Type 2 diabetes mellitus(T2DM) is regarded as one of the most severe chronic metabolic diseases worldwide, which poses a great threat to human safety and health. The main feature of T2DM is the deterioration of pancreatic beta-cell function. More and more studies have shown that the decline of pancreatic beta-cell function in T2DM can be attributable to beta-cell apoptosis, but the exact mechanisms of beta-cell apoptosis in T2DM are not yet fully clarified. Therefore, in this review, we will focus on the current status and progress of research on the mechanism of pancreatic beta-cell apoptosis in T2DM, to provide new ideas for T2DM treatment strategies.

Monocyte chemoattractant protein-1 (MCP-1) is a major chemokine that recruits monocyte/macrophage to the site of tissue injury and plays a critical role in microvascular complications of diabetes. However, the mechanisms underlying the regulation of MCP-1 are not fully understood. The present study aims to explore the role of activating transcription factor 4 (ATF4), an ER stress-inducible transcription factor, in regulation of MCP-1 expression and production in brain and retinal microvascular endothelial cells. For in vitro study, primary brain microvascular endothelial cells isolated from ATF4 knockout mice or mouse retinal endothelial cells were treated with lipopolysaccharide (LPS) to induce MCP-1 expression. ATF4 expression/function was manipulated by adenoviruses expressing wild type ATF4 (Ad-ATF4) or a dominant negative mutant of the protein (Ad-ATF4DN). For in vivo study, MCP-1 expression was induced by intravitreal injection of LPS or Ad-ATF4 in heterozygous ATF4 knockout or wild type mice. LPS treatment induced a dose- and time-dependent increase in ATF4 expression, ER stress and MCP-1 production in brain and retinal microvascular endothelial cells. Overexpression of ATF4 in endothelial cells significantly increased the secretion of MCP-1 and promoted THP-1 monocyte-endothelial cell adhesion. Conditioned medium from ATF4-overexpressiing endothelial cells significantly enhanced THP-1 cell migration. Consistently, intravitreal injection of Ad-ATF4 remarkably enhanced retinal levels of MCP-1 and promoted inflammatory cell infiltration into the vitreous and retina. In contrast, LPS-induced MCP-1 upregulation was markedly attenuated in ATF4-deficient endothelial cells and in retinas of ATF4 knockout mice, suggesting that ATF4 is essential for LPS-induced MCP-1 production in endothelial cells and in the retina. Mechanistically, overexpression of ATF4 enhanced, while inhibition of ATF4, attenuated the basal and LPS-stimulated phosphorylation of NF-κB, P38, and JNK. Furthermore, pharmacological inhibition of NF-κB, P38, or JNK significantly reduced ATF4-stimulated MCP-1 secretion from endothelial cells. Taken together, our results suggest a critical role of ATF4 in the regulation of MCP-1 production in retinal and brain microvascular endothelial cells, which may contribute to inflammation-related endothelial injury in diseases such as diabetic retinopathy.

Graves’ ophthalmopathy (GO), also known as thyroid-associated ophthalmopathy, is a common potentially vision-threatening organ-specific autoimmune disease and the most common extrathyroidal manifestation of Graves’ disease. It can happen to those who have hyperthyroidism or euthyroidism. At present, the pathogenesis of GO has not been fully elucidated, and the majority of clinical treatments are symptomatic. Therefore, we are eager to discover any new therapeutic strategies that target the etiology of GO. To provide fresh ideas for the creation of new therapeutic techniques, this study primarily discusses the research state and progress of GO-related pathogenesis from the perspectives of GO’s cellular immunity, autoantigens, non-coding RNAs, and exosomes.

Objective: We aimed to identify structural and functional alterations of gut microbiota associated with visceral obesity in adult women with polycystic ovary syndrome (PCOS). Methods: Twenty-seven adults with PCOS underwent stool and fasting blood collection, oral glucose tolerance testing, and visceral fat area (VFA) measurement via dual-bioimpedance technique. Metagenomic analysis was used to analyze gut microbiota. Results: PCOS patients were divided into three groups: visceral obesity group (PCOS-VO, n=9, age 28.33± 5.68 years, BMI 37.06± 4.27 kg/m², VFA 128.67± 22.45 cm²), non-visceral obesity group (PCOS-NVO, n=10, age 25.40± 4.53, BMI 30.74± 3.95, VFA 52.00± 24.04), normal BMI group (PCOS-NB, n=8, age 27.88± 2.53, BMI 21.56± 2.20, VFA 27.00± 21.18), with no statistical difference in age (P> 0.05) and significantly statistical differences in BMI and VFA (P< 0.05). The groups showed a significant difference in microbial β-diversity between PCOS-VO and PCOS-NVO (P=0.002) and no difference between PCOS-NVO and PCOS-NB (P=0.177). Bacteroidetes was the phylum with the highest relative abundance among all patients, followed by Firmicutes. Those with visceral obesity had a higher abundance of Prevotella, Megamonas, and Dialister genera, positively correlated with metabolic markers (r> 0.4, P< 0.05), and lower abundance of Phascolarctobacterium and Neisseria genera, negatively correlated with metabolic markers (r<-0.4, P< 0.05). Functional annotation analysis showed significant differences in relative abundance of ribosome pathway, fatty acid biosynthesis pathway, and sphingolipid signaling pathway between groups, affecting lipid homeostasis and visceral fat accumulation. Conclusion: Alteration in β-diversity of gut microbiota exists in PCOS with visceral obesity versus those without visceral obesity and relates to functional differences in ribosomes, fatty acid biosynthesis, and sphingolipid signaling pathways.