bims-kracam Biomed News
on K-Ras in cancer metabolism
Issue of 2022–12–18
fifty-six papers selected by
Yasmin Elkabani, Egyptian Foundation for Research and Community Development
  1. Anticancer potential of curcumin-cyclodextrin complexes and their pharmacokinetic properties.
  2. Harnessing bioactive nanomaterials in modulating tumor glycolysis-associated metabolism.
  3. Intracellular Glucose-Depriving Polymer Micelles for Anti-Glycolytic Cancer Treatment.
  4. Regulation of Metabolic Plasticity in Cancer Stem Cells and Implications in Cancer Therapy.
  5. Emerging Potential Mechanism and Therapeutic Target of Ferroptosis in PDAC: A Promising Future.
  6. The Role of Ketogenic Diet in the Treatment of Neurological Diseases.
  7. Evidence for Multilevel Chemopreventive Activities of Natural Phenols from Functional Genomic Studies of Curcumin, Resveratrol, Genistein, Quercetin, and Luteolin.
  8. Natural Products as Anticancer Agents: Current Status and Future Perspectives.
  9. Smart biomaterials for enhancing cancer therapy by overcoming tumor hypoxia: a review.
  10. [Natural melanin-based nanoparticles with photothermal/photodynamic activities induce ovarian cancer cell death].
  11. Insights on the Dynamic Innovative Tumor Targeted-Nanoparticles-Based Drug Delivery Systems Activation Techniques.
  12. The Spectrum of Pharmacological Actions of Syringetin and Its Natural Derivatives-A Summary Review.
  13. A Comprehensive Review of the Application of Nanoparticles in Diabetic Wound Healing: Therapeutic Potential and Future Perspectives.
  14. Combined Ibuprofen-Nanoconjugate Micelles with E-Selectin for Effective Sunitinib Anticancer Therapy.
  15. Natural essential oils as a new therapeutic tool in colorectal cancer.
  16. Dual-Drug Nanosystem: Etoposide Prodrug and Cisplatin Coloaded Nanostructured Lipid Carriers for Lung Cancer Therapy.
  17. Folate Metabolism in Hepatocellular Carcinoma. What Do We Know So Far?
  18. Effects of Curcumin and Lactoferrin to Inhibit the Growth and Migration of Prostatic Cancer Cells.
  19. Formulation, Characterization, Anti-Inflammatory and Cytotoxicity Study of Sesamol-Laden Nanosponges.
  20. Enzymatically Modified Isoquercitrin: Production, Metabolism, Bioavailability, Toxicity, Pharmacology, and Related Molecular Mechanisms.
  21. Tumor immunomodulatory effects of polyphenols.
  22. Metabolism in Cancer Stem Cells: Targets for Clinical Treatment.
  23. Liposome-based diagnostic and therapeutic applications for pancreatic cancer.
  24. Methionine deprivation inhibits glioma growth through downregulation of CTSL.
  25. The incorporated hydrogel of chitosan-oligoconjugated linoleic acid vesicles and the protective sustained release for curcumin in the gel.
  26. The Metabolic Role of Ketogenic Diets in Treating Epilepsy.
  27. Arctium lappa (Burdock): Insights from ethnopharmacology potential, chemical constituents, clinical studies, pharmacological utility and nanomedicine.
  28. Emerging current trends and research focus related to pancreatic cancer metabolism: A bibliometric and visualized analysis.
  29. Liposome based drug delivery for the management of psoriasis - A comprehensive review.
  30. Alginate-based matrix tablets for drug delivery.
  31. Applications and challenges of ultra-small particle size nanoparticles in tumor therapy.
  32. Improved Stability and In Vitro Anti-Arthritis Bioactivity of Curcumin-Casein Nanoparticles by Ultrasound-Driven Encapsulation.
  33. A Comprehensive Review of Moringa oleifera Bioactive Compounds-Cytotoxicity Evaluation and Their Encapsulation.
  34. Recent advances in responsive hydrogels for diabetic wound healing.
  35. Dual role of Nrf2 in cancer: molecular mechanisms, cellular functions and therapeutic interventions.
  36. Preparation, Characterization, Wound Healing, and Cytotoxicity Assay of PEGylated Nanophytosomes Loaded with 6-Gingerol.
  37. Src inhibitor dasatinib sensitized gastric cancer cells to cisplatin.
  38. Therapeutic effectiveness of sinensetin against cancer and other human complications: A review of biological potential and pharmacological activities.
  39. The inhibitory effect of curcumin loaded poly (vinyl caprolactam) nanohydrogel on insulin fibrillation.
  40. Improving in vivo oral bioavailability of a poorly soluble drug: a case study on polymeric versus lipid nanoparticles.
  41. Ursolic acid: a natural modulator of signaling networks in different cancers.
  42. Combined Effects of Lycopene and Metformin on Decreasing Oxidative Stress by Triggering Endogenous Antioxidant Defenses in Diet-Induced Obese Mice.
  43. Crosstalk between Resveratrol and Gut Barrier: A Review.
  44. Metabolic modulation of transcription: The role of one-carbon metabolism.
  45. Multifunctional hydrogels based on chitosan, hyaluronic acid and other biological macromolecules for the treatment of inflammatory bowel disease: A review.
  46. Fabrication of PEGylated Chitosan Nanoparticles Containing Tenofovir Alafenamide: Synthesis and Characterization.
  47. Dual drug delivery system of RAPTA-C and paclitaxel based on fructose coated nanoparticles for metastatic cancer treatment.
  48. Injectable anti-cancer drug loaded silk-based hydrogel for the prevention of cancer recurrence and post-lumpectomy tissue regeneration aiding triple-negative breast cancer therapy.
  49. Triggered release from thermosensitive liposomes improves tumor targeting of vinorelbine.
  50. Sirtuins (SIRTs) As a Novel Target in Gastric Cancer.
  51. Ketone Bodies as Metabolites and Signalling Molecules at the Crossroad between Inflammation and Epigenetic Control of Cardiometabolic Disorders.
  52. Morphine counteracts the effects of paclitaxel in triple-negative breast cancer cells.
  53. Preparation, Characterization, In Vitro Release, and Antibacterial Activity of Oregano Essential Oil Chitosan Nanoparticles.
  54. Therapeutic Targeting of Glutaminolysis as a Novel Strategy to Combat Cancer Stem Cells.
  55. Investigating the influence of ultrasound parameters on ibuprofen drug release from hydrogels.
  56. Disulfiram, an aldehyde dehydrogenase inhibitor, works as a potent drug against sepsis and cancer via NETosis, pyroptosis, apoptosis, ferroptosis, and cuproptosis.
  1. Int J Pharm. 2022 Dec 09. pii: S0378-5173(22)01029-8. [Epub ahead of print]631 122474
    Anticancer potential of curcumin-cyclodextrin complexes and their pharmacokinetic properties.
    Mahsa Shahriari, Prashant Kesharwani, Thomas P Johnston, Amirhossein Sahebkar.
      Cancer is one of the most common diseases throughout the world, with many treatment modalities currently being used, and new treatment strategies being sought. Most chemotherapeutic molecules have shown extensive toxicity for normal cells, which leads to severe adverse effects. Chemotherapy may also lead to drug resistance, which is one of the major obstacles to the clinical treatment of cancer. Curcumin, a polyphenolic natural compound, has long been considered a therapeutic molecule for a variety of diseases and possesses anti-cancer, anti-oxidant, and anti-inflammatory properties. However, its use is limited due to its hydrophobic nature, poor solubility in water at acidic or neutral pH, and limited bioavailability at the tumor site. Cyclodextrin complexes of curcumin increase curcumin's water solubility, as well as its physicochemical stability to hydrolysis and photochemical decomposition. The most common type of cyclodextrin used for pharmaceutical preparations is β-cyclodextrin. This review focuses on different curcumin-cyclodextrin formulations and compares their pharmacokinetic parameters and efficacy.
    Keywords:  Cancer; Curcumin; Cyclodextrin; Drug delivery; Nanomedicine; Solubility
    DOI:  https://doi.org/10.1016/j.ijpharm.2022.122474
  2. J Nanobiotechnology. 2022 Dec 12. 20(1): 528
    Harnessing bioactive nanomaterials in modulating tumor glycolysis-associated metabolism.
    Zhengying Gu, Chengzhong Yu.
      Glycolytic reprogramming is emerging as a hallmark of various cancers and a promising therapeutic target. Nanotechnology is revolutionizing the anti-tumor therapeutic approaches associated with glycolysis. Finely controlled chemical composition and nanostructure provide nanomaterials unique advantages, enabling an excellent platform for integrated drug delivery, biochemical modulation and combination therapy. Recent studies have shown promising potential of nanotherapeutic strategies in modulating tumor glycolytic metabolism alone or in combination with other treatments such as chemotherapy, radiotherapy and immunotherapy. To foster more innovation in this cutting-edge and interdisciplinary field, this review summarizes recent understandings of the origin and development of tumor glycolysis, then provides the latest advances in how nanomaterials modulate tumor glycolysis-related metabolism. The interplay of nanochemistry, metabolism and immunity is highlighted. Ultimately, the challenges and opportunities are presented.
    Keywords:  Bioactive nanomaterials; Cancer therapy; Glycolysis; Tumor immunity; Tumor metabolism
    DOI:  https://doi.org/10.1186/s12951-022-01740-y
  3. Adv Mater. 2022 Dec 16. e2207342
    Intracellular Glucose-Depriving Polymer Micelles for Anti-Glycolytic Cancer Treatment.
    Jangwook Lee, Kwangmeyung Kim, Ick Chan Kwon, Kuen Yong Lee.
      A new anti-cancer strategy to exploit abnormal metabolism of cancer cells rather than to merely control the drug release or rearrange the tumor microenvironment is reported herein. An anti-glycolytic amphiphilic polymer, designed considering the unique metabolism of cancer cells (Warburg effect) and aimed at the regulation of glucose metabolism, is synthesized through chemical conjugation between glycol chitosan (GC) and phenylboronic acid (PBA). GC-PBA derivatives form stable micellar structures under physiological conditions and respond to changes in glucose concentration. Once the micelles accumulate at the tumor site, intracellular glucose capture occurs, and the resultant energy deprivation through the inhibition of aerobic glycolysis remarkably suppresses tumor growth without significant side effects in vivo. This strategy highlights the need to develop safe and effective cancer treatment without the use of conventional anti-cancer drugs. This article is protected by copyright. All rights reserved.
    Keywords:  apoptosis; cancer therapy; glucose-responsive polymer; induced energy deficiency; nutrient deprivation
    DOI:  https://doi.org/10.1002/adma.202207342
  4. Cancers (Basel). 2022 Nov 30. pii: 5912. [Epub ahead of print]14(23):
    Regulation of Metabolic Plasticity in Cancer Stem Cells and Implications in Cancer Therapy.
    Styliani Papadaki, Angeliki Magklara.
      Cancer stem cells (CSCs), a subpopulation of tumor cells with self-renewal capacity, have been associated with tumor initiation, progression, and therapy resistance. While the bulk of tumor cells mainly use glycolysis for energy production, CSCs have gained attention for their ability to switch between glycolysis and oxidative phosphorylation, depending on their energy needs and stimuli from their microenvironment. This metabolic plasticity is mediated by signaling pathways that are also implicated in the regulation of CSC properties, such as the Wnt/β-catenin, Notch, and Hippo networks. Two other stemness-associated processes, autophagy and hypoxia, seem to play a role in the metabolic switching of CSCs as well. Importantly, accumulating evidence has linked the metabolic plasticity of CSCs to their increased resistance to treatment. In this review, we summarize the metabolic signatures of CSCs and the pathways that regulate them; we especially highlight research data that demonstrate the metabolic adaptability of these cells and their role in stemness and therapy resistance. As the development of drug resistance is a major challenge for successful cancer treatment, the potential of specific elimination of CSCs through targeting their metabolism is of great interest and it is particularly examined.
    Keywords:  aerobic glycolysis; autophagy; cancer stem cells; drug resistance; glycolysis; hypoxia; metabolic plasticity; metabolic reprogramming; metabolism; oxidative phosphorylation
    DOI:  https://doi.org/10.3390/cancers14235912
  5. Int J Mol Sci. 2022 Nov 30. pii: 15031. [Epub ahead of print]23(23):
    Emerging Potential Mechanism and Therapeutic Target of Ferroptosis in PDAC: A Promising Future.
    Chang Li, Xunzhe Yin, Zuojia Liu, Jin Wang.
