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Septic cardiomyopathy is characterized by impaired contractive function with mitochondrial dysregulation. Songorine is a typical active C 20 -diterpene alkaloid from the lateral root of Aconitum carmichaelii , which has been used for the treatment of heart failure. This study investigated the protective role of songorine in septic heart injury from the aspect of mitochondrial biogenesis. Songorine (10, 50 mg/kg) protected cardiac contractive function against endotoxin insult in mice with Nrf2 induction. In cardiomyocytes, lipopolysaccharide (LPS) evoked mitochondrial reactive oxygen species (ROS) production and redistributed STIM1 to interact with Orai1 for the formation of calcium release-activated calcium (CRAC) channels, mediating calcium influx, which were prevented by songorine, likely due to ROS suppression. Songorine activated Nrf2 by promoting Keap1 degradation, having a contribution to enhancing antioxidant defenses. When LPS shifted metabolism away from mitochondrial oxidative phosphorylation (OXPHOS) in cardiomyocytes, songorine upregulated mitochondrial genes involved in fatty acid β-oxidation, tricarboxylic acid (TCA) cycle and electron transport chain in a manner dependent on Nrf2, resultantly protecting the capability of OXPHOS. Songorine increased luciferase report gene activities of nuclear respiratory factor-1 ( Nrf1 ) and mitochondrial transcription factor A ( Tfam ) dependently on Nrf2, indicative of the regulation of Nrf2/ARE and NRF1 signaling cascades. Songorine promoted PGC-1α binding to Nrf2, and the cooperation was required for songorine to activate Nrf2/ARE and NRF1 for the control of mitochondrial quality and quantity. In support, the beneficial effects of songorine on cardioprotection and mitochondrial biogenesis were diminished by cardiac Nrf2 deficiency in mice subjected to challenge. Taken together, these results showed that Nrf2 transcriptionally promoted mitochondrial biogenesis in cooperation with PGC-1α. Songorine activated Nrf2/ARE and NRF1 signaling cascades to rescue cardiomyocytes from endotoxin insult, suggesting that protection of mitochondrial biogenesis was a way for pharmacological intervention to prevent septic heart injury.

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The aims were to identify the possible influencing factors of health-related quality of life (HRQoL) and its domain-specific scores in patients with coronary heart disease (CHD). A total of 1247 patients with CHD from the Henan Rural Cohort Study (n = 39,259) were included in this study. The Chinese version of the European Quality of Life Five Dimension Five level scale (EQ-5D-5L) and Visual Analogue Scale (VAS) were used to evaluate HRQoL in patients with CHD. Tobit regression, generalized linear models and binary logistic regression were applied to determine the potential factors influencing the EQ-5D utility, as well as each domain, and the VAS. CHD patients had lower per capita monthly actual income, and higher rates of diabetes mellitus, stroke, anxiety and poor sleep quality, which significantly decreased EQ-5D index and VAS scores. In addition, sex, older age, education, not having a spouse, ever drinking alcohol, a high-fat diet, physical activity, hypertension and depression affected the various domain-specific EQ-5D scores in CHD patients. CHD patients in rural areas have a lower HRQoL. Factors associated with the EQ-5D index, including each domain, and the VAS need attention. CHD patients in rural areas need to be managed systematically.

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