The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine

Atrial fibrillation (AF) is a common arrhythmia that can reduce the quality of life of patients. Observational studies have reported that work and sleep are associated with the development of AF, but the causal relationship is unclear.Based on published genome-wide association studies (GWASs), we conducted a two-sample Mendelian Randomization (MR) analysis employing inverse variance weighted (IVW), weighted median, and MR-Egger regression analyses. We chose statistical data of 3 work factors from the MRC-IEU GWAS pipeline and 2 sleep factors from the Sleep Disorders Knowledge Portal as the exposure and the FinnGen study of AF as the outcome.The study revealed that engaging in heavy physical work was associated with an increased risk of AF (IVW OR, 1.787; 95% CI, 1.082-2.853; P = 0.023), and job satisfaction was negatively correlated with AF risk (IVW OR, 0.719; 95% CI, 0.536-0.964; P = 0.028). In addition, jobs that primarily involved walking or standing, short sleep duration (< 7 hours), and long sleep duration (≥ 9 hours) were not associated with AF. The results of the sensitivity analysis are consistent with these trends.The results support a causal relationship between heavy physical labor and increased risk of AF, and that job satisfaction has some protective effect on AF.

This study aimed to observe the influences and potential mechanism of rehmannioside A (ReA) in hypertensive nephropathy (HN).

HN model in mice and rat tubular epithelial cells were constructed by angiotensin II (Ang II). The biomarkers of renal function, including uric acid (UA), creatinine (Cre), blood urea nitrogen (BUN), and urine albumin, were assessed.

Ang II induced severe kidney injury, while the injury was ameliorated by ReA. In Ang II-induced hypertensive mice model, ReA decreased the levels of UA, Cre, BUN, urine albumin, transforming growth factor (TGF)-β, Fibronectin, Collagen I, interleukin (IL)-6, IL-1β, and tumour necrosis factor (TNF)-α. In Ang II-treated cells, ReA reduced the levels of TGF-β, Fibronectin, Col1agen I, IL-6, IL-1β, and TNF-α. In vivo and in vitro, ReA promoted angiotensin converting enzyme 2 (ACE2) expression and inhibited the expression of angiotensin II type 1 receptor (AT1R), ACE, IL-17, mitogen activated protein kinase 14 (MAPK14), phosphorylated (p)-MAPK14, p-NF-κB P65, and matrix metallopeptidase 9 (MMP-9) in HN model. Moreover, there was a docking for ReA and MAPK14 protein, and ReA inhibited MAPK14 protein expression by promoting MAPK14 ubiquitination. Under Ang II treatment, MAPK14 overexpression reversed the promotive effect of ReA on cell viability and the inhibitory effects of ReA on fibrosis and inflammation in NRK-52E cells.

ReA alleviated renal dysfunction and reduced fibrosis and inflammation, which was related to the inhibition of AT1R/MAPK14/IL-17 pathway. For HN treatment, ReA may be a promising pharmacological strategy.