      Pancreatic cancer (PC) is a devastating malignant tumor of gastrointestinal (GI) tumors characterized by late diagnosis, low treatment success and poor prognosis. The most common pathological type of PC is pancreatic ductal adenocarcinoma (PDAC), which accounts for approximately 95% of PC. PDAC is primarily driven by the Kirsten rat sarcoma virus (KRAS) oncogene. Ferroptosis was originally described as ras-dependent cell death but is now defined as a regulated cell death caused by iron accumulation and lipid peroxidation. Recent studies have revealed that ferroptosis plays an important role in the development and therapeutic response of tumors, especially PDAC. As the non-apoptotic cell death, ferroptosis may minimize the emergence of drug resistance for clinical trials of PDAC. This article reviews what has been learned in recent years about the mechanisms of ferroptosis in PDAC, introduces the association between ferroptosis and the KRAS target, and summarizes several potential strategies that are capable of triggering ferroptosis to suppress PDAC progression.
    Keywords:  KRAS; PDAC; ferroptosis; therapy; tumorigenesis
    DOI:  https://doi.org/10.3390/ijms232315031
  6. Nutrients. 2022 Nov 24. pii: 5003. [Epub ahead of print]14(23):
    The Role of Ketogenic Diet in the Treatment of Neurological Diseases.
    Damian Dyńka, Katarzyna Kowalcze, Agnieszka Paziewska.
      Over a hundred years of study on the favourable effect of ketogenic diets in the treatment of epilepsy have contributed to a long-lasting discussion on its potential influence on other neurological diseases. A significant increase in the number of scientific studies in that field has been currently observed. The aim of this paper is a widespread, thorough analysis of the available scientific evidence in respect of the role of the ketogenic diet in the therapy of neurological diseases such as: epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS) and migraine. A wide range of the mechanisms of action of the ketogenic diet has been demonstrated in neurological diseases, including, among other effects, its influence on the reduction in inflammatory conditions and the amount of reactive oxygen species (ROS), the restoration of the myelin sheath of the neurons, the formation and regeneration of mitochondria, neuronal metabolism, the provision of an alternative source of energy for neurons (ketone bodies), the reduction in glucose and insulin concentrations, the reduction in amyloid plaques, the induction of autophagy, the alleviation of microglia activation, the reduction in excessive neuronal activation, the modulation of intestinal microbiota, the expression of genes, dopamine production and the increase in glutamine conversion into GABA. The studies discussed (including randomised controlled studies), conducted in neurological patients, have stressed the effectiveness of the ketogenic diet in the treatment of epilepsy and have demonstrated its promising therapeutic potential in Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS) and migraine. A frequent advantage of the diet was demonstrated over non-ketogenic diets (in the control groups) in the therapy of neurological diseases, with simultaneous safety and feasibility when conducting the nutritional model.
    Keywords:  Alzheimer’s disease (AD); Parkinson’s disease (PD); anti-inflammatory; brain; epilepsy; high fat; inflammatory; ketogenic; ketogenic diet; ketone bodies; low carb; migraine; multiple sclerosis (MS); neuroinflammation; neurological diseases; neurone; neuroplasticity; neurotransmitters; nutrition; prevention; treatment
    DOI:  https://doi.org/10.3390/nu14235003
  7. Int J Mol Sci. 2022 Nov 29. pii: 14957. [Epub ahead of print]23(23):
    Evidence for Multilevel Chemopreventive Activities of Natural Phenols from Functional Genomic Studies of Curcumin, Resveratrol, Genistein, Quercetin, and Luteolin.
    Lukasz Huminiecki.
      Herein, I present an updated and contextualized literature review of functional genomic studies of natural phenols in the context of cancer. I suggest multilevel chemopreventive and anticancer mechanisms of action, which are shared by multiple dietary natural phenols. Specifically, I cite evidence that curcumin and resveratrol have multilevel anti-cancer effects through: (1) inducing either p53-dependent or p53-independent apoptosis in cancer cell lines, (2) acting as potent regulators of expression of oncogenic and anti-oncogenic microRNAs, and (3) inducing complex epigenetic changes that can switch off oncogenes/switch on anti-oncogenes. There is no simple reductionist explanation for anti-cancer effects of curcumin and resveratrol. More generally, multilevel models of chemoprevention are suggested for related natural phenols and flavonoids such as genistein, quercetin, or luteolin.
    Keywords:  cancer; chemoprevention; curcumin; genistein; genomics; luteolin; quercetin; resveratrol
    DOI:  https://doi.org/10.3390/ijms232314957
  8. Molecules. 2022 Nov 30. pii: 8367. [Epub ahead of print]27(23):
    Natural Products as Anticancer Agents: Current Status and Future Perspectives.
    Abid Naeem, Pengyi Hu, Ming Yang, Jing Zhang, Yali Liu, Weifeng Zhu, Qin Zheng.
      Natural products have been an invaluable and useful source of anticancer agents over the years. Several compounds have been synthesized from natural products by modifying their structures or by using naturally occurring compounds as building blocks in the synthesis of these compounds for various purposes in different fields, such as biology, medicine, and engineering. Multiple modern and costly treatments have been applied to combat cancer and limit its lethality, but the results are not significantly refreshing. Natural products, which are a significant source of new therapeutic drugs, are currently being investigated as potential cytotoxic agents and have shown a positive trend in preclinical research and have prompted numerous innovative strategies in order to combat cancer and expedite the clinical research. Natural products are becoming increasingly important for drug discovery due to their high molecular diversity and novel biofunctionality. Furthermore, natural products can provide superior efficacy and safety due to their unique molecular properties. The objective of the current review is to provide an overview of the emergence of natural products for the treatment and prevention of cancer, such as chemosensitizers, immunotherapeutics, combinatorial therapies with other anticancer drugs, novel formulations of natural products, and the molecular mechanisms underlying their anticancer properties.
    Keywords:  anti-cancer plants; bioactive anti-tumor agents; chemoprevention; chemotherapy; natural products; phytochemicals
    DOI:  https://doi.org/10.3390/molecules27238367
  9. RSC Adv. 2022 Nov 22. 12(52): 33835-33851
    Smart biomaterials for enhancing cancer therapy by overcoming tumor hypoxia: a review.
    Samar A Salim, Taher A Salaheldin, Mohamed M Elmazar, A F Abdel-Aziz, Elbadawy A Kamoun.
      Hypoxia is a distinctive feature of most solid tumors due to insufficient oxygen supply of the abnormal vasculature, which cannot work with the demands of the fast proliferation of cancer cells. One of the main obstacles to limiting the efficacy of cancer medicines is tumor hypoxia. Thus, oxygen is a vital parameter for controlling the efficacy of different types of cancer therapy, such as chemotherapy (CT), photodynamic therapy (PDT), photothermal therapy (PTT), immunotherapy (IT), and radiotherapy (RT). Numerous technologies have attracted much attention for enhancing oxygen distribution in humans and improving the efficacy of cancer treatment. Such technologies include treatment with hyperbaric oxygen therapy (HBO), delivering oxygen by polysaccharides (e.g., cellulose, gelatin, alginate, and silk) and other biocompatible synthetic polymers (e.g., PMMA, PLA, PVA, PVP and PCL), decreasing oxygen consumption, producing oxygen in situ in tumors, and using polymeric systems as oxygen carriers. Herein, this review provides an overview of the relationship between hypoxia in tumor cells and its role in the limitation of different cancer therapies alongside the numerous strategies for oxygen delivery using polysaccharides and other biomaterials as carriers and for oxygen generation.
    DOI:  https://doi.org/10.1039/d2ra06036a
  10. Nan Fang Yi Ke Da Xue Xue Bao. 2022 Nov 20. 42(11): 1681-1688
    [Natural melanin-based nanoparticles with photothermal/photodynamic activities induce ovarian cancer cell death].
    J Yang, X Chen.
       OBJECTIVE: To investigate the physicochemical characteristics of natural melanin-like nanoparticles (PDA NPs) and their synergistic anti-tumor efficacy with photothermal and photodynamic (PTT/PDT) therapy.
    METHODS: The chemically synthesized PDA NPs were characterized using transmission electron microscope (TEM), dynamic light scattering (DLS) and Zeta potential analysis, and their photothermal and photodynamic properties were assessed with near-infrared excitation light (NIR). The antitumor efficacy of free PDA or PDA combined with NIR irradiation (0.7 and 1.0 W/cm2) was evaluated in ovarian cancer cells using flow cytometry, Cell Counting Kit-8 (CCK-8), and Transwell assay and in a mouse model bearing subcutaneous ovarian cancer xenograft.
    RESULTS: The synthesized PDA NPs showed a spherical morphology with diameters around 100 nm and a zeta potential of -20 mV. Upon NIR irradiation at 0.7 and 1.0 W/cm2, the particles underwent temperature changes (ΔT) of about 15 and 30 ℃, respectively, and produced a large amount of singlet oxygen, demonstrating their excellent PTT/PDT properties. In ovarian cancer cells, treatment with PDA NPs alone did not induce obvious changes in reactive oxygen species (ROS) production or mitochondrial membrane potential (MTP), but when combined with NIR irradiation, these particles caused a significant increase of ROS and a reduction of MTP (P < 0.001), and such changes were more prominent with high power NIR (P < 0.01). PDA NPs alone showed no obvious cytotoxicity, but the combination of PDA with NIR irradiation produced potent killing effect on ovarian cancer cells (P < 0.001), and the effect was much stronger with a high power irradiation (P < 0.001). While PDA alone showed no inhibitory effect on tumor cell metastasis, the combined treatment with PDA and NIR irradiation, especially at a high power, significantly suppressed invasion and migration of ovarian cancer cells (P < 0.001). In the tumor-bearing mouse model, the combined treatment, but not PDA alone, produced a significant inhibitory effect on tumor growth (P < 0.001).
    CONCLUSION: PDA NPs combined with NIR has a strong anti-tumor effect, suggesting a potential new therapeutic strategy for ovarian cancer.
    Keywords:  mear-infrared light irradiation; melanin-like nanoparticles; nanomedicine; ovarian cancer
    DOI:  https://doi.org/10.12122/j.issn.1673-4254.2022.11.12
  11. Int J Nanomedicine. 2022 ;17 6131-6155
    Insights on the Dynamic Innovative Tumor Targeted-Nanoparticles-Based Drug Delivery Systems Activation Techniques.
    Nadia M Hamdy, Georgette Eskander, Emad B Basalious.
      Anti-cancer conventional chemotherapeutic drugs novel formula progress, nowadays, uses nano technology for targeted drug delivery, specifically tailored to overcome therapeutic agents' delivery challenges. Polymer drug delivery systems (DDS) play a crucial role in minimizing off-target side effects arising when using standard cytotoxic drugs. Using nano-formula for targeted localized action, permits using larger effective cytotoxic doses on a single special spot, that can seriously cause harm if it was administered systemically. Therefore, various nanoparticles (NPs) specifically have attached groups for targeting capabilities, not seen in bulk materials, which then need activation. In this review, we will present a simple innovative, illustrative, in a cartoon-way, enumeration of NP anti-cancer drug targeting delivery system activation-types. Area(s) covered in this review are the mechanisms of various NP activation techniques.
    Keywords:  DDS; NPs; cancer biology; drug delivery systems; extrinsic-activation; intrinsic-activation; nano-bio-medicine; nanoparticles
    DOI:  https://doi.org/10.2147/IJN.S386037
  12. Nutrients. 2022 Dec 04. pii: 5157. [Epub ahead of print]14(23):
    The Spectrum of Pharmacological Actions of Syringetin and Its Natural Derivatives-A Summary Review.
    Marcelina Chmiel, Monika Stompor-Gorący.
      Mono- and poly-O-methylated flavonols and their glycoside derivatives belong to the group of natural plant polyphenols with a wide spectrum of pharmacological activities. These compounds are known for their antioxidant, antimutagenic, hepatoprotective, antidiabetic, and antilipogenic properties. Additionally, they inhibit carcinogenesis and cancer development. Having in mind the multidirectional biological activity of methylated flavonols, we would like to support further study on their health-promoting activities; in this review we summarized the most recent reports on syringetin and some of its structural analogues: laricitrin, ayanin, and isorhamnetin. Natural sources and biological potential of these substances were described based on the latest research papers.
    Keywords:  anticancer dietary compounds; ayanin; isorhamnetin; laricitrin; pharmacological effect; syringetin
    DOI:  https://doi.org/10.3390/nu14235157
  13. Int J Nanomedicine. 2022 ;17 6007-6029
    A Comprehensive Review of the Application of Nanoparticles in Diabetic Wound Healing: Therapeutic Potential and Future Perspectives.
    Wenqi Qin, Yan Wu, Jieting Liu, Xiaohuan Yuan, Jie Gao.
      Diabetic wounds are one of the most challenging public health issues of the 21st century due to their inadequate vascular supply, bacterial infections, high levels of oxidative stress, and abnormalities in antioxidant defenses, whereas there is no effective treatment for diabetic wounds. Due to the distinct properties of nanoparticles, such as their small particle size, elevated cellular uptake, low cytotoxicity, antibacterial activity, good biocompatibility, and biodegradability. The application of nanoparticles has been widely used in the treatment of diabetic wound healing due to their superior anti-inflammatory, antibacterial, and antioxidant activities. These nanoparticles can also be loaded with various agents, such as organic molecules (eg, exosomes, small molecule compounds, etc.), inorganic molecules (metals, nonmetals, etc.), or complexed with various biomaterials, such as smart hydrogels (HG), chitosan (CS), and hyaluronic acid (HA), to augment their therapeutic potential in diabetic wounds. This paper reviews the therapeutic potential and future perspective of nanoparticles in the treatment of diabetic wounds. Together, nanoparticles represent a promising strategy in the treatment of diabetic wound healing. The future direction may be to develop novel nanoparticles with multiple effects that not only act in wound healing at all stages of diabetes but also provide a stable physiological environment throughout the wound-healing process.
