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This study aims to develop, characterize, and evaluate the best statin-loaded Collagen Silver nanoparticle-coated polycaprolactone nanofibers by electrospinning technique. The characterization and evaluation results reveal that nanofibers had shown an aligned Collagen Silver nanoparticle-coated polycaprolactone nanofibers distribution of fibers and aliment of collagen and silver nanoparticle coating material on the surface of the nanofibers. Furthermore, the electrospun nanofibers have shown no interaction between the drug and collagen and PCL polymeric material and have demonstrated controlled drug release for 360 h and significant degradation for 60 days of the study. In vitro, among the nanofiber treatment groups and the control groups, Pravastatin Collagen Silver nanoparticle-coated polycaprolactone nanofibers have shown cell proliferation and migration of NHDF cells and blood vessel development in the CAM assay and potential anti-bacterial activity against S. aureus and E. coli. In vivo, the Pravastatin Collagen Silver nanoparticle-coated polycaprolactone nanofibers have demonstrated improved wound recovery, reepithelization, fibroblast cell proliferation, angiogenesis, and ECM remodeling and enhanced VEGF-sprouting in the excised tissues of streptozotocin-induced diabetic rats for 7, 14, and 21 days of the study. Therefore, the developed Pravastatin Collagen Silver nanoparticle-coated polycaprolactone nanofibers could be a promising wound-dressing platform for effectively treating and managing diabetic wounds. Highlights * Nanofiber wound dressings provide numerous structural features in biomaterials. * Polycaprolactone can release the repurposed statin molecules into the wound site in a controlled manner. * In diabetic wounds, ECM tissue remodeling stimulates repair and vessel growth. * Pravastatin has been demonstrated to improve angiogenesis and ECM secretion for wound healing in diabetic conditions. KEYWORDS diabetic wounds, electrospinning, hypoxic microenvironment, nanofibers, pro-angiogenesis, re-epithelization, wound dressing, 1 | INTRODUCTION The most prevalent cause of death in diabetic individuals is diabetic wounds. Unfortunately, the bulk of the treatment options in the market do not entirely address how [...]

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and memory deficit. Even with extensive research and studies, presently, there is no effective treatment for the management of AD. Besides, most of drugs used in the treatment of AD did not avert the AD neuropathology, and the disease still in a progressive status. For example, acetyl cholinesterase inhibitors are associated with many adverse effects, such as insomnia and nightmares. As well, acetylcholinesterase inhibitors augment cholinergic neurotransmission leading to the development of adverse effects related to high acetylcholine level, such as salivation, rhinorrhea, vomiting, loss of appetite, and seizure. Furthermore, tacrine has poor bioavailability and causes hepatotoxicity. These commonly used drugs do not manage the original causes of AD. For those reasons, natural products were repurposed for the treatment of AD and neurodegenerative diseases. It has been shown that phytochemicals produce neuroprotective effects against the development and progression of neurodegenerative diseases by different mechanisms, including antioxidant and anti-inflammatory effects. Quercetin (QCN) has been reported to exert an effective neuroprotective effect against AD and other neurodegenerative diseases by lessening oxidative stress. In this review, electronic databases such as PubMed, Scopus, and Web of Science were searched for possible relevant studies and article linking the effect of QCN on AD. Findings from this review highlighted that many studies highlighted different mechanistic signaling pathways regarding the neuroprotective effect of QCN in AD. Nevertheless, the precise molecular mechanism of QCN in AD was not completely clarified. Consequently, this review aims to discuss the molecular mechanism of QCN in AD. [ABSTRACT FROM AUTHOR]

