Oxypaeoniflorin improves myocardial ischemia/reperfusion injury by activating the Sirt1/Foxo1 signaling pathway.
氧化芍药苷通过激活 Sirt1/Foxo1 信号通路改善心肌缺血/再灌注损伤。
- 作者列表："Wang K","Hu W
Myocardial ischemia/reperfusion (MI/R) injury is a leading cause of damage to cardiac tissues and is associated with high mortality and disability rates worldwide. Oxypaeoniflorin (OPA) has been found to be the main constituent of Paeonia veitchii Lynch. This study was conducted to explore the effect of OPA on MI/R injury and its potential mechanism. An in vivo MI/R injury model was established by transient coronary ligation in BALB/c mice, and an in vitro hypoxia/reoxygenation (H/R) injury model was established with rat cardiomyocyte H9c2 cells. Echocardiographic assessments demonstrated that OPA significantly reduced disruption of cardiac function and improved the indicators of ejection fraction (EF) and fractional shortening (FS). The enzyme-linked immunosorbent assay (ELISA) results suggested that OPA significantly reduced the release of myocardial infarction-related factors, such as the creatine kinase (CK-MB), cardiac troponin I (cTnI) and cardiac troponin T (cTnT). Additionally, hematoxylin-eosin (HandE) staining demonstrated that OPA markedly inhibited the myocardial apoptosis and necrosis caused by MI/R. Consistently, the results obtained from the cell counting kit-8 (CCK-8) and flow cytometry assays revealed that OPA obviously reversed the H/R-induced decrease in cell activity and increase in apoptosis of H9c2 cells. Furthermore, western blot assays indicated that OPA inhibited apoptosis by activating the Sirt1 (silent information regulator factor 2 related enzyme 1)/Foxo1(forkhead transcription factor FKHR) signaling pathway in myocardial tissues and H9c2 cells. Collectively, these novel findings are the first to provide strong evidence that OPA attenuates MI/R injury by activating the Sirt1 (silent information regulator factor 2 related enzyme 1)/Foxo1(forkhead transcription factor FKHR) signaling-mediated anti-apoptotic pathway.
心肌缺血/再灌注 (MI/R) 损伤是心脏组织损伤的主要原因，与全球高死亡率和致残率相关。已发现氧化芍药内酯苷 (OPA) 是芍药林奇的主要成分。本研究旨在探讨 OPA 对 MI/R 损伤的影响及其潜在机制。通过 BALB/c 小鼠短暂冠脉结扎建立体内 MI/R 损伤模型，体外缺氧/复氧 (H/R) 用大鼠心肌细胞 H9c2 建立损伤模型。超声心动图评估表明，OPA 显著降低了心功能的破坏，改善了射血分数 (EF) 和缩短分数 (FS) 的指标。酶联免疫吸附试验 (ELISA) 结果提示，OPA 显著减少心肌梗死相关因子的释放，如肌酸激酶 (CK-MB) 、心肌肌钙蛋白 I (cTnI) 和心肌肌钙蛋白 T (cTnT)。此外，苏木精-伊红 (HandE) 染色显示 OPA 明显抑制 MI/R 引起的心肌细胞凋亡和坏死。一致地，从细胞计数试剂盒-8 (CCK-8) 获得的结果流式细胞仪检测发现，OPA 明显逆转了 H/R 诱导的 H9c2 细胞活性降低和凋亡增加。此外，western blot 检测表明，OPA 通过激活 Sirt1 (沉默信息调节因子 2 相关酶 1)/Foxo1 (叉头转录因子 FKHR) 抑制细胞凋亡心肌组织和 H9c2 细胞中的信号通路。总的来说，这些新发现首次提供了强有力的证据，证明 OPA 通过激活 Sirt1 (沉默信息调节因子 2 相关酶 1) 来减弱 MI/R 损伤/Foxo1 (叉头转录因子 FKHR) 信号介导的抗凋亡通路。
METHODS:BACKGROUND:Preterm birth is a risk factor for elevated blood pressure in childhood and the development of hypertension and cardiometabolic disease in adulthood; however, mechanisms for the development of both are poorly understood. Rapid weight gain early in childhood may serve as a driver directly and indirectly through cortisol levels found to be elevated in early childhood in individuals born preterm. OBJECTIVES:The objective of this pilot study was to examine the effect sizes of the relationships between weight gain and blood pressure in toddlers born very preterm. A secondary aim was to note any mediating effect of cortisol on the relationships between weight gain and blood pressure. METHODS:A cross-sectional design with a convenience sample of 36 toddlers who were born very preterm was used to examine the relationships between postnatal weight gain, cortisol, and blood pressure at follow-up. RESULTS:Many of the participants experienced rapid weight gain in the first 12 months of life. Mean systolic and diastolic readings were 94 and 56.6, respectively. Diastolic blood pressure readings were obtained from 23 participants and the majority were elevated. Weight gain was associated with diastolic blood pressure with a medium effect size. A mediating role with cortisol was not supported.Although findings need to be validated in a larger sample, the blood pressure elevations in this sample were alarming. If readings continue to amplify as these children age, the fact that elevations are already present during the toddler period could indicate more significant cardiovascular disease in adulthood for this population. Rapid weight gain in early life may be a driver for elevated blood pressure even during early childhood in individuals born preterm.
METHODS:This article presents a case series of n = 21 models of fetal cardiovascular anatomies obtained from post mortem microfocus computed tomography (micro-CT) data. The case series includes a broad range of diagnoses (e.g., tetralogy of Fallot, hypoplastic left heart syndrome, dextrocardia, double outlet right ventricle, atrio-ventricular septal defect) and cases also had a range of associated extra-cardiac malformations (e.g., VACTERL syndrome, central nervous system anomalies, renal anomalies). All cases were successfully reconstructed from the microfocus computed tomography data, demonstrating the feasibility of the technique and of the protocols, including in-house printing with a desktop 3D printer (Form2, Formlabs). All models were printed in 1:1 scale as well as with the 5-fold magnification, to provide insight into the intra-cardiac structures. Possible uses of the models include education and training.
METHODS:Abstract Background Congenital heart disease (CHD) affects ~ 1% of live births and is the most common birth defect. Although the genetic contribution to the CHD has been long suspected, it has only been well established recently. De novo variants are estimated to contribute to approximately 8% of sporadic CHD. Methods CHD is genetically heterogeneous, making pathway enrichment analysis an effective approach to explore and statistically validate CHD-associated genes. In this study, we performed novel gene and pathway enrichment analyses of high-impact de novo variants in the recently published whole-exome sequencing (WES) data generated from a cohort of CHD 2645 parent-offspring trios to identify new CHD-causing candidate genes and mutations. We performed rigorous variant- and gene-level filtrations to identify potentially damaging variants, followed by enrichment analyses and gene prioritization. Results Our analyses revealed 23 novel genes that are likely to cause CHD, including HSP90AA1, ROCK2, IQGAP1, and CHD4, and sharing biological functions, pathways, molecular interactions, and properties with known CHD-causing genes. Conclusions Ultimately, these findings suggest novel genes that are likely to be contributing to CHD pathogenesis.