Background. Diabetes mellitus (DM) can induce cardiomyocyte injury and lead to diabetic cardiomyopathy (DCM) which presently has no specific treatments and consequently increase risk of mortality. Objective. To characterize the therapeutic effect of 6-gingerol (6-G) on DCM and identify its potential mechanism. Methods. In vivo streptozotocin- (STZ-) induced DM model was established by using a high-fat diet and STZ, followed by low-dose (25 mg/kg) and high-dose (75 mg/kg) 6-G intervention. For an in vitro DCM model, H9c2 rat cardiomyoblast cells were stimulated with high glucose ( glucose = 33 mM) and palmitic acid (100 μM) and then treated with 6-G (100 μM). Histological and echocardiographic analyses were used to assess the effect of 6-G on cardiac structure and function in DCM. Western blotting, ELISA, and real-time qPCR were used to assess the expression of ferroptosis, inflammation, and the Nrf2/HO-1 pathway-related proteins and RNAs. Protein expression of collagen I and collagen III was assessed by immunohistochemistry, and kits were used to assay SOD, MDA, and iron levels. Results. The results showed that 6-G decreased cardiac injury in both mouse and cell models of DCM. The cardiomyocyte hypertrophy and interstitial fibrosis were attenuated by 6-G treatment in vivo and resulted in an improved heart function. 6-G inhibited the expression of ferroptosis-related protein FACL4 and the content of iron and enhanced the expression of anti-ferroptosis-related protein GPX4. In addition, 6-G also diminished the secretion of inflammatory cytokines, including IL-1β, IL-6, and TNF-α. 6-G treatment activated the Nrf2/HO-1 pathway, enhanced antioxidative stress capacity proved by increased activity of SOD, and decreased MDA production. Compared with in vivo, 6-G treatment of H9c2 cells treated with high glucose and palmitic acid could produce a similar effect. Conclusion. These findings suggest that 6-G could protect against DCM by the mechanism of ferroptosis inhibition and inflammation reduction via enhancing the Nrf2/HO-1 pathway.
Background Suboptimal health status (SHS) is a reversible state between ideal health and illness and it can be effectively reversed by risk prediction, disease prevention, and personalized medicine under the global background of predictive, preventive, and personalized medicine (PPPM) concepts. More and more Chinese nurses have been troubled by psychological symptoms (PS). The correlation between PS and SHS is unclear in nurses. The purpose of current study is to investigate the prevalence of SHS and PS in Chinese nurses and the relationship between SHS and PS along with predisposing factors as well as to discuss the feasibility of improving health status and preventing diseases according to PPPM concepts in Chinese nurses. Methods A cross-sectional study was conducted with the cluster sampling method among 9793 registered nurses in Foshan city, China. SHS was evaluated with the Suboptimal Health Status Questionnaire-25 (SHSQ-25). Meanwhile, the PS of depression and anxiety were evaluated with Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) self-assessment questionnaires. The relationship between PS and SHS in Chinese nurses was subsequently analyzed. Results Among the 9793 participants, 6107 nurses were included in the final analysis. The prevalence of SHS in the participants was 74.21% (4532/6107) while the symptoms of depression and anxiety were 47.62% (2908/6107) and 24.59% (1502/6107) respectively. The prevalence of SHS in the participants with depression and anxiety was significantly higher than those without the symptoms of depression (83.3% vs 16.7%, P < 0.001) and anxiety (94.2% vs 5.8%, P < 0.0001). The ratio of exercise habit was significantly lower than that of non-exercise habit (68.8% vs 78.4%, P < 0.001) in SHS group. Conclusions There is a high prevalence of SHS and PS in Chinese nurses. PS in Chinese nurses are associated with SHS. Physical exercise is a protective factor for SHS and PS so that the exercise should be strongly recommended as a valuable preventive measure well in the agreement with PPPM philosophy. Along with SDS and SAS, SHSQ-25 should also be highly recommended and applied as a novel predictive/preventive tool for the health measures from the perspectives of PPPM in view of susceptible population and individual screening, the predisposition to chronic disease preventing, personalization of intervention, and the ideal health state restoring.
BackgroundRecent studies of fibroblast growth factor 21 (FGF21), first recognized as a regulator of glucose and lipid metabolism, have found that the level of in serum FGF21 is associated with the prognosis of many cardiovascular diseases, but its relationship to acute heart failure (AHF) patients remains unknown. Our study aimed to investigate whether circulating FGF21 could predict the short-term prognosis of AHF patients.MethodsFour hundred and two AHF patients and 19 healthy controls were recruited into the prospective cohort study, and blood samples of participants were collected, in tubes without anticoagulant, within the first 24 h after hospital admission. Serum FGF21 levels were detected by enzyme-linked immunosorbent assay (ELISA). All patients were followed-up at least 6 months after discharge. The primary endpoint was all-cause death, and secondary endpoint was a composite endpoint of death and heart failure readmission. Mortality and composite end point events were analyzed using Kaplan-Meier curves. ROC curves compared the difference between the FGF21 and NT-proBNP in predicting 3- and 6-months mortality. Time-to-event data were evaluated using Kaplan-Meier estimation and Cox proportional hazards models.ResultsIn the present study, the serum FGF21 concentrations were significantly higher in the 402 AHF patients enrolled, compared with the 19 healthy controls (p < 0.001). The average age was 70 (±12) years, and 58% were males. Participants were divided into two groups according to the median FGF21 level (262 pg/ml): a high FGF21 group (n = 201, FGF21 ≥ 262 pg/ml) and low FGF21 group (n = 201, FGF21 <262 pg/ml). FGF21 was positively correlated with NT-proBNP, BUN, AST, creatinine and cholesterol, and negatively correlated with ALB and HDL. After a median follow-up of 193 days, the high FGF21 group had higher mortality and composite endpoint events compared with the low FGF21 group (HR: 3.91, 95% CI 2.21–6.92, p <0.001), even after adjusting for NT-proBNP (HR: 3.17, 95% CI 1.72–5.81, p < 0.001). ROC analysis shows that FGF21 was better than NT-proBNP in predicting death at both 3 (AUC, 0.77 vs. 0.63, p < 0.001) and 6 months (AUC, 0.78 vs. 0.66).ConclusionHigh baseline FGF21 levels are associated with adverse clinical outcomes in AHF patients. Serum FGF21 might be a potential predictive biomarker of AHF patients.
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