    Keywords:  biomaterials; diabetic complications; diabetic wound; nanoparticles; wound healing
    DOI:  https://doi.org/10.2147/IJN.S386585
  14. Int J Nanomedicine. 2022 ;17 6031-6046
    Combined Ibuprofen-Nanoconjugate Micelles with E-Selectin for Effective Sunitinib Anticancer Therapy.
    Xianhu Zeng, Yi Teng, Chunrong Zhu, Zhipeng Li, Tian Liu, Yong Sun, Shangcong Han.
       Introduction: Sunitinib, a first-line therapy with a certain effect, was utilized in the early stages of renal cell carcinoma treatment. However, its clinical toxicity, side effects, and its limited bioavailability, resulted in inadequate clinical therapeutic efficacy. Building neoteric, simple, and safe drug delivery systems with existing drugs offers new options. Therefore, we aimed to construct a micelle to improve the clinical efficacy of sunitinib by reusing ibuprofen.
    Methods: We synthesized the sialic acid-poly (ethylene glycol)-ibuprofen (SA-PEG-IBU) amphipathic conjugate in two-step reaction. The SA-PEG-IBU amphiphilic conjugates can form into stable SPI nanomicelles in aqueous solution, which can be further loaded sunitinib (SU) to obtain the SPI/SU system. Following nanomicelle creation, sialic acid exposed to the nanomicelle surface can recognize the overexpressed E-selectin receptor on the membrane of cancer cells to enhance cellular uptake. The properties of morphology, stability, and drug release about the SPI/SU nanomicelles were investigated. Confocal microscopy and flow cytometry were used to assess the cellular uptake efficiency of nanomicelles in vitro. Finally, a xenograft tumor model in nude mice was constructed to investigate the body distribution and tumor suppression of SPI/SU in vivo.
    Results: The result showed that SPI nanomicelles exhibited excellent tumor targeting performance and inhibited the migration and invasion of tumor cell in vitro. The SPI nanomicelles can improve the accumulation of drugs in the tumor site that showed effective tumor inhibition in vivo. In addition, H&E staining and immunohistochemical analysis demonstrated that the SPI/SU nanomicelles had a superior therapeutic effect and lower biotoxicity.
    Conclusion: The SPI/SU nanomicelles displayed excellent anti-tumor ability, and can suppress the metastasis of tumor cell by decreasing the expression of Cyclooxygenase-2 due to the ibuprofen, providing an optimistic clinical application potential by developing a simple but safe drug delivery system.
    Keywords:  anti-tumor therapy; ibuprofen; kidney cancer; nanomicelles; sialic acid; sunitinib
    DOI:  https://doi.org/10.2147/IJN.S388234
  15. Cancer Cell Int. 2022 Dec 13. 22(1): 407
    Natural essential oils as a new therapeutic tool in colorectal cancer.
    Stefania Garzoli, Pedro Alarcón-Zapata, Gulnaz Seitimova, Barbara Alarcón-Zapata, Miquel Martorell, Farukh Sharopov, Patrick Valere Tsouh Fokou, Darline Dize, Lauve Rachel Tchokouaha Yamthe, Francisco Les, Guillermo Cásedas, Víctor López, Marcello Iriti, Javad Sharifi Rad, Eda Sönmez Gürer, Daniela Calina, Raffaele Pezzani, Sara Vitalini.
      Colorectal cancer (CRC) is the third most revalent type of cancer in the world and the second most common cause of cancer death (about 1 million per year). Historically, natural compounds and their structural analogues have contributed to the development of new drugs useful in the treatment of various diseases, including cancer. Essential oils are natural odorous products made up of a complex mixture of low molecular weight compounds with recognized biological and pharmacological properties investigated also for the prevention and treatment of cancer. The aim of this paper is to highlight the possible role of essential oils in CRC, their composition and the preclinical studies involving them. It has been reviewed the preclinical pharmacological studies to determine the experimental models used and the anticancer potential mechanisms of action of natural essential oils in CRC. Searches were performed in the following databases PubMed/Medline, Web of science, TRIP database, Scopus, Google Scholar using appropriate MeSH terms. The results of analyzed studies showed that EOs exhibited a wide range of bioactive effects like cytotoxicity, antiproliferative, and antimetastatic effects on cancer cells through various mechanisms of action. This updated review provides a better quality of scientific evidence for the efficacy of EOs as chemotherapeutic/chemopreventive agents in CRC. Future translational clinical studies are needed to establish the effective dose in humans as well as the most suitable route of administration for maximum bioavailability and efficacy. Given the positive anticancer results obtained from preclinical pharmacological studies, EOs can be considered efficient complementary therapies in chemotherapy in CRC.
    Keywords:  Anticancer properties; Anticancer therapy; Apoptosis; Colorectal cancer; Cytotoxicity; Natural essential oils
    DOI:  https://doi.org/10.1186/s12935-022-02806-5
  16. Drug Des Devel Ther. 2022 ;16 4139-4149
    Dual-Drug Nanosystem: Etoposide Prodrug and Cisplatin Coloaded Nanostructured Lipid Carriers for Lung Cancer Therapy.
    Min Du, Jianbo Yin.
       Purpose: Cisplatin (CDDP) and etoposide (Etp) are recommended first-line therapy for lung cancer. Nanostructured lipid carriers (NLCs) are engineered to deliver drugs for lung cancer treatment. In the present study, NLCs were applied to coload an Etp prodrug (EtpP) and CDDP.
    Methods: The Etp prodrug was synthesized by linking the phenolic hydroxyl group of Etp with polyethylene glycol (PEG). EtpP and CDDP coencapsulated NLCs (EtpP-CDDP NLCs) were prepared using film ultrasound. Cytotoxicity of drugs and drug-containing NLCs was assessed by evaluating cell viability using MTT assays. In vivo antitumor efficiency of EtpP-CDDP NLCs was evaluated on lung cancer-bearing xenografts.
    Results: EtpP-CDDP NLCs showed a uniformly spherical morphology with a size of 176.8±4.9 nm and -potential of -31.9±3.2 mV. Cellular uptake efficiency of EtpP-CDDP NLCs was 57.4%±3.9% on A549/DDP cells. EtpP-CDDP NLCs exhibited more sustained plasma retention, the highest drug distribution in tumors, and the highest tumor-inhibition rates in lung tumor-bearing mice.
    Conclusion: EtpP-CDDP NLCs improved tumor-cell uptake, cytotoxicity, and tumor-inhibition efficiency, and could be used as a promising drug-delivery system for lung cancer combination therapy.
    Keywords:  cisplatin; etoposide; lung cancer; nanostructured lipid carriers; prodrug
    DOI:  https://doi.org/10.2147/DDDT.S386100
  17. Technol Cancer Res Treat. 2022 Jan-Dec;21:21 15330338221144446
    Folate Metabolism in Hepatocellular Carcinoma. What Do We Know So Far?
    Jaqueline Quevedo-Ocampo, Alejandro Escobedo-Calvario, Verónica Souza-Arroyo, Roxana U Miranda-Labra, Leticia Bucio-Ortiz, María C Gutiérrez-Ruiz, Lisette Chávez-Rodríguez, Luis E Gomez-Quiroz.
      Cancer cells are characterized by accelerated proliferation and an outstanding adaptation of their metabolic pathways to meet energy demands. The folate cycle, also known as folate metabolism or one-carbon metabolism, through enzymatic interconversions, provides metabolites necessary for nucleotide synthesis, methylation, and reduction power, helping to maintain the high rate of proliferation; therefore, the study of this metabolic pathway is of great importance in the study of cancer. Moreover, multiple enzymes involved in this cycle have been implicated in different types of cancer, corroborating the cell's adaptations under this pathology. During the last decade, nonalcoholic fatty liver disease has emerged as the leading etiology related to the rise in the incidence and deaths of hepatocellular carcinoma. Specifically, cholesterol accumulation has been a determinant promoter of tumor formation, with solid evidence that an enriched-cholesterol diet plays a crucial role in accelerating the development of an aggressive subtype of hepatocellular carcinoma compared to other models. In this review, we will discuss the most recent findings to understand the contribution of folate metabolism to cancer cells and tumor microenvironment while creating a link between the dynamics given by cholesterol and methylenetetrahydrofolate dehydrogenase 1-like, a key enzyme of the cycle located in the mitochondrial compartment.
    Keywords:  MTHFD1L; cholesterol; folate cycle; hepatocellular carcinoma
    DOI:  https://doi.org/10.1177/15330338221144446
  18. Int J Environ Res Public Health. 2022 Dec 03. pii: 16193. [Epub ahead of print]19(23):
    Effects of Curcumin and Lactoferrin to Inhibit the Growth and Migration of Prostatic Cancer Cells.
    Erica Costantini, Marta Di Nicola, Michele Marchioni, Lisa Aielli, Marcella Reale, Luigi Ships.
      Prostate cancer remains one of the main causes of death for men worldwide. Despite recent advances in cancer treatment, patients develop resistance after an initial period of optimal efficacy. Nowadays, it is accepted that natural compounds can result in health benefits with a preventive or adjuvant effect. The purpose of this study was to evaluate the effects of curcumin (CU), a bioactive compound in the spice turmeric, and lactoferrin (LF), a natural glycoprotein with immunomodulatory properties, on DU145 and PC3. Prostate cancer cells were cultured with and without LF (175 μM) and CU (2.5 μg/mL and 5 μg/mL), alone and in combination. Cell viability, migration ability, death receptors (DRs), and integrins (α3, β1) gene expression were evaluated, as well as human annexin V quantification and Akt phosphorylation. Differences among cells group, defined according to the treatment used, were assessed with ANOVA. The results showed that the effects of CU and LF are different between the two prostatic cell lines analyzed. In DU145, a reduction in cell proliferation and migration is reported both in the presence of single and combined treatments. In PC3 cells, there is a significant reduction in proliferation in the presence of CU alone, while the inhibition of migration is mainly related to the LF treatment and its combination with CU, compared to untreated cells. Moreover, the reduction in gene expression of integrins and Akt pathway activation were observed mostly in the presence of the CU and LF combination, including the upregulation of DR and annexin V levels, with greater significance for the DU145 cells. In conclusion, our results suggest that CU and LF may have a potentially beneficial effect, mainly when administered in combination, leading to a reduction in cancer cells' aggressiveness.
    Keywords:  curcumin; inflammation; lactoferrin; prostate cancer
    DOI:  https://doi.org/10.3390/ijerph192316193
  19. Nanomaterials (Basel). 2022 Nov 26. pii: 4211. [Epub ahead of print]12(23):
    Formulation, Characterization, Anti-Inflammatory and Cytotoxicity Study of Sesamol-Laden Nanosponges.
    Anroop B Nair, Pooja Dalal, Varsha Kadian, Sunil Kumar, Archana Kapoor, Minakshi Garg, Rekha Rao, Bandar Aldhubiab, Nagaraja Sreeharsha, Rashed M Almuqbil, Mahesh Attimarad, Heba S Elsewedy, Pottathil Shinu.
      Sesamol (SES) possesses remarkable chemotherapeutic activity, owing to its anti-inflammatory and antioxidant potential. However, the activity of SES is mainly hampered by its poor physicochemical properties and stability issues. Hence, to improve the efficacy of this natural anti-inflammatory and cytotoxic agent, it was loaded into β-cyclodextrin nanosponges (NS) prepared using different molar ratios of polymer and crosslinker (diphenyl carbonate). The particle size of SES-laden NS (SES-NS) was shown to be in the nano range (200 to 500 nm), with a low polydispersity index, an adequate charge (-17 to -26 mV), and a high payload. Field emission scanning electron microscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy were used to characterize the bioactive-loaded selected batch (SES-NS6). This batch of nanoformulations showed improved solubilization efficacy (701.88 µg/mL) in comparison to bare SES (244.36 µg/mL), polymer (β-CD) (261.43 µg/mL), and other fabricated batches. The drug release data displayed the controlled release behavior of SES from NS. The findings of the egg albumin denaturation assay revealed the enhanced anti-inflammatory potential of SES-NS as compared to bare SES. Further, the cytotoxicity assay showed that SES-NS was more effective against B16F12 melanoma cell lines than the bioactive alone. The findings of this assay demonstrated a reduction in the IC50 values of SES-NS (67.38 μg/mL) in comparison to SES (106 μg/mL). The present investigation demonstrated the in vitro controlled release pattern and the enhanced anti-inflammatory and cytotoxic activity of SES-NS, suggesting its potential as a promising drug delivery carrier for topical delivery.
