Conquering chemoresistance in pancreatic cancer: Exploring novel drug therapies and delivery approaches amidst desmoplasia and hypoxia.

Pancreatic cancer poses a significant challenge within the field of oncology due to its aggressive behaviour, limited treatment choices, and unfavourable outlook. With a mere 10% survival rate at the 5-year mark, finding effective interventions becomes even more pressing. The intricate relationship between desmoplasia and hypoxia in the tumor microenvironment further complicates matters by promoting resistance to chemotherapy and impeding treatment efficacy. The dense extracellular matrix and cancer-associated fibroblasts characteristic of desmoplasia create a physical and biochemical barrier that impedes drug penetration and fosters an immunosuppressive milieu. Concurrently, hypoxia nurtures aggressive tumor behaviour and resistance to conventional therapies. a comprehensive exploration of emerging medications and innovative drug delivery approaches. Notably, advancements in nanoparticle-based delivery systems, local drug delivery implants, and oxygen-carrying strategies are highlighted for their potential to enhance drug accessibility and therapeutic outcomes. The integration of these strategies with traditional chemotherapies and targeted agents reveals the potential for synergistic effects that amplify treatment responses. These emerging interventions can mitigate desmoplasia and hypoxia-induced barriers, leading to improved drug delivery, treatment efficacy, and patient outcomes in pancreatic cancer. This review article delves into the dynamic landscape of emerging anticancer medications and innovative drug delivery strategies poised to overcome the challenges imposed by desmoplasia and hypoxia in the treatment of pancreatic cancer.

Protective effects of fecal microbiota transplantation against ischemic stroke and other neurological disorders: an update.

The bidirectional communication between the gut and brain or gut-brain axis is regulated by several gut microbes and microbial derived metabolites, such as short-chain fatty acids, trimethylamine N-oxide, and lipopolysaccharides. The Gut microbiota (GM) produce neuroactives, specifically neurotransmitters that modulates local and central neuronal brain functions. An imbalance between intestinal commensals and pathobionts leads to a disruption in the gut microbiota or dysbiosis, which affects intestinal barrier integrity and gut-immune and neuroimmune systems. Currently, fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection. FMT elicits its action by ameliorating inflammatory responses through the restoration of microbial composition and functionality. Thus, FMT may be a potential therapeutic option in suppressing neuroinflammation in post-stroke conditions and other neurological disorders involving the neuroimmune axis. Specifically, FMT protects against ischemic injury by decreasing IL-17, IFN-γ, Bax, and increasing Bcl-2 expression. Interestingly, FMT improves cognitive function by lowering amyloid-ß accumulation and upregulating synaptic marker (PSD-95, synapsin-1) expression in Alzheimer's disease. In Parkinson's disease, FMT was shown to inhibit the expression of TLR4 and NF-κB. In this review article, we have summarized the potential sources and methods of administration of FMT and its impact on neuroimmune and cognitive functions. We also provide a comprehensive update on the beneficial effects of FMT in various neurological disorders by undertaking a detailed interrogation of the preclinical and clinical published literature.

Sleep apnoea, gut dysbiosis and cognitive dysfunction.

Sleep disorders are becoming increasingly common, and their distinct effects on physical and mental health require elaborate investigation. Gut dysbiosis (GD) has been reported in sleep-related disorders, but sleep apnoea is of particular significance because of its higher prevalence and chronicity. Cumulative evidence has suggested a link between sleep apnoea and GD. This review highlights the gut-brain communication axis that is mediated via commensal microbes and various microbiota-derived metabolites (e.g. short-chain fatty acids, lipopolysaccharide and trimethyl amine N-oxide), neurotransmitters (e.g. γ-aminobutyric acid, serotonin, glutamate and dopamine), immune cells and inflammatory mediators, as well as the vagus nerve and hypothalamic-pituitary-adrenal axis. This review also discusses the pathological role underpinning GD and altered gut bacterial populations in sleep apnoea and its related comorbid conditions, particularly cognitive dysfunction. In addition, the review examines the preclinical and clinical evidence, which suggests that prebiotics and probiotics may potentially be beneficial in sleep apnoea and its comorbidities through restoration of eubiosis or gut microbial homeostasis that regulates neural, metabolic and immune responses, as well as physiological barrier integrity via the gut-brain axis.

Analytical method development, validation and forced degradation studies for rutin, quercetin, curcumin, and piperine by RP-UFLC method.

SIGNIFICANCE: Curcumin, rutin, and quercetin are well-known flavonoids and piperine is an alkaloid, commonly used as spices and traditionally used to treat a variety of conditions. In the current scenario, the stability problems of phytoconstituents are a major problem for regulators and because of the complex nature of the components of plant extracts. OBJECTIVE: A simple, fast, and sensitive ultra-force reverse phase liquid chromatography (RP-UFLC) has been developed, validated, and studied for degradation studies. METHODS: Seven different plant extracts were quantified and the stability of the constituents was estimated by forced degradation studies. The separation of the phytoconstituents was performed on a Phenomenex C18 column with a mobile phase of 80% acetonitrile and 20% (25 mM) ammonium acetate (pH 3) at a flow rate of 1 mL min-1 detected at 380 nm. RESULTS: The results of the study showed that the method developed was linear with a range of correlation coefficient 0.994-0.999. The specificity, precision, and accuracy were well within the limits. Quantification showed that a maximum content of curcumin (3.61%, w/w) was found in the extract of Curcuma longa L extract, piperine in Piper nigrum L (13.92%, w/w), rutin in Glycyrrhiza glabra L (15.19%, w/w), and quercetin in Camellia sinensis L (0.36%, w/w). Forced degradation studies have shown that rutin was very stable in acidic media (6.65%, w/w) and curcumin was less stable in alkaline media (100%, w/w). CONCLUSION: The method developed was simple, fast, accurate, sensitive, and applicable for the determination of phytoconstituents in natural extracts and herbal formulations, individually or in combination and can be used as a quality control tool.

Current Perspectives on Therapies, Including Drug Delivery Systems, for Managing Glioblastoma Multiforme.

Glioblastoma multiforme (GBM), a standout among the most dangerous class of central nervous system (CNS) cancer, is most common and is an aggressive malignant brain tumor in adults. In spite of developments in modality therapy, it remains mostly incurable. Consequently, the need for novel systems, strategies, or therapeutic approaches for enhancing the assortment of active agents meant for GBM becomes an important criterion. Currently, cancer research focuses mainly on improving the treatment of GBM via diverse novel drug delivery systems. The treatment options at diagnosis are multimodal and include radiation therapy. Moreover, significant advances in understanding the molecular pathology of GBM and associated cell signaling pathways have opened opportunities for new therapies. Innovative treatment such as immunotherapy also gives hope for enhanced survival. The objective of this work was to collect and report the recent research findings to manage GBM. The present review includes existing novel drug delivery systems and therapies intended for managing GBM. Reported novel drug delivery systems and diverse therapies seem to be precise, secure, and relatively effective, which could lead to a new track for the obliteration of GBM.