Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality in the world. Despite considerable progress in the diagnosis, treatment and prognosis of CVDs, new diagnostic biomarkers and new therapeutic measures are urgently needed to reduce the mortality of CVDs and improve the therapeutic effect. RNA methylations regulate almost all aspects of RNA processing, such as RNA nuclear export, translation, splicing and non-coding RNA processing. In view of the importance of RNA methylations in the pathogenesis of diseases, this work reviews the molecular structures, biological functions of five kinds of RNA methylations (m6A, m5C, m1a, m6am and m7G) and their effects on CVDs, including pulmonary hypertension, hypertension, vascular calcification, cardiac hypertrophy, heart failure. In CVDs, m6A “writers” catalyze the installation of m6A on RNAs, while “erasers” remove these modifications. Finally, the “readers” of m6A further influence the mRNA splicing, nuclear export, translation and degradation. M5C, m1A, m6Am and m7G are new types of RNA methylations, their roles in CVDs need to be further explored. RNA methylations have become a new research hotspot and the roles in CVDs is gradually emerging, the review of the molecular characteristics, biological functions and effects of RNA methylation on CVDs will contribute to the elucidation of the pathological mechanisms of CVDs and the discovery of new diagnostic markers and therapeutic targets of CVDs.

Background: Traditional Chinese medicine (TCM) is widely used in the clinical treatment of hepatolenticular degeneration (HLD) and liver fibrosis (LF). In the present study, the curative effect was assessed using meta-analysis. The possible mechanism of TCM against LF in HLD was investigated using network pharmacology and molecular dynamics simulation.Methods: For literature collection, we searched several databases, including PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals (VIP) and Wan Fang database until February 2023, and the Review Manager 5.3 was used to analyze the data. Network pharmacology and molecular dynamics simulation were used to explore the mechanism of TCM in treating LF in HLD.Results: The results of the meta-analysis revealed that the addition of Chinese herbal medicine (CHM) in treating HLD resulted in a higher total clinical effective rate than western medicine alone [RR 1.25, 95% CI (1.09, 1.44), p = 0.002]. It not only has a better effect on liver protection [Alanine aminotransferase: SMD = −1.20, 95% CI (−1.70, −0.70), p < 0.00001; Aspartate aminotransferase: SMD = −1.41, 95% CI (−2.34, −0.49), p = 0.003; Total bilirubin: SMD = −1.70, 95% CI (−3.36, −0.03), p = 0.05] but also had an excellent therapeutic effect on LF through four indexes [Hyaluronic acid: SMD = −1.15, 95% CI (−1.76, −0.53), p = 0.0003; Procollagen peptide III: SMD = −0.72, 95% CI (−1.29, −0.15), p = 0.01; Collagen IV: SMD = −0.69, 95% CI (−1.21, −0.18), p = 0.008; Laminin: SMD = −0.47, 95% CI (−0.95, 0.01), p = 0.06]. Concurrently, the liver stiffness measurement decreased significantly [SMD = −1.06, 95% CI (−1.77, −0.36), p = 0.003]. The results of network pharmacological experiments and molecular dynamics simulation indicate that the three high-frequency TCMs (Rhei Radix Et Rhizoma-Coptidis Rhizoma-Curcumae Longae Rhizoma, DH-HL-JH) primarily act on the core targets (AKT1, SRC, and JUN) via the core components (rhein, quercetin, stigmasterol, and curcumin), regulate the signal pathway (PI3K-Akt, MAPK, EGFR, and VEGF signaling pathways), and play a role of anti-LF.Conclusion: Meta-analysis indicates that TCM is beneficial in treating HLD patients and improving LF. The present study successfully predicts the effective components and potential targets and pathways involved in treating LF for the three high-frequency CHMs of DH-HL-JH. The findings of the present study are hoped to provide some evidence support for clinical treatment.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022302374.

The Jiedu Huazhuo Quyu formula (JHQ) shows significant beneficial effects against liver fibrosis caused by Wilson’s disease (WD). Hence, this study aimed to clarify the mechanisms of the JHQ treatment in WD-associated liver fibrosis. First, we collected 103 active compounds and 527 related targets of JHQ and 1187 targets related to WD-associated liver fibrosis from multiple databases. Next, 113 overlapping genes (OGEs) were obtained. Then, we built a protein-protein interaction (PPI) network with Cytoscape 3.7.2 software and performed the Gene Ontology (GO) term and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses with GENE DENOVO online sites. Furthermore, module analysis was performed, and the core target genes in the JHQ treatment of WD-associated liver fibrosis were obtained. Pathway and functional enrichment analyses, molecular docking studies, molecular dynamic (MD) simulation, and Western blot (WB) were then performed. The results indicated that 8 key active compounds including quercetin, luteolin, and obacunone in JHQ might affect the 6 core proteins including CXCL8, MAPK1, and AKT1 and 107 related signaling pathways including EGFR tyrosine kinase inhibitor resistance, Kaposi sarcoma-associated herpesvirus infection, and human cytomegalovirus infection signaling pathways to exhibit curative effects on WD-associated liver fibrosis. Mechanistically, JHQ might inhibit liver inflammatory processes and vascular hyperplasia, regulate the cell cycle, and suppress both the activation and proliferation of hepatic stellate cells (HSCs). This study provides novel insights for researchers to systematically explore the mechanism of JHQ in treating WD-associated liver fibrosis.

Background: Gandouling (GDL) is a compound prepared in Chinese medicine and demonstrates favorable clinical efficacy. Studies have shown that sinusoid capillarization promoted hepatic fibrosis and was a potential target for preventing and treating liver fibrosis in Wilson’s disease (WD). This study aimed to explore whether GDL inhibited the sinusoid capillarization in WD by blocking the communication between hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs). Methods: In this study, Atp7b-H1071Q (TX) mice were used as the WD model mice, and CuSO₄⋅5H₂O treated LX-2 cells were used as the HSC activation model. We used scanning electron microscopy, vascular tube formation assay, Western blot, cell transfection, and co-culture system to study how GDL blocked the communication between HSCs and LSECs, as well as its inhibitory effect on the sinusoid capillarization. Results: We found that GDL alleviated liver fibrosis in TX mice, inhibited HSC activation, and sinusoid capillarization in TX mice. Excessive secreted VEGFA by LX-2 cells promoted the sinusoid capillarization, played the role of a messenger molecule, and GDL blocked the VEGFA-mediated HSCs-LSECs communication. Furthermore, bioinformatics analysis, molecular docking, and molecular dynamics suggested that GDL may exert its effect by modulating the PDGFRβ/ERK/VEGFA signaling axis. We validated the above observation through experiments, that GDL reduced PDGFRβ/ERK signal pathway in LX-2 cells, inhibited the expression of messenger molecule VEGFA, blocked HSCs-LSECs communication, inhibited sinusoid capillarization, and improved WD. Conclusions: GDL blocked the communication between HSCs and LSECs and inhibited the sinusoid capillarization associated with liver fibrosis in WD by the PDGFRβ/ERK/VEGFA signaling axis.