ketone bodies in the liver. Ketone bodies are an alternative fuel to glucose for the brain and form the structure necessary for the cell membrane and biosynthesis of triglycerides. The ketogenic diet provides evidence on seizure control with anticonvulsant effects. In this review, the positive/negative effects of KD on seizure control, place, importance, quality of life, cognition, and behavior in the treatment of resistant epilepsy were examined.
    METHODS: Scientific information on the subject was obtained from the literature accessed through databases such as MEDLINE, Embase, Web of Science, Cochrane Central, www.ClinicalTrials.gov, PubMed, Science Direct, and Google Scholar.
    RESULTS: Although it has started to be used as a treatment method in many diseases today, the main area of effect of KD is drug-resistant epilepsy. In order for the ketogenic diet to be successful in these patients, it is necessary to choose the appropriate patient, medical treatment and diet plan, inform the patient sufficiently, and perform frequent monitoring in accordance with the follow-up criteria. It is argued that KD is one of the most effective treatments for epilepsy.
    CONCLUSION: The fact that KDs generally have a restricted diet pattern, the need for supplementation, biochemical findings and possible side effects raise the issue of diet sustainability. More clinical studies are needed to generalize.
    Keywords:  Child; diet education; follow-up; ketogenic diet; ketogenic diet planning; resistant epilepsy; seizure control; types of the ketogenic diet
    DOI:  https://doi.org/10.1080/1028415X.2022.2095819
  20. Oxid Med Cell Longev. 2022 ;2022 4831833
    Flavonoids Targeting the mTOR Signaling Cascades in Cancer: A Potential Crosstalk in Anti-Breast Cancer Therapy.
    Yaseen Hussain, Haroon Khan, Waqas Alam, Michael Aschner, Abdullah, Khalaf F Alsharif, Luciano Saso.
      Cancer is one of the leading causes of death worldwide. Breast cancer is the second leading cause of death in women, with triple-negative breast cancer being the most lethal and aggressive form. Conventional therapies, such as radiation, surgery, hormonal, immune, gene, and chemotherapy, are widely used, but their therapeutic efficacy is limited due to adverse side effects, toxicities, resistance, recurrence, and therapeutic failure. Many molecules have been identified and investigated as potential therapeutic agents for breast cancer, with a focus on various signaling pathways. Flavonoids are a versatile class of phytochemicals that have been used in cancer treatment to overcome issues with traditional therapies. Cell proliferation, growth, apoptosis, autophagy, and survival are all controlled by mammalian target of rapamycin (mTOR) signaling. Flavonoids target mTOR signaling in breast cancer, and when this signaling pathway is regulated or deregulated, various signaling pathways provide potential therapeutic means. The role of various flavonoids as phytochemicals in targeting mTOR signaling pathways in breast cancer is highlighted in this review.
    DOI:  https://doi.org/10.1155/2022/4831833
  21. Sci Rep. 2022 Jul 04. 12(1): 11310
    Redox-sensitive doxorubicin liposome: a formulation approach for targeted tumor therapy.
    Elaheh Mirhadi, Mohammad Mashreghi, Anis Askarizadeh, Amin Mehrabian, Seyedeh Hoda Alavizadeh, Leila Arabi, Ali Badiee, Mahmoud Reza Jaafari.
      In this study redox-sensitive (RS) liposomes manufactured using 10,10'-diselanediylbis decanoic acid (DDA), an organoselenium RS compound, to enhance the therapeutic performance of doxorubicin (Dox). The DDA structure was confirmed by 1H NMR and LC-MS/MS. Various liposomal formulations (33 formulations) were prepared using DOPE, Egg PC, and DOPC with Tm ˂ 0 and DDA. Some formulations had mPEG2000-DSPE and cholesterol. After extrusion, the external phase was exchanged with sodium bicarbonate to create a pH gradient. Then, Dox was remotely loaded into liposomes. The optimum formulations indicated a burst release of 30% in the presence of 0.1% hydrogen peroxide at pH 6.5, thanks to the redox-sensitive role of DDA moieties; conversely, Caelyx (PEGylated liposomal Dox) showed negligible release at this condition. RS liposomes consisting of DOPE/Egg PC/DDA at 37.5 /60/2.5% molar ratio, efficiently inhibited C26 tumors among other formulations. The release of Dox from RS liposomes in the TME through the DDA link fracture triggered by ROS or glutathione is seemingly the prerequisite for the formulations to exert their therapeutic action. These findings suggest the potential application of such intelligent formulations in the treatment of various malignancies where the TME redox feature could be exploited to achieve an improved therapeutic response.
    DOI:  https://doi.org/10.1038/s41598-022-15239-x
  22. Front Pharmacol. 2022 ;13 908077
    Review of the Effects and Mechanism of Curcumin in the Treatment of Inflammatory Bowel Disease.
    Yuan Lin, Hengjian Liu, Lingling Bu, Chen Chen, Xiaofeng Ye.
      Curcumin is extracted from the rhizomes of Curcuma longa L. It is now widely used in food processing, cosmetics, dyes, etc. Current researching indicates that curcumin has high medical value, including anti-inflammatory, antioxidant, anti-tumor, anti-apoptotic, anti-fibrosis, immune regulation and other effects, and can be used to treat a variety of diseases. Inflammatory bowel disease (IBD) is a nonspecific inflammatory disease of the intestine including Crohn's disease (CD) and ulcerative colitis (UC). The drug treatment effect is often limited and accompanied by side effects. A large number of basic and clinical studies have shown that curcumin has the effect of treating IBD and also can maintain the remission of IBD. In this review, the research of curcumin on IBD in recent years is summarized in order to provide reference for further research and application of curcumin.
    Keywords:  IBD; anti-inflammatory actvity; curcumin; dietary supplements; immune regulation
    DOI:  https://doi.org/10.3389/fphar.2022.908077
  23. AAPS PharmSciTech. 2022 Jul 08. 23(6): 187
    Nanoencapsulation of Tea Catechins for Enhancing Skin Absorption and Therapeutic Efficacy.
    Ibrahim A Aljuffali, Chih-Hung Lin, Shih-Chun Yang, Ahmed Alalaiwe, Jia-You Fang.
      Tea catechins are a group of flavonoids that show many bioactivities. Catechins have been extensively reported as a potential treatment for skin disorders, including skin cancers, acne, photoaging, cutaneous wounds, scars, alopecia, psoriasis, atopic dermatitis, and microbial infection. In particular, there has been an increasing interest in the discovery of cosmetic applications using catechins as the active ingredient because of their antioxidant and anti-aging activities. However, active molecules with limited lipophilicity have difficulty penetrating the skin barrier, resulting in low bioavailability. Nevertheless, topical application is a convenient method for delivering catechins into the skin. Nanomedicine offers an opportunity to improve the delivery efficiency of tea catechins and related compounds. The advantages of catechin-loaded nanocarriers for topical application include high catechin loading efficiency, sustained or prolonged release, increased catechin stability, improved bioavailability, and enhanced accumulation or targeting to the nidus. Further, various types of nanoparticles, including liposomes, niosomes, micelles, lipid-based nanoparticles, polymeric nanoparticles, liquid crystalline nanoparticles, and nanocrystals, have been employed for topical catechin delivery. These nanoparticles can improve catechin permeation via close skin contact, increased skin hydration, skin structure disorganization, and follicular uptake. In this review, we describe the catechin skin delivery approaches based on nanomedicine for treating skin disorders. We also provide an in-depth description of how nanoparticles effectively improve the skin absorption of tea catechins and related compounds, such as caffeine. Furthermore, we summarize the possible future applications and the limitations of nanocarriers for topical delivery at the end of this review article.
    Keywords:  Cosmetic; Flavonoid; Nanoparticle; Skin delivery; Tea catechin
    DOI:  https://doi.org/10.1208/s12249-022-02344-3
  24. Front Oncol. 2022 ;12 881252
    Role of HIF-1α/ERRα in Enhancing Cancer Cell Metabolism and Promoting Resistance of Endometrial Cancer Cells to Pyroptosis.
    Pingping Su, Lirui Yu, Xiaodan Mao, Pengming Sun.
      Oxygen is critical to energy metabolism, and tumors are often characterized by a hypoxic microenvironment. Owing to the high metabolic energy demand of malignant tumor cells, their survival is promoted by metabolic reprogramming in the hypoxic microenvironment, which can confer tumor cell resistance to pyroptosis. Pyroptosis resistance can inhibit anti-tumor immunity and promote the development of malignant tumors. Hypoxia inducible factor-1α (HIF-1α) is a key regulator of metabolic reprogramming in tumor cells, and estrogen-related receptor α (ERRα) plays a key role in regulating cellular energy metabolism. Therefore, the close interaction between HIF-1α and ERRα influences the metabolic and functional changes in cancer cells. In this review, we summarize the reprogramming of tumor metabolism involving HIF-1α/ERRα. We review our understanding of the role of HIF-1α/ERRα in promoting tumor growth adaptation and pyroptosis resistance, emphasize its key role in energy homeostasis, and explore the regulation of HIF-1α/ERRα in preventing and/or treating endometrial carcinoma patients. This review provides a new perspective for the study of the molecular mechanisms of metabolic changes in tumor progression.
    Keywords:  ERRα; HIF-1α; endometrial cancer; glucose metabolism; lipid metabolism
    DOI:  https://doi.org/10.3389/fonc.2022.881252
  25. JAMA Oncol. 2022 Jul 07.
    Plant-Based and Ketogenic Diets As Diverging Paths to Address Cancer: A Review.
    Urvi A Shah, Neil M Iyengar.
       Importance: As the incidence of cancer and metabolic disorders, such as obesity, concurrently rise, there has been increasing awareness of the pervasive effect of nutrition. The whole foods plant-based diet (WFPBD) and ketogenic diet (KD) have gained popularity in oncology, and this topic is increasingly permeating clinical dialogue.
    Observations: Dietary intake is associated with multiple pathways involved in carcinogenesis and tumor progression. Consumption of a plant-enriched diet is associated with reduced cancer incidence and is recommended by dietary guidelines for cancer prevention. Despite a starkly different nutrient composition, a WFPBD and KD can be associated with weight loss, decreased inflammation, and decreased insulin levels. In addition, a WFPBD is associated with increased fiber, phytochemicals, and butyrate levels and decreased insulin-like growth factor 1 levels, whereas a KD exerts potential anticancer effects by increasing β hydroxybutyrate levels. A KD may be of interest in select, less common settings, such as tumors treated with phosphatidylinositol 3-kinase inhibitors, which induce hyperinsulinemia and hyperglycemia. Completed interventional trials have focused on increasing fruit and vegetable intake or reducing fat intake but have not specifically tested WFPBD or KD for cancer prevention or treatment. Currently available data support plant-based diets as opposed to KD as part of a lifestyle associated with reduced cancer risk. In the postdiagnosis setting, there are currently no rigorously tested approaches that support the recommendation of any diet to treat cancer.
    Conclusions and Relevance: The results of this review suggest that the collective evidence supports plant-enriched diets vs KD for the reduction of cancer risk and the improvement of metabolic disorders in survivors. Additional prospective randomized clinical trials are needed to encourage use of dietary modification across the cancer continuum. Rigorous trial designs that adapt classical oncologic end points may identify populations that are likely to benefit from starkly contrasting diets. Current data support prioritization of plant-based diets, and future data could further personalize dietary recommendations in cancer populations.
    DOI:  https://doi.org/10.1001/jamaoncol.2022.1769
  26. Cancer Metab. 2022 Jul 04. 10(1): 10
    Global metabolic alterations in colorectal cancer cells during irinotecan-induced DNA replication stress.
    Christian Marx, Jürgen Sonnemann, Oliver D K Maddocks, Lisa Marx-Blümel, Mandy Beyer, Doerte Hoelzer, René Thierbach, Claudia Maletzki, Michael Linnebacher, Thorsten Heinzel, Oliver H Krämer.
       BACKGROUND: Metabolic adaptations can allow cancer cells to survive DNA-damaging chemotherapy. This unmet clinical challenge is a potential vulnerability of cancer. Accordingly, there is an intense search for mechanisms that modulate cell metabolism during anti-tumor therapy. We set out to define how colorectal cancer CRC cells alter their metabolism upon DNA replication stress and whether this provides opportunities to eliminate such cells more efficiently.
    METHODS: We incubated p53-positive and p53-negative permanent CRC cells and short-term cultured primary CRC cells with the topoisomerase-1 inhibitor irinotecan and other drugs that cause DNA replication stress and consequently DNA damage. We analyzed pro-apoptotic mitochondrial membrane depolarization and cell death with flow cytometry. We evaluated cellular metabolism with immunoblotting of electron transport chain (ETC) complex subunits, analysis of mitochondrial mRNA expression by qPCR, MTT assay, measurements of oxygen consumption and reactive oxygen species (ROS), and metabolic flux analysis with the Seahorse platform. Global metabolic alterations were assessed using targeted mass spectrometric analysis of extra- and intracellular metabolites.
    RESULTS: Chemotherapeutics that cause DNA replication stress induce metabolic changes in p53-positive and p53-negative CRC cells. Irinotecan enhances glycolysis, oxygen consumption, mitochondrial ETC activation, and ROS production in CRC cells. This is connected to increased levels of electron transport chain complexes involving mitochondrial translation. Mass spectrometric analysis reveals global metabolic adaptations of CRC cells to irinotecan, including the glycolysis, tricarboxylic acid cycle, and pentose phosphate pathways. P53-proficient CRC cells, however, have a more active metabolism upon DNA replication stress than their p53-deficient counterparts. This metabolic switch is a vulnerability of p53-positive cells to irinotecan-induced apoptosis under glucose-restricted conditions.
    CONCLUSION: Drugs that cause DNA replication stress increase the metabolism of CRC cells. Glucose restriction might improve the effectiveness of classical chemotherapy against p53-positive CRC cells. The topoisomerase-1 inhibitor irinotecan and other chemotherapeutics that cause DNA damage induce metabolic adaptations in colorectal cancer (CRC) cells irrespective of their p53 status. Irinotecan enhances the glycolysis and oxygen consumption in CRC cells to deliver energy and biomolecules necessary for DNA repair and their survival. Compared to p53-deficient cells, p53-proficient CRC cells have a more active metabolism and use their intracellular metabolites more extensively. This metabolic switch creates a vulnerability to chemotherapy under glucose-restricted conditions for p53-positive cells.
    Keywords:  Adaptation; Colorectal cancer; Glucose; Irinotecan; Metabolism; Warburg effect; p53
    DOI:  https://doi.org/10.1186/s40170-022-00286-9
  27. Environ Sci Pollut Res Int. 2022 Jul 06.
    Fullerenes for the treatment of cancer: an emerging tool.
    Neha Benedicta Fernandes, Raghavendra Udaya Kumar Shenoy, Mandira Kashi Kajampady, Cleona E M DCruz, Rupesh K Shirodkar, Lalit Kumar, Ruchi Verma.
      Cancer is a most common cause of mortality globally. Available medicines possess severe side effects owing to their non-specific targeting. Hence, there is a need of an alternative in the healthcare system that should have high efficacy with the least side effects, also having the ability to achieve site-specific targeting and be reproducible. This is possible with the help of fullerenes. Fullerenes are having the unique physicochemical and photosensitizer properties. This article discusses the synthesis, functionalization, mechanism, various properties, and applications of C60 fullerenes in the treatment of cancer. The review article also addresses the various factors influencing the activity of fullerenes including the environmental conditions, toxicity profile, and future prospective.
    Keywords:  Biocompatibility; Biodegradability; Biosensing; Cancer therapy; Nanomedicine; Nanotechnology; Photodynamic therapy
    DOI:  https://doi.org/10.1007/s11356-022-21449-7
  28. Front Med (Lausanne). 2022 ;9 939424
    Role of Ginseng, Quercetin, and Tea in Enhancing Chemotherapeutic Efficacy of Colorectal Cancer.
    Linxian Zhao, Hongyu Zhao, Yongqing Zhao, Mingxiu Sui, Jinping Liu, Pingya Li, Ning Liu, Kai Zhang.
      As the most common gastrointestinal malignancy, colorectal cancer (CRC) remains a leading cause of cancer death worldwide. Although multimodal chemotherapy has effectively improved the prognosis of patients with CRC in recent years, severe chemotherapy-associated side effects and chemoresistance still greatly impair efficacy and limit its clinical application. In response to these challenges, an increasing number of traditional Chinese medicines have been used as synergistic agents for CRC administration. In particular, ginseng, quercetin, and tea, three common dietary supplements, have been shown to possess the potent capacity of enhancing the sensitivity of various chemotherapy drugs and reducing their side effects. Ginseng, also named "the king of herbs", contains a great variety of anti-cancer compounds, among which ginsenosides are the most abundant and major research objects of various anti-tumor studies. Quercetin is a flavonoid and has been detected in multiple common foods, which possesses a wide range of pharmacological properties, especially with stronger anti-cancer and anti-inflammatory effects. As one of the most consumed beverages, tea has become particularly prevalent in both West and East in recent years. Tea and its major extracts, such as catechins and various constituents, were capable of significantly improving life quality and exerting anti-cancer effects both in vivo and in vitro. In this review, we mainly focused on the adjunctive effects of the three herbs and their constituents on the chemotherapy process of CRC.