Due to the complex pathophysiology of AD (Alzheimer's Disease), there are currently no effective clinical treatments available, except for acetylcholinesterase inhibitors. However, CREB (cyclic AMP-responsive element binding protein) has been identified as the critical factor for the transcription in memory formation. Understanding the effect of potential drugs on the CREB pathway could lead to the development of new therapeutic molecules. Rufinamide has shown promise in improving memory in animal models, and these effects may be associated with modulation of the CREB pathway, however, this has not been previously reported. Thus, the present study aimed to determine the involvement of the CREB pathway in the cognitive improvement effects of rufinamide in STZ (streptozotocin) induced mouse model of dementia. Administration of STZ [3 mg/kg, i.c.v. (intracerebroventricular) bilaterally] significantly impaired cognitive performance in step-down passive avoidance and Morris water maze tests in animals, reduced brain endogenous antioxidant levels (GSH, superoxide dismutase, and catalase), and increased marker of brain oxidative stress [TBARS (thiobarbituric acid reactive substances)] and inflammation [IL-1β (Interleukin-1 beta), IL-6 (Interleukin-6), TNF-α (Tumor necrosis factor alpha) and NF-κB (Nuclear factor kappa B)], along with neurodegeneration. These effects were markedly reversed by rufinamide (50 and 100 mg/kg) when administered to STZ animals. However, the pre-treatment with the CREB inhibitor (666-15) in STZ and rufinamide-administered animals neutralized the beneficial influence of rufinamide. Our data suggest that rufinamide, acting via CREB signaling, reduced oxidative stress and inflammatory markers while elevating anti-oxidant levels. Our study has established that rufinamide may act through CREB signaling in an investigational AD model, which could be crucial for developing new treatments beneficial in progressive neurological disorders. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a chronic metabolic disorder caused by defective insulin signaling, insulin resistance, and impairment of insulin secretion. Autophagy is a conserved lysosomal‐dependent catabolic cellular pathway involved in the pathogenesis of T2D and its complications. Basal autophagy regulates pancreatic β‐cell function by enhancing insulin release and peripheral insulin sensitivity. Therefore, defective autophagy is associated with impairment of pancreatic β‐cell function and the development of insulin rersistance (IR). However, over‐activated autophagy increases apoptosis of pancreatic β‐cells leading to pancreatic β‐cell dysfunction. Hence, autophagy plays a double‐edged sword role in T2D. Therefore, the use of autophagy modulators including inhibitors and activators may affect the pathogenesis of T2D. Hence, this review aims to clarify the potential role of autophagy inhibitors and activators in T2D. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is developed due to the development of insulin resistance (IR) and pancreatic β cell dysfunction with subsequent hyperglycaemia. Hyperglycaemia‐induced oxidative stress and endoplasmic reticulum (ER) stress enhances inflammatory disorders, leading to further pancreatic β cell dysfunction. These changes trigger autophagy activation, which recycles cytoplasmic components and injured organelles. Autophagy regulates pancreatic β cell functions by different mechanisms. Though the exact role of autophagy in T2DM is not completely elucidated, that could be beneficial or detrimental. Therefore, this review aims to discuss the exact role of autophagy in the pathogenesis of T2DM. [ABSTRACT FROM AUTHOR]

The metabolic syndrome or syndrome X is a clustering of different components counting insulin resistance (IR), glucose intolerance, visceral obesity, hypertension and dyslipidemia. It has been shown that IR and dysregulation of insulin signalling play a critical role in the development of metabolic syndrome by initiating the pathophysiology of metabolic syndrome through induction of glucolipotoxicity, impairment of glucose disposal and triggering of pro‐inflammatory response. Furthermore, metabolic syndrome unfavourably affects the cognitive function and the development of different neurodegenerative diseases such as Alzheimer disease (AD) by inducing oxidative stress, neuroinflammation and brain IR. These changes together with brain IR impair cerebrovascular reactivity leading to cognitive impairment. In addition, metabolic syndrome increases the risk for the development of AD. However, the central mechanisms by which metabolic syndrome amplify AD risk are not completely elucidated. Consequently, this narrative review aims to revise from published articles the association between metabolic syndrome and AD regarding cellular and subcellular pathways. In conclusion, metabolic syndrome is regarded as a potential risk factor for the induction of AD neuropathology by different signalling pathways such as initiation of brain IR, activation of inflammatory signalling pathways and neuroinflammation. [ABSTRACT FROM AUTHOR]

