Jie Wang

Coronary artery disease (CAD) is one of the most common heart diseases, characterized by the hardening and narrowing of arteries, resisting blood supply to cardiac muscle. Despite extensive research, the pathogenesis and therapeutic options for CAD remain limited. Epigenetic regulation plays a critical role in CAD progression. Here, we report a unique DNA methylation-miRNA-mRNA regulatory network for CAD, delineated through DNA methylation assays, miRNA and mRNA sequencing, bioinformatics analyses. We also identified key signaling pathways in this network, including the miR194 promoter-miR194-MAPK signaling pathway by pyrosequencing, methylation PCR, qRT-PCR. This pathway could play a role in CAD by apoptosis. Our findings suggested that this signaling pathway may be a potential therapeutic target for CAD. We believe that our study significantly contributes to an improved understanding of the role of specific miRNAs methylation, miRNA, and mRNAs in CAD pathogenesis.

Background:Panax notoginseng saponins (PNS) may have an inhibitory effect against coronary artery disease (CAD); however, the mechanism is unclear. Recent research has begun to evaluate the role of epigenetics in CAD. Our team found that hypomethylation of miR-194 could be an important mechanism of CAD.Purpose: The aim of this study was to investigate the effect of PNS against CAD and evaluate whether the mechanism is related to methylation of mi-R194.Methods: We conducted a randomized controlled trial with a double-blind placebo design on 84 patients with CAD. Treatment was continued for 4 weeks, and the clinical effect of PNS on CAD was observed. Methylation of miR-194, its promoter, and the key nodes of the MAPK pathway were measured by pyrosequencing and qRT-PCR. We then conducted a pharmacological analysis of the active components of PNS. The effects of PNS on oxidized human umbilical vein endothelial cells and the methylation of miR-194, its promoter, and the key nodes of the MAPK pathway were measured in vitro through methylation-specific PCR (MSPCR), qRT-PCR, Western blot analysis, and annexin V/propidium iodide apoptosis assay.Results: PNS improved symptoms of CAD. High-density lipoprotein and white blood cell count demonstrated significant changes after treatment in the PNS group. No significant difference was observed between miR-194 and mRNA MAPK, FAS, RAS, and FOS in the PNS group after treatment. However, some notable trends were observed in these genes. The targets of PNS were predicted by the pharmacological components. Some targets were found to be differentially expressed genes in CAD sequencing. Six genes, including MAPK1, RAS, and FASL, were common targets of PNS in CAD sequencing. Correlations were observed between genes in the interaction network and clinical parameters. In vitro experiments confirmed that PNS could change the methylation of miR-194, its promoter, and MAPK, FAS, RAS, and FOS. Intervention with PNS is likely to improve apoptosis.Conclusion: We reported the regulation of miR-194 promoter, miR-194, and MAPK methylation by PNS through cell experiments and a randomized controlled trial. PNS can be used for intervention in CAD by targeting the miR-194 promoter-miR-194-MAPK signaling pathway.Clinical Trial Registration: https://www.clinicaltrials.gov/, NCT03083119.

Background and Purpose: Two Chinese herbal medicines Huang Qi (HQ, Astragalus mongholicus) and Dan Shen (DS, Salvia miltiorrhiza) are often combined to treat coronary heart disease (CHD). The purpose of this study was to identify the underlying synergistic effects and mechanisms of HQ and DS against CHD. Methods: The active components and targets of HQ and DS, CHD-related genes, and the biological progression were analysed by network pharmacology. The myocardial infarction (MI) rat model was established by ligating the left anterior descending coronary artery. Cardiac function was detected by ultrasonic electrocardiography. The MI size, fibrosis, cardiac hypertrophy, lipid metabolism, blood viscosity, and coagulation indexes were analysed by histological staining or chemical methods, respectively. Results: A total of 170 shared and specific seed genes of HQ and DS against CHD were identified. The shared and specific biological processes of HQ and DS against CHD were obtained. The LVEF and LVFS values significantly increased, the myocardium infarct size and fibrosis significantly decreased, the values of lipid metabolism indexes and blood viscosity indexes significantly reduced in the HQ + DS treatment group vs HQ or DS single treatment (P < 0.05); the LVEDd, LVEDs, and the CSA values significantly reduced in HQ single and HQ + DS treatment groups vs MI group (P < 0.05); the coagulation index (APTT, PT, TT, and FIB) values decreased significantly in the DS single and HQ + DS treatment groups vs MI group (P < 0.05). Conclusion: In MI rats, HQ and DS exhibited synergistic effects on improving cardiac function, reducing MI size, fibrosis, regulating hyperlipidaemia, and maintaining circulatory system homeostasis; HQ had the specific advantage of alleviating cardiac remodelling; DS had the specific advantage of regulating hypercoagulability. This study revealed that HQ and DS not only exerted synergistic effects but also exhibited complementary effects on CHD.