    Keywords:  chemoresistance; chemotherapy; colorectal cancer; ginseng; quercetin; tea
    DOI:  https://doi.org/10.3389/fmed.2022.939424
  29. Biochem Pharmacol. 2022 Jun 30. pii: S0006-2952(22)00253-2. [Epub ahead of print]202 115159
    Trabectedin suppresses escape from therapy-induced senescence in tumor cells by interfering with glutamine metabolism.
    Francesco Pacifico, Stefano Mellone, Maurizio D'Incalci, Mariano Stornaiuolo, Antonio Leonardi, Elvira Crescenzi.
      Conventional and targeted cancer therapies may induce a cellular senescence program termed therapy-induced senescence. However, unlike normal cells, cancer cells are able to evade the senescence cell cycle arrest and to resume proliferation, driving tumor recurrence after treatments. Cells that escape from therapy-induced senescence are characterized by a plastic, cancer stem cell-like phenotype, and recent studies are beginning to define their unique metabolic features, such as glutamine dependence. Here, we show that the antineoplastic drug trabectedin suppresses escape from therapy-induced senescence in all cell lines studied, and reduces breast cancer stem-like cells, at concentrations that do not affect the viability of senescent tumor cells. We demonstrate that trabectedin downregulates both the glutamine transporter SLC1A5 and glutamine synthetase, thereby interfering with glutamine metabolism. On the whole, our results indicate that trabectedin targets a glutamine-dependent cancer stem-like cell population involved in evasion from therapy-induced senescence and suggest a therapeutic potential for trabectedin combined with pro-senescence chemotherapy in tumor treatment.
    Keywords:  Escape; Glutamine; Glutamine synthetase; SLC1A5; Therapy-induced senescence; Trabectedin
    DOI:  https://doi.org/10.1016/j.bcp.2022.115159
  30. Polymers (Basel). 2022 Jun 28. pii: 2633. [Epub ahead of print]14(13):
    A Poly (Caprolactone)-Cellulose Nanocomposite Hydrogel for Transdermal Delivery of Hydrocortisone in Treating Psoriasis Vulgaris.
    Pierre P D Kondiah, Thankhoe A Rants'o, Sipho Mdanda, Lauwrence M Mohlomi, Yahya E Choonara.
      Psoriasis vulgaris (PV) is a common chronic disease, affecting much of the population. Hydrocortisone (HCT) is currently utilized as a PV treatment; however, it is associated with undesirable side effects. The aim of this research was to create a thermo-responsive nano-hydrogel delivery system. HCT-loaded sorbitan monostearate (SMS)-polycaprolactone (PCL) nanoparticles, encapsulated with thermo-responsive hydrogel carboxymethyl cellulose (CMC), were synthesized by applying the interfacial polymer-deposition method following solvent displacement. The nanoparticles' properties were evaluated employing Differential Scanning Colorimetry, Thermogravimetric Analysis, Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, Zeta sizer, Ultraviolet/Visual spectroscopy, and cytotoxicity testing. The nanoparticle sizes were 110.5 nm, with polydispersity index of 0.15 and zeta potential of -58.7 mV. A drug-entrapment efficacy of 76% was attained by the HCT-loaded SMS-PCL nanoparticles and in vitro drug-release profiles showed continuous drug release over a period of 24 hrs. Keratinocyte skin cells were treated with HCT-loaded SMS-PCL nanoparticles encapsulated with CMC; the results indicated that the synthesized drug-delivery system was less toxic to the keratinocyte cells compared to HCT. The combined trials and results from the formulation of HCT-loaded SMS-PCL nanoparticles encapsulated with CMC showed evidence that this hydrogel can be utilized as a potentially invaluable formulation for transdermal drug delivery of HCT, with improved efficacy and patient conformity.
    Keywords:  drug delivery; hydrogels; nanoparticles; polymers; psoriasis vulgaris
    DOI:  https://doi.org/10.3390/polym14132633
  31. Biomater Sci. 2022 Jul 05.
    Design and structural regulation of AIE photosensitizers for imaging-guided photodynamic anti-tumor application.
    Shaochuan Jia, Huanxiang Yuan, Rong Hu.
      In recent years, photodynamic therapy (PDT) has become one of the important therapeutic methods for treating cancer. Aggregation-induced emission (AIE) photosensitizers (PSs) overcome the aggregation-caused quenching (ACQ) effects of conventional PSs in aggregation or high concentration states, showing enhanced reactive oxygen species (ROS) generating capacity and improved therapeutic efficiency. Meanwhile, connecting different donor and acceptor groups gives the PSs a lower energy level and the absorption/emission of a long wavelength, which makes the PSs produce more ROS and penetrate deeper into the tissue for imaging. As a promising tool for achieving efficient PDT applications, numerous studies have demonstrated the advantages and potential medical applications of AIE PSs in the diagnosis and treatment of various diseases. Herein, we outline the research progress of AIE PSs with different representative structures in fluorescence imaging and photodynamic anti-tumor therapy, and expound the design strategy of the donor-acceptor (D-A) framework for constructing practical AIE PSs in the past three years. Furthermore, this review addresses the underlying challenges and opportunities of AIE PSs in PDT, aiming to grasp the striving directions of the next generation of AIE PSs.
    DOI:  https://doi.org/10.1039/d2bm00864e
  32. Int J Mol Sci. 2022 Jun 28. pii: 7156. [Epub ahead of print]23(13):
    Glioblastoma and Methionine Addiction.
    Mark L Sowers, Lawrence C Sowers.
      Glioblastoma is a fatal brain tumor with a bleak prognosis. The use of chemotherapy, primarily the alkylating agent temozolomide, coupled with radiation and surgical resection, has provided some benefit. Despite this multipronged approach, average patient survival rarely extends beyond 18 months. Challenges to glioblastoma treatment include the identification of functional pharmacologic targets as well as identifying drugs that can cross the blood-brain barrier. To address these challenges, current research efforts are examining metabolic differences between normal and tumor cells that could be targeted. Among the metabolic differences examined to date, the apparent addiction to exogenous methionine by glioblastoma tumors is a critical factor that is not well understood and may serve as an effective therapeutic target. Others have proposed this property could be exploited by methionine dietary restriction or other approaches to reduce methionine availability. However, methionine links the tumor microenvironment with cell metabolism, epigenetic regulation, and even mitosis. Therefore methionine depletion could result in complex and potentially undesirable responses, such as aneuploidy and the aberrant expression of genes that drive tumor progression. If methionine manipulation is to be a therapeutic strategy for glioblastoma patients, it is essential that we enhance our understanding of the role of methionine in the tumor microenvironment.
    Keywords:  epigenetics; glioblastoma; metabolism; methionine; therapeutic development; tumor microenvironment
    DOI:  https://doi.org/10.3390/ijms23137156
  33. J Control Release. 2022 Jul 05. pii: S0168-3659(22)00386-8. [Epub ahead of print]349 67-96
    An update on dual targeting strategy for cancer treatment.
    Yasamin Davatgaran Taghipour, Amir Zarebkohan, Roya Salehi, Fariborz Rahimi, Vladimir P Torchilin, Michael R Hamblin, Alexander Seifalian.
      The key issue in the treatment of solid tumors is the lack of efficient strategies for the targeted delivery and accumulation of therapeutic cargoes in the tumor microenvironment (TME). Targeting approaches are designed for more efficient delivery of therapeutic agents to cancer cells while minimizing drug toxicity to normal cells and off-targeting effects, while maximizing the eradication of cancer cells. The highly complicated interrelationship between the physicochemical properties of nanoparticles, and the physiological and pathological barriers that are required to cross, dictates the need for the success of targeting strategies. Dual targeting is an approach that uses both purely biological strategies and physicochemical responsive smart delivery strategies to increase the accumulation of nanoparticles within the TME and improve targeting efficiency towards cancer cells. In both approaches, either one single ligand is used for targeting a single receptor on different cells, or two different ligands for targeting two different receptors on the same or different cells. Smart delivery strategies are able to respond to triggers that are typical of specific disease sites, such as pH, certain specific enzymes, or redox conditions. These strategies are expected to lead to more precise targeting and better accumulation of nano-therapeutics. This review describes the classification and principles of dual targeting approaches and critically reviews the efficiency of dual targeting strategies, and the rationale behind the choice of ligands. We focus on new approaches for smart drug delivery in which synthetic and/or biological moieties are attached to nanoparticles by TME-specific responsive linkers and advanced camouflaged nanoparticles.
    Keywords:  Aptamer; Cancer; Drug delivery; Dual targeting; Ligands; Nanomaterials; Nanoparticle; Peptide; Receptor; Responsive linker; Stealth; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.jconrel.2022.06.044
  34. Cancer Lett. 2022 Jul 05. pii: S0304-3835(22)00298-1. [Epub ahead of print] 215814
    Exercise in cancer prevention and anticancer therapy: Efficacy, molecular mechanisms and clinical information.
    Chuanmei Zhu, Hongbo Ma, Anqi He, Yi Li, Chengqi He, Yong Xia.
      Modifiable lifestyle factors are the strongest determinants and major preventable causes of most type of cancer. Exercise has shown many beneficial effects in cancer prevention and anticancer treatment. However, the underlying mechanisms remain unclear. To contribute to our understanding of the role of exercise regulation in cancer and provide recommendations for future preclinical and clinical exercise oncology research, we examine the functions of exercise in cancer and its underlying mechanisms. In addition to reducing the incidence of cancer, exercise can enhance the efficacy of certain types of approved anticancer treatments (e.g., targeted therapy, immunotherapy, and radiotherapy) and reduce the symptoms/side effects of cancer and its treatment (e.g., fatigue, cancer cachexia, cognitive impairment, and depression). The mechanisms mediating these effects include the regulation of intratumoral angiogenesis, myokines, adipokines and their associated pathways, cancer metabolism, and anticancer immunity. Cancer rehabilitation guidelines advise cancer survivors to perform exercises. Many ongoing clinical trials have investigated the effects and mechanisms of exercise in cancer. This review supports the prescription of exercise for cancer prevention to sensitize cancer to anticancer therapy and manage associated symptoms and side effects after cancer diagnosis.
    Keywords:  Anticancer immunity; Cancer rehabilitation; Exercise-oncology; Intratumoral angiogenesis; Myokine and adipokine
    DOI:  https://doi.org/10.1016/j.canlet.2022.215814
  35. Molecules. 2022 Jul 04. pii: 4304. [Epub ahead of print]27(13):
    Pharmacological Properties of 4', 5, 7-Trihydroxyflavone (Apigenin) and Its Impact on Cell Signaling Pathways.
    Rameesha Abid, Shakira Ghazanfar, Arshad Farid, Samra Muhammad Sulaman, Maryam Idrees, Radwa Abdallnasser Amen, Muhammad Muzammal, Muhammad Khurram Shahzad, Mohamed Omar Mohamed, Alaa Ashraf Khaled, Waqas Safir, Ifra Ghori, Abdelbaset Mohamed Elasbali, Bandar Alharbi.
      Plant bioactive compounds, particularly apigenin, have therapeutic potential and functional activities that aid in the prevention of infectious diseases in many mammalian bodies and promote tumor growth inhibition. Apigenin is a flavonoid with low toxicities and numerous bioactive properties due to which it has been considered as a traditional medicine for decades. Apigenin shows synergistic effects in combined treatment with sorafenib in the HepG2 human cell line (HCC) in less time and statistically reduces the viability of tumor cells, migration, gene expression and apoptosis. The combination of anti-cancerous drugs with apigenin has shown health promoting potential against various cancers. It can prevent cell mobility, maintain the cell cycle and stimulate the immune system. Apigenin also suppresses mTOR activity and raises the UVB-induced phagocytosis and reduces the cancerous cell proliferation and growth. It also has a high safety threshold, and active (anti-cancer) doses can be gained by consuming a vegetable and apigenin rich diet. Apigenin also boosted autophagosome formation, decreased cell proliferation and activated autophagy by preventing the activity of the PI3K pathway, specifically in HepG2 cells. This paper provides an updated overview of apigenin's beneficial anti-inflammatory, antibacterial, antiviral, and anticancer effects, making it a step in the right direction for therapeutics. This study also critically analyzed the effect of apigenin on cancer cell signaling pathways including the PI3K/AKT/MTOR, JAK/STAT, NF-κB and ERK/MAPK pathways.
    Keywords:  ROS; apigenin; apoptosis; flavonoid; signaling cascades
    DOI:  https://doi.org/10.3390/molecules27134304
  36. Front Neurosci. 2022 ;16 899612
    Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer's Disease.
    Matthew K Taylor, Debra K Sullivan, Jessica E Keller, Jeffrey M Burns, Russell H Swerdlow.
      Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by clinical decline in memory and other cognitive functions. A classic AD neuropathological hallmark includes the accumulation of amyloid-β (Aβ) plaques, which may precede onset of clinical symptoms by over a decade. Efforts to prevent or treat AD frequently emphasize decreasing Aβ through various mechanisms, but such approaches have yet to establish compelling interventions. It is still not understood exactly why Aβ accumulates in AD, but it is hypothesized that Aβ and other downstream pathological events are a result of impaired bioenergetics, which can also manifest prior to cognitive decline. Evidence suggests that individuals with AD and at high risk for AD have functional brain ketone metabolism and ketotherapies (KTs), dietary approaches that produce ketone bodies for energy metabolism, may affect AD pathology by targeting impaired brain bioenergetics. Cognitively normal individuals with elevated brain Aβ, deemed "preclinical AD," and older adults with peripheral metabolic impairments are ideal candidates to test whether KTs modulate AD biology as they have impaired mitochondrial function, perturbed brain glucose metabolism, and elevated risk for rapid Aβ accumulation and symptomatic AD. Here, we discuss the link between brain bioenergetics and Aβ, as well as the potential for KTs to influence AD risk and progression.
    Keywords:  Alzheimer’s disease; amyloid; exogenous ketones; ketogenic diet; ketotherapy; medium chain triglyceride (MCT); mitochondria
    DOI:  https://doi.org/10.3389/fnins.2022.899612
  37. Curr Drug Metab. 2022 Jun 30.
    Pharmaceutical Nanoemulsion System: A Strategy to Enhance the Bioavailability of Drugs.
    Shobhit Kumar, Parul Waliyan, Rakesh Pahwa, Javed Ali, Sanjula Baboota, Shrestha Sharma, Faheem Hyder Pottoo.
      Nanoemulsions have attracted tremendous consideration of scientific community across the globe in recent years as the most promising strategy of drug delivery, targeting potential, bioavailability enhancement etc. These are efficient heterogeneous dispersions comprising of oily and aqueous phases, and can be stabilized by surfactants and co-surfactants. Such fascinating and sophisticated systems can improve the bioavailability of various therapeutic entities along with precise targeting of specific organs. Additionally, nano-sized emulsions of various actives offer numerous salient benefits such as effective release of drug, extended efficacy, controlled drug utilization, lesser adverse effects and fortification of drug from degradation whether enzymatic or oxidative. Nanotech based emulsions also facilitate remarkable and wonderful pharmaceutical and cosmeceutical applications through myriad technological approaches. By perfectly controlling the composition, arrangement of nanoemulsion ingredients and technique of preparation, nanoemulsions with desired attributes and high performance can be developed. The rationale of this review is to represent salient advantages, formulation techniques, characterization aspects and promising applications of various multitalented and impressive nanoemulsions. Current marketed formulations, recent patents, significant clinical practices etc. in the vistas of nanoemulsion technology are also highlighted in the present manuscript. This review also provides deep insights on the precise attributes, utilization facts and stability aspects of various nanoemulsions. Elucidation of scientific advancements in conjunction with encouraging findings concerning the future perspectives and challenges of nanoemulsions has also been discussed. Relevant literature for this manuscript was collected from comprehensive and systematic search of databases for example PubMed, Science Direct, Google Scholar and others using specific keyword combination, including "pharmaceutical nanoemulsions", "nanoemulsions for drug delivery", "applications of nanoemulsions" and several others.
    Keywords:  Nanoemulsions; bioavailability enhancement; drug delivery; hydrophobic bioactives; improved solubility; salient applications
    DOI:  https://doi.org/10.2174/1389200223666220630161615
  38. Semin Cancer Biol. 2022 Jun 30. pii: S1044-579X(22)00155-9. [Epub ahead of print]
    Benefits and limitations of nanomedicine treatment of brain cancers and age-dependent neurodegenerative disorders.
    Margarita E Neganova, Yulia R Aleksandrova, Olga A Sukocheva, Sergey G Klochkov.
      The treatment of central nervous system (CNS) malignancies, including brain cancers, is limited by a number of obstructions, including the blood-brain barrier (BBB), the heterogeneity and high invasiveness of tumors, the inaccessibility of tissues for early diagnosis and effective surgery, and anti-cancer drug resistance. Therapies employing nanomedicine have been shown to facilitate drug penetration across the BBB and maintain biodistribution and accumulation of therapeutic agents at the desired target site. The application of lipid-, polymer-, or metal-based nanocarriers represents an advanced drug delivery system for a growing group of anti-cancer chemicals. The nanocarrier surface is designed to contain an active ligand (cancer cell marker or antibody)-binding structure which can be modified to target specific cancer cells. Glioblastoma, ependymoma, neuroblastoma, medulloblastoma, and primary CNS lymphomas were recently targeted by easily absorbed nanocarriers. The metal- (such as transferrin drug-loaded systems), polymer- (nanocapsules and nanospheres), or lipid- (such as sulfatide-containing nanoliposomes)-based nano-vehicles were loaded with apoptosis- and/or ferroptosis-stimulating agents and demonstrated promising anti-cancer effects. This review aims to discuss effective nanomedicine approaches designed to overcome the current limitations in the therapy of brain cancers and age-dependent neurodegenerative disorders. To accent current obstacles for successful CNS-based cancer therapy, we discuss nanomedicine perspectives and limitations of nanodrug use associated with the specificity of nervous tissue characteristics and the effects nanocarriers have on cognition.
