{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:11:52Z","timestamp":1772601112530,"version":"3.50.1"},"reference-count":26,"publisher":"Portland Press Ltd.","issue":"4","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":1112,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:p>Using an in\u00a0vitro model in which flatmounts of oesophagus was periodically exposed to bile acids, we demonstrate, using multiple methods, that the bile acid receptor TGR5, inducible nitric oxide synthase (iNOS) and \u03b3-histone family 2A variant (\u03b3-H2AX) are up-regulated. This indicates that bile acids cause up-regulation of iNOS, which further causes genotoxic stress as evidenced by increase of the highly sensitive marker, phosphorylated histone. In\u00a0vitro nitric oxide (NO) assays showed increased production of nitric acid in the oesophageal epithelium exposed to the bile acids. This increase was inhibited in the presence of the nonspecific iNOS inhibitor aminoguanidine (AG). Cumulatively, the results of the present study provide suggestion that not only acid reflux, but also non-acid reflux of bile may cause genotoxic stress. These aspects merit to be tested in wide spectrum of Barrett epithelial tissues.<\/jats:p>","DOI":"10.1042\/bsr20160124","type":"journal-article","created":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T03:08:42Z","timestamp":1464750522000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Controlled bile acid exposure to oesophageal mucosa causes up-regulation of nuclear \u03b3-H2AX possibly via iNOS induction"],"prefix":"10.1042","volume":"36","author":[{"given":"Bo","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengqian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Neurology, The General Hospital of Jinan Military Command of PLA, Jinan, Shandong 250031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yancheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongling","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aimin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathology, The 159th Hospital of PLA, Zhumadian, Henan 463000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2016,7,8]]},"reference":[{"key":"2021111618285915700_B1","first-page":"1241","article-title":"Endoscopic follow-up and management of Barrett's esophagus in relation to its preneoplastic potential","volume":"61","author":"Navarro-Dourdil","year":"2014","journal-title":"Hepatogastroenterology"},{"key":"2021111618285915700_B2","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1177\/1756283X14538689","article-title":"The role of obesity in oesophageal cancer development","volume":"7","author":"Long","year":"2014","journal-title":"Therap. Adv. Gastroenterol."},{"key":"2021111618285915700_B3","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1136\/jclinpath-2014-202518","article-title":"The surgeon's perspective on oesophageal disease, and what it means to pathologists","volume":"67","author":"Greene","year":"2014","journal-title":"J. Clin. Pathol."},{"key":"2021111618285915700_B4","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.critrevonc.2014.05.002","article-title":"Embryological signaling pathways in Barrett's metaplasia development and malignant transformation; mechanisms and therapeutic opportunities","volume":"92","author":"Pavlov","year":"2014","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"2021111618285915700_B5","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1111\/j.1365-2982.2012.01977.x","article-title":"Poor effectiveness of proton pump inhibitors in non-erosive reflux disease: the truth in the end!","volume":"24","author":"Scarpignato","year":"2012","journal-title":"Neurogastroenterol. Motil."},{"key":"2021111618285915700_B6","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1007\/BF02282326","article-title":"Origin of atypical reflux symptoms. A case study showing the importance of reflux composition and posture","volume":"41","author":"Shay","year":"1996","journal-title":"Dig. Dis. Sci."},{"key":"2021111618285915700_B7","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1111\/nyas.12253","article-title":"Defining esophageal landmarks, gastroesophageal reflux disease, and Barrett's esophagus","volume":"1300","author":"DeVault","year":"2013","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"2021111618285915700_B8","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1111\/j.1365-2982.2009.01306.x","article-title":"Relationship between gastro-oesophageal reflux pattern and severity of mucosal damage","volume":"21","author":"Bredenoord","year":"2009","journal-title":"Neurogastroenterol. Motil."