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Background: Chronic heart failure (CHF) patients exhibit alterations in cerebral cortical structure and cognitive function. However, the mechanisms by which CHF affects cortical structure and functional regions remain unknown. This study aims to investigate potential causal relationship between CHF and cerebral cortical structure through Mendelian randomization (MR)., Methods: The research utilized genome-wide association studies (GWAS) to explore the causal association between CHF and cerebral cortical structure. The results were primarily analyzed using the inverse-variance weighted (IVW). The reliability of the data was verified through horizontal pleiotropy and heterogeneity analysis by MR-Egger intercept test and Cochran's Q -test, respectively. Replication analysis was conducted in the Integrative Epidemiology Unit (IEU) OpenGWAS project for further validation. In addition, we collected mediator genes that mediate causality to reveal potential mechanisms. Integrated bioinformatics analysis was conducted using the Open Target Genetics platform, the STRING database, and Cytoscape software., Results: The IVW results did not reveal any significant causal association between genetically predicted CHF and the overall structure of the cerebral cortex or the surface area (SA) of the 34 functional regions of the cerebral cortex ( P  > 0.05). However, the results revealed that CHF increased the thickness (TH) of pars opercularis (IVW: β  = 0.015, 95% CI: 0.005-0.025, P   =  3.16E-03). Replication analysis supported the causal association between CHF and pars opercularis TH (IVW: β  = 0.02, 95% CI: 0.010-0.033, P  = 1.84E-04). We examined the degree centrality values of the top 10 mediator genes, namely CDKN1A, CELSR2, NME5, SURF4, PSMA5, TSC1, RPL7A, SURF6, PRDX3, and FTO., Conclusion: Genetic evidence indicates a positive correlation between CHF and pars opercularis TH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Peng, Cai, Tang, Zhou, Liu, Xu, Chen and Chen.)

Background: Despite a crucial role of miR-155 in human cancers, its function in heart failure (HF) is still under investigation. This study was designed to explore its association with HF., Methods: The abdominal transverse aortic constriction (TAC) was adopted for establishment of mouse HF models. qRT-PCR and WB were adopted to detect the changes of miR-155, HIF-1α, Cle-caspase-3, BCL2 and Bax levels in myocardial cells and heart tissues. The changes of cardiac function were checked by ultrasound. Additionally, luciferase reporter gene was adopted for interaction analysis of miR-155 with HIF-1α, and in situ end labelling method was used for detecting myocardial apoptosis., Results: MiR-155 in myocardial tissue of HF mice was significantly down regulated. In HF mice injected with agomiR-155, the up-regulation of miR-155 strongly improved cardiac function, and also significantly lowered the protein levels of apoptosis-associated markers, C-caspase-3 and Bax, but up regulated Bcl-2. Additionally, HIF-1α was identified as the direct target of miR-155. As expected, over-expression of HIF-1α greatly reversed the effects of agomiR-155 on cardiac function and the expression of apoptosis-associated markers in heart tissues of HF mice., Conclusion: MiR-155 overexpression can suppress myocardial cell apoptosis through HIF-1α, and strongly alleviate the cardiac function damage in HF mice, indicating the potential of miR-155/HIF-1α axis to be a target for the diagnosis and therapy of HF., Competing Interests: None., (AJTR Copyright © 2023.)