    Keywords:  Blood-brain barrier; Brain tumors; Drug delivery; Nanocarriers; Nanodrugs; Nanomedicine; Neurodegenerative diseases
    DOI:  https://doi.org/10.1016/j.semcancer.2022.06.011
  39. Plants (Basel). 2022 Jun 21. pii: 1637. [Epub ahead of print]11(13):
    Computation Screening of Multi-Target Antidiabetic Properties of Phytochemicals in Common Edible Mediterranean Plants.
    Vlasios Goulas, Antonio J Banegas-Luna, Athena Constantinou, Horacio Pérez-Sánchez, Alexandra Barbouti.
      Diabetes mellitus is a metabolic disease and one of the leading causes of deaths worldwide. Numerous studies support that the Mediterranean diet has preventive and treatment effects on diabetes. These effects have been attributed to the special bioactive composition of Mediterranean foods. The objective of this work was to decipher the antidiabetic activity of Mediterranean edible plant materials using the DIA-DB inverse virtual screening web server. A literature review on the antidiabetic potential of Mediterranean plants was performed and twenty plants were selected for further examination. Subsequently, the most abundant flavonoids, phenolic acids, and terpenes in plant materials were studied to predict their antidiabetic activity. Results showed that flavonoids are the most active phytochemicals as they modulate the function of 17 protein-targets and present high structural similarity with antidiabetic drugs. Their antidiabetic effects are linked with three mechanisms of action, namely (i) regulation of insulin secretion/sensitivity, (ii) regulation of glucose metabolism, and (iii) regulation of lipid metabolism. Overall, the findings can be utilized to understand the antidiabetic activity of edible Mediterranean plants pinpointing the most active phytoconstituents.
    Keywords:  DIA-DB web server; antidiabetic activity; diabetes; flavonoids; in silico study; mechanism of action; phenolic acids; terpenes
    DOI:  https://doi.org/10.3390/plants11131637
  40. Adv Drug Deliv Rev. 2022 Jul 01. pii: S0169-409X(22)00305-2. [Epub ahead of print] 114415
    Nanotherapeutic treatment of the invasive glioblastoma tumor microenvironment.
    Nikhil Pandey, Pavlos Anastasiadis, Christine P Carney, Pranjali P Kanvinde, Graeme F Woodworth, Jeffrey A Winkles, Anthony J Kim.
      Glioblastoma (GBM) is the most common and malignant adult brain cancer with no curative treatment strategy. A significant hurdle in GBM treatment is effective therapeutic delivery to the brain-invading tumor cells that remain following surgery within functioning brain regions. Developing therapies that can either directly target these brain-invading tumor cells or act on other cell types and molecular processes supporting tumor cell invasion and recurrence are essential steps in advancing new therapies in the clinic. This review highlights some of the drug delivery strategies and nanotherapeutic technologies that are designed to target brain-invading GBM cells or non-neoplastic, invasion-supporting cells residing within the GBM tumor microenvironment.
    Keywords:  blood-brain barrier; brain invasion; focused ultrasound; glioblastoma; high-grade glioma; nanoparticles; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.addr.2022.114415
  41. Nutrients. 2022 Jun 24. pii: 2622. [Epub ahead of print]14(13):
    Current Advancements in Antitumor Properties and Mechanisms of Medicinal Components in Edible Mushrooms.
    Jing Xu, Rui Shen, Zhuoya Jiao, Weidong Chen, Daiyin Peng, Lei Wang, Nianjun Yu, Can Peng, Biao Cai, Hang Song, Fengyuan Chen, Bin Liu.
      Edible and medicinal fungi, a group of eukaryotic organisms with numerous varieties, including Coriolus versicolor, Ganoderma lucidum, Cordyceps sinensis, Pleurotus ostreatus, and Grifola frondosa, have been demonstrated to possess a board range of pharmaceutical properties, including anti-virus, anti-inflammation, and neuroprotection. Moreover, edible and medicinal fungi have been traditionally consumed as food to provide multiple nutrients and as drugs owing to having the activities of invigorating blood circulation, reinforcing the healthy qi, clearing away heat, and eliminating stasis for thousands of years in China. Malignant tumors, well-known as the second leading cause of death globally, accounted for nearly 10 million deaths in 2020. Thus, in-depth exploration of strategies to prevent and treat cancer is extremely urgent. A variety of studies have reported that the main bioactive components of edible and medicinal fungi, mainly polysaccharides and triterpenoids, exhibit diverse anticancer activities via multiple mechanisms, including inhibition of cell proliferation and metastasis, induction of apoptosis and autophagy, reversing multidrug resistance, and regulation of immune responses, thus suggesting their substantial potential in the prevention and treatment of cancer. Our review summarizes the research progress on the anticancer properties of edible and medicinal fungi and the underlying molecular mechanism, which may offer a better understanding of this field. Additionally, few studies have reported the safety and efficacy of extracts from edible and medicinal fungi, which may limit their clinical application. In summary, there is a need to continue to explore the use of those extracts and to further validate their safety and efficacy.
    Keywords:  anticancer; clinical application; edible and medicinal fungi; malignant tumors; molecular mechanism
    DOI:  https://doi.org/10.3390/nu14132622
  42. Int J Mol Sci. 2022 Jun 25. pii: 7077. [Epub ahead of print]23(13):
    Molecular Basis Underlying the Therapeutic Potential of Vitamin D for the Treatment of Depression and Anxiety.
    Bruna R Kouba, Anderson Camargo, Joana Gil-Mohapel, Ana Lúcia S Rodrigues.
      Major depressive disorder and anxiety disorders are common and disabling conditions that affect millions of people worldwide. Despite being different disorders, symptoms of depression and anxiety frequently overlap in individuals, making them difficult to diagnose and treat adequately. Therefore, compounds capable of exerting beneficial effects against both disorders are of special interest. Noteworthily, vitamin D deficiency has been associated with an increased risk of developing depression and anxiety, and individuals with these psychiatric conditions have low serum levels of this vitamin. Indeed, in the last few years, vitamin D has gained attention for its many functions that go beyond its effects on calcium-phosphorus metabolism. Particularly, antioxidant, anti-inflammatory, pro-neurogenic, and neuromodulatory properties seem to contribute to its antidepressant and anxiolytic effects. Therefore, in this review, we highlight the main mechanisms that may underlie the potential antidepressant and anxiolytic effects of vitamin D. In addition, we discuss preclinical and clinical studies that support the therapeutic potential of this vitamin for the management of these disorders.
    Keywords:  anti-inflammatory effect; anxiety; depression; neuromodulator; pro-neurogenic effect; vitamin D
    DOI:  https://doi.org/10.3390/ijms23137077
  43. Nat Commun. 2022 Jul 02. 13(1): 3821
    An in situ hydrogel-mediated chemo-immunometabolic cancer therapy.
    Bo Wang, Jing Chen, Julia S Caserto, Xi Wang, Minglin Ma.
      Metabolic reprogramming of the tumor microenvironment (TME) and poor immunogenicity are two of the challenges that cancer immunotherapies have to overcome for improved clinical benefits. Among various immunosuppressive metabolites that keep anti-tumor immunity in check, the tryptophan catabolite kynurenine (Kyn) is an attractive target for blockade given its role in mediating immunosuppression through multiple pathways. Here, we present a local chemo-immunometabolic therapy through injection of a supramolecular hydrogel concurrently releasing doxorubicin that induces immunogenic tumor cell death and kynureninase that disrupts Kyn-mediated immunosuppressive pathways in TME. The combination synergically enhances tumor immunogenicity and unleashes anti-tumor immunity. In mouse models of triple negative breast cancer and melanoma, a single low dose peritumoral injection of the therapeutic hydrogel promotes TME transformation toward more immunostimulatory, which leads to enhanced tumor suppression and extended mouse survival. In addition, the systemic anti-tumor surveillance induced by the local treatment exhibits an abscopal effect and prevents tumor relapse post-resection. This versatile approach for local chemo-immunometabolic therapy may serve as a general strategy for enhancing anti-tumor immunity and boosting the efficacy of cancer immunotherapies.
    DOI:  https://doi.org/10.1038/s41467-022-31579-8
  44. Bosn J Basic Med Sci. 2022 Jun 30.
    Reactive oxygen species activated by mitochondria-specific camptothecin prodrug for enhanced chemotherapy.
    Zhaopei Guo, Zian Wang, Ruifeng Liang, Huayu Tian, Xuesi Chen, Meiwan Chen.
      Camptothecin (CPT) has attracted much attention due to its potent antitumor activities. However, the undesirable physicochemical properties, including poor water-solubility, unstable lactone ring and severe adverse effects limit its further application. In this study, two water-soluble prodrugs, CPT-lysine (CPTK) and CPT-arginine (CPTR), were designed and synthesized by conjugating lysine or arginine with CPT, improving its solubility, pharmacokinetic properties and tumor penetration. Importantly, the introduction of arginine into CPTR contributed to the mitochondria-specific delivery, which increased mitochondrial reactive oxygen species (ROS) generation, induced mitochondria dysfunction and enhanced cell apoptosis and in vivo anti-cancer effect. This strategy is believed to hold great potential for organelle-specific synergistic anti-tumor therapy.
    DOI:  https://doi.org/10.17305/bjbms.2022.7194
  45. Postepy Biochem. 2022 06 30. 68(2): 196-208
    Nanoparticles in chemotherapy: characteristics, design strategies, mechanism of internalization and intracellular degradation
    Joanna Pilch.
      Although significant advances have been made in cancer treatment, effective methods of treatment are still limited. Classical chemotherapy is one of the main cancer treatments, but it often causes many side effects that may cause non-specific drug action. This is mainly due to the lack of significant differences between cancer and normal cells as well as drug resistance. To reduce the side effects and increase the specificity and the selectivity of chemotherapeutics to cancer cells, new methods of their delivery to tumors are being sought. One of these methods is the application of nanoparticles (NPs), e.g. Quantum Dots (QDs) as drug delivery platforms. This review describes the most popular NPs in chemotherapy, including quantum dots, gold nanoparticles, dendrimers, micelles, and liposomes. The review describes also a strategy of design and synthesis of NPs, mechanism of cellular uptake, as well as intracellular degradation and toxicity of NPs.
    DOI:  https://doi.org/10.18388/pb.2021_441
  46. Small. 2022 Jul 03. e2202337
    DNA Base Pairing-Inspired Supramolecular Nanodrug Camouflaged by Cancer-Cell Membrane for Osteosarcoma Treatment.
    Yucheng Fu, Guoyu He, Zhuochao Liu, Jun Wang, Meng Li, Zhusheng Zhang, Qiyuan Bao, Junxiang Wen, Xinyuan Zhu, Chuan Zhang, Weibin Zhang.
      Osteosarcoma (OS) is one of the most common bone malignant tumors which mainly develops in adolescents. Although neoadjuvant chemotherapy has improved the prognosis of patients, numerous chemotherapeutic challenges still limit their use. Here, inspired by the Watson-Crick base pairing in nucleic acids, hydrophobic (methotrexate) and hydrophilic (floxuridine) chemo-drugs are mixed and self-assembled into M:F nanoparticles (M:F NPs) through molecular recognition. Then, the obtained NPs are co-extruded with membranes derived from OS cells to form cancer-cell membrane-coated NPs (CCNPs). With protected membranes at the outer layer, CCNPs are highly stable in both physiological and weak acid tumor conditions and possess homologous tumor targeted capability. Furthermore, the proteomic analysis first identifies over 400 proteins reserved in CCNPs, most of them participating in tumor cell targeting and adhesion processes. In vitro studies reveal that CCNPs significantly inhibit the PI3K/AKT/mTOR pathway, which promotes cell apoptosis and cell cycle arrest. More importantly, cell membrane camouflage significantly prolongs the circulation half-life of CCNPs, elevates the drug accumulation at tumor sites, and promotes anti-tumor efficacy in vivo. As a convenient and effective strategy to construct a biomimetic NP with high drug loading ratio, the CCNPs provide new potentials for precise and synergistic antitumor treatment.
    Keywords:  biomimetic nanoparticles; chemotherapy; homologous targeting; membrane coating; osteosarcoma; self-assembly
    DOI:  https://doi.org/10.1002/smll.202202337
  47. ACS Omega. 2022 Jun 28. 7(25): 22003-22014
    Research on the Construction of Bispecific-Targeted Sustained-Release Drug-Delivery Microspheres and Their Function in Treatment of Hepatocellular Carcinoma.
    Zi Li Huang, Feng Li, Jun Tao Zhang, Xiang Jun Shi, Yong Hua Xu, Xiu Yan Huang.
      Lenvatinib (LEN) is approved as one of the commonly used drugs in the treatment of hepatocellular carcinoma (HCC). It is recognized to be a novel therapeutic choice for the direct and targeted delivery of effective drugs to HCC tumor sites. The key to the proposed method lies in the requirement for efficient targeted drug delivery carriers with targeting performance to deliver effective drugs directly and safely to tumor lesions. Methods: Here, magnetic liposomes (MLs) were modified by phosphatidylinositol proteoglycan 3 (GPC3) and epithelial cell adhesion molecules (EpCAMs). Subsequently, bispecific-targeted sustained-release drug-loaded microspheres containing LEN (GPC3/EpCAM-LEN-MLs) were constructed. In addition, both cytotoxicity and magnetic resonance imaging (MRI) analyses were performed to establish a mouse model and further perform corresponding performance assessments. Results: The corresponding results showed that GPC3/EpCAM-LEN-MLs were spherical-shaped and evenly dispersed. The encapsulation and drug-loading efficiencies were 91.08% ± 1.83% and 8.22% ± 1.24%, respectively. Meanwhile, GPC3/EpCAM-LEN-MLs showed a high inhibition rate on the proliferation of HCC cells and significantly increased their apoptosis. Furthermore, MRI revealed that the system possessed the function of tracking and localizing tumor cells, and animal experiments verified that it could exert the function of disease diagnosis. Conclusions: Our experiments successfully constructed a safe and efficient bispecific-targeted sustained-release drug delivery system for HCC tumor cells. It provides a useful diagnostic and therapeutic scheme for the clinical diagnosis and targeted therapy of HCC. Moreover, it can be used as a potential tumor-specific MRI contrast agent for the localization and diagnosis of malignant tumors.
    DOI:  https://doi.org/10.1021/acsomega.2c02584
  48. Front Cell Dev Biol. 2022 ;10 882571
    The Critical Role of Ferroptosis in Hepatocellular Carcinoma.
    Fan Pan, Xinrong Lin, Liping Hao, Ting Wang, Haizhu Song, Rui Wang.
      Liver cancer is the sixth most frequently diagnosed cancer and the third dominant cause of cancer death worldwide. Ferroptosis is characterized as an iron-dependent form of regulated cell death, with accumulation of lipid peroxides to lethal amounts. Evidences have showed that ferroptosis is closely associated with HCC, but the mechanisms are still poorly understood. In this review, we mainly summarize the roles of several typical molecules as well as radiotherapy in regulating the ferroptosis process in HCC. Chances are that this review may help address specific issues in the treatment of HCC.
    Keywords:  GPx4; ferroptosis; hepatocellular carcinoma; iron metabolism; lipid peroxidation; system xc-
    DOI:  https://doi.org/10.3389/fcell.2022.882571
  49. Biomater Res. 2022 Jul 06. 26(1): 30
    Surface-mediated high antioxidant and anti-inflammatory effects of astaxanthin-loaded ultrathin graphene oxide film that inhibits the overproduction of intracellular reactive oxygen species.
    Seon Yeong Chae, Rowoon Park, Suck Won Hong.
       BACKGROUND: Astaxanthin (AST) is known as a powerful antioxidant that affects the removal of active oxygen and inhibits the production of lipid peroxide caused by ultraviolet light. However, it is easily decomposed by heat or light during production and storage because of the unsaturated compound nature with a structural double bond. The activity of AST can be reduced and lose its antioxidant capability. Graphene oxide (GO) is an ultrathin nanomaterial produced by oxidizing layered graphite. The chemical combination of AST with GO can improve the dispersion properties to maintain structural stability and antioxidant activity because of the tightly bonded functionalized GO surface.
    METHODS: Layered GO films were used as nanocarriers for the AST molecule, which was produced via flow-enabled self-assembly and subsequent controlled solution deposition of RGD peptide and AST molecules. Synthesis of the GO-AST complex was also carried out for the optimized concentration. The characterization of prepared materials was analyzed through transmission electron microscopy (TEM), scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FT-IR), atomic force microscope (AFM), and Raman spectroscopy. Antioxidant activity was tested by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2.2-diphenyl-1-picrylhydrazyl (DPPH) assays. The antibacterial effect and antioxidant effects were monitored for the ultrathin GO/RGD/AST Film. Further, reactive oxygen species (ROS) assay was used to evaluate the anti-inflammatory effects on L-929 fibroblasts.
