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重新定位:基于多组学数据集聚焦 β-丙氨酸代谢及其代谢物的抗炎作用。

Reposition: Focalizing β-Alanine Metabolism and the Anti-Inflammatory Effects of Its Metabolite Based on Multi-Omics Datasets.

机构信息

State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.

出版信息

Int J Mol Sci. 2024 Sep 24;25(19):10252. doi: 10.3390/ijms251910252.

DOI:10.3390/ijms251910252
PMID:39408583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11476852/
Abstract

The incorporation of multi-omics data methodologies facilitates the concurrent examination of proteins, metabolites, and genes associated with inflammation, thereby leveraging multi-dimensional biological data to achieve a comprehensive understanding of the complexities involved in the progression of inflammation. Inspired by ensemble learning principles, we implemented ID normalization preprocessing, categorical sampling homogenization, and pathway enrichment across each sample matrix derived from multi-omics datasets available in the literature, directing our focus on inflammation-related targets within lipopolysaccharide (LPS)-stimulated RAW264.7 cells towards β-alanine metabolism. Additionally, through the use of LPS-treated RAW264.7 cells, we tentatively validated the anti-inflammatory properties of the metabolite Ureidopropionic acid, originating from β-alanine metabolism, by evaluating cell viability, nitric oxide production levels, and mRNA expression of inflammatory biomarkers. In conclusion, our research represents the first instance of an integrated analysis of multi-omics datasets pertaining to LPS-stimulated RAW264.7 cells as documented in the literature, underscoring the pivotal role of β-alanine metabolism in cellular inflammation and successfully identifying Ureidopropionic acid as a novel anti-inflammatory compound. Moreover, the findings from database predictions and molecular docking studies indicated that the inflammatory-related pathways and proteins may serve as potential mechanistic targets for Ureidopropionic acid.

摘要

多组学数据方法的结合有助于同时检测与炎症相关的蛋白质、代谢物和基因,从而利用多维生物数据全面了解炎症进展过程中的复杂性。受集成学习原理的启发,我们对文献中多组学数据集中的每个样本矩阵执行了 ID 归一化预处理、类别采样均匀化和途径富集,将重点放在脂多糖 (LPS) 刺激的 RAW264.7 细胞中与炎症相关的目标上,针对β-丙氨酸代谢。此外,通过使用 LPS 处理的 RAW264.7 细胞,我们通过评估细胞活力、一氧化氮产生水平和炎症生物标志物的 mRNA 表达,初步验证了源自β-丙氨酸代谢的代谢物 Ureidopropionic acid 的抗炎特性。总之,我们的研究代表了文献中首次对 LPS 刺激的 RAW264.7 细胞的多组学数据集进行综合分析,强调了β-丙氨酸代谢在细胞炎症中的关键作用,并成功鉴定出 Ureidopropionic acid 是一种新型抗炎化合物。此外,数据库预测和分子对接研究的结果表明,炎症相关途径和蛋白质可能作为 Ureidopropionic acid 的潜在机制靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57f8/11476852/baf5c57e2a12/ijms-25-10252-g010.jpg
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