    Keywords:  Sesamum indicum; anti-inflammatory; cell viability; melanoma; nanosponges; phenolic bioactive
    DOI:  https://doi.org/10.3390/nano12234211
  20. Int J Mol Sci. 2022 Nov 26. pii: 14784. [Epub ahead of print]23(23):
    Enzymatically Modified Isoquercitrin: Production, Metabolism, Bioavailability, Toxicity, Pharmacology, and Related Molecular Mechanisms.
    Aleksandra Owczarek-Januszkiewicz, Anna Magiera, Monika Anna Olszewska.
      Quercetin and its glycosides, such as isoquercitrin or rutin, are among the most ubiquitous flavonoids present in plants. They possess numerous health-promoting properties, whose applicability is, however, limited by poor water solubility and absorption issues. Enzymatically modified isoquercitrin (EMIQ) is an isoquercitrin derivative obtained from rutin via enzymatic transformations that greatly enhance its bioavailability. Due to advantageous reports on its safety and bioactivity, EMIQ is currently gaining importance as a food additive and a constituent of dietary supplements. This review summarizes the thus-far-conducted investigations into the metabolism, toxicity, biological properties, and molecular mechanisms of EMIQ and presents a comprehensive characterization of this valuable substance, which might represent the future of flavonoid supplementation.
    Keywords:  ADME; AGIQ; absorption; anti-inflammatory; cardioprotective; chemopreventive; flavonols; isoquercitrin oligoglucosides; musculotropic; neuroprotective
    DOI:  https://doi.org/10.3390/ijms232314784
  21. Front Immunol. 2022 ;13 1041138
    Tumor immunomodulatory effects of polyphenols.
    Qin Wang, Bin Yang, Nan Wang, Jian Gu.
      Polyphenols, commonly found in various plants, have attracted enormous attention due to their potential pharmacological activity, especially antitumor activity dependent on immune function. In recent years, the development of nanomedicine can counteract the low bioavailability of polyphenols and improve the effect of tumor treatment. Among them, metal-phenolic networks (MPNs), which utilize various metal ions and phenolic ligands for coordination binding, have now become candidates for polyphenol-based nanomedicine treatment of tumors. In this mini-review, we described the classification of polyphenols and their mechanisms in antitumor immune responses, and provided suggestions for the next steps of treating tumors with polyphenols.
    Keywords:  MPNs; bioavailability; natural compounds; polyphenols; tumor immunity
    DOI:  https://doi.org/10.3389/fimmu.2022.1041138
  22. Cells. 2022 Nov 26. pii: 3790. [Epub ahead of print]11(23):
    Metabolism in Cancer Stem Cells: Targets for Clinical Treatment.
    Gui-Min Wen, Xiao-Yan Xu, Pu Xia.
      Cancer stem cells (CSCs) have high tumorigenicity, high metastasis and high resistance to treatment. They are the key factors for the growth, metastasis and drug resistance of malignant tumors, and are also the important reason for the occurrence and recurrence of tumors. Metabolic reprogramming refers to the metabolic changes that occur when tumor cells provide sufficient energy and nutrients for themselves. Metabolic reprogramming plays an important role in regulating the growth and activity of cancer cells and cancer stem cells. In addition, the immune cells or stromal cells in the tumor microenvironment (TME) will change due to the metabolic reprogramming of cancer cells. Summarizing the characteristics and molecular mechanisms of metabolic reprogramming of cancer stem cells will provide new ideas for the comprehensive treatment of malignant tumors. In this review, we summarized the changes of the main metabolic pathways in cancer cells and cancer stem cells.
    Keywords:  ALDH1; cancer stem cell; ferroptosis; metabolism; tumor microenvironment
    DOI:  https://doi.org/10.3390/cells11233790
  23. Acta Biomater. 2022 Dec 12. pii: S1742-7061(22)00816-9. [Epub ahead of print]
    Liposome-based diagnostic and therapeutic applications for pancreatic cancer.
    Faisal Raza, Lauren Evans, Mahzad Motallebi, Hajra Zafar, Miguel Pereira-Silva, Kalsoom Saleem, Diana Peixoto, Abbas Rahdar, Esmaeel Sharifi, Francisco Veiga, Clare Hoskins, Ana Cláudia Paiva-Santos.
      Pancreatic cancer is one of the harshest and most challenging cancers to treat, often labeled as incurable. Chemotherapy continues to be the most popular treatment yet yields a very poor prognosis. The main barriers such as inefficient drug penetration and drug resistance, have led to the development of drug carrier systems. The benefits, ease of fabrication and modification of liposomes render them as ideal future drug delivery systems. This review delves into the versatility of liposomes to achieve various mechanisms of treatment for pancreatic cancer. Not only are there benefits of loading chemotherapy drugs and targeting agents onto liposomes, as well as mRNA combined therapy, but liposomes have also been exploited for immunotherapy and can be programmed to respond to photothermal therapy. Multifunctional liposomal formulations have demonstrated significant pre-clinical success. Functionalising drug-encapsulated liposomes has resulted in triggered drug release, specific targeting, and remodeling of the tumor environment. Suppressing tumor progression has been achieved, due to their ability to more efficiently and precisely deliver chemotherapy. Currently, no multifunctional surface-modified liposomes are clinically approved for pancreatic cancer thus we aim to shed light on the trials and tribulations and progress so far, with the hope for liposomal therapy in the future and improved patient outcomes. STATEMENT OF SIGNIFICANCE: : Considering that conventional treatments for pancreatic cancer are highly associated with sub-optimal performance and systemic toxicity, the development of novel therapeutic strategies holds outmost relevance for pancreatic cancer management. Liposomes are being increasingly considered as promising nanocarriers for providing not only an early diagnosis but also effective, highly specific, and safer treatment, improving overall patient outcome. This manuscript is the first in the last 10 years that revises the advances in the application of liposome-based formulations in bioimaging, chemotherapy, phototherapy, immunotherapy, combination therapies, and emergent therapies for pancreatic cancer management. Prospective insights are provided regarding several advantages resulting from the use of liposome technology in precision strategies, fostering new ideas for next-generation diagnosis and targeted therapies of pancreatic cancer.
    Keywords:  cancer; controlled release; drug delivery; intratumor; liposomes; nanocarrier; stroma remodeling
    DOI:  https://doi.org/10.1016/j.actbio.2022.12.013
  24. Am J Cancer Res. 2022 ;12(11): 5004-5018
    Methionine deprivation inhibits glioma growth through downregulation of CTSL.
    Feng Qian, Haoyue Xu, Yongkang Zhang, Linfeng Li, Rutong Yu.
      The metabolism of tumor cells is characterized by the regulation of demand, nutrient supply and metabolic enzymes, which are different in cancer tissues from those in corresponding healthy tissues. There is growing evidence that dietary composition influences biological processes that contribute to tumor incidence and progression as much as genetic status. One possibility for specific dietary interventions in cancer patients is to limit methionine intake. The role of methionine metabolism in tumors suggests that interference with the methionine metabolism network by either drug or environmental effects may show substantial therapeutic effects, but the molecular mechanism is not completely clear. In this study, methionine deprivation was found to downregulate cathepsin L (CTSL) and induce proliferation inhibition in glioma cells. We also demonstrated that CTSL is a tumor-related gene, and promotes the proliferation and invasion of glioma. Our results showed that the treatment of methionine metabolism and CTSL related genes in glioma cells may be a novel strategy for glioma therapy in the future.
    Keywords:  CTSL; Tumor metabolism; cathepsin L; glioma; methionine deprivation
  25. Int J Biol Macromol. 2022 Dec 08. pii: S0141-8130(22)02951-8. [Epub ahead of print]
    The incorporated hydrogel of chitosan-oligoconjugated linoleic acid vesicles and the protective sustained release for curcumin in the gel.
    Huan Liu, Xinyu Meng, Lei Li, Yongmei Xia, Xueyi Hu, Yun Fang.
      Assemblies of as called "chitosan hydrogel-liposome" are expected for overcoming the burst effect in drug release from chitosan (CS) hydrogels. Herein, a hydrogel delivery system made of chitosan incorporated fatty acid vesicles was constructed for protective sustained release of curcumin (Cur). The curcumin was encapsulated in the prepared oligo-conjugated linoleic acid vesicles (OCLAVs), and then the drug-embedded vesicles were constructed to Cur-OCLAVs-CS hydrogels with CS solution. The fabricated Cur-OCLAVs-CS hydrogel was fluidic at room temperature and could be rapidly gelled at 37 °C. Morphology study proves that the OCLAVs stayed as nano-vesicles in the gel. The Cur-OCLAVs-CS hydrogels effectively declined the burst effect with enhanced antioxidant activity. The Cur (400 μM)-OCLAVs-CS gel presented a cumulative release rate of 51.23 % of curcumin in 96 h, comparing to 93.37 % of that from the Cur-CS gel. Moreover, the corporation of OCLAVs and CS made the gel exhibited strong synergistic effect on the antioxidant activity, with an enhancement of up to 148.1 % on the ferric reducing power. Therefore, the hydrogel carrier made of incorporated fatty acid vesicles-chitosan can be served as an injectable or 3D printable drug delivery system, which may provide a hint to overcome the burst effect that existed in chitosan and other polysaccharide-based gels.
    Keywords:  Antioxidant activity; Chitosan; Conjugated linoleic acid; Hydrogel; Liposome; Sustained release
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.12.049
  26. Nutrients. 2022 Nov 29. pii: 5074. [Epub ahead of print]14(23):
    The Metabolic Role of Ketogenic Diets in Treating Epilepsy.
    Kaleem Imdad, Turki Abualait, Ammara Kanwal, Ziyad Tareq AlGhannam, Shahab Bashir, Anum Farrukh, Sahir Hameed Khattak, Raidah Albaradie, Shahid Bashir.
      Epilepsy is a long-term neurological condition that results in recurrent seizures. Approximately 30% of patients with epilepsy have drug-resistant epilepsy (DRE). The ketogenic diet (KD) is considered an effective alternative treatment for epileptic patients. The aim of this study was to identify the metabolic role of the KD in epilepsy. Ketone bodies induce chemical messengers and alterations in neuronal metabolic activities to regulate neuroprotective mechanisms towards oxidative damage to decrease seizure rate. Here, we discuss the role of KD on epilepsy and related metabolic disorders, focusing on its mechanism of action, favorable effects, and limitations. We describe the significant role of the KD in managing epilepsy disorders.
    Keywords:  biomarkers; drug-resistant epilepsy; epilepsy; ketogenic diet; parameters
    DOI:  https://doi.org/10.3390/nu14235074
  27. Biomed Pharmacother. 2022 Dec 12. pii: S0753-3322(22)01493-7. [Epub ahead of print]158 114104
    Arctium lappa (Burdock): Insights from ethnopharmacology potential, chemical constituents, clinical studies, pharmacological utility and nanomedicine.
    Nermeen Yosri, Sultan M Alsharif, Jianbo Xiao, Syed G Musharraf, Chao Zhao, Aamer Saeed, Ruichang Gao, Noha S Said, Alessandro Di Minno, Maria Daglia, Zhiming Guo, Shaden A M Khalifa, Hesham R El-Seedi.
      Arctium lappa L. is a medicinal edible homologous plant, commonly known as burdock or bardana, which belongs to the Asteraceae family. It is widely distributed throughout Northern Asia, Europe, and North America and has been utilized for hundreds of years. The roots, fruits, seeds, and leaves of A. lappa have been extensively used in traditional Chinese Medicine (TCM). A. lappa has attracted a great deal of attention due to its possession of highly recognized bioactive metabolites with significant therapeutic potential. Numerous pharmacological effects have been demonstrated in vitro and in vivo by A. lappa and its bioactive metabolites, including antimicrobial, anti-obesity, antioxidant, anticancer, anti-inflammatory, anti-diabetic, anti-allergic, antiviral, gastroprotective, hepatoprotective, and neuroprotective activities. Additionally, A. lappa has demonstrated considerable clinical efficacies and valuable applications in nanomedicine. Collectively, this review covers the properties of A. lappa and its bioactive metabolites, ethnopharmacology aspects, pharmacological effects, clinical trials, and applications in the field of nanomedicine. Hence, a significant attention should be paid to clinical trials and industrial applications of this plant with particular emphasis, on drug discovery and nanotechnology.
    Keywords:  Arctium lappa L.; Bioactive constituents; Clinical trials; Folk medicine; Nanomedicine; Preclinical trials
    DOI:  https://doi.org/10.1016/j.biopha.2022.114104
  28. Front Oncol. 2022 ;12 1009700
    Emerging current trends and research focus related to pancreatic cancer metabolism: A bibliometric and visualized analysis.
    Qian Shen, Chuanlong Zhang, Xiaochen Jiang, Junchen Li, Fudong Liu, Xiyuan Zhang, Ge'er En, Bo Pang.