    RESULTS: Cotreatment of GO-AST solution demonstrated a high antioxidant combined effect with a high ABTS and DPPH radicals scavenging activity. The GO/RGD/AST film was produced by the self-assembly process exhibited excellent antibacterial effects based on physicochemical damage against E. coli and S. aureus. In addition, the GO/RGD/AST film inhibited H2O2-induced intracellular ROS, suppressed the toxicity of lipopolysaccharide (LPS)-induced cells, and restored it, thereby exhibiting strong antioxidant and anti-inflammatory effects.
    CONCLUSION: As GO nanocarrier-assisted AST exerted promising antioxidant and antibacterial reactions, presented a new concept to expand basic research into the field of tissue engineering.
    Keywords:  Anti-inflammation; Antioxidant; Astaxanthin; Graphene oxide; Wound healing
    DOI:  https://doi.org/10.1186/s40824-022-00276-4
  50. J Mater Chem B. 2022 Jul 05.
    Enzyme-activated prodrugs and their release mechanisms for the treatment of cancer.
    Xinyu Li, Fangjun Huo, Yongbin Zhang, Fangqin Cheng, Caixia Yin.
      Enzyme-activated prodrugs have received a lot of attention in recent years. These prodrugs have low toxicity to cells before they are activated; when they interact with specific enzymes, they can effectively release anticancer drugs, thereby achieving the effect of treating cancer. At the same time, compared with other thiol-activated prodrugs, reactive oxygen species-activated prodrugs, and acid-activated prodrugs, the specificity of enzyme-activated prodrugs is stronger; therefore, these prodrugs have greater development potential. In this review, we summarize the different release mechanisms of prodrugs on the basis of enzyme-activated prodrugs, such as enzyme reduction, enzymatic hydrolysis, enzyme-activated and light-radiation-assisted release, and enzymatic-activated and nanoparticle-assisted release mechanisms. A profound understanding of these release mechanisms will contribute to the design of enzyme-activated prodrugs.
    DOI:  https://doi.org/10.1039/d2tb00922f
  51. Molecules. 2022 Jul 01. pii: 4254. [Epub ahead of print]27(13):
    Anthocyanins as Key Phytochemicals Acting for the Prevention of Metabolic Diseases: An Overview.
    Madalina Nistor, Roxana Pop, Adela Daescu, Adela Pintea, Carmen Socaciu, Dumitrita Rugina.
      Anthocyanins are water-soluble pigments present in fruits and vegetables, which render them an extensive range of colors. They have a wide distribution in the human diet, are innocuous, and, based on numerous studies, have supposed preventive and therapeutical benefits against chronic affections such as inflammatory, neurological, cardiovascular, digestive disorders, diabetes, and cancer, mostly due to their antioxidant action. Despite their great potential as pharmaceutical applications, they have a rather limited use because of their rather low stability to environmental variations. Their absorption was noticed to occur best in the stomach and small intestine, but the pH fluctuation of the digestive system impacts their rapid degradation. Urine excretion and tissue distribution also occur at low rates. The aim of this review is to highlight the chemical characteristics of anthocyanins and emphasize their weaknesses regarding bioavailability. It also targets to deliver an update on the recent advances in the involvement of anthocyanins in different pathologies with a focus on in vivo, in vitro, animal, and human clinical trials.
    Keywords:  absorption; anthocyanins; bioavailability; cancer; cardiovascular diseases; diabetes; inflammatory disorders; neuropathologies; oxidative stress
    DOI:  https://doi.org/10.3390/molecules27134254
  52. ACS Appl Bio Mater. 2022 Jul 05.
    Nanoencapsulation of Ru(p-cymene) Complex Bearing Ginger-based Natural Product into Liposomal Nanoformulation to Improve Its Cellular Uptake and Antiproliferative Activity.
    Chezhiyan Sumithaa, Tamilvelan Manjunathan, Olga Mazuryk, Silda Peters, Renjith S Pillai, Malgorzata Brindell, Pushparathinam Gopinath, Mani Ganeshpandian.
      The organometallic compounds are prospective candidates in the row of developing metallochemotherapeutics with the aim of overcoming the limitations of platinum drugs. In order to explore the anticancer properties of organometallic compounds with the natural medicines, two Ru(II)-p-cymene complexes containing the natural products, viz., 6-gingerol (6G) and benzylated-6-gingerdione (B-6GD) have been synthesized and characterized well. The phenolic group of the Ru(6G) complex facilitates its higher cell-free antioxidant activity than its analogue complex. Also, the same complex shows higher cytotoxicity toward A549 lung and HeLa-S3 cervical cancer cells than the Ru(B-6GD) complex but lower cytotoxicity toward A2058 metastatic melanoma cancer cells. Both complexes are shown to easily accumulate in melanoma cancer cells, and their degree of cytotoxicity in the same cells is found to be positively correlated with cell uptake. The cytotoxicity of complexes arises from their intracellular activity, mainly due to the induction of singlet oxygen production in cancer cells. The subcellular fractionation study shows that mitochondria and ER-Golgi membranes might be their predominant targets. Also, the mechanistic investigation revealed that Ru(B-6GD) induces caspase-dependent non-apoptotic cell death whereas Ru(6G) can induce caspase-independent non-apoptotic cell death. Furthermore, both complexes are found to moderately alter the adhesion properties of cancer cells, which is beneficial for antimetastatic treatment. Despite the potential pharmacological activity, Ru(6G) is encapsulated into polymer-supported liposomes to reduce its toxicity and further improve its anticancer potency. The π-conjugated yne-ene chain of polydiacetylene aids in the development of a stable nanoformulation, which achieved a slow release of the complex. Most importantly, the cancer cell uptake of the liposome-encapsulated Ru(6G) complex is 20 times enhanced and the total ROS formation in cancer cells is significantly increased compared to the non-encapsulated complex. However, the nanoformulation does not alter the antimetastatic potency of the encapsulated complex.
    Keywords:  6-gingerol; ROS-generation; Ru(p-cymene) complexes; intracellular uptake; nanoencapsulation; polydiacetylene−phospholipid assembly
    DOI:  https://doi.org/10.1021/acsabm.2c00231
  53. Nutrients. 2022 Jun 23. pii: 2604. [Epub ahead of print]14(13):
    Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review.
    Robert Kubina, Kamil Krzykawski, Agata Kabała-Dzik, Robert D Wojtyczka, Ewa Chodurek, Arkadiusz Dziedzic.
      Diet plays a crucial role in homeostasis maintenance. Plants and spices containing flavonoids have been widely used in traditional medicine for thousands of years. Flavonols present in our diet may prevent cancer initiation, promotion and progression by modulating important enzymes and receptors in signal transduction pathways related to proliferation, differentiation, apoptosis, inflammation, angiogenesis, metastasis and reversal of multidrug resistance. The anticancer activity of fisetin has been widely documented in numerous in vitro and in vivo studies. This review summarizes the worldwide, evidence-based research on the activity of fisetin toward various types of cancerous conditions, while describing the chemopreventive and therapeutic effects, molecular targets and mechanisms that contribute to the observed anticancer activity of fisetin. In addition, this review synthesized the results from preclinical studies on the use of fisetin as an anticancer agent. Based on the available literature, it might be suggested that fisetin has a bioactive potential to become a complementary drug in the prevention and treatment of cancerous conditions. However, more in-depth research is required to validate current data, so that this compound or its derivatives can enter the clinical trial phase.
    Keywords:  anticancer; cancer; fisetin; flavonoid; flavonol
    DOI:  https://doi.org/10.3390/nu14132604
  54. Front Toxicol. 2022 ;4 895667
    Safety and Toxicity Implications of Multifunctional Drug Delivery Nanocarriers on Reproductive Systems In Vitro and In Vivo.
    Anas Ahmad.
      In the recent past, nanotechnological advancements in engineered nanomaterials have demonstrated diverse and versatile applications in different arenas, including bio-imaging, drug delivery, bio-sensing, detection and analysis of biological macromolecules, bio-catalysis, nanomedicine, and other biomedical applications. However, public interests and concerns in the context of human exposure to these nanomaterials and their consequential well-being may hamper the wider applicability of these nanomaterial-based platforms. Furthermore, human exposure to these nanosized and engineered particulate materials has also increased drastically in the last 2 decades due to enormous research and development and anthropocentric applications of nanoparticles. Their widespread use in nanomaterial-based industries, viz., nanomedicine, cosmetics, and consumer goods has also raised questions regarding the potential of nanotoxicity in general and reproductive nanotoxicology in particular. In this review, we have summarized diverse aspects of nanoparticle safety and their toxicological outcomes on reproduction and developmental systems. Various research databases, including PubMed and Google Scholar, were searched for the last 20 years up to the date of inception, and nano toxicological aspects of these materials on male and female reproductive systems have been described in detail. Furthermore, a discussion has also been dedicated to the placental interaction of these nanoparticles and how these can cross the blood-placental barrier and precipitate nanotoxicity in the developing offspring. Fetal abnormalities as a consequence of the administration of nanoparticles and pathophysiological deviations and aberrations in the developing fetus have also been touched upon. A section has also been dedicated to the regulatory requirements and guidelines for the testing of nanoparticles for their safety and toxicity in reproductive systems. It is anticipated that this review will incite a considerable interest in the research community functioning in the domains of pharmaceutical formulations and development in nanomedicine-based designing of therapeutic paradigms.
    Keywords:  drug delivery; fetal toxicity; multifunctional nanoparticles; nanotoxicology; reproductive toxicology
    DOI:  https://doi.org/10.3389/ftox.2022.895667
  55. Integr Cancer Ther. 2022 Jan-Dec;21:21 15347354221096766
    Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation.
    Hamid A Bakshi, Hakkim L Faruck, Zeinab Ravesh, Prawej Ansari, J M A Hannan, Rina Hashimoto, Kazuo Takayama, Rabia Farzand, Mohamed M Nasef, Adelaide Mensah, Alaa A A Aljabali, Vijay Mishra, Nitin B Charbe, Rohit Goyal, Poonam Negi, Ángel Serrano-Aroca, Bojlul Bahar, Mohamed El-Tanani, Aaron J Courtenay, Paul McCarron, Iain G Jack, Murtaza M Tambuwala.
      The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa, has been recognized previously, increased attention was generated after discovering the endocannabinoid system and the successful production of cannabinoid receptors. In vitro and in vivo studies on various tumor models have shown therapeutic efficiency by modifying the tumor microenvironment. However, despite extensive attention regarding potential therapeutic implications of cannabinoids, considerable clinical and preclinical analysis is needed to adequately define the physiological, pharmacological, and medicinal aspects of this range of compounds in various disorders covered in this review. This review summarizes the key literature surrounding the role of cannabinoids in the tumor microenvironment and their future promise in cancer treatment.
    Keywords:  angiogenic factor; cannabinoids; combination therapy; hypoxia; signaling pathways; tumor genesis
    DOI:  https://doi.org/10.1177/15347354221096766
  56. Front Bioeng Biotechnol. 2022 ;10 837693
    Tissue Engineering and Photodynamic Therapy: A New Frontier of Science for Clinical Application -An Up-To-Date Review.
    Mariza Aires-Fernandes, Camila Fernanda Amantino, Stéphanie Rochetti do Amaral, Fernando Lucas Primo.
      Tissue engineering (TE) connects principles of life sciences and engineering to develop biomaterials as alternatives to biological systems and substitutes that can improve and restore tissue function. The principle of TE is the incorporation of cells through a 3D matrix support (scaffold) or using scaffold-free organoid cultures to reproduce the 3D structure. In addition, 3D models developed can be used for different purposes, from studies mimicking healthy tissues and organs as well as to simulate and study different pathologies. Photodynamic therapy (PDT) is a non-invasive therapeutic modality when compared to conventional therapies. Therefore, PDT has great acceptance among patients and proves to be quite efficient due to its selectivity, versatility and therapeutic simplicity. The PDT mechanism consists of the use of three components: a molecule with higher molar extinction coefficient at UV-visible spectra denominated photosensitizer (PS), a monochromatic light source (LASER or LED) and molecular oxygen present in the microenvironment. The association of these components leads to a series of photoreactions and production of ultra-reactive singlet oxygen and reactive oxygen species (ROS). These species in contact with the pathogenic cell, leads to its target death based on necrotic and apoptosis ways. The initial objective of PDT is the production of high concentrations of ROS in order to provoke cellular damage by necrosis or apoptosis. However, recent studies have shown that by decreasing the energy density and consequently reducing the production of ROS, it enabled a specific cell response to photostimulation, tissues and/or organs. Thus, in the present review we highlight the main 3D models involved in TE and PS most used in PDT, as well as the applications, future perspectives and limitations that accompany the techniques aimed at clinical use.
    Keywords:  bioprinting; photobiostimulation; photodynamic therapy; skin model; tissue engineering
    DOI:  https://doi.org/10.3389/fbioe.2022.837693
  57. Biomed Pharmacother. 2022 Jul 01. pii: S0753-3322(22)00758-2. [Epub ahead of print]153 113369
    Drug delivery based on chitosan, β-cyclodextrin and sodium carboxymethyl cellulose as well as nanocarriers for advanced leukemia treatment.
    Melika Hosseini, Mahnaz Amiri, Mojgan Ghanbari, Makarim A Mahdi, Waleed K Abdulsahib, Masoud Salavati-Niasari.
      Medicine/nanotechnology as a new and applicable technique according to drug delivery systems has gained great consideration for cancer treatment. Polysaccharides including, cellulose, β-cyclodextrin and sodium carboxymethyl cellulose and chitosan as natural bio-materials, are appropriate candidates for designing and formulations of these nanosystems because of the exceptional advantages such as bio-compatibility, bio-degradability, non-toxicity, and gelling characteristics. An intelligent drug delivery platform based on these hybrids nowadays is developed, which can be used for dual-responsive dual-drug delivery. Nanotechnology accompany with biological molecules has been carefully considered to decrease the drawbacks of conventional cancer treatments. Consequently, this review is intended to state and investigate on the latest development on the combination treatment of platforms based on the hybrids of anticancer drugs/nanoparticles/Polysaccharides in the fields of biomedical therapeutics and cancer therapy owing to the bio-compatibility, great surface area, good chemical and mechanical features, the challenges and future perspectives are reported as well.
    Keywords:  Biocompatible; Biopolymer: chitosan, cellulose, β-cyclodextrin; Leukemia; Nanocarriers; Nanostructures; Targeting drug release
    DOI:  https://doi.org/10.1016/j.biopha.2022.113369
  58. Comput Math Methods Med. 2022 ;2022 2813142
    Examination of Combined Treatment of Ginsenoside Rg3 and 5-Fluorouracil in Lung Adenocarcinoma Cells.
    Kuizhong Shan, Yujiang Deng, Zhiquan Du, Peiyu Yue, Sufang Yang.
      Chemotherapy is a commonly used strategy for advanced lung cancer patients. However, its clinical application is restrained due to its toxicity and drug resistance. Ginsenoside Rg3 (Rg3) has a strong anticancer influence on colon cancer, breast cancer, lung cancer, and other malignant tumors. However, it is still unclear whether Rg3 can cooperate with 5-FU to inhibit the tumor growth and angiogenesis of lung adenocarcinoma (LUAD). This study examined the combined treatment of Rg3 and 5-FU in LUAD. It was revealed that the combined treatment could notably enhance the suppression on proliferative, invasive, and migratory abilities and angiogenesis in LUAD cells A549 and SPC-A-1. On the other hand, we also discovered that Rg3 or 5-FU could suppress the activity of the NF-κB signaling pathway and downregulate VEGFA expression in LUAD cells. Collectively, this study suggested that Rg3 combined chemotherapy may perform a more powerful drug efficiency in LUAD cells.
    DOI:  https://doi.org/10.1155/2022/2813142
  59. Drug Des Devel Ther. 2022 ;16 1963-1974
    Human Growth Hormone Fragment 176-191 Peptide Enhances the Toxicity of Doxorubicin-Loaded Chitosan Nanoparticles Against MCF-7 Breast Cancer Cells.
    Mahmoud M Habibullah, Syam Mohan, Nabeel Kashan Syed, Hafiz A Makeen, Qazi Mohammad Sajid Jamal, Hani Alothaid, Farkad Bantun, Alaa Alhazmi, Ali Hakamy, Yahia A Kaabi, Ghalia Samlan, Mohtashim Lohani, Neelaveni Thangavel, Mohamed Ahmed Al-Kasim.
       Introduction: Numerous drugs with potent toxicity against cancer cells are available for treating malignancies, but therapeutic efficacies are limited due to their inefficient tumor targeting and deleterious effects on non-cancerous tissue. Therefore, two improvements are mandatory for improved chemotherapy 1) novel delivery techniques that can target cancer cells to deliver anticancer drugs and 2) methods to specifically enhance drug efficacy within tumors. The loading of inert drug carriers with anticancer agents and peptides which are able to bind (target) tumor-related proteins to enhance tumor drug accumulation and local cytotoxicity is a most promising approach.
    Objective: To evaluate the anticancer efficacy of Chitosan nanoparticles loaded with human growth hormone hGH fragment 176-191 peptide plus the clinical chemotherapeutic doxorubicin in comparison with Chitosan loaded with doxorubicin alone.
