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网络药理学和生物信息学分析确定心房颤动的核心基因和焦亡相关机制

Network Pharmacology and Bioinformatics Analyses Identify the Core Genes and Pyroptosis-Related Mechanisms of for Atrial Fibrillation.

作者信息

Xue Weiqi, Luo Yuan, He Weifeng, Yan Mengyuan, Zhao Huanyi, Qing Lijin

机构信息

First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.

First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Curr Comput Aided Drug Des. 2024;20(7):1070-1086. doi: 10.2174/0115734099259071231115072421.

DOI:10.2174/0115734099259071231115072421
PMID:38178669
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11475257/
Abstract

BACKGROUND

is an herbal medicine widely used in the treatment of atrial fibrillation (AF), but the mechanism is unclear.

OBJECTIVE

To explore the molecular mechanism of against AF.

METHODS

The TCMSP was used to screen the active compounds and their targets. Differentially expressed genes (DEGs) for AF were identified using open-access databases. Using Venn diagrams, the cross-targets of , pyroptosis, and AF were obtained. The genes underwent molecular docking as well as gene set enrichment analysis (GSEA). A nomogram based on candidate genes was constructed and evaluated with the clinical impact curve. After that, the immune infiltration of the dataset was analyzed by single sample GSEA (ssGSEA). Finally, microRNAs (miRNAs) and transcription factors (TFs) were predicted based on candidate genes.

RESULTS

Tumor necrosis factor (TNF) and caspase-8 (CASP8) were obtained as candidate genes by taking the intersection of DEGs, targets of , and pyroptosis-related genes. Tolllike receptor (TLR) and peroxisome proliferator-activated receptor (PPAR) signaling pathways were linked to candidate genes. Additionally, immune cell infiltration analysis revealed that CASP8 was associated with natural killer T cells, natural killer cells, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSC), macrophages, CD8 T cells, and CD4 T cells. Finally, miR-34a-5p and several TFs were found to regulate the expression of CASP8 and TNF.

CONCLUSION

CASP8 and TNF are potential targets of intervention in pyroptosisrelated AF, and the TLR/NLRP3 signaling pathway may be associated with this process.

摘要

背景

是一种广泛用于治疗心房颤动（AF）的草药，但作用机制尚不清楚。

目的

探讨治疗AF的分子机制。

方法

利用中药系统药理学数据库与分析平台（TCMSP）筛选活性化合物及其靶点。使用开放获取数据库鉴定AF的差异表达基因（DEG）。通过维恩图获得、细胞焦亡和AF的交叉靶点。对这些基因进行分子对接以及基因集富集分析（GSEA）。构建基于候选基因的列线图并用临床影响曲线进行评估。之后，通过单样本GSEA（ssGSEA）分析数据集的免疫浸润情况。最后，基于候选基因预测微小RNA（miRNA）和转录因子（TF）。

结果

通过DEG、的靶点和细胞焦亡相关基因的交集，获得肿瘤坏死因子（TNF）和半胱天冬酶8（CASP8）作为候选基因。Toll样受体（TLR）和过氧化物酶体增殖物激活受体（PPAR）信号通路与候选基因相关。此外，免疫细胞浸润分析显示，CASP8与自然杀伤T细胞、自然杀伤细胞、调节性T细胞（Treg）、髓源性抑制细胞（MDSC）、巨噬细胞、CD8 T细胞和CD4 T细胞有关。最后，发现miR-34a-5p和几种TF可调节CASP8和TNF的表达。

结论

CASP8和TNF是干预细胞焦亡相关AF的潜在靶点，TLR/NLRP3信号通路可能与此过程有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/322c/11475257/a5f8e3b51dfe/CCADD-20-1070_F11.jpg
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