       Background: As a malignant digestive system tumor, pancreatic cancer has unique metabolic characteristics. In recent years, the study of pancreatic cancer metabolism is in full swing, which provides a new direction for the treatment of pancreatic cancer patients. However, there is no systematic report of pancreatic cancer metabolism. In this paper, bibliometrics and visualization methods were used to analyze the number of publications, countries/regions, authors, institutions, journals, co-cited references, and keywords of pancreatic cancer metabolism articles, to summarize the research trends and predict research hotspots.
    Methods: We searched, screened and downloaded articles on pancreatic cancer metabolism through the Web of Science Core Collection (WoSCC). Using CiteSpace, VOSviewer and Bibliometrix Package to analyze publications, countries/regions, authors, institutions, journals, co-cited references, and keywords of pancreatic cancer metabolism to identify research trends and predict research hotspots.
    Results: According to the inclusion and exclusion criteria, a total of 5,255 articles were retrieved during the period 1943-2022. The number of publications on pancreatic cancer metabolism is increasing year by year. The United States (n=1602, 30.49%), China (n=1074, 20.44%), and Italy (n=313, 5.96%) are the three countries with the largest number of publications and citations, and there is close cooperation between countries. LI J (n=55) is the most prolific author. FUDAN UNIV (n=348) is the most published institution. CANCERS (n=118), PLOS ONE (n=93), and CANCER RESEARCH (n=80) are the most popular journals in this field. "Nutriment-deficient environment", "cancer chemoprevention" and "targeting cancer stem cell" are the main areas of focus. "immunotherapy", "ferroptosis" and "targeted therapy" are hot keywords in recent years. Taking pancreatic cancer metabolism as an entry point to study the role of traditional Chinese medicine (TCM) mainly focuses on curcumin and resveratrol, lack of broader and deeper research on TCM.
    Conclusions: The number of publications on pancreatic cancer metabolism has generally increased, and scholars have generally paid more attention to this field. "immunotherapy", "ferroptosis" and "targeted therapy" are the current research hotspots. The in-depth study of pancreatic cancer metabolism will provide new ideas for the treatment of pancreatic cancer.
    Keywords:  CiteSpace; VOSviewer; bibliometric analysis; metabolism; pancreatic cancer
    DOI:  https://doi.org/10.3389/fonc.2022.1009700
  29. Curr Pharm Biotechnol. 2022 Dec 13.
    Liposome based drug delivery for the management of psoriasis - A comprehensive review.
    Shiv Bahadur, Manisha Sharma.
      Psoriasis has been considered as a chronic inflammatory skin disease which leads to the dysfunction of immune systems. According to the World Psoriasis Day consortium, psoriasis affects around 125 million individuals globally or about 2% to 3% of the overall population. Most of the conventional drug delivery systems primarily attempt to relieve symptoms of psoriasis and are ineffective in providing targeted action and higher bioavailability because of the drug's short half-life and instability, as well as they lack safety and efficacy. The shortcomings of conventional drug delivery systems give rise to the development of novel drug delivery systems which includes liposomes, transferosomes, ethosomes, niosomes, emulsomes, dendrimers, hydrogel, nanoparticles, etc. These novel formulations may enhance the therapeutic effects by changing physiological and pharmacokinetic parameters. Several research reports suggest that these novel drug delivery systems may enhance therapeutic effects which can be used as a promising approach for the treatment of psoriasis. The liposomes based drug delivery system have been considered as most promising vehicles for enhancing therapeutic potentials of drugs into or through the skin upon topical application. Liposomes have small unilamellar vesicles which may enhance the penetration ability through stratum corneum layer of skin. Therefore, present review article highlights on the different aspects of the liposomes as potential drug delivery system for the treatment of psoriasis.
    Keywords:  Delivery; Liposomes; Psoriasis; Skin disease; Stratum; Topical; corneum
    DOI:  https://doi.org/10.2174/1389201024666221213144228
  30. Expert Opin Drug Deliv. 2022 Dec 12.
    Alginate-based matrix tablets for drug delivery.
    Natalia Veronica, Paul Wan Sia Heng, Celine Valeria Liew.
       INTRODUCTION: As a nature-derived polymer with swelling and gelling properties, alginate has found wide biopharma-relevant applications, particularly in tissue engineering and wound healing. However, there is comparatively limited attention on alginate in tablet formulations. Therefore, this review aimed to provide an overview of the applications of alginate in solid dosage form formulations.
    AREAS COVERED: This review outlines the role of alginate for oral sustained release drug delivery systems. For better insights into its application in drug delivery, the mechanisms of drug release from alginate matrices are discussed alongside the alginate inherent properties and drug properties. Specifically, the influence of alginate properties and formulation components on the resultant alginate gel and subsequent drug release is reviewed. Lastly, modifications of the alginate to improve its properties in modulating drug release are briefly discussed.
    EXPERT OPINION: Alginate-based matrix tablets provide an alternative method for sustaining drug release. Being a nature-derived polymer, batch consistency and stability of the alginate raise some concerns about employing alginate in formulations. Furthermore, the alginate gel properties can be affected by formulation component, pH of the dissolution environment and the tablet matrix micro-environment pH. Conscientious efforts are pivotal to addressing these formulation challenges to increase the utilization of alginate in oral solid dosage forms.
    Keywords:  Alginate; Drug delivery; Matrix tablet; Sustained release
    DOI:  https://doi.org/10.1080/17425247.2023.2158183
  31. J Control Release. 2022 Dec 12. pii: S0168-3659(22)00841-0. [Epub ahead of print]
    Applications and challenges of ultra-small particle size nanoparticles in tumor therapy.
    Jiaqi Xu, Mengdi Song, Zhou Fang, Lanxi Zheng, Xiaoya Huang, Kehai Liu.
      With the development of nanotechnology, nanomedicines are widely used in tumor therapy. However, biological barriers in the delivery of nanoparticles still limit their application in tumor therapy. As one of the most fundamental properties of nanoparticles, particle size plays a crucial role in the process of the nanoparticles delivery process. It is difficult for large size nanoparticles with fixed size to achieve satisfactory outcomes in every process. In order to overcome the poor penetration of larger size, nanoparticles with ultra-small particle size are proposed, which are more conducive to deep tumor penetration and uniform drug distribution. In this review, the latest progresses and advantages of ultra-small nanoparticles are systematically summarized, the perspectives and challenges of ultra-small nanoparticles strategy for cancer treatment are also discussed.
    Keywords:  Cancer treatment; Drug delivery; Size-shrinkable; Tumor permeation; Ultra-small nanoparticles
    DOI:  https://doi.org/10.1016/j.jconrel.2022.12.028
  32. Nutrients. 2022 Dec 06. pii: 5192. [Epub ahead of print]14(23):
    Improved Stability and In Vitro Anti-Arthritis Bioactivity of Curcumin-Casein Nanoparticles by Ultrasound-Driven Encapsulation.
    Kexin Li, Yahui Zhang, Xueyan Hao, Dongchao Xie, Chongchong Wang, Haihua Zhang, Peng Jin, Qizhen Du.
      Curcumin possesses beneficial biological functions, namely anti-inflammation and anti-diabetic functions. However, due to its low solubility and crystallinity, its applications are limited. In this work, curcumin was encapsulated in casein micelles in order to form curcumin-casein nanoparticles by ultrasound treatment (5 min). The ultrasound treatment induced the entry of the hydrophobic groups to the inner micelles and the polar sulfydryl groups to the surface of the micelles in order to form compact curcumin-casein nanoparticles of an appropriate size (100-120 nm) for cellular endocytosis. The product exhibited excellent stability during 8 months of cold storage, 6 days at room temperature, and 2 days at body temperature. Advanced in vitro experiments demonstrated that curcumin-casein nanoparticles displayed significantly greater inhibitory activity against the proliferation and proinflammatory cytokines of human fibroblast-like synoviocyte-osteo arthritis (HFLS-OA) cells and HFLS-rheumatoid (RA) cells than native curcumin due to better cellular uptake as a result of the low crystallinity and the appropriate nano-size of the nano-form. The results provide a reference for the use of ultrasound treatment to encapsulate other drug molecules and curcumin-casein nanoparticles as potential treatment for arthritis.
    Keywords:  arthritis; curcumin; nanoparticles; sodium caseinate; ultrasound treatment
    DOI:  https://doi.org/10.3390/nu14235192
  33. Foods. 2022 Nov 24. pii: 3787. [Epub ahead of print]11(23):
    A Comprehensive Review of Moringa oleifera Bioactive Compounds-Cytotoxicity Evaluation and Their Encapsulation.
    Oana Lelia Pop, Andreea Diana Kerezsi, Călina Ciont Nagy.
      Moringa oleifera Lam. has gained a lot of attention due to its potential use as a functional food not only for human health but also for animal health. Its bioactive molecules include carbohydrates, phenolic compounds, carotenoids, fatty acids, essential amino acids, and functional peptides. Despite significant efforts to isolate and characterize bioactive metabolites with health functions, few effective metabolites are accessible. The current review aims to describe the main processes for extracting and encapsulating bioactive compounds from Moringa oleifera for potential impact on food science and public health. Researchers have shown that different extraction techniques significantly impact the Moringa polysaccharides' molecular structure and biological activity. Encapsulation has been proposed to reduce oxidative stability and entrap active agents within a carrier material to deliver bioactive molecules into foods. Currently, polysaccharides and proteins, followed by lipids, are used for material encapsulation. Recent techniques include spray drying, cross-linking gelation, freeze-drying, nanoencapsulation, electrospinning, and electrospraying. Moreover, these encapsulations can overlap concerns regarding the Moringa oleifera compounds' cytotoxicity. Future studies should prioritize the effect of new encapsulation materials on Moringa extract and develop new techniques that consider both encapsulation cost and efficiency.
    Keywords:  Moringa oleifera; bioactive compounds; cytotoxicity; encapsulation; extraction techniques
    DOI:  https://doi.org/10.3390/foods11233787
  34. Mater Today Bio. 2023 Feb;18 100508
    Recent advances in responsive hydrogels for diabetic wound healing.
    Siming Zhang, Gaoran Ge, Yi Qin, Wenhao Li, Jiale Dong, Jiawei Mei, Ruixiang Ma, Xianzuo Zhang, Jiaxiang Bai, Chen Zhu, Weiwei Zhang, Dechun Geng.
      Poor wound healing after diabetes mellitus remains a challenging problem, and its pathophysiological mechanisms have not yet been fully elucidated. Persistent bleeding, disturbed regulation of inflammation, blocked cell proliferation, susceptible infection and impaired tissue remodeling are the main features of diabetic wound healing. Conventional wound dressings, including gauze, films and bandages, have a limited function. They generally act as physical barriers and absorbers of exudates, which fail to meet the requirements of the whol diabetic wound healing process. Wounds in diabetic patients typically heal slowly and are susceptible to infection due to hyperglycemia within the wound bed. Once bacterial cells develop into biofilms, diabetic wounds will exhibit robust drug resistance. Recently, the application of stimuli-responsive hydrogels, also known as "smart hydrogels", for diabetic wound healing has attracted particular attention. The basic feature of this system is its capacities to change mechanical properties, swelling ability, hydrophilicity, permeability of biologically active molecules, etc., in response to various stimuli, including temperature, potential of hydrogen (pH), protease and other biological factors. Smart hydrogels can improve therapeutic efficacy and limit total toxicity according to the characteristics of diabetic wounds. In this review, we summarized the mechanism and application of stimuli-responsive hydrogels for diabetic wound healing. It is hoped that this work will provide some inspiration and suggestions for research in this field.
    Keywords:  Biomaterials; Diabetic wound; Hydrogel; Skin tissue engineering; Smart responsiveness
    DOI:  https://doi.org/10.1016/j.mtbio.2022.100508
  35. Mol Biol Rep. 2022 Dec 13.
    Dual role of Nrf2 in cancer: molecular mechanisms, cellular functions and therapeutic interventions.
    M Poornashree, Hitesh Kumar, Ramkishan Ajmeer, Rupshee Jain, Vikas Jain.
       BACKGROUND: Nrf2 regulates oxidative stress, which is essential for cellular function. Fundamental initiation of Nrf2 in many malignancies increases prosurvival genes & endorses tumour cell propagation via metabolic reprogramming, suppression of tumour programmed cell death, & increased cancer stem cell self-renewal potential. More specifically, Nrf2 has been associated with cancer cell chemoresistance, radioresistance & inflammation-induced carcinogenesis.  METHODS AND RESULTS: Many Nrf2 inhibitors have been revealed for tumour treatment and targeting Nrf2 could be an effective cancer therapeutic method. Before spreading, cancer cells adapt to their surroundings. Cancer cells usually have mutations in tumor suppressor genes. In a variety of malignancies, somatic mutations & other anomalies in the Nrf2 genes, as well as renowned cancer suppressor genes including TP53, CDKN2A, PTEN & PIK3CA, have been found. In tumour cells, somatic mutations in the Nrf2 genes, as well as additional mechanisms that affect Nrf2 binding, and produce aberrant Nrf2 activation. Uncontrolled Nrf2 causes tumour cells to become resistant to antineoplastic drugs & reactive oxygen species (ROS), as well as guiding them toward metabolic reprogramming.  CONCLUSIONS: As a result, Nrf2 has been studied as potential malignancy treatment target. We covered the pathways, mechanisms, and dual characteristics of Nrf2 in malignancy in this article. We also discussed how Nrf2 inhibitors are targeted against cancer in this review.