    Methods: Two sets of in silico experiments were performed using molecular docking simulations to determine the influence of hGH fragment 176-191 peptide on the anticancer efficacy of doxorubicin 1) the binding affinities of hGH fragment 176-191 peptide to the breast cancer receptors, 2) the effects of hGH fragment 176-191 peptide binding on doxorubicin binding to these same receptors. Further, the influence of hGH fragment 176-191 peptide on the anticancer efficacy of doxorubicin was validated using viability assay in Human MCF-7 breast cancer cells.
    Results: In silico analysis suggested that addition of the hGH fragment to doxorubicin-loaded Chitosan nanoparticles can enhance doxorubicin binding to multiple breast cancer protein targets, while photon correlation spectroscopy revealed that the synthesized dual-loaded Chitosan nanoparticles possess clinically favorable particle size, polydispersity index, as well as zeta potential.
    Conclusion: These dual-loaded Chitosan nanoparticles demonstrated greater anti-proliferative activity against a breast cancer cell line (MCF-7) than doxorubicin-loaded Chitosan. This dual-loading strategy may enhance the anticancer potency of doxorubicin and reduce the clinical side effects associated with non-target tissue exposure.
    Keywords:  anticancer potency; cytotoxicity; docking analysis; nanoparticles
    DOI:  https://doi.org/10.2147/DDDT.S367586
  60. J Pharm Sci. 2022 Jun 30. pii: S0022-3549(22)00287-8. [Epub ahead of print]
    Preparation, physical characterization, pharmacokinetics and anti-hyperglycemic activity of esculetin-loaded mixed micelles.
    Xiaoxiao Li, Xiaoli Xia, Jian Zhang, Michael Adu-Frimpong, Xinyi Shen, Wenxiong Yin, Qing He, Wanjing Rong, Feng Shi, Xia Cao, Hao Ji, Elmurat Toreniyazov, Qilong Wang, Jiangnan Yu, Ximing Xu.
      Despite its low water solubility, esculetin (EC) have been described to demonstrate various health benefits. Thus, we sought to develop esculetin-loaded mixed micelles (EC-M) delivery system to purposively improve biological availability and anti-hyperglycemia activity of EC. Thin-film hydration method was employed to fabricate EC-M, amid characterization with transmission electron microscopic analysis (TEM), coupled with physical properties such as particle size (PS), poly-dispersity index (PDI), zeta-potential (ZP) and stability testing. We analyzed in-vitro release and studied EC-M pharmacokinetics in rats. The hyperglycemic mice model was established with streptozotocin (STZ) to evaluate anti-hyperglycemic activity of EC-M. The PS, PDI and ZP of EC-M were 47.97 ± 0.41 nm, 0.189 ± 0.005 and -25.55 ± 0.28 mV, respectively. The release rate of EC-M increased comparable to free EC in the three media. The oral biological availability and half-life of EC-M increased respectively by 3.06 and 1.45 folds compared to free EC. Besides, we observed 46.21% decrease in blood glucose of mice in EC-M group comparable to the model control, wherein, the anti-hyperglycemic effect of EC-M was better compared to free EC. Conclusively, EC-M may ideally serve as a novel approach to enhance biological availability and increased anti-hyperglycemic activity of EC.
    Keywords:  Anti- hyperglycemia; EC-M; Esculetin; Oral bioavailability
    DOI:  https://doi.org/10.1016/j.xphs.2022.06.022
  61. Molecules. 2022 Jun 29. pii: 4203. [Epub ahead of print]27(13):
    Antitumor Effect of Glandora rosmarinifolia (Boraginaceae) Essential Oil through Inhibition of the Activity of the Topo II Enzyme in Acute Myeloid Leukemia.
    Manuela Labbozzetta, Paola Poma, Chiara Occhipinti, Maurizio Sajeva, Monica Notarbartolo.
      It was previously shown that the antitumor and cytotoxic activity of the essential oil (EO) extracted from the aerial parts of Glandora rosmarinifolia appears to involve a pro-oxidant mechanism in hepatocellular carcinoma (HCC) and in triple-negative breast cancer (TNBC) cell lines. Its most abundant compound is a hydroxy-methyl-naphthoquinone isomer. Important pharmacological activities, such as antitumor, antibacterial, antifungal, antiviral and antiparasitic activities, are attributed to naphthoquinones, probably due to their pro-oxidant or electrophilic potential; for some naphthoquinones, a mechanism of action of topoisomerase inhibition has been reported, in which they appear to act both as catalytic inhibitors and as topoisomerase II poisons. Our aim was to evaluate the cytotoxic activity of the essential oil on an acute myeloid leukemia cell line HL-60 and on its multidrug-resistant (MDR) variant HL-60R and verify its ability to interfere with topoisomerase II activity. MTS assay showed that G. rosmarinifolia EO induced a decrease in tumor cell viability equivalent in the two cell lines; this antitumor effect could depend on the pro-oxidant activity of EO in both cell lines. Furthermore, G. rosmarinifolia EO reduced the activity of Topo II in the nuclear extracts of HL-60 and HL-60R cells, as inferred from the inability to convert the kinetoplast DNA into the decatenated form and then not inducing linear kDNA. Confirming this result, flow cytometric analysis proved that EO induced a G0-G1 phase arrest, with cell reduction in the S-phase. In addition, the combination of EO with etoposide showed a good potentiation effect in terms of cytotoxicity in both cell lines. Our results highlight the antitumor activity of EO in the HL-60 cell line and its MDR variant with a peculiar mechanism as a Topo II modulator. Unlike etoposide, EO does not cause stabilization of a covalent Topo II-DNA intermediate but acts as a catalytic inhibitor. These data make G. rosmarinifolia EO a potential anticancer drug candidate due to its cytotoxic action, which is not affected by multidrug resistance.
    Keywords:  EOs; Topo II; multidrug resistance; napthoquinone
    DOI:  https://doi.org/10.3390/molecules27134203
  62. Cancer Cell Int. 2022 Jul 05. 22(1): 224
    Lipid metabolism in tumor microenvironment: novel therapeutic targets.
    Xingkai Liu, Ping Zhang, Jing Xu, Guoyue Lv, Yan Li.
      Bioactive lipid molecules have been proposed to play important roles linking obesity/metabolic syndrome and cancers. Studies reveal that aberrant lipid metabolic signaling can reprogram cancer cells and non-cancer cells in the tumor microenvironment, contributing to cancer initiation, progression, metastasis, recurrence, and poor therapeutic response. Existing evidence indicates that controlling lipid metabolism can be a potential strategy for cancer prevention and therapy. By reviewing the current literature on the lipid metabolism in various cancers, we summarized major lipid molecules including fatty acids and cholesterol as well as lipid droplets and discussed their critical roles in cancer cells and non-cancer in terms of either promoting- or anti-tumorigenesis. This review provides an overview of the lipid molecules in cellular entities and their tumor microenvironment, adding to the existing knowledge with lipid metabolic reprogramming in immune cells and cancer associated cells. Comprehensive understanding of the regulatory role of lipid metabolism in cellular entities and their tumor microenvironment will provide a new direction for further studies, in a shift away from conventional cancer research. Exploring the lipid-related signaling targets that drive or block cancer development may lead to development of novel anti-cancer strategies distinct from traditional approaches for cancer prevention and treatment.
    Keywords:  Cholesterol; Fatty acid; Lipid; Lipid metabolism; Tumor microenvironment
    DOI:  https://doi.org/10.1186/s12935-022-02645-4
  63. Curr Drug Deliv. 2022 Jun 30.
    A Co-Encapsulation of Coenzyme Q10 and Curcumin in Liposomes Coated with Chitosan (Q10-Cur-Lip-Chi) with Enhanced Solubility and Stability for Good Release Performance and Antioxidative Activity.
    Linjin Yu, Chuyan Chao, Qinglan Li, Songling Ye, Jiasen Lin, Shuling Zhong, Qiancheng Xuan, Kailin Xu, Suqing Zhao.
       BACKGROUND: Coenzyme Q10 (Q10) is a powerful lipophilic antioxidant with poor solubility in aqueous media. Curcumin (Cur) is a natural polyphenolic phytochemical molecule with poor aqueous solubility. Liposome is an improved administration of drugs yet with some drawbacks, such as low bioavailability, poor water solubility. It's found biocompatible and permeable for nutraceutical delivery. Chitosan, a hydrophilic polymer, is often used as a polymer coating for its good biocompatible and biodegradable properties, and its relatively low toxicity level.
    METHODS: Q10 and Cur co-loaded liposomes coated with chitosan (Q10-Cur-Lip-Chi) was constructed. The co-encapsulation of Q10 and Cur in liposomes coated with chitosan was verified by TEM, DLS, DSC, FT-IR, and XRPD. The release profile and antioxidant activity of Q10-Cur-Lip-Chi were accessed.
    RESULTS: The particle size of Q10-Cur-Lip-Chi was about 1440 nm with narrow particle distribution with satisfying encapsulation efficiency (EE) above 98% for Q10 and 25% for Cur. Q10-Cur-Lip-Chi showed higher solubility and better pH resistance with 98.5% of Q10 and Cur retention at pH 7.0 - 9.0. Besides, Q10-Cur-Lip showed great salt stability with vesicle size change less than 5%. And PS of Q10-Cur-Lip-Chi changed less than 10% at 4 °C of storage. Additionally, Q10-Cur-Lip-Chi exhibited a good controlled release profile with its accumulative release less than 34% for Q10 and 30% for curcumin after 24 h. And the Q10-Cur-Lip-Chi performed synergistic effect on antioxidant activity reached 41.86±1.84%, which was 5.9 times higher than that of Q10, 2.5 times higher than that of Cur, and 1.7 times higher than that of the Mixture.
    CONCLUSION: Q10-Cur-Lip-Chi improves the solubility and stability of poorly water-soluble Q10 and Cur for good release performance and antioxidative activity.
    Keywords:  Co-encapsulation; Coenzyme Q10; Curcumin; Liposomes
    DOI:  https://doi.org/10.2174/1567201819666220630122755
  64. Dis Markers. 2022 ;2022 5709259
    Metformin Can Enhance the Inhibitory Effect of Olaparib in Bladder Cancer Cells.
    Bao-Jin Chi, Yao Sun, Ling-Li Quan, Jin-Tao Zhao, Bo Wei, Shu-Qiu Wang.
       Background: Bladder cancer is a common urinary system tumor. In the treatment of clinical patients, it is particularly important to find an effective treatment method to inhibit tumor growth. The world's first PARP inhibitor olaparib is mainly used for the treatment of BRCA1/BRCA2 mutated tumors. Metformin, an antidiabetic drug, has been reported to reduce cancer incidence in humans and improve survival in cancer patients.
    Methods: Cell viability and proliferation were detected by CCK-8 assay and colony formation assay; cell apoptosis was detected by flow cytometry; cell migration and invasion abilities were detected by scratch assay and Transwell assay; STAT3/C-MYC signaling pathway protein were detected by western blotting.
    Results: Olaparib combined with metformin has better effects on the proliferation, clone formation, migration, invasion, and apoptosis of bladder cancer cells than single drug, indicating that metformin can enhance the inhibitory effect of olaparib on tumor growth and regulate the expression of STAT3/C-MYC signaling pathway proteins.
    Conclusion: The results of this study showed that metformin could significantly enhance the antitumor effect of olaparib on bladder cancer cells, and these effects were mediated by downregulating STAT3/C-MYC signaling pathway proteins. This finding may have potential clinical application in the treatment of bladder cancer.
    DOI:  https://doi.org/10.1155/2022/5709259
  65. Molecules. 2022 Jun 30. pii: 4240. [Epub ahead of print]27(13):
    Ziziphus nummularia: A Comprehensive Review of Its Phytochemical Constituents and Pharmacological Properties.
    Joelle Mesmar, Rola Abdallah, Adnan Badran, Marc Maresca, Abdullah Shaito, Elias Baydoun.
      Ziziphus nummularia, a small bush of the Rhamnaceae family, has been widely used in traditional folk medicine, is rich in bioactive molecules, and has many reported pharmacological and therapeutic properties. Objective: To gather the current knowledge related to the medicinal characteristics of Z. nummularia. Specifically, its phytochemical contents and pharmacological activities in the treatment of various diseases such as cancer, diabetes, and cardiovascular diseases, are discussed. Methods: Major scientific literature databases, including PubMed, Scopus, ScienceDirect, SciFinder, Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, Henriette's Herbal Homepage, Dr. Duke's Phytochemical and Ethnobotanical Databases, were searched to retrieve articles related to the review subject. General web searches using Google and Google scholar were also utilized. The search period covered articles published between 1980 and the end of October 2021.The search used the keywords 'Ziziphus nummularia', AND ('phytochemical content', 'pharmacological properties, or activities, or effects, or roles', 'anti-inflammatory', 'anti-drought', 'anti-thermal', 'anthelmintic', 'antidiabetic',' anticancer', 'anticholinesterase', 'antimicrobial', 'sedative', 'antipyretic', 'analgesic', or 'gastrointestinal'). Results: This plant is rich in characteristic alkaloids, especially cyclopeptide alkaloids such as nummularine-M. Other phytochemicals, including flavonoids, saponins, glycosides, tannins, and phenolic compounds, are also present. These phytochemicals are responsible for the reported pharmacological properties of Z. nummularia, including anti-inflammatory, antioxidant, antimicrobial, anthelmintic, antidiabetic, anticancer, analgesic, and gastrointestinal activities. In addition, Z. nummularia has anti-drought and anti-thermal characteristics. Conclusion: Research into the phytochemical and pharmacological properties of Z. nummularia has demonstrated that this plant is a rich source of novel bioactive compounds. So far, Z. nummularia has shown a varied pharmacological profile (antioxidant, anticancer, anti-inflammatory, and cardioprotective), warranting further research to uncover the therapeutic potential of the bioactives of this plant. Taken together, Z. nummularia may represent a new potential target for the discovery of new drug leads.
    Keywords:  Ziziphus nummularia; anti-inflammatory; antioxidant; cyclopeptide alkaloids; nummularine-M; phytochemicals
    DOI:  https://doi.org/10.3390/molecules27134240
  66. Molecules. 2022 Jul 05. pii: 4313. [Epub ahead of print]27(13):
    Nutritional Values of Minikiwi Fruit (Actinidia arguta) after Storage: Comparison between DCA New Technology and ULO and CA.
    Tomasz Krupa, Kamila Klimek, Ewa Zaraś-Januszkiewicz.
      The dietary properties of minikiwi make them, along with other fruits and vegetables, suitable as the basis for many slimming and pro-health diets. Prolonging the availability of minikiwi can be provided by different storage technologies. This experiment focused on evaluating the effect of various O2 and CO2 concentrations, i.e., low-oxygen atmosphere (DCA, 0.4% CO2:0.4% O2; ULO, 1.5% CO2:1.5% O2) or high-CO2 (CA, 5% CO2:1.5% O2) storage, in order to provide the consumer with fruits with comparable high nutritional values. Evaluation gave the basic characteristics of the fruits that characterize their health-promoting properties, i.e., total polyphenols (TPC), phenolic acids and flavonols, antioxidant activity (AA), monosaccharides, and acid content. The atmosphere with a higher CO2 content of 5% (CA) effectively influenced the high value of ascorbic acid even after 12 weeks of storage. DCA technology contributed to a significant inhibition of phenol loss but not as effectively as CA technology. In contrast, glucose and fructose contents were found to be significantly higher after storage in ULO or DCA, while sucrose content was more stable in fruit stored in CA or DCA. CA technology conditions stabilized the citric acid content of minikiwi, while DCA technology was less effective in inhibiting acid loss. The nutritional value of the fruit after storage in CA or DCA was not significantly reduced, which will allow the supply of fresh minikiwi fruit to be extended and provide a valuable component of the human diet.
    Keywords:  controlled atmosphere; flavonols; hardy kiwi; organic acid; polyphenols; storage; sugar; ultra-low oxygen
    DOI:  https://doi.org/10.3390/molecules27134313
  67. Life Sci. 2022 Jun 29. pii: S0024-3205(22)00452-0. [Epub ahead of print]305 120752
    Naringenin: A potential flavonoid phytochemical for cancer therapy.
    Mahzad Motallebi, Mohammed Bhia, Huda Fatima Rajani, Iman Bhia, Hadi Tabarraei, Niloufar Mohammadkhani, Miguel Pereira-Silva, Maryam Sadat Kasaii, Saeedeh Nouri-Majd, Anna-Lena Mueller, Francisco J B Veiga, Ana Cláudia Paiva-Santos, Mehdi Shakibaei.
      Naringenin is an important phytochemical which belongs to the flavanone group of polyphenols, and is found mainly in citrus fruits like grapefruits and others such as tomatoes and cherries plus medicinal plants derived food. Available evidence demonstrates that naringenin, as herbal medicine, has important pharmacological properties, including anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. Collected data from in vitro and in vivo studies show the inactivation of carcinogens after treatment with pure naringenin, naringenin-loaded nanoparticles, and also naringenin in combination with anti-cancer agents in various malignancies, such as colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancer, bladder neoplasms, gastric cancer, and osteosarcoma. Naringenin inhibits cancer progression through multiple mechanisms, like apoptosis induction, cell cycle arrest, angiogenesis hindrance, and modification of various signaling pathways including Wnt/β-catenin, PI3K/Akt, NF-ĸB, and TGF-β pathways. In this review, we demonstrate that naringenin is a natural product with potential for the treatment of different types of cancer, whether it is used alone, in combination with other agents, or in the form of the naringenin-loaded nanocarrier, after proper technological encapsulation.
