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The endoplasmic reticulum (ER) is an essential organelle for protein synthesis, folding and modification, lipid synthesis, and calcium storage. When endogenous or exogenous stimuli lead to ER‑synthesized protein folding dysfunction, numerous unfolded or misfolded proteins accumulate in the ER cavity and cause a series of subsequent responses, referred to as ER stress. If ER stress is continuous, the unfolded protein response (UPR) is not enough to remove the accumulated unfolded and misfolded proteins, and thus, UPR signaling pathways will drive cell apoptosis. Glioblastoma (GBM) is currently the most aggressive and common malignant tumor of the nervous system. Since ER stress may increase the sensitivity of GBM to temozolomide, this article reviews the possible mechanisms of ER stress‑induced apoptosis and the factors affecting ER stress, and evaluates the potential of ER stress as a therapeutic target.Intrinsic or acquired resistance to temozolomide (TMZ) is a frequent occurrence in patients with glioblastoma (GBM). Accumulating evidence has indicated that the exosomal transfer of proteins and RNAs may confer TMZ resistance to recipient cells; however, the potential molecular mechanisms are not fully understood. Thus, the aim of the present study was to elucidate the possible role of exosomal microRNAs (miRNAs/miRs) in the acquired resistance to TMZ in GBM. A TMZ‑resistant GBM cell line (A172R) was used, and exosomes derived from A172R cells were extracted. Exosomal miR‑25‑3p was identified as a miRNA associated with TMZ resistance. The potential functions of exosomal miR‑25‑3p were evaluated by reverse transcription‑quantitative PCR, as well as cell viability, colony formation and soft agar assay, flow cytometry, western blot analysis, BrdU incorporation assay, tumor xenograft formation, luciferase reporter assay and RNA immunoprecipitation. It was found that A172R‑derived exosomes promoted the proliferation and TMZ resistance of sensitive GBM cells. Moreover, miR‑25‑3p epxression was upregulated in the exosomes of A172R cells and in serum samples of patients with GBM treated with TMZ. The depletion of exosomal miR‑25‑3p partially abrogated the effects induced by the transfer of exosomes from A172R cells. By contrast, miR‑25‑3p overexpression facilitated the proliferation and TMZ resistance of sensitive GBM cells. F‑box and WD repeat domain‑containing‑7 (FBXW7) was identified as a direct target of miR‑25‑3p. FBXW7 knockdown promoted the proliferation and TMZ resistance of GBM cells. Furthermore, the exosomal transfer of miR‑25‑3p promoted c‑Myc and cyclin E expression by downregulating FBXW7. Our results provided a novel insight into exosomal microRNAs in acquired TMZ resistance of GBM cells. Besides, exosomal miR‑25‑3p might be a potential prognostic marker for GBM patients.Diabetic nephropathy (DN) is a primary cause of end‑stage renal disease. Despite the beneficial effects of astragaloside IV (AS)‑IV on renal disease, the underlying mechanism of its protective effects against DN has not been fully determined. The aims of the present study were to assess the effects of AS‑IV against DN in db/db mice and to explore the mechanism of AS‑IV involving the NLR family pyrin domain containing 3 (NLRP3), caspase‑1 and interleukin (IL)‑1β pathways. The 8‑week‑old db/db mice received 40 mg/kg AS‑IV once a day for 12 weeks via intragastric administration. Cultured mouse podocytes were used to further confirm the underlying mechanism in vitro. AS‑IV effectively reduced weight gain, hyperglycemia and the serum triacylglycerol concentration in db/db mice. AS‑IV also reduced urinary albumin excretion, urinary albumin‑to‑creatinine ratio and creatinine clearance rate, as well as improved renal structural changes, accompanied by the upregulation of the podocyte markers podocin and synaptopodin. AS‑IV significantly inhibited the expression levels of NLRP3, caspase‑1 and IL‑1β in the renal cortex, and reduced the serum levels of tumor necrosis factor (TNF)‑α and monocyte chemoattractant protein‑1. https://www.selleckchem.com/products/cabotegravir-gsk744-gsk1265744.html In high glucose‑induced podocytes, AS‑IV significantly improved the expression levels of NLRP3, pro‑caspase‑1 and caspase‑1, and inhibited the cell viability decrease in a dose‑dependent manner, while NLRP3 overexpression eliminated the effect of AS‑IV on podocyte injury and the inhibition of the NLRP3 and caspase‑1 pathways. The data obtained from in vivo and in vitro experiments demonstrated that AS‑IV ameliorated renal functions and podocyte injury and delayed the development of DN in db/db mice via anti‑NLRP3 inflammasome‑mediated inflammation.Diabetes is a serious metabolic disease, and the kidney damage induced by diabetes also seriously affects the survival of patients. Apelin is a molecule that plays a crucial role in lipid metabolism, and recent studies have revealed that apelin‑13, a subtype of apelin, plays an important role in regulating blood glucose levels. However, the role of apelin‑13 in diabetic nephropathy remains unclear. In the present study, a rat model of diabetic nephropathy was constructed by the injection of streptozocin (STZ). During this process, these rats were injected with apelin‑13. The blood glucose, urine protein and insulin levels were determined weekly. Next, the expression of angiotensin domain type 1 receptor‑associated protein (APJ), endothelial nitric oxide synthase (eNOS), E‑cadherin and α‑smooth muscle actin (α‑SMA) in the kidney tissues was determined with western blotting. Then, the endothelial cells of glomerular vessels were cultured with high glucose medium. These cells were treated with apelin‑13 for 24 h. Finally, cell viability of these cells and the expression of APJ, eNOS, E‑cadherin and α‑SMA in these cells were determined with western blotting. As a result, treatment of apelin‑13 induced the lower levels of blood glucose and urine protein. In addition, application of apelin‑13 promoted the production of insulin and alleviated the insulin resistance. Treatment with apelin‑13 promoted the expression of APJ, eNOS and E‑cadherin while it suppressed the expression of α‑SMA in kidney tissues of rats and endothelial cells of glomerular vessels. Furthermore, application of apelin‑13 also promoted the cell viability of these cells. In conclusion, apelin‑13 relieved diabetic nephropathy by promoting the production of nitric oxide (NO) and alleviating the fibrosis of kidney tissues.
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