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Exploring the link between Di-2-ethylhexyl phthalate (DEHP) exposure and muscle mass: A systematic investigation utilizing NHANES data analysis, network toxicology and molecular docking approaches

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机构: [1]Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China [2]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China [3]Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China [4]Neonatology Department, Children’s Hospital of Chongqing Medical University, Chongqing, China [5]Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China [6]Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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关键词: DEHP Appendicular lean mass Sarcopenia NHANES Network toxicology Molecular docking

摘要:
Sarcopenia is a syndrome characterized by a progressive, widespread decline in muscle mass and strength. DEHP, a plasticizer involved in daily life and widely used, has been found in various everyday items and causes developmental dysregulation, reproductive impairments, tumorigenesis, and transgenerational disease. However, much remains to be discovered regarding the association between exposure to this environmental toxin and sarcopenia, as well as the toxic targets and molecular mechanisms. This research elucidated the relationship between contact with DEHP and the development of sarcopenia by integrating NHANES data analysis, network toxicology, and molecular docking. 3199 adults were enrolled, and multiple linear regressions were performed to reveal a significant negative correlation between lnDEHP and ALMBMI. Eighty-eight targets associated with DEHP and sarcopenia were identified. Subsequent STRING and Cytoscape screening stressed 20 key targets, including CASP3, BCL2, MMP9, BCL2L1, APP, and CTSS. GO and KEGG enrichment analyses revealed that these targets are involved in ligand-receptor interactions, apoptosis, and calcium signaling pathways. Molecular docking simulations using CB-dock confirmed the high-affinity binding interactions between DEHP and these key targets. This study validated the relationship between DEHP exposure and muscle mass. Further, it provided a theoretical basis for investigating the molecular mechanisms of DEHP exposure-induced skeletal muscle toxicity.Copyright © 2025. Published by Elsevier Inc.

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出版当年[2025]版:
大类 | 2 区 环境科学与生态学
小类 | 1 区 毒理学 2 区 环境科学
最新[2025]版:
大类 | 2 区 环境科学与生态学
小类 | 1 区 毒理学 2 区 环境科学
第一作者:
第一作者机构: [1]Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China [3]Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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通讯机构: [1]Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China [3]Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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