    Keywords:  Cancer therapy; Nanomedicine; Naringenin; Phytochemicals; Polyphenols; Tumor
    DOI:  https://doi.org/10.1016/j.lfs.2022.120752
  68. Polymers (Basel). 2022 Jun 27. pii: 2601. [Epub ahead of print]14(13):
    Approaches to Improve Macromolecule and Nanoparticle Accumulation in the Tumor Microenvironment by the Enhanced Permeability and Retention Effect.
    Victor Ejigah, Oluwanifemi Owoseni, Perpetue Bataille-Backer, Omotola D Ogundipe, Funmilola A Fisusi, Simeon K Adesina.
      Passive targeting is the foremost mechanism by which nanocarriers and drug-bearing macromolecules deliver their payload selectively to solid tumors. An important driver of passive targeting is the enhanced permeability and retention (EPR) effect, which is the cornerstone of most carrier-based tumor-targeted drug delivery efforts. Despite the huge number of publications showcasing successes in preclinical animal models, translation to the clinic has been poor, with only a few nano-based drugs currently being used for the treatment of cancers. Several barriers and factors have been adduced for the low delivery efficiency to solid tumors and poor clinical translation, including the characteristics of the nanocarriers and macromolecules, vascular and physiological barriers, the heterogeneity of tumor blood supply which affects the homogenous distribution of nanocarriers within tumors, and the transport and penetration depth of macromolecules and nanoparticles in the tumor matrix. To address the challenges associated with poor tumor targeting and therapeutic efficacy in humans, the identified barriers that affect the efficiency of the enhanced permeability and retention (EPR) effect for macromolecular therapeutics and nanoparticle delivery systems need to be overcome. In this review, approaches to facilitate improved EPR delivery outcomes and the clinical translation of novel macromolecular therapeutics and nanoparticle drug delivery systems are discussed.
    Keywords:  Zwitterionic polymers; enhanced permeability and retention effect; liposomes; macrophages; nanotechnology; synthetic microbe; tumor microenvironment
    DOI:  https://doi.org/10.3390/polym14132601
  69. J Colloid Interface Sci. 2022 Jun 25. pii: S0021-9797(22)01106-7. [Epub ahead of print]626 77-88
    Multifunctional hemoporfin-Cu9S8-MnO2 for magnetic resonance imaging-guided catalytically-assisted photothermal-sonodynamic therapies.
    Mei Wen, Xiaohan Liu, Nuo Yu, Pu Qiu, Daniel K Macharia, Maoquan Li, Haijun Zhang, Zhigang Chen, Weishuai Lian.
      Integrated theranostic nanoplatforms with multi-model imaging and therapeutic functions are attracting great attention in cancer treatments, while the design and preparation of such nanoplatforms remain an open challenge. Herein, we report hemoporfin@Cu9S8@MnO2 nanoparticles (H@Cu9S8@MnO2 NPs) as multifunctional nanoplatforms for magnetic resonance imaging-guided catalytically-assisted photothermal-sonodynamic therapies of tumors. Cu9S8 hollow spherical nanoparticles were firstly prepared by in-situ vulcanization of Cu2O, and the growth of MnO2 shell was realized by the reduction of manganese permanganate, where the hollow structure of Cu9S8 could be used to load hemoporfin sonosensitizer. Cu9S8@MnO2 nanoparticles with diameters of ∼ 130 nm exhibit increased photoabsorption in near-infrared (NIR) region (680-1100 nm) due to the plasmonic effect of Cu9S8, and the photothermal conversion efficiency is determined to be 32.5% under 1064 nm laser irradiation. Furthermore, MnO2 shells can mimic catalase to trigger the decomposition of endogenous H2O2 into O2 with a significant O2 elevation (14.7 mg L-1) within 8 min and then promote the production of 1O2 via sonodynamic effect of hemoporfin. Meanwhile, MnO2 shells provide the T1-weight magnetic resonance (MR) imaging function. When H@Cu9S8@MnO2 NPs solution is administered to the mice, the tumor growth can be effectively inhibited due to catalytically-assisted synergetic photothermal-sonodynamic therapies which have superior therapeutic effect compared to mono-model therapy alone. Thus, H@Cu9S8@MnO2 NPs present a promising strategy for the development of integrated theranostic nanoplatforms with multi-model imaging and therapy functions.
    Keywords:  Cancer; Hemoporfin@Cu(9)S(8)@MnO(2) nanoparticles; Mimetic Catalase; Photothermal therapy; Sonodynamic therapy
    DOI:  https://doi.org/10.1016/j.jcis.2022.06.116
  70. Semin Cancer Biol. 2022 Jul 03. pii: S1044-579X(22)00158-4. [Epub ahead of print]
    Green nanoparticles as multifunctional nanomedicines: Insights into anti-inflammatory effects, growth signaling and apoptosis mechanism in cancer.
    Faiza Naseer, Madiha Ahmed, Abdul Majid, Warda Kamal, Abdul Rehman Phull.
      Recently, green nanotechnology got great attention due to their reliable, sustainable, and eco-friendly synthesis protocols. The green nanoparticles (GNPs) are preferred over chemically synthesized nanoparticles owing to less destructive effects associated with the synthesis procedures as well as therapeutic involvement. In this review, we have discussed the applications of GNPs in inflammation-mediated disorders, with special emphasis on cancer, initiated due to oxidative stress and inflammatory cascade. Real-time mechanism based studies on GNPs have suggested their anticancer effects through inducing apoptosis, inhibiting angiogenesis, tissue invasion metastasis, reduced replicative capabilities in addition to target specific different signaling molecules and cascades involved in the development or progression of cancer. Moreover, the association of GNPs with the inhibition or induction of autophagy for the management of cancer has also been discussed. A large number of studies showed the GNPs have multifunctional biomedical properties of theranostic prominence. Therefore, the development of GNPs with naturally established systems could upsurge their definite applications as biomedicines including target specific destruction of the cancerous cells.
    Keywords:  Autophagy; Cancer; Green nanoparticles; Inflammation; Molecular mechanism; Nanomedicine
    DOI:  https://doi.org/10.1016/j.semcancer.2022.06.014
  71. Cancer Lett. 2022 Jul 04. pii: S0304-3835(22)00299-3. [Epub ahead of print] 215815
    N6-methyladenosine modification and metabolic reprogramming of digestive system malignancies.
    Xianlei Cai, Chao Liang, Miaozun Zhang, Yuan Xu, Yihui Weng, Xueying Li, Weiming Yu.
      N6-methyladenosine (m6A) is a eukaryotic post-transcriptional modification involved in cell growth and developmental processes, including RNA transcription, alternative splicing, degradation, and translation. It is also involved in the development of various cancers. Metabolic reprogramming enables cancer cells to obtain nutrition from the tumor microenvironment, which is a hallmark of cancer. Numerous studies have shown that m6A modification induces metabolic reprogramming in cancer by regulating the expression of metabolic core genes or activation of metabolic signaling pathways. Digestive system malignancies include esophageal, gastric, colorectal, liver, pancreatic, and other cancers, all of which are associated with poor outcomes. This review summarizes the role of m6A modification in the metabolic reprogramming of digestive system malignancies, with the aim of identifying therapeutic strategies.
    Keywords:  Epigenetic modification; Glucose metabolism; Glutamine metabolism; Lipid metabolism
    DOI:  https://doi.org/10.1016/j.canlet.2022.215815
  72. J Agric Food Chem. 2022 Jul 06.
    Paradigm Shift in Phytochemicals Research: Evolution from Antioxidant Capacity to Anti-Inflammatory Effect and to Roles in Gut Health and Metabolic Syndrome.
    Lihua Xiao, Yong Sun, Rong Tsao.
      Food bioactive components, particularly phytochemicals with antioxidant capacity, have been extensively studied over the past two decades. However, as new analytical and molecular biological tools advance, antioxidants related research has undergone significant paradigm shifts. This review is a high-level overview of the evolution of phytochemical antioxidants research. Early research used chemical models to assess the antioxidant capacity of different phytochemicals, which provided important information about the health potential, but the results were overused and misinterpreted despite the lack of biological relevance (Antioxidants v1.0). This led to findings in the anti-inflammatory properties and modulatory effects of cell signaling of phytochemicals (Antioxidants v2.0). Recent advances in the role of diet in modulating gut microbiota have suggested a new phase of food bioactives research along the phytochemicals-gut microbiota-intestinal metabolites-low-grade inflammation-metabolic syndrome axis (Antioxidants v3.0). Polyphenols and carotenoids were discussed in-depth, and future research directions were also provided.
    Keywords:  anti-inflammation; antioxidant; carotenoids; food bioactives; gut microbiota; immune response; metabolic syndrome; phytochemicals; polyphenolics
    DOI:  https://doi.org/10.1021/acs.jafc.2c02326
  73. J Drug Target. 2022 Jul 03. 1-21
    Trends in iron oxide nanoparticles: a nano-platform for theranostic application in breast cancer.
    Jitu Halder, Deepak Pradhan, Prativa Biswasroy, Vineet Kumar Rai, Biswakanth Kar, Goutam Ghosh, Goutam Rath.
      Breast cancer (BC) is the deadliest malignant disorder globally, with a significant mortality rate. The development of tolerance throughout cancer treatment and non-specific targeting limits the drug's response. Currently, nano therapy provides an interdisciplinary area for imaging, diagnosis, and targeted drug delivery for BC. Several overexpressed biomarkers, proteins, and receptors are identified in BC, which can be potentially targeted by using nanomaterial for drug/gene/immune/photo-responsive therapy and bio-imaging. In recent applications, magnetic iron oxide nanoparticles (IONs) have shown tremendous attention to the researcher because they combine selective drug delivery and imaging functionalities. IONs can be efficaciously functionalised for potential application in BC therapy and diagnosis. In this review, we explored the current application of IONs in chemotherapeutics delivery, gene delivery, immunotherapy, photo-responsive therapy, and bio-imaging for BC based on their molecular mechanism. In addition, we also highlighted the effect of IONs' size, shape, dimension, and functionalization on BC targeting and imaging. To better comprehend the functionalization potential of IONs, this paper provides an outline of BC cellular development. IONs for BC theranostic are also reviewed based on their clinical significance and future aspects.
    Keywords:  Breast cancer; bio-imaging; gene delivery; immunotherapy; iron oxide nanoparticles; molecular targeting; photo responsive therapy
    DOI:  https://doi.org/10.1080/1061186X.2022.2095389
  74. Molecules. 2022 Jun 21. pii: 3970. [Epub ahead of print]27(13):
    Novel Iron Oxide Nanoparticles Induce Ferroptosis in a Panel of Cancer Cell Lines.
    Roberto Fernández-Acosta, Claudia Iriarte-Mesa, Daniel Alvarez-Alminaque, Behrouz Hassannia, Bartosz Wiernicki, Alicia M Díaz-García, Peter Vandenabeele, Tom Vanden Berghe, Gilberto L Pardo Andreu.
      The use of nanomaterials rationally engineered to treat cancer is a burgeoning field that has reported great medical achievements. Iron-based polymeric nano-formulations with precisely tuned physicochemical properties are an expanding and versatile therapeutic strategy for tumor treatment. Recently, a peculiar type of regulated necrosis named ferroptosis has gained increased attention as a target for cancer therapy. Here, we show for the first time that novel iron oxide nanoparticles coated with gallic acid and polyacrylic acid (IONP-GA/PAA) possess intrinsic cytotoxic activity on various cancer cell lines. Indeed, IONP-GA/PAA treatment efficiently induces ferroptosis in glioblastoma, neuroblastoma, and fibrosarcoma cells. IONP-GA/PAA-induced ferroptosis was blocked by the canonical ferroptosis inhibitors, including deferoxamine and ciclopirox olamine (iron chelators), and ferrostatin-1, the lipophilic radical trap. These ferroptosis inhibitors also prevented the lipid hydroperoxide generation promoted by the nanoparticles. Altogether, we report on novel ferroptosis-inducing iron encapsulated nanoparticles with potent anti-cancer properties, which has promising potential for further in vivo validation.
    Keywords:  IONP–GA/PAA; cancer cells; ferroptosis
    DOI:  https://doi.org/10.3390/molecules27133970
  75. Pak J Pharm Sci. 2022 May;35(3(Special)): 953-964
    Formulation development and evaluation of transdermal emulgel using Aloevera extract and natural penetration enhancers.
    Nida Javed, Syed Nisar Hussain Shah, Javaria Saeed, Memoona Nisar, Hina Javed, Rommana Riaz, Khadija Karim.
      This study was to formulate Aloevera extract loaded emulsion (O/W) based gels, by using various concentrations of rose oil, olive oil and Lemon oil as natural penetration enhancers for transdermal effect to treat skin problems. By using RSM, Aloevera emulgels were formulated and then optimized. Stability studies, physico-chemical characteristics, spreadability, skin protection factor, thermal analysis, FTIR, antimicrobial activity, in vitro drug release study (at 37ºC with 100 rpm for 180 minute in release medium at pH 5.5) and in vivo skin evaluation tests were performed. The results were then statistically analyzed. Among all formulations, G12 has shown maximum 93.53% Aloevera release at higher concentration of Olive oil with decreased concentration of Rose oil and Lemon oil. Analysis of variance (ANOVA) was conducted to evaluate the results exhibited independent variables have remarkable effects on dependent variables. Contour plot is also drawn to express the response between independent and dependent variables. All formulations have followed Korsmeyer-Peppas kinetic model. In summary, the combination of penetration enhancers in Aloevera emulgel can be successfully utilized for treatment of mild-moderate acne vulgaris and other skin problems, as optimized emulgel has shown good permeability, prolonged residence time on skin surface and proved good anti-microbial activity.
  76. Curr Neuropharmacol. 2022 Jul 06.
    Nanocarrier based Drug Delivery to Brain: Interventions of Surface Modification.
    Surbhi Sharma, Shweta Dang.
      Brain disorders are one of the prevalent and rapidly growing problems in the medical field as they adversely affect the quality of life of a human. With increase in life expectancy, it has been reported that diseaseslike Alzheimer's, Parkinson's, stroke and brain tumor along with neuropsychological disorders are also being reported at an alarmingly high rate. Despite various therapeutic being developed for the treatment of brain disorders, drug delivery to brain has been a challenging task because of the presence of a very complex Blood Brain Barrier, which precludes most of the drugs from entering the brain in effective concentrations. To overcome this barrier layer, nano- carrier based drug delivery systems have been reported widely by the researchers. These systems owing to their small size offer numerous advantages, however, their short residence time in body owing to opsonization poses a hinderance to their success in vivo. This review article focusses on the various aspects to modify the surfaces of these nano-carriers with polymers, surfactant, protein, antibodies, cell penetrating peptides, integrin binding peptides and glycoproteins such as transferrin & lactoferrin leading to enhanced residence time, desirable characteristics such as ability to cross blood brain barrier (BBB), increased bioavailability in regions of brain and targeted drug delivery.
    Keywords:  Blood Brain Barrier; CNS Disorders; Lactoferrin; Mucoadhesive; Antibodies; Nanoparticles; Surface Modification; Transferrin
    DOI:  https://doi.org/10.2174/1570159X20666220706121412
  77. Life Sci. 2022 Jul 02. pii: S0024-3205(22)00478-7. [Epub ahead of print] 120778
    Optimum inhibition of MCF-7 breast cancer cells by efficient targeting of the macropinocytosis using optimized paclitaxel-loaded nanoparticles.
    Razan B AlHumaidi, Bahgat Fayed, Sarra B Shakartalla, Jayalakshmi Jagal, Manju N Jayakumar, Zainab M Al Shareef, Suleiman I Sharif, Ayman Noreddin, Mohammad H Semreen, Hany M Omar, Mohamed Haider, Sameh S M Soliman.
       AIMS: Breast cancer (BC) is the third leading cause of death among other cancer types. Worldwide, it is the most common harmful disease in women, representing 1/4 of all cancers. Treatment of BC remains an ongoing challenge to most researchers. Understanding how cancer cells differ from normal cells can enhance drug targeting and overall disease progression. Endocytosis is a major physiological process modified in cancer cells and affects the cellular uptake of chemotherapeutic agents. MCF-7 breast cancer cells exhibit constitutive macropinocytic activity in comparison to normal non-macropinocytic MCF-10A breast cells. Therefore, we hypothesized that blocking the macropinocytosis mechanism in MCF-7 cells may inhibit the cancer progression while maintaining the safety of normal cells.
    MAIN METHODS: Using nano-precipitation technique, paclitaxel-PLGA-NPs were successfully prepared in the size range and charge required to opt for macropinocytosis in MCF-7 cells.
    KEY FINDINGS: Uptake and endocytosis inhibitor assays indicated that the developed NPs acquired size and surface charges that efficiently target macropinocytosis of MCF-7 cells. Paclitaxel-loaded PLGA-NPs showed higher efficacy against MCF-7 cells, while providing no toxicity on normal MCF-10A cells. Metabolomics analysis indicated the nutrients deprivation because of occupying the macropinocytosis. However, treatment of fresh MCF-7 cancer cells by metabolites secreted from PLGA-NPs-treated MCF-7 cells showed a potential metastatic activity. Thus, co- administration with an anti-metastatic drug is advised.
    SIGNIFICANCE: Collectively, adjusting the size and surface characteristics of a drug can critically control its cellular uptake, affecting the efficacy of drugs and the microenvironment of cancer cells.
