{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:07:18Z","timestamp":1789754838352,"version":"4.0.1"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangzhou Panyu District science and technology plan major medical and health projects","award":["2022-Z04-113"],"award-info":[{"award-number":["2022-Z04-113"]}]},{"name":"Guangzhou health and wellness general guidance project","award":["20251A010109"],"award-info":[{"award-number":["20251A010109"]}]},{"name":"Guangdong Provincial Science and Technology Research Fund for Medical Science","award":["2024111911713273"],"award-info":[{"award-number":["2024111911713273"]}]},{"name":"General Research Project of Guangdong Health Economics Association","award":["2025-WJHX-16"],"award-info":[{"award-number":["2025-WJHX-16"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Preeclampsia (PE) is a serious complication of pregnancy, with vascular endothelial dysfunction being a core pathological feature. This study aimed to investigate whether L-(+)-ergothioneine (LET) ameliorates PE-associated endothelial dysfunction by regulating the Nrf2-PPAR\u03b3-sFlt-1 axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A LPS-induced trophoblast dysfunction model was established using lipopolysaccharide (LPS)-induced human trophoblast cells (HTR8\/SVneo). Techniques including CCK-8 assay, flow cytometry, wound healing assay, ELISA, qPCR, Western blot, and immunofluorescence were employed to assess the effects of LET on cell viability, apoptosis, invasion, inflammatory cytokine levels, and the expression of key molecules in the signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LET significantly increased the viability of LPS-induced trophoblasts, promoted migration, inhibited apoptosis, and downregulated pro-inflammatory cytokines (IL-6, TNF-\u03b1, IFN-\u03b3) and endothelial dysfunction markers (sFlt-1, ET-1, PAI-1), while upregulating the anti-inflammatory cytokine IL-4 and plasminogen activators (tPA, uPA). Mechanistically, LET inhibited Nrf2 nuclear translocation and promoted PPAR\u03b3 expression, consequently reducing sFlt-1 levels. The protective effects of LET were mimicked by the PPAR\u03b3 activator pioglitazone and reversed by the inhibitor FX-909. Furthermore, the supernatant from LET-treated trophoblasts promoted the viability and invasion of human umbilical vein endothelial cells (HUVECs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>L-(+)-Ergothioneine improves trophoblast function and indirectly promotes endothelial recovery by modulating the Nrf2-PPAR\u03b3-sFlt-1 axis, suggesting a potential therapeutic target for preeclampsia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0358574","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:25:36Z","timestamp":1789752336000},"page":"e0358574","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["L-(+)-Ergothioneine ameliorates preeclampsia-associated vascular endothelial dysfunction by modulating the Nrf2-PPAR\u03b3-sFlt-1 axis"],"prefix":"10.1371","volume":"21","author":[{"given":"Jingjin","family":"Gong","sequence":"first","affiliation":[{"name":"Guangdong Medical University (Guangzhou Panyu District Maternal and Child Health Hospital)","place":["Guangzhou, Guangdong, China"],"department":["Obstetrics Department, Affiliated Hospital Group of Guangdong Medical University Panyu He Xian Memorial Hospital\/Panyu Women and Children\u2019s Medical Center"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2649-2552","authenticated-orcid":true,"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Medical University","place":["Zhanjiang, Guangdong, China"],"department":["Department of Biochemistry and Molecular Biology, School of Basic Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingju","family":"Meng","sequence":"additional","affiliation":[{"name":"Guangdong Medical University (Guangzhou Panyu District Maternal and Child Health Hospital)","place":["Guangzhou, Guangdong, China"],"department":["Obstetrics Department, Affiliated Hospital Group of Guangdong Medical University Panyu He Xian Memorial Hospital\/Panyu Women and Children\u2019s Medical Center"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Medical University (Guangzhou Panyu District Maternal and Child Health Hospital)","place":["Guangzhou, Guangdong, China"],"department":["Obstetrics Department, Affiliated Hospital Group of Guangdong Medical University Panyu He Xian Memorial Hospital\/Panyu Women and Children\u2019s Medical Center"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Medical University (Guangzhou Panyu District Maternal and Child Health Hospital)","place":["Guangzhou, Guangdong, China"],"department":["Obstetrics Department, Affiliated Hospital Group of Guangdong Medical University Panyu He Xian Memorial Hospital\/Panyu Women and Children\u2019s Medical Center"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangdong Medical University (Guangzhou Panyu District Maternal and Child Health Hospital)","place":["Guangzhou, Guangdong, China"],"department":["Obstetrics Department, Affiliated Hospital Group of Guangdong Medical University Panyu He Xian Memorial Hospital\/Panyu Women and Children\u2019s Medical Center"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiu","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Medical University (Guangzhou Panyu District Maternal and Child Health Hospital)","place":["Guangzhou, Guangdong, China"],"department":["Obstetrics Department, Affiliated Hospital Group of Guangdong Medical University Panyu He 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