Identification of Novel Hub Genes Associated with Inflammation and Autophagy in Astragaloside Membranaceus ameliorates Lupus Nephritis by Bioinformatics Analysis and Molecular Dynamics Simulation.

IF 1.6 4区医学 Q4 BIOCHEMICAL RESEARCH METHODS

Combinatorial chemistry & high throughput screening Pub Date : 2025-01-01 DOI:10.2174/0113862073255980231113071412

Kaili Kong, Xiaomei Qiao, Ting Liu, Xiaoxia Wang, Rui Li, Jingai Fang, Xiaodong Zhang

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引用次数: 0

Abstract

Background: Lupus nephritis is an autoimmune disease, and its pathogenesis involves inflammation and autophagy disorders. Studies have demonstrated that Astragalus membranaceus can effectively suppress the progression of LN, but the underlying therapeutic target is still unclear.

Objection: This study aimed to investigate the therapeutic target whereby AM ameliorates LN.

Method: We downloaded AM and LN-related chips from the TCMSP and GEO databases, respectively. We selected the two compound targets for the subsequent analysis via WGCNA, and constructed protein interaction networks of compound targets and determined the core targets. GO, KEGG analyses were conducted on compound targets to identify enriched functional and genomic pathways. The core genes were further validated in clinical and external datasets. Molecular docking of AS with the core targets was performed using the AutoDock software, and molecular dynamics simulation was conducted for the optimal core protein ligand obtained by molecular docking by Gromacs 2020.6 software.

Result: We obtained 10 core targets, namely IL-1β, EGF, CCND1, CASP3, STAT1, PTGS2, PPARγ, AR, CXCL10, and KDR, from the 24 compound targets identified. The results of the GO enrichment analysis mainly included cell growth regulation. The results of the KEGG enrichment analysis showed that 7 out of 23 valid targets were significantly enriched in the mitogen-activated protein kinase pathway (p < 0.01). Combined with the clinical datasets, we found that IL-1β, EGF, CCND1, CASP3, STAT1, PTGS2, and PPARγ have high diagnostic values for LN. In the validation dataset, all the core targets were significantly differentially expressed, except for EGF deletion. The molecular docking and molecular dynamics simulation results showed that AM and IL- 1β, CASP3, STAT1, and PPARγ all had binding energies < -5 kJ·mol-1 and good binding properties.

Conclusion: IL-1β, CASP3, STAT1, and PPARγ could be potential biomarkers and therapeutic targets in AM ameliorates LN.

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通过生物信息学分析和分子动力学模拟鉴定黄芪中与炎症和自噬相关的新枢纽基因可改善狼疮性肾炎

背景：狼疮性肾炎是一种自身免疫性疾病，其发病机制包括炎症和自噬障碍。研究表明，黄芪能有效抑制狼疮性肾炎的发展，但其潜在的治疗靶点尚不清楚：本研究旨在探讨 AM 改善 LN 的治疗靶点：方法：我们分别从 TCMSP 和 GEO 数据库中下载了 AM 和 LN 相关芯片。方法：分别从 TCMSP 和 GEO 数据库中下载 AM 和 LN 相关芯片，通过 WGCNA 筛选出两个化合物靶点进行后续分析，并构建化合物靶点的蛋白质相互作用网络，确定核心靶点。我们对化合物靶点进行了GO、KEGG分析，以确定富集的功能通路和基因组通路。核心基因在临床和外部数据集中得到了进一步验证。使用 AutoDock 软件对 AS 与核心靶点进行分子对接，并使用 Gromacs 2020.6 软件对分子对接得到的最佳核心蛋白配体进行分子动力学模拟：结果：我们从鉴定的 24 个复合靶点中获得了 10 个核心靶点，即 IL-1β、EGF、CCND1、CASP3、STAT1、PTGS2、PPARγ、AR、CXCL10 和 KDR。GO 富集分析的结果主要包括细胞生长调控。KEGG富集分析结果显示，23个有效靶点中有7个显著富集于丝裂原活化蛋白激酶通路（p < 0.01）。结合临床数据集，我们发现IL-1β、EGF、CCND1、CASP3、STAT1、PTGS2和PPARγ对LN具有很高的诊断价值。在验证数据集中，除 EGF 基因缺失外，所有核心靶标都有显著的差异表达。分子对接和分子动力学模拟结果显示，AM与IL-1β、CASP3、STAT1和PPARγ的结合能均小于-5 kJ-mol-1，具有良好的结合特性：结论：IL-1β、CASP3、STAT1 和 PPARγ 可作为 AM 改善 LN 的潜在生物标志物和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Combinatorial chemistry & high throughput screening 化学-生化研究方法

CiteScore

3.10

自引率

5.60%

发文量

327

审稿时长

7.5 months

期刊介绍： Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.