Sphingosine-1-Phosphate Protects Against the Development of Cardiac Remodeling via Sphingosine Kinase 2 and the S1PR2/ERK Pathway.

OBJECTIVE: Cardiac remodeling is a common pathological change in various cardiovascular diseases and can ultimately result in heart failure. Thus, there is an urgent need for more effective strategies to aid in cardiac protection. Our previous work found that sphingosine-1-phosphate (S1P) could ameliorate cardiac hypertrophy. In this study, we aimed to investigate whether S1P could prevent cardiac fibrosis and the associated mechanisms in cardiac remodeling. METHODS: Eight-week-old male C57BL/6 mice were randomly divided into a sham, transverse aortic constriction (TAC) or a TAC+S1P treatment group. RESULTS: We found that S1P treatment improved cardiac function in TAC mice and that the cardiac fibrosis ratio in the TAC+S1P group was significantly lower and was accompanied by a decrease in α-smooth muscle actin (α-SMA) and collagen type I (COL I) expression compared with the TAC group. We also found that one of the key S1P enzymes, sphingosine kinase 2 (SphK2), which was mainly distributed in cytoblasts, was downregulated in the cardiac remodeling case and recovered after S1P treatment in vivo and in vitro. In addition, our in vitro results showed that S1P treatment activated extracellular regulated protein kinases (ERK) phosphorylation mainly through the S1P receptor 2 (S1PR2) and spurred p-ERK transposition from the cytoplasm to cytoblast in H9c2 cells exposed to phenylephrine. CONCLUSION: These findings suggest that SphK2 and the S1PR2/ERK pathway may participate in the anti-remodeling effect of S1P on the heart. This work therefore uncovers a novel potential therapy for the prevention of cardiac remodeling.

[Randomized controlled trials of acupuncture and moxibustion in China in past 45-year (1975-2019): hotspots and trends].

By searching the randomized controlled trials (RCTs) of acupuncture and moxibustion from CNKI since its inception date to december 31 of 2019, the development status and hot trend of RCTs of acupuncture and moxibustion in China were summarized. The CiteSpace and VOSviewer software were used to perform keyword co-occurrence analysis, clustering analysis, time-zone analysis and citation-burst analysis, and visual map was drawn. As a result, a total of 60 995 articles were included, which were published in 1027 academic journals with 1787 keywords. The publication date was from 1975 to 2019. During the past 45 years, the publications of RCTs on acupuncture and moxibustion had shown an overall growth trend with characteristics of the times. The RCTs of manual acupuncture ranked the top, and its proportion of publications every 5 years was stable in the past 30 years. Since 1994, the hot words such as electroacupuncture, warming needling, auricular point sticking and various acupoint therapies had emerged; meanwhile, the spectrum of diseases had broadened, and an evolutionary trend corresponding to therapies and disease systems had been formed. In recent decade, the RCTs using moxibustion therapy have increased significantly, and the hot words such as "sub-health" "winter diseases being treated in summer" and "acupoint application/ moxibustion during the dog days" had indicated that acupuncture clinical research was further inclined to the field of chronic disease prevention and health services, which was in line with social development and the needs of the times.