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通过使用生物信息学分析,构建双甲的心脏毒性不良结果途径

Leyan Zhang¹, Lin Tian¹, Baofang Liang¹

¹Department of Nutrition and Food Safety, West China School of Public Health/West China Fourth Hospital, Sichuan University, Chengdu, China; Food Safety Monitoring and Risk Assessment Key Laboratory of Sichuan Province, Chengdu, China.

|September 20, 2024

概括

双甲 (BPA) 是一种内分泌干扰物,可以引起心脏问题. 这项研究概述了BPA心脏毒性的一种新的不良结果途径 (AOP),确定了关键的基因和涉及的生物过程.

科学领域:

环境毒理学环境毒理学
心血管科学心血管科学
生物信息学是一种生物信息学.

背景情况:

双甲 (BPA) 是一种广泛存在的内分泌干扰物,在流行病学和实验研究中与心血管毒性有关.
对于BPA诱导的心脏毒性的特定不良结局途径 (AOP) 仍然在很大程度上没有特征.

研究的目的:

使用生物信息学方法开发和评估双A (BPA) 的心脏毒性不良结果途径 (AOP).
确定关键的基因,表型和参与BPA诱导心脏毒性的分子信号通路.

主要方法:

利用生物信息学分析,整合来自多个数据库的数据 (例如,比较毒基因组学数据库,DisGeNet).
进行了Venn分析,文献选和基因本体学/基因和基因组丰富分析的京都百科全书.
应用了基于布拉德福德-希尔因果考虑的量化证据权重 (QWOE) 方法来评估AOP.

主要成果:

确定了包括ESR2,MAPK1,TGFB1和ESR1在内的基因,以及诸如心脏收缩,Ca2+稳态和代谢过程等表型.
描述了AOP:BPA与ERα/β结合,激活MAPK,AKT和IL-17通路,导致Ca2+疾病和炎症.
已建立的AOP表现出中度的信心 (QWOE得分为69),将BPA暴露与各种心脏病联系起来.

结论:

为BPA心脏毒性推断了一个全面的AOP,突出了它通过特定的分子机制引起心脏病的潜力.
这些发现为心脏毒性评估提供了关键的见解,并指导未来对Bisphenol A心血管影响的研究.

关键词:

负面结果的途径.生物信息学是一种生物信息学.双 A 是一种双.对心脏有毒性的心脏毒性证据的数量权重是指证据的数量权重.

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