Efficacy and safety of Shenfu injection in the treatment of sepsis: A protocol for systematic review and meta-analysis.

BACKGROUND: Sepsis is a syndrome of infection-induced systemic inflammatory response. Conventional treatment combined with Shenfu injection (SFI) has been previously validated clinical effective in alleviating inflammatory response in patients with septic shock. However, evidence-based medical evidence is scant. Herein, we designed the protocol of a proposed study based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, aiming to systematically evaluate the efficacy and safety of SFI in patients with sepsis. METHODS: Eligible studies reporting the efficacy and safety of SFI in the treatment of sepsis published before August 2021 will be searched from online databases, including the PubMed, Web of Science, EMBASE, Ovid, the Cochrane Library, Wanfang Database, China National Knowledge Infrastructure, and China Biology Medicine Disc. The literature selection process will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. After data extraction and methodological quality evaluation, Stata 12.0 software will be used to synthesize the data through fixed/random effects of meta-analysis models. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide reliable evidence-based basis for the clinical application of SFI in the treatment of sepsis. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/KCMDQ.

Inhibition of Exo-miR-19a-3p derived from cardiomyocytes promotes angiogenesis and improves heart function in mice with myocardial infarction via targeting HIF-1α.

BACKGROUND: Myocardial infarction (MI), a common presentation for cardiovascular disease, is caused by reduction of blood flow and oxygen supply and is one of the main causes of death worldwide. MicroRNAs participate in multiple physiological and pathological processed and play crucial role in myocardial infarction. RESULTS: qRT-PCR analysis showed that expression level of miR-19a-3p was increased in serum of patient with MI. In vitro study indicated that the miR-19a-3p level was upregulated in response to H2O2 treatment and transferred by exosome, and then, uptake occurred in endothelial cells. Furthermore, western blot and immunostaining showed that treatment of exosome enriched miR-19a-3p suppressed the proliferation of endothelial cells and induced cell death, which was inhibited by AMO-19 transfection. Administration of antagomiR-19a-3p promoted angiogenesis and improved heart function of MI mice. Moreover, miR-19a-3p overexpression downregulated the protein level of HIF-1α and transfection of si-HIF-1α reversed the promotion of endothelial cells proliferation caused by AMO-19 transfection. In addition, antagomiR-19a-3p treatment accelerated angiogenesis and infection of AAV5-shHIF-1α inhibited that effect in MI mice. CONCLUSIONS: In conclusion, our finding indicated that miR-19a-3p inhibited endothelial cells proliferation and angiogenesis via targeting HIF-1α and attenuated heart function of mice after MI, and suggested a new mechanism of cell-to-cell communication between cardiomyocytes and endothelial cells.

[Effect of lovastatin and rosiglitazone on cholesterol reverse transportation in foam cell].

OBJECTIVES: This study was designed to explore the function of ATP binding cassette transporter 1 (ABCA1) and Apolipoprotein A-I (ApoA-I) in cholesterol reverse transportation (RCT), the influence of lovastatin and rosiglitazone on the concentration of cholesterol (CHO) in THP-1 (human monocytic leukemia cell line) derived foam cells. METHODS: LDL from healthy volunteers was obtained by density-gradient ultracentrifugation and was oxidized by incubation with Cu2+ and ox-LDL was identified.Macrophages were induced from THP-1 cell by phorbol ester (PMA). Models of foam cells were built by incubating macrophages with oxLDL. The effect of lovastatin and rosiglitazone on ABCA1 protein expression in THP-1 cell line derived macrophage were detected by western blot. Foam cells were divided into 9 groups: control, ApoA-I, lovastatin, rosiglitazone lovastatin+ApoA-I, rosiglitazone+ApoA-I, ABCA1 monoclonal antibody pretreatment+ApoA-I, ABCA1 monoclonal antibody pretreatment+lovastatin+ApoA-I, ABCA1 monoclonal antibody pretreatment+rosiglitazone+ApoA-I. The concentration of intracellular CHO in each group was detected by using cholesterol kit. RESULTS: As compared with control group, there are no big differences of CHO concentration within the cell of group lovastatin, rosiglitazone, and each ABCA1 monoclonal antibody pretreatment group (P>0.05), but the CHO concentration within the cells of group ApoA-I, lovastatin+ApoA-I, rosiglitazone+ApoA-I decreased obviously as compared with the control (P<0.05), and CHO concentration in group rosiglitazone+ApoA-I have a further decrease than the former two groups (P<0.05). CONCLUSIONS: CHO concentration can be decreased in foam cells by cooperation of ABCA1 and ApoA-I mediate cholesterol efflux. Rosiglitazone can enhance this procedure in THP-1 macrophages derived foam cells which means that they can promote ABCA1 mediated cholesterol reverse transportation through improve ABCA1 protein expression.