Cheng Menghang, Li Mengnan, Zhang Yunmei, Gu Xuyang, Gao Wenshan, Zhang Shuling, Liu Jianfeng
School of Life Sciences, Hebei University, Baoding 071002, PR China.
School of Life Sciences, Hebei University, Baoding 071002, PR China; Hebei Basic Science Center for Biotic Interaction, Hebei University, Baoding 071002, PR China.
Environ Int. 2025 Feb;196:109324. doi: 10.1016/j.envint.2025.109324. Epub 2025 Feb 10.
This research endeavor seeks to delve into the potential mechanisms by which pharmaceutical and personal care products (PPCPs), recognized as emerging pollutants, could contribute to the human metabolic disorders and then trigger metabolic diseases. Therefore, we have selected lipid and atherosclerosis, Alzheimer's disease, and type Ⅱ diabetes mellitus as representative metabolic diseases, aiming to systematically explore the critical molecular pathways that may be disrupted by PPCPs for the metabolic disease development. By employing advanced network toxicology and molecular docking techniques, we have successfully elucidated the molecular mechanisms that trigger the three diseases. We pinpointed the potential targets associated with the disease by leveraging databases including PubChem, ADEMTlab2.0, SwissADME, and GeneCards. We further employed STRING analysis and Cytoscape software to pinpoint the core targets that were most significantly associated with these metabolic diseases. In addition, enrichment analysis of these core targets was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways within the David database. To obtain the structural aspects of the target proteins, we also employed AlphaFold 3 for protein structure prediction. Finally, we validated the binding affinity of PPCPs to these target proteins using molecular docking with AutoDock Vina. Our findings suggested that PPCPs could potentially trigger metabolic diseases by modulating the expression of microRNAs, influencing cellular apoptosis and proliferation, and affecting signal transduction pathways. Interestingly, we also found the correlations among lipid and atherosclerosis, Alzheimer's disease, and type Ⅱ diabetes mellitus. Taken together, our study provides innovative insights into both the mechanisms of how environmental pollutants trigger human diseases and revealing the correlations among different diseases, thereby laying a theoretical foundation for disease prevention and treatment.
本研究旨在深入探究药物和个人护理产品（PPCPs）作为新兴污染物可能导致人类代谢紊乱进而引发代谢性疾病的潜在机制。因此，我们选择了脂质与动脉粥样硬化、阿尔茨海默病和Ⅱ型糖尿病作为代表性代谢疾病，旨在系统地探索可能被PPCPs破坏的、与代谢性疾病发展相关的关键分子途径。通过运用先进的网络毒理学和分子对接技术，我们成功阐明了引发这三种疾病的分子机制。我们利用包括PubChem、ADEMTlab2.0、SwissADME和GeneCards在内的数据库确定了与疾病相关的潜在靶点。我们进一步使用STRING分析和Cytoscape软件确定了与这些代谢性疾病最显著相关的核心靶点。此外，利用David数据库中的基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路对这些核心靶点进行了富集分析。为了获得靶蛋白的结构信息，我们还使用AlphaFold 3进行蛋白质结构预测。最后，我们使用AutoDock Vina分子对接验证了PPCPs与这些靶蛋白的结合亲和力。我们的研究结果表明，PPCPs可能通过调节微小RNA的表达、影响细胞凋亡和增殖以及影响信号转导通路来引发代谢性疾病。有趣的是，我们还发现了脂质与动脉粥样硬化、阿尔茨海默病和Ⅱ型糖尿病之间的关联。综上所述，我们的研究为环境污染物引发人类疾病的机制以及揭示不同疾病之间的关联提供了创新性见解，从而为疾病的预防和治疗奠定了理论基础。
