SIFs ameliorate NAFLD by suppressing the cGAS–STING pathway via ER activation, countering SNS-induced hepatic inflammation and lipid accumulation.

Endothelial dysfunction appears early in the development of cardiovascular disease and is associated with type 2 diabetes. We, therefore, tested the hypothesis that endothelial dysfunction is already present in healthy Chinese adolescent participants at risk of type 2 diabetes and associates with physical activity. We investigated the flow-mediated dilation in 65 first-degree relatives (normal tension, normal glucose tolerance) and 62 age-, sex- and BMI-matched controls without a family history of type 2 diabetes by ultrasound. Physical activity level was assessed using the Global Physical Activity Questionaire and type 2 diabetes family history through self-reporting. The association between physical activity and flow-mediated dilation was evaluated by Pearson correlations and multiple regressions in adolescents with or without a family history of type 2 diabetes. Female adolescents display better flow-mediated dilation than males. Adolescents with a family history of type 2 diabetes had significantly impaired flow-mediated dilation than healthy controls. Among the parameter detection in the blood, the flow-mediated dilation is only positively associated with high-density lipoprotein cholesterol level, but not others. Interestingly, flow-mediated dilation is positively corrected with physical activity scores in both the male and female adolescents, while slightly impaired but not significant in adolescents with a family history of type 2 diabetes. Studies in adolescents are important to understand the early pathogenesis of type 2 diabetes. Findings of this investigation suggest that family history of type 2 diabetes may play a role in regulating the vascular function in Chinese adolescents. Given the impaired flow-mediated dilation in individuals with family history and the effects of physical activity in improved flow-mediated dilation, people with a family history of type 2 diabetes may need higher physical activity levels to attenuate their susceptibility to impaired flow-mediated dilation.

This study sought to investigate the link between sleep disorders and cardiac microvascular injury in myocardial ischemia–reperfusion injury (MI/RI) mice. Mice were subjected to a sleep deprivation protocol within a designated chamber. During the light phase (ZT0 to ZT12), a sweep bar moved across the cage floor at 2-min intervals, whereas it remained static throughout the dark phase (ZT12 to ZT24), with this routine maintained for 16 weeks. Subsequently, an MI/RI model was established to assess the extent of cardiac microvascular injury, and the underlying mechanisms were explored via proteomic analyses. It was demonstrated that 16 weeks of sleep fragmentation (SF) intensified cardiac microvascular damage in MI/RI mice. From a mechanistic perspective, SF was found to induce sympathetic hyperactivity, elevate plasma epinephrine levels, and consequently facilitate neutrophil chemotaxis and the generation of neutrophil extracellular traps (NETs). Moreover, the findings revealed that NETs suppressed Atox1 expression, impaired ATP7A-mediated copper transport, and contributed to copper accumulation within cardiac microvascular endothelial cells (CMECs) and oxidative stress. This copper overload further augmented cuproptosis, while these pathological alterations were shown to be reversible through sympathetic denervation, vagal electrical stimulation (ES), targeted delivery of copper chelators, or the inhibition of NETs. Overall, our data established that SF exacerbated MI/RI by promoting copper overload in CMECs. This study elucidated a molecular pathway through which sleep disturbances aggravated cardiac microvascular damage and suggested prospective targets for treatment strategies.