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生理重要金属的毒代基因组学分析:一种综合的计算方法。

Toxicogenomic analysis of physiologically important metals: An integrated in silico approach.

机构信息

Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, India.

Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, India.

出版信息

Food Chem Toxicol. 2023 Aug;178:113895. doi: 10.1016/j.fct.2023.113895. Epub 2023 Jun 15.

Abstract

Biologically important metals regulate cellular homeostasis in living systems. Anthropogenic exposure to these metals can cause adverse effects, including an increased incidence of diseases in humans such as cancer, lung, and cardiovascular defects. However, the effects of metals and the common genes/signaling pathways involved in metal toxicity have not been elucidated. Hence, the present study used toxicogenomic data mining with the comparative toxicogenomics database to explore the impact of these metals. The metals were categorized into transition, alkali, and alkaline earth. The common genes were identified and subjected to functional enrichment analysis. Further, gene-gene and protein-protein interactions were assessed. Also, the top ten transcription factors and miRNAs that regulate the genes were identified. The phenotypes and diseases that have increased incidence upon alterations of these genes were detected. Overall, we were able to identify IL1B and SOD2 as the common genes, along with the AGE-RAGE signaling pathway in diabetic complications as the common pathway altered. Enriched genes and pathways specific to each metal category were also found. Further, we identified heart failure as the major disease that could have increase in the incidence upon these metals' exposure. In conclusion, exposure to essential metals might cause adverse effects via inflammation and oxidative stress.

摘要

生物体内重要的金属元素调节着生命系统中的细胞内稳态。人为接触这些金属可能会导致不良影响,包括人类疾病(如癌症、肺部和心血管缺陷)发病率的增加。然而,金属的作用以及金属毒性涉及的常见基因/信号通路尚未阐明。因此,本研究使用毒理基因组学数据挖掘和比较毒理基因组学数据库来探讨这些金属的影响。这些金属分为过渡金属、碱金属和碱土金属。确定了常见基因,并进行了功能富集分析。此外,还评估了基因-基因和蛋白质-蛋白质相互作用。还鉴定了调节这些基因的前 10 个转录因子和 miRNA。检测到这些基因改变后发病率增加的表型和疾病。总的来说,我们能够确定 IL1B 和 SOD2 是常见基因,以及糖尿病并发症中 AGE-RAGE 信号通路是改变的常见通路。还发现了每个金属类别特有的富集基因和通路。此外,我们确定心力衰竭是这些金属暴露后发病率可能增加的主要疾病。总之,暴露于必需金属可能会通过炎症和氧化应激引起不良影响。

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