Introduction: Objective: bioinformatic methods and molecular docking technology were used to predict the active components, targets, and related biological pathways of the Xiexin capsule in the intervention for dyslipidemia, exploring its mechanism. Methods: the active components and targets of the Xiexin capsule were screened by the TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform )database. Genecards (The Human Gene Database), OMIM (Online Mendelian Inheritance in Man), PharmGkb (Pharmacogenomics Knowledge Base database), TTD (Therapeutic Target Database), and Drugbank platforms were used to search the disease targets of dyslipidemia. The Cytoscape 3.8.0 software was used to construct the 'component-target' network diagram, and the STRING (functional protein association networks) platform was used to analyze protein-protein interaction (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) enrichment analyses were performed by R language data packets to predict the mechanism of action. The AutoDockVina and PyMol software were used to dock the key active components in the Xiexin capsule and the core proteins in PPI. Results: a total of 66 effective components were screened, involving 114 targets; 87 key active compounds were screened from the 'drug-component-target' diagram. The PPI network mainly involved core proteins such as PTGS2 (prostaglandin-endoperoxide synthase 2), PTGS1 (prostaglandin-endoperoxide synthase 1), and HSP90AA1 (heat shock protein 90 alpha family class A member 1). GO and KEGG enrichment analysis results of common targets mainly involved hormone-mediated signaling pathway, steroid hormone response, lipid transport and metabolism, regulation of cholesterol storage, cyclooxygenase pathway, and other biological pathways, as well asMM PPAR (peroxisome proliferators-activated receptor) signaling pathway, IL-17 (interleukin 17) signaling pathway, PI3K-Akt (protein kinase b) signaling pathway, FcεRI signaling pathway, and other related pathways. Molecular docking verification showed that quercetin had the best binding with the core target protein HSP90AA1, and HSP90AA1 was the target protein with the best binding activity for the key chemical components in Xiexin capsules. Conclusion: the main chemical components in the Xiexin capsules may participate in the regulation of PPAR and other signaling pathways by regulating key genes such as ESR1 (estrogen receptor 1), MAPK14 (mitogen-activated protein kinase 14), and HSP90AA1, to exert the pharmacological effect of the intervention on dyslipidemia.

Chronic heart failure (CHF) refers to the state of persistent heart failure, which is a complex clinical syndrome of various advanced heart diseases. The toll-like receptor 2 (TLR2)/nuclear transcription factor- κ B (NF- κ B) signal transduction pathway is one of the pathological mechanisms of CHF. Adriamycin can significantly induce the upregulation of TLR2 expression. Angiotensin-converting enzyme inhibitors (ACEI) are commonly used drugs for the treatment of CHF. In our study, the CHF model was established by injection of doxorubicin into the rabbit ear vein. The effect of enalapril on the TLR2/NF- κ B signaling pathway in CHF rabbits has been analyzed and determined. Our research results showed that enalapril reduced the inflammatory response by inhibiting the activation of the TLR2/NF- κ B signaling pathway, thereby improving cardiac structure, myocardial remodeling, and cardiac function., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Yanping Tang et al.)

Objective: To elucidate the effects of Wenyangzhenshuai granule on expression of extracellular signal-regulated kinase 1/2 (ERK1/2) and 5 (ERK5) in the myocardial tissue using a rabbit model of adriamycin-induced chronic heart failure., Materials and Methods: Rabbits were divided into heart failure positive control, adriamycin injection, and adriamycin injection with Wenyangzhenshuai treatment (low, medium and high dose) groups. Cardiac function and cardiac hypotrophy were measured in all groups. Besides, myocardial expression of ERK1/2 and ERK5 phosphorylation were evaluated by Western blotting and ERK1/2 and ERK5 mRNA levels by RT-PCR. The cardiac structure and cardiac function were also compared using histology staining and electron microscope., Results: Adriamycin injection led to cardiac failure reflected by decreased left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), E/A ratio, and increased cardiac hypertrophy, both of which have been improved by Wenyangzhenshuai granule treatment (all P<0.05). Mechanistically, increased P-ERK1/2 and decreased P-ERK5 levels were observed in myocardial tissues of mice treated with Adriamycin for 8 weeks. However, such signaling change could be partially corrected by Wenyangzhenshuai treatment. In addition, no significant difference was detected in the expression of ERK1/2 and ERK5 mRNA levels between adriamycin injection groups and Wenyangzhenshuai treatment groups (P>0.05), indicating an alteration in the activity/phosphorylation levels of these proteins instead of the transcription levels., Conclusion: we found a beneficial effect of Wenyangzhenshuai treatment in partially decelerating the progression of CHF. Such effect was probably through the role of Wenyangzhenchuan in diminishing p-ERK1/2 and raising p-ERK5 level in myocardial tissue.