Objective. Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas‐exchange impairment due to a severe inflammatory process known as cytokine storm. Xuebijing injection (hereinafter referred to as Xuebijing) is a patent drug that was used to treat ARDS or severe pneumonia (SP) in China. However, its efficacy and mechanism of actions remain unclear. In this study, we used meta‐analysis and network pharmacology to assess these traits of Xuebijing. Methods. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases for randomized controlled trials (RCTs) that evaluated Xuebijing therapy for ARDS or SP. The outcomes were total mortality, intensive care unit (ICU) stay time, and TNF‐α and IL‐6 levels. We performed a meta‐analysis using RevMan 5.3 software. The putative targets, top 10 proteins, and possible pathway of Xuebinjing on ARDS were analyzed by network pharmacology. TNF‐α and IL‐6 were further docked with the six main active components of Xuebinjing using AutoDock 4.2.6 and PyMol 1.5.0.3 software. Results. Fifteen RCTs involving 2778 patients (13 ARDS and 2 SP) were included. Compared with the control, Xuebijing treatment significantly reduced the mortality rate (risk ratio, 0.64 (95% credible interval (CrI), 0.54–0.77)), reduced the ICU stay time (mean difference (MD), ‐4.51 (95% CrI, ‐4.97–‐4.06)), reduced the TNF‐α ((MD), ‐1.23 (95% CrI, ‐1.38–‐1.08)) and IL‐6 ((MD), ‐1.15 (95% CrI, ‐1.52–‐0.78)) levels. The 56 putative targets, top 10 proteins (MAPK1 (mitogen‐activated protein kinase 1), MAPK8 (mitogen‐activated protein kinase 8), RELA (transcription factor p65), NFKB1 (nuclear factor NF‐kappa‐B p105 subunit), JUN (transcription factor AP‐1), SRC (proto‐oncogene tyrosine‐protein kinase), TNF (tumor necrosis factor), HRAS (GTPase HRas), IL6 (interleukin‐6), and APP (amyloid‐beta A4 protein)), and possible pathways (Ret tyrosine kinase, IL2‐mediated signaling events, CD4+/CD8+ T cell‐related TCR signaling, p75(NTR)‐mediated signaling, CXCR4‐mediated signaling events, LPA receptor‐mediated events, IL12‐mediated signaling events, FAS (CD95) signaling pathway, and immune system) of Xuebinjing’s action on ARDS were obtained. The molecular docking results showed that all the six components of Xuebinjing docked with TNF‐α, and two components docked with IL‐6 got the binding energies lower than ‐5. Conclusion. Our results recommended Xuebijing treatment for patients with ARDS. Xuebijing has therapeutic effects on ARDS patients partly by regulating the immune cell/cytokine pathways and thus inhibiting the cytokine storm. TNF‐α is the cytokine both directly and indirectly inhibited by Xuebijing, and IL‐6 is the cytokine mainly indirectly inhibited by Xuebijing.

OBJECTIVE: To evaluate the effectiveness and safety of Suxiao Jiuxin pill (SX) in acute coronary syndrome (ACS) treatment. METHODS: An extensive search of four English databases (Medline/PubMed, Cochrane Library, Embase, and World Health Organization International Clinical Trials Registration Platform) and four Chinese databases (Chinese National Knowledge Infrastructure, Wanfang, China Science and Technology Journal, and Chinese Biomedical Literature Service System) was performed. Randomized, controlled trials (RCTs) involving SX combined with conventional therapy versus conventional therapy were included. The extracted data included populations, interventions, outcomes, and risk of bias. The cardiovascular events served as the primary outcome. Review Manager 5.3 software was used for data analysis. Relative risks (RRs) with 95% confidence intervals (CIs) were the effect measure. RESULTS: A total of eight RCTs with 979 patients were included. There were 559 patients with unstable angina (UA) in six RCTs and 420 patients with acute myocardial infarction (AMI) in two RCTs. Our review showed that SX plus conventional therapy might reduce the incidence of the total endpoint (RR: 0.34, 95% CI: 0.17, 0.68, P = 0.002), with no obvious adverse events (RR: 1.29, 95% a 0.60, 2.77, P = 0.52) compared with conventional therapy for patients with UA. Additionally, SX plus conventional therapy also reduced the incidence of the total endpoint (RR: 0.35, 95% CI: 0.18, 0.68, P = 0.002) compared with conventional therapy in patients with AMI. SX plus conventional therapy also reduced the incidence of ventricular fibrillation (RR: 0.23, 95% CI: 0.10, 0.57, P = 0.001) compared with conventional therapy in patients with AMI. CONCLUSION: Our results suggest that SX is beneficial for treating patients with UA or AMI. However, our findings should be treated with caution because of the poor methodological quality of the included trials. Therefore, more multicenter, large-sample, high-quality RCTs are required to provide high-quality evidence. (C) 2020 JTCM. All rights reserved.

Coronary artery disease (CAD) is a major public health problem and the chief cause of morbidity and mortality worldwide. Panax notoginseng, a valuable herb in traditional Chinese medicine (TCM) with obvious efficacy and favourable safety, exhibits a great promise as a novel option for CAD and is increasingly recognized clinically. Firstly, this review introduced the mechanisms of panax notoginseng and panax notoginseng saponins (PNS), which can regulate signalling pathways associated with inflammation, lipid metabolism, the coagulation system, apoptosis, angiogenesis, atherosclerosis and myocardial ischaemia. Secondly, recent clinical trials on treatment with PNS either alone or in combination with conventional drugs are considered as novel treatment strategies.