The metabolic syndrome (MetS) is a clustering of abdominal obesity, hypertension, hyperglycaemia, hypertriglyceridemia and low high‐density lipoprotein (HDL) level. MetS development is affected by endocrine hormones such as prolactin (PRL) hormone which induce insulin resistance and central obesity because PRL is implicated in the pathogenesis of MetS. Pituitary PRL controls mammary gland, however extra‐pituitary PRL is highly intricate in the regulation of adipose tissue function. In addition, cAMP activators enhance expression and release of PRL which involved in the control of lipogenesis and energy homeostasis. Consequently, hyperprolactinaemia may be associated with the development of MetS. However, normal physiological level of PRL is essential for insulin sensitivity and regulation of adipose tissue function and energy metabolism. Therefore, PRL has dual effects on the components of MetS. Hence, the present review aims to discuss the modulatory mechanistic role of PRL on MetS regarding its beneficial and detrimental effects. [ABSTRACT FROM AUTHOR]

Leukaemia, a group of haematological malignancies, presents ongoing diagnosis, prognosis, and treatment challenges. A major obstacle in treating this disease is the development of drug resistance. Overcoming drug resistance poses a significant barrier to effective leukaemia treatment. The emergence of exosome research has unveiled new insights into the probable theragnostic implementations in leukaemia. Various research has exhibited the diagnostic possibilities of exosomes in identifying leukaemia‐specific biomarkers, including genetic mutations and fusion transcripts. Additionally, exosomes have been implicated in disease progression and treatment response, rendering them appealing targets for therapeutics. Exosomes, originating from diverse cell types, are instrumental in intercellular communication as they participate in the functional transportation of molecules like proteins, nucleic acids and lipids across space. Exosomes have a dual role in immune regulation, mediating immune suppression and modulating anti‐leukaemia immune responses. Interestingly, exosomes can even act as drug transport vehicles. This review delves into the intricate process of exosome biogenesis, shedding light on their formation and release from donor cells. The key mechanisms engaged in exosome biogenesis, for instance, the endosomal sorting complexes required for transport (ESCRT) machinery and ESCRT‐independent pathways, are thoroughly discussed. Looking ahead, future approaches that leverage innovative technologies hold the promise of revolutionizing disease management and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a major human disease of public health importance. Freshwater snails serving as intermediary hosts and human interaction with surface water tainted by feces or urine are both necessary components of the transmission cycle. Schistosoma haematobium, Schistosoma mansoni, and Schistosoma japonicum are the primary pathogen species. Over 250 million individuals are infected globally, according to the World Health Organization, causing significant morbidity and an estimated loss of 1.9 million disability‐adjusted life years, a number that is probably underestimated. Immunological protection is slowly built up through complex immunological systems, although innate factors also play a role. Chronic schistosomiasis affects mainly individuals residing in poor rural area. Vaccination is considered as one of the most sustainable options for the control of any pathogen, but schistosomiasis vaccine for humans or animals is not available till now despite the discovery of numerous potentially promising schistosome vaccine antigens. Objective: To provide an overview of the schistosomiasis chemotherapy, chemoprevention, and vaccines history and progress. Design: Review article. Data Sources: PubMed, ISI Web of Science, Science Direct, and the World Health Organization database. Conclusion: Favorably praziquantel (PZQ) is a medication with excellent chemopreventive treatment compliance. Due to the extensive usage of PZQ, there is a great deal of debate surrounding the emergence of drug resistance. PZQ is effective against all species of schistosomes, schistosomiasis prevalence has remained largely unaffected, due to reinfection in high transmission areas and growing juvenile worms that were not affected by the drug, even though the need for a schistosomiasis vaccine is even more pressing. [ABSTRACT FROM AUTHOR]