Xiangyi Pu

• Interaction between DUSP1 and PHB2 significantly contributes to cardiomyocyte injury following SCM. • AS mitigated myocardial inflammatory damage and oxidative stress, enhanced myocardial cell energy metabolism, addressed cardiac structural abnormalities, and preserved cardiac function through modulating the DUSP1-PHB2 interaction. • AS normalizes mitochondrial quality control via the DUSP1-PHB2 interaction. Septic cardiomyopathy (SCM) is a complication of myocardial injury in patients with severe sepsis. This study highlights the potential of Astragaloside IV(AS) in the treatment of septic cardiomyopathy and provides a reference for developing cardioprotective drugs targeting DUSP1-PHB2-related mitochondria-ER interaction. Dual specificity phosphatase-1 (DUSP1)/Prohibitin 2 cardiomyocyte-specific knockout mice (DUSP1/PHB2 CKO ) /DUSP1 transgenic mice (DUSP1/PHB2 TG ) were used to generate LPS-induced sepsis models. The pathological mechanism by which AS-IV improves heart injury was detected using cardiac ultrasound, fluorescence staining, transmission electron microscopy, and western blotting. After siRNA treatment of cardiomyocytes with DUSP-1/PHB2, changes in mitochondrial function and morphology were determined using qPCR, western blotting, ELISA, and laser confocal microscopy, and the targeted therapeutic effects of AS-IV were further examined. SCM treatment leads to severe mitochondrial dysfunction. However, Astragaloside IV (AS) treatment normalizes mitochondrial homeostasis and ER function. Notably, the protective effect was blocked in DUSP1/Prohibitin 2 cardiomyocyte-specific knockout mice (DUSP1/PHB2 CKO ) but remained unaffected in DUSP1 transgenic mice (DUSP1/PHB2 TG ). This study highlights the potential of AS in the treatment of septic cardiomyopathy and provides a reference for developing cardioprotective drugs targeting DUSP1-PHB2 related mitochondria-ER interaction.

Sick sinus syndrome (SSS), also known as sinoatrial node dysfunction, has been widely concerned by the medical community. The incidence rate of SSS is increasingly, which poses a great threat to public health. Through decades of repeated research in the medical field, great progress has been made in the pathogenesis of SSS and the interaction mechanism between SSS and other cardiovascular diseases. In this paper, we pay special attention to the mental stimulation factors under various pressures such as society and work, and the influence of smoking, drinking, and unhealthy diet on the pathogenesis of SSS. It also explains the mechanism of negative factors in the pathogenesis of SSS. These unhealthy lifestyle will lead to the occurrence of sinoatrial node disease and arrhythmia, and then induce SSS. Therefore, in the premise of increasing incidence rate of SSS and difficult to cure, how to avoid these harmful factors and ensure a healthy lifestyle is extremely important for preventing and treating SSS. This study also has guiding significance for the daily life of high-risk population of SSS and reducing the mortality of SSS patients.

Ginsenoside Rb1 is a prominent bioactive component in traditional Chinese medicine. This study investigated the molecular mechanisms underlying the protective effects of Ginsenoside Rb1 on endothelium during ischemia-reperfusion (I/R) injury. To enrich for marker genes and investigate the differential expression of DUSP1 and NDUFS4 in coronary artery disease, single-cell transcriptome sequencing was utilized. SIRT5 CKO/TG and NDUFS4 CKO/TG mouse models were established using gene modification techniques. Si-DUSP-1/ad-DUSP-1 and si-SIRT5/ad-SIRT5 cell models were constructed. Fluorescence detection, mitochondrial membrane potential assays, RT-PCR, and Western blotting were employed to detect the mitochondrial function. NDUFS4 and DUSP1 regulate the mitochondrial unfolded protein response (mtUPR), energy metabolism, and dynamics, and may be crucial regulatory genes in the development of coronary artery disease. Ginsenoside Rb1 modulates the NDUFS4-SIRT5-DUSP1 axis, regulates the mitochondrial quality control network, and alleviates coronary microvascular inflammatory injury. Ginsenoside Rb1 regulates the NDUFS4-SIRT5-DUSP1 axis, modulating the mitochondrial quality control network, inhibiting the inflammatory cascade response, and improved myocardial function. • Expression interactions between SIRT5, DUSP1, and NDUFS4 co-regulate the mitochondrial quality monitoring network. • Ginsenoside Rb1 regulates NDUFS4-SIRT5-DUSP1-mediated mitochondrial quality monitoring and inflammatory crosstalk to improve coronary microvascular ischemia-reperfusion injury.