    Keywords:  Breast cancer; Cytotoxicity; Endocytosis; Macropinocytosis; Metabolomics; Metastasis; Paclitaxel-PLGA-NPs
    DOI:  https://doi.org/10.1016/j.lfs.2022.120778
  78. Foods. 2022 Jul 05. pii: 1990. [Epub ahead of print]11(13):
    Food-Grade Microencapsulation Systems to Improve Protection of the Epigallocatechin Gallate.
    Mathis Ralaivao, Jade Lucas, Fernando Rocha, Berta N Estevinho.
      Epigallocatechin gallate (EGCG) is a catechin and one of the most abundant polyphenols in green tea, and it is under research for its potential benefit to human health and for its potential to be used in disease treatments, such as for cancer. However, the effectiveness of polyphenols depends on preserving their bioactivity, stability, and bioavailability. The EGCG was microencapsulated by a spray-drying process, using different biopolymers as encapsulating agents (gum arabic, modified chitosan and sodium alginate), in order to overcome some of the limitations of this compound. The microparticles showed a diameter around 4.22 to 41.55 µm (distribution in volume) and different morphologies and surfaces, depending on the encapsulating agent used. The EGCG release was total, and it was achieved in less than 21 min for all the formulations tested. The EGCG encapsulation efficiency ranged between 78.5 and 100.0%. The release profiles were simulated and evaluated using three kinetic models: Korsmeyer-Peppas (R2: 0.739-0.990), Weibull (R2: 0.963-0.994) and Baker-Lonsdale (R2: 0.746-0.993). The Weibull model was the model that better adjusted to the experimental EGCG release values. This study proves the success of the EGCG microencapsulation, using the spray-drying technique, opening the possibility to insert dried EGCG microparticles in different food and nutraceutical products.
    Keywords:  catechin; controlled release studies; epigallocatechin gallate (EGCG); microencapsulation; polyphenols; spray drying
    DOI:  https://doi.org/10.3390/foods11131990
  79. Curr Pharm Des. 2022 Jul 05.
    Role of Drug Delivery System in Improving the Bioavailability of Resveratrol.
    Zonish Saleem, Kanwal Rehman, Muhammad Sajid Hamid Akash.
      Resveratrol (RSV) is a natural polyphenolic compound known for its therapeutic activities but has limited bioavailability. The aim of our study was to explore various drug-delivering methods that are being employed to achieve target-oriented delivery and therapeutic performance of RSV. To improve the bioavailability and pharmacokinetic properties of RSV, efforts are being made to produce efficient formulations accompanying efficient drug delivery strategies. Several clinical trial studies have been conducted on RSV isomers, and the majority of studies indicated that trans-RSV had better clinical potential and therapeutic effectiveness in various types of complications such as colorectal cancer, metabolic syndrome, hypertension, obesity, neurodegenerative diseases, diabetes, hepatic disease, cardiac disorders, and breast cancer. However, multiple research studies enable us to understand various strategies that can enhance the systemic availability and efficacy of topical RSV formulations. In this article, we emphasize the hurdles of RSV delivery processes. We summarized that the micro- particulate system works efficiently for delivering liquid and solid microparticles of RSV. Another technique in which a coating encloses particles is called microencapsulation. This technique reduces the degradation of pharmaceutical compounds. Similarly, the cyclodextrin system is mainly used for poorly soluble drugs. On the other hand, the vesicular system is another micro-particulate system that can encapsulate hydrophilic and hydrophobic drugs. However, the RSV nanosponge formulations have advanced nano drug delivery systems, making it possible to use RSV for its antioxidant potential.
    Keywords:  Resveratrol; bioavailability; clinical trials; delivery systems; safety; target-oriented; therapeutic activity.
    DOI:  https://doi.org/10.2174/1381612828666220705113514
  80. Materials (Basel). 2022 Jul 05. pii: 4717. [Epub ahead of print]15(13):
    Temperature-Responsive Polysaccharide Microparticles Containing Nanoparticles: Release of Multiple Cationic/Anionic Compounds.
    Takumi Sato, Yoshihiko Murakami.
      Most drug carriers used in pulmonary administration are microparticles with diameters over 1 µm. Only a few examples involving nanoparticles have been reported because such small particles are readily exhaled. Consequently, the development of microparticles capable of encapsulating nanoparticles and a wide range of compounds for pulmonary drug-delivery applications is an important objective. In this study, we investigated the development of polysaccharide microparticles containing nanoparticles for the temperature-responsive and two-step release of inclusions. The prepared microparticles containing nanoparticles can release two differently charged compounds in a stepwise manner. The particles have two different drug release pathways: one is the release of nanoparticle inclusions from the nanoparticles and the other is the release of microparticle inclusions during microparticle collapse. The nanoparticles can be efficiently delivered deep into the lungs and a wide range of compounds are released in a charge-independent manner, owing to the suitable roughness of the microparticle surface. These polysaccharide microparticles containing nanoparticles are expected to be used as temperature-responsive drug carriers, not only for pulmonary administration but also for various administration routes, including transpulmonary, intramuscular, and transdermal routes, that can release multiple drugs in a controlled manner.
    Keywords:  carrageenan; nanoparticle; polysaccharide; pulmonary drug delivery
    DOI:  https://doi.org/10.3390/ma15134717
  81. Carbohydr Polym. 2022 Oct 01. pii: S0144-8617(22)00627-0. [Epub ahead of print]293 119722
    An injectable, self-healing carboxymethylated chitosan hydrogel with mild photothermal stimulation for wound healing.
    Xu Zhang, Bowen Tan, Yanting Wu, Min Zhang, Xi Xie, Jinfeng Liao.
      Hydrogels can mimic extracellular matrix and provide a suitable microenvironment for accelerating wound healing. Nevertheless, the complicated wound condition, the disturbance of external forces, and the manufacturing process of the dressing were still difficult problems. An injectable self-healing hydrogel with mild photothermal therapy (MPTT) was developed for wound healing via dynamic Schiff bonds. After covalently incorporating GO-BPEI (branched polyethyleneimine grafting graphene oxide), an observable mechanical strength improvement and photothermal conversion property of GO-BPEI/carboxymethylated chitosan (CMCS) /aldehyde terminated polyethylene glycol (PEG-CHO) (GCP) hydrogel has been witnessed. MPTT induced by near-infrared (NIR) irradiation could accelerate NIH-3 T3 cells proliferation in vitro. Moreover, in vivo wound defect healing and histological analysis suggested that GCP hydrogels incorporated with MPTT significantly accelerated wound healing by improving collagen fibers deposition, enhancing re-epithelialization, and promoting granulation tissue neogenesis. The GCP hydrogels provide a unique route for wound dressing and present new inspirations for complicated wound management.
    Keywords:  Carboxymethylated chitosan; Hydrogels; Mild photothermal therapy; Self-healing; Wound healing
    DOI:  https://doi.org/10.1016/j.carbpol.2022.119722
  82. Molecules. 2022 Jul 02. pii: 4272. [Epub ahead of print]27(13):
    Origanum syriacum Phytochemistry and Pharmacological Properties: A Comprehensive Review.
    Joelle Mesmar, Rola Abdallah, Adnan Badran, Marc Maresca, Elias Baydoun.
      Herbal medicine has been gaining special interest as an alternative choice of treatment for several diseases, being generally accessible, cost-effective and safe, with fewer side-effects compared to chemically synthesized medicines. Over 25% of drugs worldwide are derived from plants, and surveys have shown that, when available, herbal medicine is the preferred choice of treatment. Origanum syriacum (Lamiaceae) is a widely used medicinal plant in the Middle East, both as a home and a folk remedy, and in the food and beverage industry. Origanum syriacum contains numerous phytochemical compounds, including flavonoids, phenols, essential oils, and many others. Because of its bioactive compounds, O. syriacum possesses antioxidant, antimicrobial, and antiparasitic capacities. In addition, it can be beneficial in the treatment of various diseases such as cancer, neurodegenerative disorders, and peptic ulcers. In this review, the chemical compositions of different types of extracts and essential oils from this herb will first be specified. Then, the pharmacological uses of these extracts and essential oils in various contexts and diseases will be discussed, putting emphasis on their efficacy and safety. Finally, the cellular and molecular mechanisms of O. syriacum phytochemicals in disease treatment will be described as a basis for further investigation into the plant's pharmacological role.
    Keywords:  Lamiaceae; Origanum syriacum; anticancer; antimicrobial; antioxidant; herbal medicine; pharmacology; phytochemistry
    DOI:  https://doi.org/10.3390/molecules27134272
  83. J Mater Chem B. 2022 Jul 04.
    Vascularized nanocomposite hydrogel mechanically reinforced by polyelectrolyte-modified nanoparticles.
    Qianqian Zhang, Qingguo Pei, Jin Yang, Shuting Guo, Ai Yang, Yuhan Qian, Chenglin Li, Qian Feng, Huijuan Lv, Xiaojun Zhou, Chuanglong He.
      Vascularization plays an important role in the initial stage of triggering bone defect repair. The combination of bioactive small molecule drugs and biomaterials has been a powerful strategy for vascularization in bone tissue engineering. In this study, an in situ crosslinked aldehyde hyaluronic acid (AHA)/N,O-carboxymethyl chitosan (NOCC) nanocomposite hydrogel doped with sphingosine 1-phosphate (S1P)-loaded polyelectrolyte-modified mesoporous silica nanoparticles (MSNs) was developed. The alginate/chitosan polyelectrolyte-modified MSNs (MSNs-ALG/CHI) were prepared via the electrostatic interaction. The incorporation of MSNs-ALG/CHI not only achieved a sustained release profile of the angiogenic drug, but also improved the mechanical property of the AHA/NOCC hydrogel due to the Schiff base reaction between the amino group in chitosan and the aldehyde group in AHA. In addition, in vitro cell experiments demonstrated that the nanocomposite hydrogel provided favorable support for cell adhesion and proliferation, and the S1P-loaded nanocomposite hydrogel was able to recruit endothelial cells. More importantly, the chicken chorioallantoic membrane (CAM) assay confirmed that the S1P-loaded nanocomposite hydrogel could significantly enhance capillary formation. More cell infiltration and better angiogenesis in the S1P loaded nanocomposite hydrogel were observed compared to the group without S1P loading after being implanted subcutaneously for 2 weeks. Furthermore, the subcutaneous implantation experiment further demonstrated that the incorporation of the S1P-loaded nanocomposite hydrogel could improve the tissue infiltration and new vessel formation within the macroporous poly(L-lactic acid)/polycaprolactone scaffold. Our results suggest that the nanocomposite hydrogel will be an excellent drug delivery system and the S1P-loaded nanocomposite hydrogel has great potential for vascularized bone regeneration application.
    DOI:  https://doi.org/10.1039/d2tb00735e
  84. Macromol Rapid Commun. 2022 Jul 08. e2200124
    Lipid-Head-Polymer-Tail Chimeric Vesicles.
    Kan Hu, Aoyuan Cheng, Dingcheng Zhou, Yi Luo, Guoqing Zhang.
      Lipid nanovesicles (LNVs) and polymer nanovesicles (PNVs), also known as liposomes and polymersomes, are becoming increasingly vital in global health. However, the two major classes of nanovesicles both exhibit their own issues that significantly limit potential applications. Here, by covalently attaching a naturally occurring phosphate "lipid head" and a synthetic polylactide "polymer tail" via facile ring-opening polymerization on a 500-gram scale, a type of "chimeric" nanovesicles (CNVs) can be easily produced. Compared to LNVs, the reported CNVs exhibit reduced permeability for small and large molecules; on the other hand, the CNVs are less hydrophobic and exhibit enhanced tolerance toward proteins in buffer solutions without the need for hydrophilic polymeric corona such as poly(ethylene glycol), in contrast to conventional PNVs. The proof-of-concept in vitro delivery experiments using hydrophilic solutions of fluorescein-PEG, rhodamine-PEG, and anti-cancer drug doxorubicin demonstrate that these CNVs, as a structurally diverse class of nano-materials, are highly promising as alternative carriers for therapeutic molecules in translational nanomedicine. This article is protected by copyright. All rights reserved.
    Keywords:  cell imaging; drug delivery; liposome; nanomedicine; nanovesicle; polymersome
    DOI:  https://doi.org/10.1002/marc.202200124
  85. Nanomaterials (Basel). 2022 Jun 23. pii: 2160. [Epub ahead of print]12(13):
    Hypolipidemic Activity of Olive Oil-Based Nanostructured Lipid Carrier Containing Atorvastatin.
    Heba S Elsewedy, Tamer M Shehata, Mervt M Almostafa, Wafaa E Soliman.
      Currently, hyperlipidemia is a growing health issue that is considered a risk factor for obesity. Controlling body weight and modifying life style in most of cases are not adequate and the condition requires medical treatment. Statin drugs (mainly Atorvastatin (ATO)), have been used broadly and for long time as medications for handling higher levels of lipid, especially bad cholesterol, which accordingly controls the prevalence of obesity. Still, the obstacle that stands in front of any formulation is the poor solubility of the drug. Low solubility of ATO came up with poor absorption as well as poor bioavailability. This paved the way for the present study, which aimed to exploit nanotechnology and develop certain nanolipid carriers that could accommodate hydrophobic drugs, such as ATO. Nanostructured lipid carrier (NLC) containing ATO was fabricated using olive oil. Olive oil is natural plant oil possessing confirmed hypolipidemic activity that would help in improving the efficacy of the formulation. Via applying the Quality by Design (QbD) approach, one NLC formula was selected to be optimized based on appropriate size and higher entrapment. Optimized ATO-NLC was scrutinized for zeta potential, in vitro study and kinetic profile. Moreover, stability testing and in vivo hypolipidemic behavior was conducted. The optimized NLC formulation seemed to show particle size (254.23 nm) with neutral zeta potential (-1.77 mV) and entrapment efficiency (69.56%). The formulation could be prolonged for 12 h and provided higher % of release (97.17%). Stability testing confirmed the role of modifying the surface of the formulation with PEG-DSPE in providing a highly stable formulation that could withstand three months storage in two altered conditions. Ultimately, optimized ATO-NLC could successfully lower total cholesterol level in rats induced with obesity and fed a high-fat diet. Remarkably, ATO-NLC prepared with olive oil, in addition to shielding its surface, would provide a stable formulation that holds up the synergistic action between olive oil and ATO.
    Keywords:  atorvastatin; hypolipidemic; nanostructured lipid carrier; obesity; olive oil
    DOI:  https://doi.org/10.3390/nano12132160
  86. Polymers (Basel). 2022 Jun 30. pii: 2693. [Epub ahead of print]14(13):
    Preparation, Characterization and In Vitro Evaluation of Eudragit S100-Coated Bile Salt-Containing Liposomes for Oral Colonic Delivery of Budesonide.
    Hamid Alghurabi, Tatsuaki Tagami, Koki Ogawa, Tetsuya Ozeki.
      The aim of this study was to prepare a liposomal formulation of a model drug (budesonide) for colonic delivery by incorporating a bile salt (sodium glycocholate, SGC) into liposomes followed by coating with a pH-responsive polymer (Eudragit S100, ES100). The role of the SGC is to protect the liposome from the emulsifying effect of physiological bile salts, while that of ES100 is to protect the liposomes from regions of high acidity and enzymatic activity in the stomach and small intestine. Vesicles containing SGC were prepared by two preparation methods (sonication and extrusion), and then coated by ES100 (ES100-SGC-Lip). ES100-SGC-Lip showed a high entrapment efficiency (>90%) and a narrow size distribution (particle size = 275 nm, polydispersity index < 0.130). The characteristics of liposomes were highly influenced by the concentration of incorporated SGC. The lipid/polymer weight ratio, liposome charge, liposome addition, and mixing rate were critical factors for efficient and uniform coating. In vitro drug release studies in various simulated fluids indicate a pH-dependent dissolution of the coating layer, and the disintegration process of ES100-SGC-Lip was evaluated. In conclusion, the bile salt-containing ES100-coated liposomal formulation has potential for effective oral colonic drug delivery.
    Keywords:  colonic-targeted delivery; pH sensitive polymer; polymer-coated liposomes; sodium glycocholate
    DOI:  https://doi.org/10.3390/polym14132693
  87. Plants (Basel). 2022 Jun 24. pii: 1680. [Epub ahead of print]11(13):
    The Polyphenolic Profile and Antioxidant Activity of Five Vegetal Extracts with Hepatoprotective Potential.
    Liliana Costea, Carmen Lidia Chițescu, Rica Boscencu, Manuela Ghica, Dumitru Lupuliasa, Dragoș Paul Mihai, Teodora Deculescu-Ioniță, Ligia Elena Duțu, Maria Lidia Popescu, Emanuela-Alice Luță, George Mihai Nițulescu, Octavian Tudorel Olaru, Cerasela Elena Gîrd.
