{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T01:41:26Z","timestamp":1777081286147,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,5,31]],"date-time":"2013-05-31T00:00:00Z","timestamp":1369958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2014,5]]},"abstract":"Aim<\/jats:title>To investigate tumor necrosis factor (TNF<\/jats:styled-content>)\u2010\u03b1 expression and its relationship with serum bile acids in placental trophoblasts from patients with intrahepatic cholestasis of pregnancy (ICP<\/jats:styled-content>).<\/jats:p><\/jats:sec>Methods<\/jats:title>Human placenta, including normal pregnancies (n<\/jats:italic>\u2009=\u200910) and patients with ICP<\/jats:styled-content> (n<\/jats:italic>\u2009=\u200910), were collected at term and subject to TNF<\/jats:styled-content>\u2010\u03b1 measurements. Bile acid\u2010induced TNF<\/jats:styled-content>\u2010\u03b1 expression and cell apoptosis were evaluated in cultured syncytiotrophoblasts in vitro<\/jats:italic>.<\/jats:p><\/jats:sec>Results<\/jats:title>ICP<\/jats:styled-content> placental trophoblasts displayed apoptotic histological abnormalities. TNF<\/jats:styled-content>\u2010\u03b1 levels in ICP<\/jats:styled-content> tissue were significantly greater than those of controls as measured by quantitative polymerase chain reaction and western blot. Levels of placental TNF<\/jats:styled-content>\u2010\u03b1 mRNA<\/jats:styled-content> were positively correlated with serum bile acid concentration in ICP<\/jats:styled-content> patients. In vitro<\/jats:italic>, lithocholic acid (LCA<\/jats:styled-content>) significantly enhanced TNF<\/jats:styled-content>\u2010\u03b1 mRNA<\/jats:styled-content> at both doses, by 2.07\u2010fold at 15\u2009\u03bcm<\/jats:sc> and by 3.41\u2010fold at 30\u2009\u03bcm<\/jats:sc>, whereas deoxycholic acid mildly increased TNF<\/jats:styled-content>\u2010\u03b1 mRNA<\/jats:styled-content> by 1.41\u2010fold at 100\u2009\u03bcm<\/jats:sc> only. LCA<\/jats:styled-content> treatment produced significantly higher percentage of caspase\u20103 positive cells than vehicle treatment, rescuable by the addition of a TNF<\/jats:styled-content>\u2010\u03b1 inhibitor, indicative of apoptosis induced by LCA\u2013TNF<\/jats:styled-content>\u2010\u03b1 pathway.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>This study shows that the increase of TNF<\/jats:styled-content>\u2010\u03b1 expression in placental trophoblasts is strongly associated with ICP<\/jats:styled-content> pathology and is inducible by LCA<\/jats:styled-content>\u2005in vitro<\/jats:italic>, suggesting its potential value in the clinical prevention, diagnosis and treatment of ICP<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.12150","type":"journal-article","created":{"date-parts":[[2013,4,30]],"date-time":"2013-04-30T12:56:35Z","timestamp":1367326595000},"page":"532-541","source":"Crossref","is-referenced-by-count":18,"title":["Lithocholic acid\u2010induced placental tumor necrosis factor\u2010\u03b1 upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy"],"prefix":"10.1111","volume":"44","author":[{"given":"Qiaoling","family":"Du","sequence":"first","affiliation":[{"name":"Department of Obstetrics Shanghai First Maternity and Infant Hospital Tongji University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youdong","family":"Pan","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Shanghai First Maternity and Infant Hospital Tongji University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,5,31]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006254-200201000-00023"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20336"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.17.9.709"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1007357"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1665-2681(19)32188-X"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1067\/S0002-9378(03)00545-3"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-2243(91)90222-7"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.02.028"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs1000363"},{"key":"e_1_2_6_11_1","first-page":"451","article-title":"Immunohistochemical study on the expression of TNF\u2010\u03b1 in placenta in intrahepatic cholestasis of pregnancy (in Chinese)","volume":"27","author":"Zhang S","year":"2007","journal-title":"Acta Acad Med Xuzhou"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.02.042"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-118-4-1567"},{"key":"e_1_2_6_14_1","first-page":"267","article-title":"Advanced glycation end products\u2010induced vascular calcification is mediated by oxidative stress: functional roles of NAD(P)H\u2010oxidase","volume":"45","author":"Tada Y","year":"2013","journal-title":"Horm Metab Res"},{"key":"e_1_2_6_15_1","first-page":"428","article-title":"The relationship between intrahepatic cholestasis and placenta cells apoptosis in pregnancy (in Chinese)","volume":"35","author":"Chen M","year":"2007","journal-title":"Mod Med"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2005.12.009"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(97)00012-9"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/138945010790309885"},{"key":"e_1_2_6_19_1","first-page":"1059","article-title":"Pregnancy appears difficult to obtain and TNF\u2010alpha blockers cannot always be discontinued in women with rheumatic diseases","volume":"27","author":"Gaujoux\u2010Viala C","year":"2009","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.4.571"},{"key":"e_1_2_6_21_1","doi-asserted-by":"crossref","unstructured":"TerranovaPF HunterVJ RobyKF HuntJS.Tumor necrosis factor\u2010alpha in the female reproductive tract. 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