{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:15:22Z","timestamp":1790079322937,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81860735"],"award-info":[{"award-number":["81860735"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Tris(2\u2010chloroethyl) phosphate (TCEP) is a ubiquitous organophosphorus flame retardant and an emerging environmental contaminant of concern; however, the specific molecular mechanisms underlying its respiratory toxicity remain poorly understood. This study aimed to systematically elucidate the respiratory toxicity mechanisms of TCEP using an integrated toxicological approach. An integrated strategy combining network toxicology, molecular docking, surface plasmon resonance (SPR), and in vitro experimental validation was adopted to systematically explore the respiratory toxicity mechanisms of TCEP in human bronchial epithelial BEAS\u20102B cells. Network analysis revealed that potential TCEP targets were significantly enriched in pathways associated with inflammation and oxidative stress. Molecular docking identified MMP\u20109, MMP\u20102, and PTGS2 as core targets with strong binding affinities (\u22125.1 to \u22125.4\u2009kcal\/mol), and these results were further verified by SPR assays, which confirmed the direct binding of TCEP to these targets with micromolar affinities (\n                      <jats:italic>K<\/jats:italic>\n                      <jats:sub>D<\/jats:sub>\n                      \u2009=\u200942.4\u201392.0\u2009\u03bcM). In vitro experiments revealed that TCEP exposure triggered concentration\u2010dependent cytotoxicity and marked oxidative stress in BEAS\u20102B cells, characterized by glutathione depletion, catalase inhibition, increased lipid peroxidation, and compensatory upregulation of superoxide dismutase. Additionally, TCEP significantly upregulated the protein expression levels of MMP\u20109, MMP\u20102, and PTGS2, while pretreatment with the ROS scavenger N\u2010acetylcysteine (NAC) significantly mitigated this upregulation, indicating that oxidative stress acts as a key upstream mediator responsible for the activation of these targets. These findings collectively demonstrate that TCEP impairs respiratory epithelial homeostasis via a synergistic multi\u2010target mechanism involving oxidative stress, inflammation, and tissue remodeling, which provides important theoretical support for environmental risk assessment and the development of targeted therapeutic interventions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbt.70987","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:48:26Z","timestamp":1782906506000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tris(2\u2010Chloroethyl) Phosphate (TCEP) Induces Respiratory Toxicity Through Oxidative Stress and Multi\u2010Target Interactions: Evidence From Network Toxicology, Molecular Docking, and Experimental Validation"],"prefix":"10.1002","volume":"40","author":[{"given":"Ruoyu","family":"Geng","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, School of Pharmacy Xinjiang Medical University Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health Sciences, School of Public Health Xinjiang Medical University Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health Sciences, School of Public Health Xinjiang Medical University Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Core Laboratory, School of Public Health Xinjiang Medical University Urumqi 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