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
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 transgene...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-04-01
|
| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325004683 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850265883692236800 |
|---|---|
| author | Jia-qi Hao Biao Ran Shu-yue Hu Zi-xuan Zhuang Jia-wan Zhang Meng-rui Xiong Rui Wang Wen Zhuang Mo-jin Wang |
| author_facet | Jia-qi Hao Biao Ran Shu-yue Hu Zi-xuan Zhuang Jia-wan Zhang Meng-rui Xiong Rui Wang Wen Zhuang Mo-jin Wang |
| author_sort | Jia-qi Hao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-be05d22ffcbd4f9c949703ae51b7880f |
| institution | OA Journals |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-be05d22ffcbd4f9c949703ae51b7880f2025-08-20T01:54:18ZengElsevierEcotoxicology and Environmental Safety0147-65132025-04-0129511813210.1016/j.ecoenv.2025.118132Exploring the link between Di-2-ethylhexyl phthalate (DEHP) exposure and muscle mass: A systematic investigation utilizing NHANES data analysis, network toxicology and molecular docking approachesJia-qi Hao0Biao Ran1Shu-yue Hu2Zi-xuan Zhuang3Jia-wan Zhang4Meng-rui Xiong5Rui Wang6Wen Zhuang7Mo-jin Wang8Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, ChinaNeonatology Department, Children's Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaGastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaGastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaGastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaGastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Corresponding author at: Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.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.http://www.sciencedirect.com/science/article/pii/S0147651325004683DEHPAppendicular lean massSarcopeniaNHANESNetwork toxicologyMolecular docking |
| spellingShingle | Jia-qi Hao Biao Ran Shu-yue Hu Zi-xuan Zhuang Jia-wan Zhang Meng-rui Xiong Rui Wang Wen Zhuang Mo-jin Wang 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 Ecotoxicology and Environmental Safety DEHP Appendicular lean mass Sarcopenia NHANES Network toxicology Molecular docking |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | DEHP Appendicular lean mass Sarcopenia NHANES Network toxicology Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325004683 |
| work_keys_str_mv | AT jiaqihao exploringthelinkbetweendi2ethylhexylphthalatedehpexposureandmusclemassasystematicinvestigationutilizingnhanesdataanalysisnetworktoxicologyandmoleculardockingapproaches AT biaoran exploringthelinkbetweendi2ethylhexylphthalatedehpexposureandmusclemassasystematicinvestigationutilizingnhanesdataanalysisnetworktoxicologyandmoleculardockingapproaches AT shuyuehu exploringthelinkbetweendi2ethylhexylphthalatedehpexposureandmusclemassasystematicinvestigationutilizingnhanesdataanalysisnetworktoxicologyandmoleculardockingapproaches AT zixuanzhuang exploringthelinkbetweendi2ethylhexylphthalatedehpexposureandmusclemassasystematicinvestigationutilizingnhanesdataanalysisnetworktoxicologyandmoleculardockingapproaches AT jiawanzhang exploringthelinkbetweendi2ethylhexylphthalatedehpexposureandmusclemassasystematicinvestigationutilizingnhanesdataanalysisnetworktoxicologyandmoleculardockingapproaches AT mengruixiong exploringthelinkbetweendi2ethylhexylphthalatedehpexposureandmusclemassasystematicinvestigationutilizingnhanesdataanalysisnetworktoxicologyandmoleculardockingapproaches AT ruiwang exploringthelinkbetweendi2ethylhexylphthalatedehpexposureandmusclemassasystematicinvestigationutilizingnhanesdataanalysisnetworktoxicologyandmoleculardockingapproaches AT wenzhuang exploringthelinkbetweendi2ethylhexylphthalatedehpexposureandmusclemassasystematicinvestigationutilizingnhanesdataanalysisnetworktoxicologyandmoleculardockingapproaches AT mojinwang exploringthelinkbetweendi2ethylhexylphthalatedehpexposureandmusclemassasystematicinvestigationutilizingnhanesdataanalysisnetworktoxicologyandmoleculardockingapproaches |