ABSTRACT
Background: Aerobic glycolysis has recently demonstrated promising potential in mitigating the effects of ischemia-reperfusion (IR) injury. Scutellarin (Scu) possesses various cardioprotective properties that warrant investigation. To mimic IR injury in vitro, this study employed hypoxia/reoxygenation (H/R) injury. Methods and Results: First, we conducted an assessment of the protective properties of Scu against HR in H9c2 cells, encompassing inflammation damage, apoptosis injury, and oxidative stress. Then, we verified the effects of Scu on the Warburg effect in H9c2 cells during HR injury. The findings indicated that Scu augmented aerobic glycolysis by upregulating p-PKM2/PKM2 levels. Following, we built a panel of six long noncoding RNAs and seventeen microRNAs that were reported to mediate the Warburg effect. Based on the results, miR-34c-5p was selected for further experiments. Then, we observed Scu could mitigate the HR-induced elevation of miR-34c-5p. Upregulation of miR-34c-5p could weaken the beneficial impacts of Scu in cellular viability, inflammatory damage, oxidative stress, and the facilitation of the Warburg effect. Subsequently, our investigation revealed a decrease in both ALDOA mRNA and protein levels following HR injury, which could be restored by Scu administration. Downregulation of ALDOA or Mimic of miR-34c-5p could reduce these effects induced by Scu. Conclusions: Scu provides cardioprotective effects against IR injury by upregulating the Warburg effect via miR-34c-5p/ALDOA.
ABSTRACT
Aims: To determine the impact of dietary protein intake and protein sources on all-cause and cardiovascular mortality of selective glomerular hypofiltration syndrome (SGHS) patients. Methods: This study recruited participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004. Cox proportional hazard models and competing risk models were employed to investigate the effects of dietary protein intake and protein sources on all-cause and cardiovascular mortality in SGHS patients. Additionally, Cox regression models utilizing restricted cubic splines (RCS) were used to explore potential non-linear associations. Results: Over a median follow-up period of 204 months, 20.71% (449/2168) participants died, with 5.40% (117/2168) experiencing cardiovascular mortality. In the fully adjusted model, participants with the highest dietary protein intake (Q4, ≥107.13 g d-1) exhibited a 40% reduced risk of all-cause mortality (HR: 0.60, 95% CI: 0.39 to 0.94) and an 88% reduced risk of cardiovascular mortality (HR: 0.12, 95% CI: 0.04 to 0.35) compared to those with the lowest dietary protein intake (Q1, < 57.93 g d-1). Notably, non-red meat protein sources were found to reduce the risk of all-cause and cardiovascular mortality, whereas no significant association was observed with red meat consumption. Conclusion: Adequate dietary protein intake has been linked to a decreased risk of all-cause and cardiovascular mortality in individuals with selective glomerular hypofiltration syndromes. This protective effect seems to be primarily associated with protein obtained from non-red meat sources.
