{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T10:44:34Z","timestamp":1777632274889,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to investigate the role of neurotrophin\u20104 (NTF4) in gestational diabetes mellitus (GDM) and to elucidate the underlying mechanism by which NTF4 regulates high glucose\u2010induced apoptosis and inflammation in HTR\u20108\/SVneo cells via the PI3K\/AKT signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptomic analysis combined with public database screening revealed that NTF4 is significantly upregulated in placental tissues from GDM patients. In a high glucose\u2010induced HTR\u20108\/SVneo cell model, NTF4 was silenced using small interfering RNA to evaluate the effects on cell proliferation, apoptosis, and inflammatory responses. Cell proliferation was evaluated using the CCK\u20108 assay, apoptosis by flow cytometry, inflammatory cytokine secretion by ELISA, and cell migration and invasion by Transwell assays. Western blotting was performed to detect protein levels. Additionally, the PI3K\u2010specific inhibitor LY294002 was used to determine the pathway dependence of NTF4\u2010mediated effects. Results: NTF4 is upregulated in GDM placentas and high glucose\u2010induced HTR\u20108\/SVneo cells. Knockdown of NTF4 significantly ameliorated high glucose\u2010induced cell damage by enhancing cell viability, suppressing apoptosis, and inflammation. Mechanistic investigations revealed that NTF4 contributes to cellular injury by activating the PI3K\/AKT signaling pathway, while the PI3K inhibitor LY294002 further amplified the protective effects of NTF4 silencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identified the role of NTF4 in promoting trophoblast injury by activating the PI3K\/AKT signaling pathway in high\u2010glucose\u2010stimulated HTR\u20108\/SVneo cells, which provides a preliminary experimental basis for exploring its potential role in the pathogenesis of GDM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70460","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T04:18:01Z","timestamp":1777263481000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of NTF4 Attenuates High Glucose\u2010Induced Apoptosis and Inflammation in HTR\u20108\/SVneo Cells via the PI3K\/AKT Pathway"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5805-0068","authenticated-orcid":false,"given":"Li","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1650-5248","authenticated-orcid":false,"given":"Juan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.5772\/intechopen.1002793"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2013.11.003"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.12381"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60731-5"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00306"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000455904"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.14341"},{"issue":"2","key":"e_1_2_14_9_1","first-page":"799","article-title":"High Glucose Suppresses the Viability and Proliferation of HTR\u20118\/SVneo Cells Through Regulation of the miR\u2011137\/PRKAA1\/IL\u20116 Axis","volume":"42","author":"Peng H. Y.","year":"2018","journal-title":"International Journal of Molecular Medicine"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.7.3060"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1994.tb00559.x"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9078012"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2016.05.007"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13275"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e32518"},{"issue":"16","key":"e_1_2_14_16_1","first-page":"5056","article-title":"ANGPTL4 Participates in Gestational Diabetes Mellitus via Regulating Akt Pathway","volume":"22","author":"Li M.","year":"2018","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.722024"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2021.152135"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.24557"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-018-3408-7"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17941"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/01443615.2024.2350761"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01835-z"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/19768354.2017.1289980"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.79435"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoae005"}],"container-title":["Immunity, Inflammation and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.70460","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/iid3.70460","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.70460","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:56:51Z","timestamp":1777435011000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/iid3.70460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/iid3.70460"],"URL":"https:\/\/doi.org\/10.1002\/iid3.70460","archive":["Portico"],"relation":{},"ISSN":["2050-4527","2050-4527"],"issn-type":[{"value":"2050-4527","type":"print"},{"value":"2050-4527","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-09-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70460"}}