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使用比较毒理基因组数据库预测水烟相关化学物质引起的血栓性心血管结局:基因、表型和途径。

Predicting thrombotic cardiovascular outcomes induced by waterpipe-associated chemicals using comparative toxicogenomic database: Genes, phenotypes, and pathways.

机构信息

Department of Pharmacy Practice, Irma Lerma Rangel School of Pharmacy, Texas A&M University, Kingsville, TX, USA.

Artificial Intelligence Center for Health and Biomedical Research (ArCHER), National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.

出版信息

Life Sci. 2023 Jun 15;323:121694. doi: 10.1016/j.lfs.2023.121694. Epub 2023 Apr 15.

DOI:10.1016/j.lfs.2023.121694
PMID:37068705
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10798163/
Abstract

Hookah, or waterpipe, is a tobacco smoking device that has gained popularity in the United States. A growing body of evidence demonstrates that waterpipe smoke (WPS) is associated with various adverse effects on human health, including infectious diseases, cancer, and cardiovascular diseases (CVDs), particularly thrombotic events. However, the molecular mechanisms through which WPS contributes to disease development remain unclear. In this study, we utilized an analytical approach based on the Comparative Toxicogenomics Database (CTD) to integrate chemical, gene, phenotype, and disease data to predict potential molecular mechanisms underlying the effects of WPS, based on its chemical and toxicant profile. Our analysis revealed that CVDs were among the top disease categories with regard to the number of curated interactions with WPS chemicals. We identified 5674 genes common between those modulated by WPS chemicals and traditional tobacco smoking. The CVDs with the most curated interactions with WPS chemicals were hypertension, atherosclerosis, and myocardial infarction, whereas "particulate matter", "heavy metals", and "nicotine" showed the highest number of curated interactions with CVDs. Our analysis predicted that the potential mechanisms underlying WPS-induced thrombotic diseases involve common phenotypes, such as inflammation, apoptosis, and cell proliferation, which are shared across all thrombotic diseases and the three aforementioned chemicals. In terms of enriched signaling pathways, we identified several, including chemokine and MAPK signaling, with particulate matter exhibiting the most statistically significant association with all 12 significant signaling pathways related to WPS chemicals. Collectively, our predictive comprehensive analysis provides evidence that WPS negatively impacts health and offers insights into the potential mechanisms through which it exerts these effects. This information should guide further research to explore and better understand the WPS and other tobacco product-related health consequences.

摘要

水烟,又称水管烟,是一种在美国流行的烟草吸食装置。越来越多的证据表明,水烟烟雾(WPS)与人类健康的各种不良影响有关,包括传染病、癌症和心血管疾病(CVDs),特别是血栓事件。然而,WPS 促进疾病发展的分子机制尚不清楚。在这项研究中,我们利用基于比较毒理学基因组数据库(CTD)的分析方法,整合化学物质、基因、表型和疾病数据,根据 WPS 的化学物质和毒物特征,预测其潜在的分子机制。我们的分析表明,心血管疾病是与 WPS 化学物质相互作用数量最多的疾病类别之一。我们确定了 5674 个基因,这些基因在 WPS 化学物质和传统烟草吸烟所调节的基因中是共有的。与 WPS 化学物质相互作用最多的心血管疾病是高血压、动脉粥样硬化和心肌梗死,而“颗粒物”、“重金属”和“尼古丁”与 CVDs 的相互作用最多。我们的分析预测,WPS 引起的血栓性疾病的潜在机制涉及常见的表型,如炎症、细胞凋亡和细胞增殖,这些表型在所有血栓性疾病和上述三种化学物质中都存在。在富集的信号通路方面,我们确定了几个信号通路,包括趋化因子和 MAPK 信号通路,其中颗粒物与与 WPS 化学物质相关的 12 个显著信号通路中所有通路的关联最为显著。总的来说,我们的预测综合分析提供了证据表明 WPS 对健康有负面影响,并为其发挥这些作用的潜在机制提供了见解。这些信息应该指导进一步的研究,以探索和更好地理解 WPS 和其他烟草产品相关的健康后果。

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