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

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

Background: Nardostachys chinensis 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 N. chinensis against AF.

Methods: The TCMSP was used to screen the active N. chinensis compounds and their targets. Differentially expressed genes (DEGs) for AF were identified using open-access databases. Using Venn diagrams, the cross-targets of N. chinensis, 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 N. chinensis, 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 N. chinensis intervention in pyroptosisrelated AF, and the TLR/NLRP3 signaling pathway may be associated with this process.

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网络药理学和生物信息学分析确定了鸦胆子治疗心房颤动的核心基因和相关机制
背景:Nardostachys chinensis是一种广泛用于治疗心房颤动(AF)的中药,但其机制尚不清楚:目的:探讨槟榔碱治疗心房颤动的分子机制:方法:利用 TCMSP 筛选 N. chinensis 活性化合物及其靶点。方法:利用 TCMSP 筛选 N. chinensis 活性化合物及其靶标。通过维恩图,获得了N. chinensis、热核变性和AF的交叉靶标。对这些基因进行了分子对接和基因组富集分析(GSEA)。根据候选基因构建了提名图,并用临床影响曲线进行了评估。之后,通过单样本 GSEA(ssGSEA)分析了数据集的免疫浸润情况。最后,根据候选基因预测了微RNA(miRNA)和转录因子(TF):结果:通过对 DEGs、N. chinensis 的靶标以及热蛋白沉积相关基因的交叉分析,得出肿瘤坏死因子(TNF)和 Caspase-8 (CASP8)为候选基因。Tolllike受体(TLR)和过氧化物酶体增殖激活受体(PPAR)信号通路与候选基因相关。此外,免疫细胞浸润分析表明,CASP8 与自然杀伤 T 细胞、自然杀伤细胞、调节性 T 细胞(Tregs)、髓源抑制细胞(MDSC)、巨噬细胞、CD8 T 细胞和 CD4 T 细胞有关。最后,研究发现 miR-34a-5p 和几种 TFs 可调控 CASP8 和 TNF 的表达:结论:CASP8和TNF是N.chinensis干预与热蛋白沉积相关的房颤的潜在靶点,TLR/NLRP3信号通路可能与这一过程有关。
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