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Pancreatic β-cell dysfunction caused by obesity can be associated with alterations in the levels of miRNAs. However, the role of miRNAs in such processes remains elusive. Here, we show that pancreatic islet miR-27a-5p, which is markedly increased in obese mice and impairs insulin secretion, is mainly delivered by visceral adipocyte–derived extracellular vesicles (EVs). Depleting miR-27a-5p significantly improved insulin secretion and glucose intolerance in db / db mice. Supporting the function of EV miR-27a-5p as a key pathogenic factor, intravenous injection of miR-27a-5p–containing EVs showed their distribution in mouse pancreatic islets. Tracing the injected adeno-associated virus (AAV)-miR-27a-5p (AAV-miR-27a) or AAV-FABP4-miR-27a-5p (AAV-FABP4-miR-27a) in visceral fat resulted in upregulating miR-27a-5p in EVs and serum and elicited mouse pancreatic β-cell dysfunction. Mechanistically, miR-27a-5p directly targeted L-type Ca2+ channel subtype CaV1.2 (Cacna1c) and reduced insulin secretion in β-cells. Overexpressing mouse CaV1.2 largely abolished the insulin secretion injury induced by miR-27a-5p. These findings reveal a causative role of EV miR-27a-5p in visceral adipocyte–mediated pancreatic β-cell dysfunction in obesity-associated type 2 diabetes mellitus. Article Highlights: miR-27a-5p expression in the islets is increased in obesity-associated diabetes mouse models. miR-27a-5p overexpression in β-cells impairs β-cell function in vitro and in vivo. Visceral adipocyte–derived extracellular vesicles and their cargo miR-27a-5p lead to β-cell insulin secretion injury and glucose intolerance by targeting L-type Ca2+ channel subtype CaV1.2. Blockage of visceral adipocyte extracellular vesicle miR-27a-5p expression improves β-cell insulin secretion and glucose tolerance in db / db mice. [ABSTRACT FROM AUTHOR]

Aim: To assess the expression and function of miR‐483‐5p in diabetic β cells. Methods: The expression of miR‐483‐5p was evaluated in the pancreatic islets of obesity mouse models by quantitative reverse transcription polymerase chain reaction. Dual‐luciferase activity, and western blotting assays, were utilized for miR‐483‐5p target gene verification. Mice with β cell‐specific miR‐483‐5p downregulation were studied under metabolic stress (i.e. a high‐fat diet) condition. Lineage tracing was used to determine β‐cell fate. Results: miR‐483‐5p increased in the islets of obese mouse models. Expression levels of miR‐483‐5p were significantly upregulated with the treatment of high glucose and palmitate, in both MIN6 cells and mouse islets. Overexpression of miR‐483‐5p in β cells results in impaired insulin secretion and β‐cell identity. Cell lineage‐specific analyses revealed that miR‐483‐5p overexpression deactivated β‐cell identity genes (insulin, Pdx1 and MafA) and derepressed β‐cell dedifferentiation (Ngn3) genes. miR‐483‐5p downregulation in β cells of high‐fat diet‐fed mice alleviated diabetes and improved glucose intolerance by enhancing insulin secretory capacity. These detrimental effects of miR‐483‐5p relied on its seed sequence recognition and repressed expression of its target genes Pdx1 and MafA, two crucial markers of β‐cell maturation. Conclusions: These findings indicate that the miR‐483‐5p–mediated reduction of mRNAs specifies β‐cell identity as a contributor to β‐cell dysfunction via the loss of cellular differentiation. [ABSTRACT FROM AUTHOR]

This study sought to identify drug target genes and their associated molecular mechanisms during isoflurane-induced anesthesia in clinical applications. Microarray data (ID: GSE64617; isoflurane-treated vs. normal samples) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened and hub genes were investigated using weighted correlation network analysis (WGCNA). Protein–protein interactions (PPIs) were constructed among the co-DEGs (common genes between DEGs and hub genes), followed by functional enrichment analyses. Then, three machine learning methods were used to reveal drug targets, followed by validation, nomogram analysis, and gene set enrichment analysis. Finally, an miRNA-target network was constructed. A total of 686 DEGs were identified between the two groups—of which, 183 DEGs integrated with genes revealed by WCGNA were identified as co-genes. These genes, including contactin-associated protein 1 (CNTNAP1), are mainly involved in functions such as action potentials. PPI network analysis revealed three models, with the machine learning analysis exploring four drug target genes: A2H, FAM155B, SCARF2, and SDR16C5. ROC and nomogram analyses demonstrated the ideal diagnostic value of these target genes. Finally, miRNA–mRNA pairs were constructed based on the four mRNAs and associated 174 miRNAs. FA2H, FAM155B, SCARF2, and SDR16C5 may be novel drug target genes for isoflurane-induced anesthesia. CNTNAP1 may participate in the progression of isoflurane-induced anesthesia via its action potential function. [ABSTRACT FROM AUTHOR]

A new combined system of ultrasound (US)/ H2O2/KI was presented in this study for the degradation of amoxicillin (AMX). Various parameters that influencing the degradation efficiency, such as ultrasonic power, pH value of the solution, concentrations of H2O2 and KI, initial concentration of AMX were investigated. The maximum degradation efficiency of 84.1% in 60 min was obtained under the optimal conditions when the ultrasonic power was 195 W, the solution pH was 3.2, the concentrations of H2O2 and KI were 120 and 2.4 mmol/L, respectively. Results also showed US/H2O2/KI system possessed better degradation efficiency compared with that by using the systems of US alone, H2O2, US/H2O2, US/KI and H2O2/KI. The degradation reaction of AMX should be a very complex process, and the corresponding degradation pathways may change at different concentrations or under different reaction conditions. The results indicate that the combined system of US/ H2O2/KI has great potential applications for the treatment of wastewater containing antibiotics with high concentrations. [ABSTRACT FROM AUTHOR]