      Oxidative stress is among the major triggers for many important human functional disorders, which often lead to various metabolic or tissue diseases. The aim of the study is to obtain five standardized vegetal extracts (Cynarae extractum-CE, Rosmarini extractum-RE, Taraxaci extractum-TE, Cichorii extractum-CHE, and Agrimoniae extractum-AE) that contain active principles with an essential role in protecting liver cells against free radicals and quantify their antioxidant actions. The compounds of therapeutic interest from the analyzed extracts were identified and quantified using the UHPLC-HRMS/MS technique. Thus, the resulting identified compounds were 28 compounds in CE, 48 compounds in RE, 39 compounds in TE, 43 compounds in CHE, and 31 compounds in AE. These compounds belong to the class of flavonoids, isoflavones, phenolic acids and dicarboxylic acids, depsides, diterpenes, triterpenes, sesquiterpenes, proanthocyanidins, or coumarin derivatives. From the major polyphenolic compounds quantified in all the extracts analyzed by UHPLC-HRMS/MS, considerable amounts have been found for chlorogenic acid (619.8 µg/g extract for TE-2032.4 µg/g extract for AE), rutoside (105.1 µg/g extract for RE-1724.7 µg/g extract for AE), kaempferol (243 µg/g extract for CHE-2028.4 µg/g extract for CE), and for naringenin (383 µg/g extract for CHE-1375.8 µg/g extract for AE). The quantitative chemical analysis showed the highest content of total phenolic acids for AE (24.1528 ± 1.1936 g chlorogenic acid/100 g dry extract), the highest concentration of flavones for RE (6.0847 ± 0.3025 g rutoside/100 g dry extract), and the richest extract in total polyphenols with 31.7017 ± 1.2211 g tannic acid equivalent/100 g dry extract for AE. Several methods (DPPH, ABTS, and FRAP) have been used to determine the in vitro total antioxidant activity of the extracts to evaluate their free radical scavenging ability, influenced by the identified compounds. As a result, the correlation between the content of the polyphenolic compounds and the antioxidant effect of the extracts has been demonstrated. Statistically significant differences were found when comparing the antiradical capacity within the study groups. Although all the analyzed extracts showed good IC50 values, which may explain their antihepatotoxic effects, the highest antioxidant activity was obtained for Agrimoniae extractum (IC50ABTS = 0.0147 mg/mL) and the lowest antioxidant activity was obtained for Cynarae extractum (IC50ABTS = 0.1588 mg/mL). Furthermore, the hepatoprotective potential was evaluated in silico by predicting the interactions between the determined phytochemicals and key molecular targets relevant to liver disease pathophysiology. Finally, the evaluation of the pharmacognostic and phytochemical properties of the studied extracts validates their use as adjuvants in phytotherapy, as they reduce oxidative stress and toxin accumulation and thus exert a hepatoprotective effect at the cellular level.
    Keywords:  UHPLC–HRMS/MS; antioxidant activity; hepatoprotective effect; molecular docking; phytochemicals; polyphenolic profile; vegetal extracts
    DOI:  https://doi.org/10.3390/plants11131680
  88. Anal Chem. 2022 Jul 07.
    Self-Assembled ATP-Responsive DNA Nanohydrogel for Specifically Activated Fluorescence Imaging and Chemotherapy in Cancer Cells.
    Xin Xu, Yifan Jiang, Chunhua Lu.
      Tumor marker-responsive drug delivery systems have been developed for cancer imaging and chemotherapy. However, improving their ability of controlled drug release remains a challenge. In this study, we have developed an adenosine triphosphate (ATP)-responsive DNA nanohydrogel for specifically activated fluorescence imaging and chemotherapy in cancer cells. Acrylamide and acrydite-modified DNAs were polymerized to obtain DNA-grafted polyacrylamide copolymers. Then, the copolymers acted as the backbone of the nanohydrogel and were assembled by base complementation with ATP aptamer linkers to construct an ATP-responsive nanohydrogel. Meanwhile, the chemotherapeutic drug doxorubicin (DOX) was added and loaded into the ATP-responsive nanohydrogel during the assembly process. After endocytosis by cancer cells and response to a high intracellular ATP level, the DOX-loaded nanohydrogel disassembled due to the formation of aptamer/ATP complexes. Subsequently, the released DOX played a role in fluorescence imaging and chemotherapy of cancer cells. Through the ATP-responsive property and satisfying drug delivery capability, this nanohydrogel realized fluorescence imaging and specific cancer cell killing capabilities due to different intracellular ATP levels in normal and cancer cell lines. In summary, this study has provided a novel strategy of constructing a tumor microenvironment-responsive drug delivery system triggered by the tumor markers for tumor intracellular imaging and chemotherapy.
    DOI:  https://doi.org/10.1021/acs.analchem.2c01760
  89. Photodiagnosis Photodyn Ther. 2022 Jul 05. pii: S1572-1000(22)00287-3. [Epub ahead of print] 103001
    Photodynamic therapy to a primary cancer of the peripheral lung: Case report.
    Ron R Allison, J Scott Ferguson.
      Photodynamic therapy (PDT) is an FDA approved treatment for lung cancer. In the United States the photosensitizer porfimer sodium (Photofrin®, Pinnacle Biologics) is intravenously introduced at 2mg/kg. After approximately 48 hours, illumination to activate the photosensitizer is initiated, with 630nm red light at 200J/cm, delivered by fiber-optic catheter, brought to the tumor endo- bronchially, and delivered for 500 seconds. This will create, in the presence of oxygen, a Type II Photodynamic Reaction (PDR) which generates singlet oxygen species that are tumor ablative. Classically, PDT for lung cancer has been employed for symptomatic central and obstructing tumors with great success. This case report describes an innovative approach to treat a peripheral, early stage lung cancer employing magnetic navigation and endobronchial treatment. We report on a 79 year old male with numerous comorbidities including pulmonary fibrosis, who was found to have a biopsy proven peripheral and solitary non-small cell cancer. Due to prior SBRT (stereotactic body radiation therapy) dose levels causing radiation fibrosis, he was not a candidate for repeat SBRT, and he was not a surgical candidate due to comorbidities. Tumor control with PDT was achieved without treatment related morbidity. This report details our findings.
    Keywords:  Lung cancer; Navigational Bronchoscopy; Peripheral Lung Cancer; Photodynamic therapy; Photofrin
    DOI:  https://doi.org/10.1016/j.pdpdt.2022.103001
  90. Drug Metab Bioanal Lett. 2022 Jun 09.
    Assessment of nano lipid carrier loaded transdermal patch of rizatriptan benzoate.
    Sayani Bhattacharyya, Lavanya Nanjareddy.
       BACKGROUND: Migraine is a neurological disorder and is accompanied by different painful episodes. Hence the maintenance of a steady-state concentration of drug can be beneficial for the patients suffering with migraine. The present investigation focuses on the development of nano lipid carriers (NLCs) loaded transdermal patch of rizatriptan benzoate to sustain the effect of the drug for the enhancement of therapeutic effects.
    METHOD: Stearic acid and peanut oil were used to make the NLCs. A central composite design was employed to observe the effect of formulation factors like solid lipid ratio, phase volume ratio, and concentration of surfactants on the formation of nanoparticles. The effects were evaluated for the responses like particle size and entrapment of the drug in the nanocarriers. The optimized formulation was subjected to compatibility, thermal, surface characteristics, and surface morphology studies. The optimized formulation was dispersed in HPMC 15CPS and PVP K30 polymer matrix and the transdermal patch was evaluated for its mechanical properties, drug release study, and skin irritation study.
    RESULTS: The experimental design was suitable to produce nanosized stable lipid carriers of the drug with high drug entrapment. The drug and excipients were found to be compatible. The thermal and surface characteristics study proved the high loading of drug in the nanoparticles. The surface morphology study showed the formation of irregular-shaped NLCs. The transdermal patch had good mechanical properties. The ex vivo study of the formulated patch showed a sustained release of the drug over 24h. No skin irritation was reported from the transdermal patch.
    CONCLUSION: Therefore, it can be concluded that the nanoparticles loaded transdermal patch of rizatriptan benzoate can be promising in controlling the divergent phases of migraine.
    Keywords:  Ex vivo diffusion.; Experimental design; Migraine; Nanoparticles; Rizatriptan benzoate; Transdermal patch
    DOI:  https://doi.org/10.2174/2949681015666220609095706
  91. Front Immunol. 2022 ;13 880810
    The Promise of Targeting Hypoxia to Improve Cancer Immunotherapy: Mirage or Reality?
    Bassam Janji, Salem Chouaib.
      Almost all solid tumors display hypoxic areas in the tumor microenvironment associated with therapeutic failure. It is now well established that the abnormal growth of malignant solid tumors exacerbates their susceptibility to hypoxia. Therefore, targeting hypoxia remains an attractive strategy to sensitize tumors to various therapies. Tumor cell adaptions to hypoxia are primarily mediated by hypoxia-inducible factor-1 alpha (HIF-1α). Sensing hypoxia by HIF-1α impairs the apoptotic potential of tumor cells, thus increasing their proliferative capacity and contributing to the development of a chaotic vasculature in the tumor microenvironment. Therefore, in addition to the negative impact of hypoxia on tumor response to chemo- and radio-therapies, hypoxia has also been described as a major hijacker of the tumor response by impairing the tumor cell susceptibility to immune cell killing. This review is not intended to provide a comprehensive overview of the work published by several groups on the multiple mechanisms by which hypoxia impairs the anti-tumor immunity and establishes the immunosuppressive tumor microenvironment. There are several excellent reviews highlighting the value of targeting hypoxia to improve the benefit of immunotherapy. Here, we first provide a brief overview of the mechanisms involved in the establishment of hypoxic stress in the tumor microenvironment. We then discuss our recently published data on how targeting hypoxia, by deleting a critical domain in HIF-1α, contributes to the improvement of the anti-tumor immune response. Our aim is to support the current dogma about the relevance of targeting hypoxia in cancer immunotherapy.
    Keywords:  cancer immunotherapy; cold and hot tumor; hypoxia; immune checkpoints; immune landscape; innate and adaptive immune response; pro-inflammatory chemokines
    DOI:  https://doi.org/10.3389/fimmu.2022.880810
  92. Nanomaterials (Basel). 2022 Jun 24. pii: 2173. [Epub ahead of print]12(13):
    A Combined Cyanine/Carbomer Gel Enhanced Photodynamic Antimicrobial Activity and Wound Healing.
    Ming Guan, Guangyu Chu, Jiale Jin, Can Liu, Linxiang Cheng, Yi Guo, Zexing Deng, Yue Wang.
      As a non-invasive and non-specific therapeutic approach, photodynamic therapy (PDT) has been used to treat antibiotic-resistant bacteria with encouraging efficacy. Inspired by light, the photosensitizers can produce excessive reactive oxygen species (ROS) and, thus, effectively destroy or kill bacteria. Cyanine (Cy), a traditional photosensitizer for PDT, has the advantages of low cytotoxicity and high ROS yield. Yet, the water solubility and photostability for Cy are poor, which substantially limit its antibacterial efficiency and clinical translation. Herein, we combined Cy with carbomer gel (CBMG) to form a photodynamic Cy-CBMG hydrogel. In this system, Cy was evenly dispersed in CBMG, and CBMG significantly improved the water solubility and photostability of Cy via electrostatic interactions. The developed Cy-CBMG gel had less photodegradation under laser irradiation and thus can effectively elevate ROS accumulation in bacteria. The Cy-CBMG compound presented remarkable ROS-induced killing efficacy against methicillin-resistant Staphylococcus aureus (93.0%) and extended-spectrum β-lactamase-producing Escherichia coli (88.7%) in vitro. Moreover, as a potential wound dressing material, the Cy-CBMG hydrogel exhibited excellent biocompatibility and effective antimicrobial ability to promote wound healing in vivo. Overall, this work proposed a practical strategy to synthesize a photosensitizer-excipient compound to enhance the photophysical property and antibacterial efficacy for PDT.
    Keywords:  PDT; antibacterial property; carbomer; cyanine; wound repair
    DOI:  https://doi.org/10.3390/nano12132173
  93. Nutrients. 2022 Jun 27. pii: 2649. [Epub ahead of print]14(13):
    Dietary Therapy in Prevention of Cardiovascular Disease (CVD)-Tradition or Modernity? A Review of the Latest Approaches to Nutrition in CVD.
    Elżbieta Szczepańska, Agnieszka Białek-Dratwa, Barbara Janota, Oskar Kowalski.
      The development of cardiovascular diseases is undoubtedly influenced by improper dietary behavior. The most common mistakes include irregularity of meal consumption, high dietary atherogenicity: snacking on sweets between meals, low supply of dietary fiber, unsaturated fatty acids, legume seeds, and high supply of meat and meat products. Among many food components, some are characterized by a specific cardioprotective effect, which means that their supply of food may prevent the occurrence of cardiovascular disease or improve the health of the sick. Coenzyme Q10 (CoQ10) is one of the ingredients showing cardioprotective effects on the heart and blood vessels. Antioxidant and lipid profile-enhancing effects are also attributed to sitosterol which is one of the plant-derived sterols. A very important argument indicating the necessity of a varied diet rich in a variety of plant products is the beneficial effect of polyphenols, which are most abundant in multicolored vegetables and fruits. Numerous studies show their effectiveness in lowering blood pressure, improving lipid profile, and regeneration of vascular endothelium. The collected publications from the field of lifestyle medicine can be a source of knowledge for dieticians, physicians, and people associated with physical culture and human mental health to prevent the development of cardiovascular diseases and reduce the risk of death from this cause.
    Keywords:  CVD; cardioprotective food; cardiovascular disease; diet; diet therapy; prevention
    DOI:  https://doi.org/10.3390/nu14132649
  94. Curr Mol Pharmacol. 2022 Jul 05.
    Carvacrol as a prospective regulator of cancer targets/signalling pathways.
    Jyoti Singh, Suaib Luqman, Abha Meena.
       BACKGROUND: Carvacrol is a naturally occurring phenolic isopropyl monoterpene isolated from oregano, thyme, pepperwort, ajwain, marjoram, and wild bergamot. It possesses pharmacological activities, including anticancer, anti-genotoxic, and anti-inflammation associated with antioxidant properties. The antioxidant property of carvacrol is found to be accountable for its anticancer property. Thus, the present review summarizes and discusses the anticancer potential of carvacrol, revealing its target, signalling pathways, efficacy, pharmacokinetics, and toxicity.
    OBJECTIVE: Carvacrol showed promising activity to be considered in more detail for cancer treatment. This review aimed to summarize the evidence concerning understanding the anticancer potential of carvacrol. However, the mode of action of carvacrol is not yet fully explored and hence requires detailed exploratory studies. This review consists of carvacol's in vitro, in vivo, preclinical and clinical studies.
    METHOD: A literature search was done by searching various online databases like Pubmed, Scopus, and Google Scholar with the specific keyword "Carvacrol," along with other keywords such as "Antioxidant properties," "oncology research," "genotoxicity," and "anti-inflammatory property."
    RESULTS: Carvacrol possesses weak mutagenic and genotoxic potential at nontoxic doses. Carvacrol alone shows the potential to target cancerous cells and significantly deter the growth of cancer cells; this is a targeted method. It offers anti-inflammatory effects by decreasing oxidative stress, which primarily targets ER and mitochondria. Carvacrol depicts targeted explicitly ROS-dependent and mitochondrial-mediated apoptosis in different cancer cells. Moreover, carvacrol significantly regulates the cell cycle and prevents tumor progression. Few reports also suggest its a significant role in inhibiting cell migration, invasion, and angiogenesis in tumor cells. Hence, carvacrol affects cell survival and cell-killing activity by targeting key biomarkers and major signalling pathways, including PI3K/AKT/mTOR, MAPK, STAT3, and Notch.
    CONCLUSION: Until now, its anticancer mechanism is not yet fully explored. A limited number of research studies have been done on carvacrol instead of possessing promising anti-cancer potential. It possesses both cancer prevention and cancer therapeutic properties. This molecule needs more validatory research so that it could be analyzed precisely and sensibly.
    Keywords:  Anti-cancer; Biomarker; Carvacrol; Phytochemicals; Signalling pathway; Terpenoids
    DOI:  https://doi.org/10.2174/1874467215666220705142954
  95. Asian J Pharm Sci. 2022 May;17(3): 412-424
    Elaborately engineering of a dual-drug co-assembled nanomedicine for boosting immunogenic cell death and enhancing triple negative breast cancer treatment.
    Chen Wang, Han Yu, Xiaohong Yang, Xuanbo Zhang, Yuequan Wang, Tianrui Gu, Shenwu Zhang, Cong Luo.
      Pure drug-assembled nanosystem provides a facile and promising solution for simple manufacturing of nanodrugs, whereas a lack of understanding of the underlying assembly mechanism and the inefficient and uncontrollable drug release still limits the development and application of this technology. Here, a simple and practical nanoassembly of DOX and DiR is constructed on basis of their co-assembly characteristics. Multiple interaction forces are found to drive the co-assembly process. Moreover, DOX release from the nanoassembly can be well controlled by the acidic tumor microenvironment and laser irradiation, resulting in favorable delivery efficiency of DiR and DOX in vitro and in vivo. As expected, the nanoassembly with high therapeutic safety completely eradicated the mice triple negative breast cancer cells (4T1) on BALB/c mice, owing to synergistic chemo-photothermal therapy. More interestingly, DiR and DOX synergistically induce immunogenic cell death (ICD) of tumor cells after treatment, enabling the mice to acquire immune memory against tumor growth and recurrence. Such a facile nanoassembly technique provides a novel multimodal cancer treatment platform of chemotherapy/phototherapy/immunotherapy.
    Keywords:  Carrier-free; Immune activation; Pure drug co-assembly; Synergistic chemo-photothermal therapy
    DOI:  https://doi.org/10.1016/j.ajps.2022.02.004
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