    Keywords:  Anti-oncogenic; Anti-oxidation; Dual role; Nrf2; Pro-oncogenic; Therapeutics
    DOI:  https://doi.org/10.1007/s11033-022-08126-1
  36. Nutrients. 2022 Dec 05. pii: 5170. [Epub ahead of print]14(23):
    Preparation, Characterization, Wound Healing, and Cytotoxicity Assay of PEGylated Nanophytosomes Loaded with 6-Gingerol.
    Ali Al-Samydai, Moath Al Qaraleh, Walhan Alshaer, Lidia K Al-Halaseh, Reem Issa, Fatima Alshaikh, Aseel Abu-Rumman, Hayat Al-Ali, Emad A S Al-Dujaili.
       BACKGROUND: Nutrients are widely used for treating illnesses in traditional medicine. Ginger has long been used in folk medicine to treat motion sickness and other minor health disorders. Chronic non-healing wounds might elicit an inflammation response and cancerous mutation. Few clinical studies have investigated 6-gingerol's wound-healing activity due to its poor pharmacokinetic properties. However, nanotechnology can deliver 6-gingerol while possibly enhancing these properties. Our study aimed to develop a nanophytosome system loaded with 6-gingerol molecules to investigate the delivery system's influence on wound healing and anti-cancer activities.
    METHODS: We adopted the thin-film hydration method to synthesize nanophytosomes. We used lipids in a ratio of 70:25:5 for DOPC(dioleoyl-sn-glycero-3-phosphocholine): cholesterol: DSPE/PEG2000, respectively. We loaded the 6-gingerol molecules in a concentration of 1.67 mg/mL and achieved size reduction via the extrusion technique. We determined cytotoxicity using lung, breast, and pancreatic cancer cell lines. We performed gene expression of inflammation markers and cytokines according to international protocols.
    RESULTS: The synthesized nanophytosome particle sizes were 150.16 ± 1.65, the total charge was -13.36 ± 1.266, and the polydispersity index was 0.060 ± 0.050. Transmission electron microscopy determined the synthesized particles' spherical shape and uniform size. The encapsulation efficiency was 34.54% ± 0.035. Our biological tests showed that 6-gingerol nanophytosomes displayed selective antiproliferative activity, considerable downregulation of inflammatory markers and cytokines, and an enhanced wound-healing process.
    CONCLUSIONS: Our results confirm the anti-cancer activity of PEGylated nanophytosome 6-gingerol, with superior activity exhibited in accelerating wound healing.
    Keywords:  6-gingerol; cytotoxicity; liposomes; nanoparticles; phytosomes; wound healing
    DOI:  https://doi.org/10.3390/nu14235170
  37. Med Oncol. 2022 Dec 16. 40(1): 49
    Src inhibitor dasatinib sensitized gastric cancer cells to cisplatin.
    Huizhen Wang, Yida Lu, Mingliang Wang, Aolin Shen, Youliang Wu, Xin Xu, Yongxiang Li.
      Gastric cancer (GC) is characterized by high incidence and mortality, and lacks effective treatment. Surgery, combined with chemo- and radiation therapy, represents the cornerstones of GC treatment. Although platinum is commonly used, severe side effects and drug resistance limited its application. Cisplatin-induced cell death mainly relies on the increment of reactive oxygen species (ROS), while the effect of dasatinib on ROS is inconclusive. In this article, dasatinib and cisplatin showed various anti-cancer properties on GC cells, which might be related to the changes of ROS levels. However, NAC enhanced cell death induced by dasatinib, although it elevated ROS levels in GES1 and AGS cells, suggesting that the elevation of ROS levels was not the responsible mechanism. Notably, dasatinib markedly synergized cells against cisplatin. Dasatinib decreased pSer473 Akt levels, and increased p53 expression, which was confirmed by LY294002 or Nutlin-3a co-treatment. Furthermore, transcriptome sequencing also confirmed that the PI3K/AKT pathway was involved in the anti-cancer effect of dasatinib or combined with cisplatin. Additionally, GC cells with higher Src activity (AGS) elicited more sensitive to dasatinib than lower cells (SGC7901 and MGC803), suggesting that the Src levels could be applied to pre-select patients who would benefit from dasatinib and/or combined with platinum compounds.
    Keywords:  Cisplatin; Dasatinib; Gastric cancer; Reactive oxygen species
    DOI:  https://doi.org/10.1007/s12032-022-01879-6
  38. Cardiovasc Hematol Disord Drug Targets. 2022 Dec 07.
    Therapeutic effectiveness of sinensetin against cancer and other human complications: A review of biological potential and pharmacological activities.
    Kanika Patel, Dinesh Kumar Patel.
       BACKGROUND: Plant and their active phytoproducts have been used in modern medicine and playing an important role in the health sectors since a very early age. Human beings need a considerable amount of these plant-based phytochemicals for their health. The flavonoidal class phytochemical is an important class of natural products in modern healthcare because of their different pharmacological activities and health benefits. Flavonoidal class phytochemicals have been used to treat diabetes and related secondary complications in humans. Flavonoids have anti-apoptotic, anti-hyperlipidemic, anti-inflammatory, and anti-oxidant potential in the health sectors. Sinensetin, also called 3',4',5,6,7-pentametoksiflavon is a colorless compound with a molecular weight 372.37g/mol and is found to be present in the Orthosiphon stamineus.
    METHODS: In the present investigation, we aim to collect scientific information on sinensetin and analyze it for its biological potential and therapeutic benefits against various types of disorders and complications. Medicinal importance and pharmacological activities data have been collected and analyzed in the present work for sinensetin through literature data analysis of different research works. Google Science Direct, PubMed, Scopus, and Google Scholar were mainly searched to collect the scientific information in the present work. The present work analyzed sinensetin's biological potential, pharmacological activities, and analytical aspects.
    RESULTS: Literature data analysis of different scientific research works revealed the biological potential of phytochemicals in medicine, including flavonoids. Sinensetin has anti-tumor, anti-inflammatory, anti-oxidant, anti-diabetic, and antibacterial activities through their testing in different in vitro and in vivo models. Sinensetin has physiological functions, including anti-oxidant, anti-inflammation, and anti-cancer potential in medicine. Scientific data analysis signified the biological importance of sinensetin against tumors, gastric cancer, colorectal cancer, breast cancer, diabetes, influenza H1N1 infection, obesity, inflammation, colitis, brain disorders, and microbial infections. Further biological potential of sinensetin on enzymes and angiogenesis has been analyzed in the present work. Sinensetin was isolated through different analytical and extraction techniques, including chromatographic techniques.
    CONCLUSION: Literature data analysis signified sinensetin's biological potential and pharmacological activities in medicine.
    Keywords:  Brain disorders; Breast cancer; Colitis; Colorectal cancer; Diabetes; Gastric cancer; Inflammation; Influenza H1N1 infection; Obesity; Sinensetin tumors
    DOI:  https://doi.org/10.2174/1871529X23666221207121955
  39. Process Biochem. 2022 Jun;117 209-218
    The inhibitory effect of curcumin loaded poly (vinyl caprolactam) nanohydrogel on insulin fibrillation.
    Marzieh Bahmani, Mohsen Akbarian, Lobat Tayebi, Fatemeh Farjadian.
      Amyloidosis refers to a group of diseases caused by the deposition of abnormal proteins in tissues. Herein, curcumin was loaded in a nanohydrogel made of poly (vinylcaprolactam) to improve its solubility and was employed to exert an inhibitory effect on insulin fibrillation, as a protein model. Poly (vinyl caprolactam), cross-linked with polyethylene glycol diacrylate, was synthesized by the reversible addition-fragmentation chain transfer method. The release profile of curcumin exhibited a first-order kinetic model, signifying that the release of curcumin was mainly dominated by diffusion processes. The study of curcumin release showed that 78% of the compound was released within 72 h. The results also revealed a significant decline in insulin fibrillation in the presence of curcumin-loaded poly (vinyl caprolactam). These observations confirmed that increasing the ratio of curcumin-loaded poly (vinyl caprolactam) to insulin concentration would increase the hydrogel's inhibitory effect (P-value < 0.05). Furthermore, transmission electron and fluorescence microscopies and Fourier-transform infrared spectroscopy made it possible to study the size and interaction of fibrils. Based on the results, this nanohydrogel combination could protect the structure of insulin and had a deterrent effect on fibril formation.
    Keywords:  Curcumin; Fibrillation; Insulin; Nano-hydrogel; PEGDA; PVCL; Poly (vinylcaprolactam); RAFT
    DOI:  https://doi.org/10.1016/j.procbio.2022.04.009
  40. Drug Deliv Transl Res. 2022 Dec 12.
    Improving in vivo oral bioavailability of a poorly soluble drug: a case study on polymeric versus lipid nanoparticles.
    Giovanna Rassu, Antonella Obinu, Carla Serri, Sandra Piras, Antonio Carta, Luca Ferraro, Elisabetta Gavini, Paolo Giunchedi, Alessandro Dalpiaz.
      Poorly soluble drugs must be appropriately formulated for clinical use to increase the solubility, dissolution rate, and permeation across the intestinal epithelium. Polymeric and lipid nanocarriers have been successfully investigated for this aim, and their physicochemical properties, and in particular, the surface chemistry, significantly affect the pharmacokinetics of the drugs after oral administration. In the present study, PLGA nanoparticles (SS13NP) and solid lipid nanoparticles (SS13SLN) loaded with SS13, a BCS IV model drug, were prepared. SS13 bioavailability following the oral administration of SS13 (free drug), SS13NP, or SS13SLN was compared. SS13NP had a suitable size for oral administration (less than 300 nm), a spherical shape and negative zeta potential, similarly to SS13SLN. On the contrary, SS13NP showed higher physical stability but lower encapsulation efficiency (54.31 ± 6.66%) than SS13SLN (100.00 ± 3.11%). When orally administered (0.6 mg of drug), SS13NP showed higher drug AUC values with respect to SS13SLN (227 ± 14 versus 147 ± 8 µg/mL min), with higher Cmax (2.47 ± 0.14 µg/mL versus 1.30 ± 0.15 µg/mL) reached in a shorter time (20 min versus 60 min). Both formulations induced, therefore, the oral bioavailability of SS13 (12.67 ± 1.43% and 4.38 ± 0.39% for SS13NP and SS12SLN, respectively) differently from the free drug. These in vivo results confirm that the chemical composition of nanoparticles significantly affects the in vivo fate of a BCS IV drug. Moreover, PLGA nanoparticles appear more efficient and rapid than SLN in allowing drug absorption and transport to systemic circulation.
    Keywords:  BCS IV drug; Oral bioavailability; PLGA nanoparticle; Poorly soluble drug; SLN
    DOI:  https://doi.org/10.1007/s13346-022-01278-4
  41. Cancer Cell Int. 2022 Dec 10. 22(1): 399
    Ursolic acid: a natural modulator of signaling networks in different cancers.
    Sameen Zafar, Khushbukhat Khan, Amna Hafeez, Muhammad Irfan, Muhammad Armaghan, Anees Ur Rahman, Eda Sönmez Gürer, Javad Sharifi-Rad, Monica Butnariu, Iulia-Cristina Bagiu, Radu Vasile Bagiu.
      Incidence rate of cancer is estimated to increase by 40% in 2030. Furthermore, the development of resistance against currently available treatment strategies has contributed to the cancer-associated mortality. Scientists are now looking for the solutions that could help prevent the disease occurrence and could provide a pain-free treatment alternative for cancers. Therefore, efforts are now put to find a potent natural compound that could sever this purpose. Ursolic acid (UA), a triterpene acid, has potential to inhibit the tumor progression and induce sensitization to conventional treatment drugs has been documented. Though, UA is a hydrophobic compound therefore it is usually chemically modified to increase its bioavailability prior to administration. However, a thorough literature indicating its mechanism of action and limitations for its use at clinical level was not reviewed. Therefore, the current study was designed to highlight the potential mechanism of UA, its anti-cancer properties, and potential applications as therapeutic compound. This endeavour is a valuable contribution in understanding the hurdles preventing the translation of its potential at clinical level and provides foundations to design new studies that could help enhance its bioavailability and anti-cancer potential for various cancers.
    Keywords:  Anti-cancer potential; Cell signaling; Drug resistance; Natural compound; Ursolic acid
    DOI:  https://doi.org/10.1186/s12935-022-02804-7
  42. Molecules. 2022 Dec 03. pii: 8503. [Epub ahead of print]27(23):
    Combined Effects of Lycopene and Metformin on Decreasing Oxidative Stress by Triggering Endogenous Antioxidant Defenses in Diet-Induced Obese Mice.
    Bruno Pereira Motta, Camila Graça Pinheiro, Ingrid Delbone Figueiredo, Felipe Nunes Cardoso, Juliana Oriel Oliveira, Rachel Temperani Amaral Machado, Patrícia Bento da Silva, Marlus Chorilli, Iguatemy Lourenço Brunetti, Amanda Martins Baviera.
      Since lycopene has antioxidant activity, its combination with metformin may be useful to contrast diabetic complications related to oxidative stress. This study aimed to investigate the effects of metformin combined with lycopene on high-fat diet (HFD)-induced obese mice. Seventy-two C57BL-6J mice were divided into six groups: C (control diet-fed mice), H (HFD-fed mice for 17 weeks), H-V (HFD-fed mice treated with vehicle), H-M (HFD-fed mice treated with 50 mg/kg metformin), H-L (HFD-fed mice treated with 45 mg/kg lycopene), and H-ML (HFD-fed mice treated with 50 mg/kg metformin + 45 mg/kg lycopene). Treatments were administered for 8 weeks. Glucose tolerance, insulin sensitivity, fluorescent AGEs (advanced glycation end products), TBARS (thiobarbituric acid-reactive substances), and activities of antioxidant enzymes paraoxonase-1 (PON-1; plasma), superoxide dismutase, catalase and glutathione peroxidase (liver and kidneys) were determined. Metformin plus lycopene reduced body weight; improved insulin sensitivity and glucose tolerance; and decreased AGEs and TBARS in plasma, liver and kidneys. Combined therapy significantly increased the activities of antioxidant enzymes, mainly PON-1. Lycopene combined with metformin improved insulin resistance and glucose tolerance, and caused further increases in endogenous antioxidant defenses, arising as a promising therapeutic strategy for combating diabetic complications resulting from glycoxidative stress.
    Keywords:  advanced glycation end products; carotenoids; glycoxidative stress; metabolic memory; paraoxonase-1
    DOI:  https://doi.org/10.3390/molecules27238503
  43. Int J Mol Sci. 2022 Dec 03. pii: 15279. [Epub ahead of print]23(23):
    Crosstalk between Resveratrol and Gut Barrier: A Review.
    Natalia Drabińska, Elżbieta Jarocka-Cyrta.
      The plant-based nutraceuticals are receiving increasing interest in recent time. The high attraction to the phytochemicals is associated with their anti-inflammatory and antioxidant activities, which can lead to reduced risk of the development of cardiovascular and other non-communicable diseases. One of the most disseminated groups of plant bioactives are phenolic compounds. It was recently hypothesized that phenolic compounds can have the ability to improve the functioning of the gut barrier. The available studies showed that one of the polyphenols, resveratrol, has great potential to improve the integrity of the gut barrier. Very promising results have been obtained with in vitro and animal models. Still, more clinical trials must be performed to evaluate the effect of resveratrol on the gut barrier, especially in individuals with increased intestinal permeability. Moreover, the interplay between phenolic compounds, intestinal microbiota and gut barrier should be carefully evaluated in the future. Therefore, this review offers an overview of the current knowledge about the interaction between polyphenols with a special emphasis on resveratrol and the gut barrier, summarizes the available methods to evaluate the intestinal permeability, discusses the current research gaps and proposes the directions for future studies in this research area.
    Keywords:  gut barrier; intestinal permeability; leaky gut; polyphenols; resveratrol
    DOI:  https://doi.org/10.3390/ijms232315279
  44. Cell Chem Biol. 2022 Dec 01. pii: S2451-9456(22)00415-9. [Epub ahead of print]
    Metabolic modulation of transcription: The role of one-carbon metabolism.
    Jung-Ming G Lin, Savvas Kourtis, Ritobrata Ghose, Natalia Pardo Lorente, Stefan Kubicek, Sara Sdelci.
      While it is well known that expression levels of metabolic enzymes regulate the metabolic state of the cell, there is mounting evidence that the converse is also true, that metabolite levels themselves can modulate gene expression via epigenetic modifications and transcriptional regulation. Here we focus on the one-carbon metabolic pathway, which provides the essential building blocks of many classes of biomolecules, including purine nucleotides, thymidylate, serine, and methionine. We review the epigenetic roles of one-carbon metabolic enzymes and their associated metabolites and introduce an interactive computational resource that places enzyme essentiality in the context of metabolic pathway topology. Therefore, we briefly discuss examples of metabolic condensates and higher-order complexes of metabolic enzymes downstream of one-carbon metabolism. We speculate that they may be required to the formation of transcriptional condensates and gene expression control. Finally, we discuss new ways to exploit metabolic pathway compartmentalization to selectively target these enzymes in cancer.
    Keywords:  cancer; chromatin; epigenetics; folate metabolism; metabolic condensates; nuclear condensates; nuclear metabolism; nucleotides; one-carbon metabolism; phase separation; purinergic signaling; transcription regulation; transcriptional condensates
    DOI:  https://doi.org/10.1016/j.chembiol.2022.11.009
  45. Int J Biol Macromol. 2022 Dec 07. pii: S0141-8130(22)02926-9. [Epub ahead of print]
    Multifunctional hydrogels based on chitosan, hyaluronic acid and other biological macromolecules for the treatment of inflammatory bowel disease: A review.
    Yongliang Ouyang, Jiulong Zhao, Shige Wang.
      Hydrogel is a three-dimensional network polymer material rich in water. It is widely used in the biomedical field because of its unique physical and chemical properties and good biocompatibility. In recent years, the incidence of inflammatory bowel disease (IBD) has gradually increased, and the disadvantages caused by traditional drug treatment have emerged. Therefore, there is an urgent need for new treatments to alleviate IBD. Hydrogel has become a potential therapeutic platform. However, there is a lack of comprehensive review of functional hydrogels for IBD. This paper first summarizes the pathological changes in IBD sites. Then, the action mechanism of hydrogels prepared from chitosan, sodium alginate, hyaluronic acid, functionalized polyethylene glycol, cellulose, pectin, and γ-polyglutamic acid on IBD was described including drug delivery, peptide and protein delivery, biologic therapies, loading probiotics, etc., were elaborated. In addition, the advanced functions of IBD hydrogels were summarized, with emphasis on adhesion, synergistic therapy, pH sensitivity, particle size, and temperature sensitivity. Finally, the future development direction of IBD hydrogel has been prospected.
    Keywords:  Biological macromolecules; Chitosan; Hyaluronic acid; Inflammatory bowel disease; Multifunctional hydrogel
    DOI:  https://doi.org/10.1016/j.ijbiomac.2022.12.032
  46. Molecules. 2022 Dec 01. pii: 8401. [Epub ahead of print]27(23):
    Fabrication of PEGylated Chitosan Nanoparticles Containing Tenofovir Alafenamide: Synthesis and Characterization.
    Muhammad Zaman, Muhammad Hammad Butt, Waqar Siddique, Muhammad Omer Iqbal, Naveed Nisar, Asma Mumtaz, Hafiza Yusra Nazeer, Abdulrahman Alshammari, Muhammad Shahid Riaz.
      Tenofovir alafenamide (TAF) is an antiretroviral (ARV) drug that is used for the management and prevention of human immunodeficiency virus (HIV). The clinical availability of ARV delivery systems that provide long-lasting protection against HIV transmission is lacking. There is a dire need to formulate nanocarrier systems that can help in revolutionizing the way to fight against HIV/AIDS. Here, we aimed to synthesize a polymer using chitosan and polyethylene glycol (PEG) by the PEGylation of chitosan at the hydroxyl group. After successful modification and confirmation by FTIR, XRD, and SEM, TAF-loaded PEGylated chitosan nanoparticles were prepared and analyzed for their particle size, zeta potential, morphology, crystallinity, chemical interactions, entrapment efficacy, drug loading, in vitro drug release, and release kinetic modeling. The fabricated nanoparticles were found to be in a nanosized range (219.6 nm), with ~90% entrapment efficacy, ~14% drug loading, and a spherical uniform distribution. The FTIR analysis confirmed the successful synthesis of PEGylated chitosan and nanoparticles. The in vitro analysis showed ~60% of the drug was released from the PEGylated polymeric reservoir system within 48 h at pH 7.4. The drug release kinetics were depicted by the Korsmeyer-Peppas release model with thermodynamically nonspontaneous drug release. Conclusively, PEGylated chitosan has the potential to deliver TAF from a nanocarrier system, and in the future, cytotoxicity and in vivo studies can be performed to further authenticate the synthesized polymer.
    Keywords:  antiretroviral drugs; chitosan; nanocarrier system; nanoparticles; polyethylene glycol; polymer synthesis; tenofovir alafenamide
    DOI:  https://doi.org/10.3390/molecules27238401
  47. Biochem Biophys Res Commun. 2022 Dec 05. pii: S0006-291X(22)01680-1. [Epub ahead of print]640 134-141
    Dual drug delivery system of RAPTA-C and paclitaxel based on fructose coated nanoparticles for metastatic cancer treatment.
    Mingxia Lu, Sen Wang, Yee Yee Khine, Yanchen Hong, Jiayu Zheng, Hongxu Lu, Martina H Stenzel.
      Ruthenium complexes have been widely studied as potential alternatives to platinum-type anticancer drugs due to their unique medical properties such as high selectivity, strong ability to inhibit solid tumour metastasis. However, non-specific biodistribution, and weak lethality of ruthenium to cancer cells limit its use in medical application. Drug delivery systems offer the ability to integrate multiple drugs in one system, which is particularly important to enhance the chemotherapeutic efficacy and to potentially achieve a synergistic effect of both drugs. Here, we report a dual drug nanocarrier that is based on a self-assembled biodegradable block copolymer, where the ruthenium complex (RAPTA-C) is chemically attached to the polymer chain, while another drug, paclitaxel (PTX), is entrapped in the core of the micelle. The dual drug delivery system was studied via in vitro tests using MDA-MB-231 breast cancer cells and it was observed that RAPTA-C in combination with PTX significantly enhanced anti-tumour and anti-metastasis activity.
    Keywords:  Cancer treatment; Combination therapy; Dual drug delivery; Paclitaxel; Polymeric micelles; Ruthenium complexes
    DOI:  https://doi.org/10.1016/j.bbrc.2022.12.013
  48. Biomater Adv. 2022 Dec 05. pii: S2772-9508(22)00501-5. [Epub ahead of print]145 213224
    Injectable anti-cancer drug loaded silk-based hydrogel for the prevention of cancer recurrence and post-lumpectomy tissue regeneration aiding triple-negative breast cancer therapy.
    Chitra Jaiswal, Tarishi Gupta, Praveen Kumar Jadi, Joseph Christakiran Moses, Biman B Mandal.
      A single system capable of delivering anticancer drugs and growth factors by a minimally invasive approach is in demand for effective treatment of triple-negative breast cancer (TNBC) after lumpectomy. Here, we showcase one such holistic system for TNBC therapy and its assessment via 3D in vitro lumpectomy model, a first of its kind. Firstly, Bombyx mori silk fibroin (BMSF) and Antheraea assamensis silk fibroin (AASF) blended hydrogels were prepared and biophysically characterized. Secondly, a 3D in vitro lumpectomy model was developed using MDA-MB-231 cell line to assess the efficacy of localized delivery of doxorubicin (dox) using injectable hydrogel system in terminating remaining breast cancer after lumpectomy. Additionally, we have also evaluated the adipose tissue regeneration in the lumpectomy region by delivering dexamethasone (dex) using injectable hydrogels. Rheological studies showed that the BMSF/AASF blended hydrogels exhibit viscoelasticity and injectability conducive for minimally invasive application. The developed hydrogels by virtue of its slow and sustained release of dox exerted cytotoxicity towards MDA-MB-231 cells assessed through in vitro studies. Further, dex loaded hydrogel supported adipogenic differentiation of adipose tissue derived stem cells (ADSCs), while the secreted factors were found to aid in vascularization and macrophage polarization. This was confirmed through in vitro angiogenic tube formation assay and macrophage polarization study respectively. The corroborated results vouch for potential application of this injectable hydrogels for localized anticancer drug delivery and aiding in breast reconstruction, post lumpectomy.
    Keywords:  Drug delivery; In vitro cancer model; Injectable hydrogel; Silk fibroin; cancer therapy
    DOI:  https://doi.org/10.1016/j.bioadv.2022.213224
  49. J Control Release. 2022 Dec 08. pii: S0168-3659(22)00824-0. [Epub ahead of print]
    Triggered release from thermosensitive liposomes improves tumor targeting of vinorelbine.
    Maximilian Regenold, Kan Kaneko, Xuehan Wang, H Benson Peng, James C Evans, Pauric Bannigan, Christine Allen.
      Triggered drug delivery strategies have been shown to enhance drug accumulation at target diseased sites in comparison to administration of free drug. In particular, many studies have demonstrated improved targetability of chemotherapeutics when delivered via thermosensitive liposomes. However, most studies continue to focus on encapsulating doxorubicin while many other drugs would benefit from this targeted and localized delivery approach. The proposed study explores the therapeutic potential of a thermosensitive liposome formulation of the commonly used chemotherapy drug vinorelbine in combination with mild hyperthermia (39-43 °C) in a murine model of rhabdomyosarcoma. Rhabdomyosarcoma, the most common soft tissue sarcoma in children, is largely treated using conventional chemotherapy which is associated with significant adverse long-term sequelae. In this study, mild hyperthermia was pursued as a non-invasive, non-toxic means to improve the efficacy and safety profiles of vinorelbine. Thorough assessment of the pharmacokinetics, biodistribution, efficacy and toxicity of vinorelbine administered in the thermosensitive liposome formulation was compared to administration in a traditional, non-thermosensitive liposome formulation. This study shows the potential of an advanced formulation technology in combination with mild hyperthermia as a means to target an untargeted therapeutic agent and result in a significant improvement in its therapeutic index.
    Keywords:  Drug delivery; Drug release; Hyperthermia; Nanomedicine; Rhabdomyosarcoma; Thermosensitive liposome; Vinorelbine
    DOI:  https://doi.org/10.1016/j.jconrel.2022.12.010
  50. Int J Mol Sci. 2022 Dec 01. pii: 15119. [Epub ahead of print]23(23):
    Sirtuins (SIRTs) As a Novel Target in Gastric Cancer.
    Agata Poniewierska-Baran, Paulina Warias, Katarzyna Zgutka.
      Gastric cancer is a major health burden worldwide. Among all neoplasms, gastric cancer is the fifth most common and the third most deadly type of cancer. It is known that sirtuins (SIRTs), are NAD+-dependent histone deacetylases regulating important metabolic pathways. High expression of SIRTs in the human body can regulate metabolic processes; they prevent inflammation but also resist cell death and aging processes. The seven members of this family enzymes can also play a fundamental role in process of carcinogenesis by influencing cell viability, apoptosis and metastasis. This review collects and discusses the role of all seven sirtuins (SIRT1-SIRT7) in the pathogenesis of gastric cancer (GC).
    Keywords:  SIRT family; gastric adenocarcinoma; gastric cancer; pathogenesis; sirtuins; stomach cancer
    DOI:  https://doi.org/10.3390/ijms232315119
  51. Int J Mol Sci. 2022 Nov 23. pii: 14564. [Epub ahead of print]23(23):
    Ketone Bodies as Metabolites and Signalling Molecules at the Crossroad between Inflammation and Epigenetic Control of Cardiometabolic Disorders.
    Nadia Bendridi, Anna Selmi, Aneta Balcerczyk, Luciano Pirola.
      For many years, it has been clear that a Western diet rich in saturated fats and sugars promotes an inflammatory environment predisposing a person to chronic cardiometabolic diseases. In parallel, the emergence of ketogenic diets, deprived of carbohydrates and promoting the synthesis of ketone bodies imitating the metabolic effects of fasting, has been shown to provide a possible nutritional solution to alleviating diseases triggered by an inflammatory environment. The main ketone body, β-hydroxybutyrate (BHB), acts as an alternative fuel, and also as a substrate for a novel histone post-translational modification, β-hydroxybutyrylation. β-hydroxybutyrylation influences the state of chromatin architecture and promotes the transcription of multiple genes. BHB has also been shown to modulate inflammation in chronic diseases. In this review, we discuss, in the pathological context of cardiovascular risks, the current understanding of how ketone bodies, or a ketogenic diet, are able to modulate, trigger, or inhibit inflammation and how the epigenome and chromatin remodeling may be a key contributor.
    Keywords:  cardiovascular diseases; histone PTMs; histone β-hydroxybutyrylation; ketone bodies
    DOI:  https://doi.org/10.3390/ijms232314564
  52. Indian J Med Res. 2022 Jan;156(1): 70-76
    Morphine counteracts the effects of paclitaxel in triple-negative breast cancer cells.
    Gülay Sezer, Armağan Caner, Müge Gülcihan Önal, Ahmet Cumaoğlu.
       Background & objectives: Several studies have provided evidence that opioids may play a role in cancer recurrence and metastasis. Multiple research data indicate that morphine can act as a proliferative or suppressive agent on tumour cells depending on the applied concentration. Therefore, this study was aimed to investigate whether the presence of clinically relevant concentrations of morphine has any effect on the efficacy of paclitaxel, a widely used chemotherapeutic drug, on the viability and apoptosis of human triple-negative breast cancer cell line.
    Methods: MDA.MB.231 cells were treated with paclitaxel in the presence or absence of morphine and examined for cell proliferation by the MTT assay. In addition, the effect of morphine on paclitaxel-induced apoptosis was investigated by flow cytometric assay and by the ratio of Bax/Bcl-2 mRNA expression levels with quantitative real-time (qRT)-PCR.
    Results: Morphine significantly increased the proliferation of breast cancer cells at low concentrations (0.1-2.5 μM) but higher concentrations showed cytotoxic effect. Pre-treatment with 0.1 or 1 μM of morphine decreased the paclitaxel-induced cytotoxicity, the proportion of apoptotic cell, and the ratio of Bax/Bcl-2 mRNA expressions.
    Interpretation & conclusions: Our data suggest that morphine promotes breast cancer cell viability at clinically relevant plasma concentrations and reduces the apoptotic effect of paclitaxel. This interaction may be very important in clinical settings; however, more studies are needed to explore the plausible mechanisms of interaction and to correlate such findings through in vivo animal studies as well as clinically.
    Keywords:  Apoptosis; MDA.MB.231; in vitro; morphine; opioid; paclitaxel; triple-negative breast cancer
    DOI:  https://doi.org/10.4103/ijmr.IJMR_2443_19
  53. Foods. 2022 Nov 22. pii: 3756. [Epub ahead of print]11(23):
    Preparation, Characterization, In Vitro Release, and Antibacterial Activity of Oregano Essential Oil Chitosan Nanoparticles.
    Yuan Ma, Ping Liu, Kunyue Ye, Yezheng He, Siqi Chen, Anqi Yuan, Fang Chen, Wanli Yang.
      Essential oils have unique functional properties, but their environmental sensitivity and poor water solubility limit their applications. Therefore, we encapsulated oregano essential oil (OEO) in chitosan nanoparticles (CSNPs) and used tripolyphosphate (TPP) as a cross-linking agent to produce oregano essential oil chitosan nanoparticles (OEO-CSNPs). The optimized conditions obtained using the Box-Behnken design were: a chitosan concentration of 1.63 mg/mL, TPP concentration of 1.27 mg/mL, and OEO concentration of 0.30%. The OEO-CSNPs had a particle size of 182.77 ± 4.83 nm, a polydispersity index (PDI) of 0.26 ± 0.01, a zeta potential of 40.53 ± 0.86 mV, and an encapsulation efficiency of 92.90%. The success of OEO encapsulation was confirmed by Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). The scanning electron microscope (SEM) analysis showed that the OEO-CSNPs had a regular distribution and spherical shape. The in vitro release profile at pH = 7.4 showed an initial burst release followed by a sustained release of OEO. The antibacterial activity of OEO before and after encapsulation was measured using the agar disk diffusion method. In conclusion, OEO can be used as an antibacterial agent in future food processing and packaging applications because of its high biological activity and excellent stability when encapsulated.
    Keywords:  Box–Behnken design; antibacterial; chitosan nanoparticles; oregano essential oil
    DOI:  https://doi.org/10.3390/foods11233756
  54. Int J Mol Sci. 2022 Dec 04. pii: 15296. [Epub ahead of print]23(23):
    Therapeutic Targeting of Glutaminolysis as a Novel Strategy to Combat Cancer Stem Cells.
    Ting-Wan Kao, Yao-Chen Chuang, Hsin-Lun Lee, Chia-Chun Kuo, Yao-An Shen.
      Rare subpopulations of cancer stem cells (CSCs) have the ability to self-renew and are the primary driving force behind cancer metastatic dissemination and the preeminent hurdle to cancer treatment. As opposed to differentiated, non-malignant tumor offspring, CSCs have sophisticated metabolic patterns that, depending on the kind of cancer, rely mostly on the oxidation of major fuel substrates such as glucose, glutamine, and fatty acids for survival. Glutaminolysis is a series of metabolic reactions that convert glutamine to glutamate and, eventually, α-ketoglutarate, an intermediate in the tricarboxylic acid (TCA) cycle that provides biosynthetic building blocks. These building blocks are mostly utilized in the synthesis of macromolecules and antioxidants for redox homeostasis. A recent study revealed the cellular and molecular interconnections between glutamine and cancer stemness in the cell. Researchers have increasingly focused on glutamine catabolism in their attempt to discover an effective therapy for cancer stem cells. Targeting catalytic enzymes in glutaminolysis, such as glutaminase (GLS), is achievable with small molecule inhibitors, some of which are in early-phase clinical trials and have promising safety profiles. This review summarizes the current findings in glutaminolysis of CSCs and focuses on novel cancer therapies that target glutaminolysis in CSCs.
    Keywords:  cancer stem cells; glutaminase; glutaminolysis; metabolic compensation; therapeutic resistance
    DOI:  https://doi.org/10.3390/ijms232315296
  55. Drug Deliv Transl Res. 2022 Dec 12.
    Investigating the influence of ultrasound parameters on ibuprofen drug release from hydrogels.
    Svenja Meissner, Jhansi H Akepogu, Samantha M Arnet, Mohammed Z Dean, Jessie Ji, Grace Wright, Bruce Harland, Brad Raos, Darren Svirskis, Sachin S Thakur.
      Hydrogels are promising ultrasound-responsive drug delivery systems. In this study, we investigated how different ultrasound parameters affected drug release and structural integrity of self-healing hydrogels composed of alginate or poloxamers. The effects of amplitude and duty cycle at low frequency (24 kHz) ultrasound stimulation were first investigated using alginate hydrogels at 2% w/v and 2.5% w/v. Increasing ultrasound amplitude increased drug release from these gels, although high amplitudes caused large variations in release and damaged the gel structure. Increasing duty cycle also increased drug release, although a threshold was observed with the lower pulsed 50% duty cycle achieving similar levels of drug release to a continuous 100% duty cycle. Poloxamer-based hydrogels were also responsive to the optimised parameters at low frequency (24 kHz, 20% amplitude, 50% duty cycle for 30 s) and showed similar drug release results to a 2.5% w/v alginate hydrogel. Weight loss studies demonstrated that the 2% w/v alginate hydrogel underwent significant erosion following ultrasound application, whereas the 2.5% w/v alginate and the poloxamer gels were unaffected by application of the same parameters (24 kHz, 20% amplitude, 50% duty cycle for 30 s). The rheological properties of the hydrogels were also unaffected and the FTIR spectra remained unchanged after low frequency ultrasound stimulation (24 kHz, 20% amplitude, 50% duty cycle for 30 s). Finally, high-frequency ultrasound stimulation (1 MHz, 3 W.cm-2, 50% duty cycle) was also trialled; the alginate gels were less responsive to this frequency, while no statistically significant impact on drug release was observed from the poloxamer gels. This study demonstrates the importance of ultrasound parameters and polymer selection in designing ultrasound-responsive hydrogels.
    Keywords:  Alginate; On-demand; Poloxamer; Smart hydrogels; Stimuli-responsive; Ultrasound
    DOI:  https://doi.org/10.1007/s13346-022-01277-5
  56. Blood Sci. 2022 Jul;4(3): 152-154
    Disulfiram, an aldehyde dehydrogenase inhibitor, works as a potent drug against sepsis and cancer via NETosis, pyroptosis, apoptosis, ferroptosis, and cuproptosis.
    Dingrui Nie, Cunte Chen, Yangqiu Li, Chengwu Zeng.
      Regulated cell death (RCD) is essential for maintaining cell homeostasis and preventing diseases. Besides classical apoptosis, several novel nonapoptotic forms of RCD including NETosis, pyroptosis, ferroptosis, and cuproptosis have been reported and are increasingly being implicated in various cancers and inflammation. Disulfiram (DSF), an aldehyde dehydrogenase inhibitor, has been used clinically for decades as an anti-alcoholic drug. New studies have shown that DSF possesses potent anti-inflammatory and anti-cancer effects by regulating these new types of RCD. Here, we summarize the mechanisms and discuss the potential application of DSF in the treatment of cancers and inflammatory diseases.
    Keywords:  Apoptosis; Cuproptosis; Disulfiram; Ferroptosis; NETosis; Pyroptosis; Sepsis
    DOI:  https://doi.org/10.1097/BS9.0000000000000117
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