},{"key":"2021111618285915700_B9","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1136\/gutjnl-2012-302645","article-title":"In\u00a0vivo evaluation of acid-induced changes in oesophageal mucosa integrity and sensitivity in non-erosive reflux disease","volume":"62","author":"Woodland","year":"2013","journal-title":"Gut"},{"key":"2021111618285915700_B10","doi-asserted-by":"publisher","first-page":"G129","DOI":"10.1152\/ajpgi.00085.2014","article-title":"In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids","volume":"307","author":"Peng","year":"2014","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"2021111618285915700_B11","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/S1499-3872(14)60307-6","article-title":"Bile acid signaling through farnesoid and TGR5 receptors in hepatobiliary and intestinal diseases","volume":"14","author":"Stanimirov","year":"2015","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"2021111618285915700_B12","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1111\/iep.12083","article-title":"Pulsatile exposure to simulated reflux leads to changes in gene expression in a 3D model of oesophageal mucosa","volume":"95","author":"Green","year":"2014","journal-title":"Int. J. Exp. Pathol."},{"key":"2021111618285915700_B13","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1111\/dote.12308","article-title":"High-definition endoscopy with iScan and Lugol's solution for the detection of inflammation in patients with nonerosive reflux disease: histologic evaluation in comparison with a control group","volume":"29","author":"Rey","year":"2014","journal-title":"Dis. Esophagus"},{"key":"2021111618285915700_B14","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1111\/jgh.12696","article-title":"Risk for esophageal neoplasia in Barrett's esophagus patients with mucosal changes indefinite for dysplasia","volume":"30","author":"Horvath","year":"2015","journal-title":"J. Gastroenterol. Hepatol."},{"key":"2021111618285915700_B15","doi-asserted-by":"publisher","first-page":"2012","DOI":"10.1245\/s10434-014-3537-5","article-title":"Impact of inflammation-metaplasia-adenocarcinoma sequence and inflammatory microenvironment in esophageal carcinogenesis using surgical rat models","volume":"21","author":"Miyashita","year":"2014","journal-title":"Ann. Surg. Oncol."},{"key":"2021111618285915700_B16","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.freeradbiomed.2014.11.012","article-title":"Cancer cell metabolism and the modulating effects of nitric oxide","volume":"79C","author":"Chang","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"2021111618285915700_B17","doi-asserted-by":"publisher","first-page":"478","DOI":"10.3389\/fimmu.2014.00478","article-title":"Nitric oxide synthase: non-canonical expression patterns","volume":"5","author":"Mattila","year":"2014","journal-title":"Front. Immunol."},{"key":"2021111618285915700_B18","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.canlet.2011.12.025","article-title":"Use of the \u03b3-H2AX assay to monitor DNA damage and repair in translational cancer research","volume":"327","author":"Ivashkevich","year":"2012","journal-title":"Cancer Lett."},{"key":"2021111618285915700_B19","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.ecoenv.2014.03.035","article-title":"\u03b3-H2AX as a biomarker for DNA double-strand breaks in ecotoxicology","volume":"105","author":"Geri\u0107","year":"2014","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"2021111618285915700_B20","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/j.bbagrm.2012.02.021","article-title":"\u03b3-H2AX and other histone post-translational modifications in the clinic","volume":"1819","author":"Redon","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"2021111618285915700_B21","doi-asserted-by":"publisher","first-page":"623019","DOI":"10.1155\/2012\/623019","article-title":"Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis","volume":"2012","author":"Murata","year":"2012","journal-title":"J. Biomed. Biotechnol."},{"key":"2021111618285915700_B22","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/leu.2010.6","article-title":"gammaH2AX: a sensitive molecular marker of DNA damage and repair","volume":"24","author":"Mah","year":"2010","journal-title":"Leukemia"},{"key":"2021111618285915700_B23","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1097\/MOG.0b013e328362282f","article-title":"Molecular markers for Barrett's esophagus and its progression to cancer","volume":"29","author":"Fels Elliott","year":"2013","journal-title":"Curr. Opin. Gastroenterol."},{"key":"2021111618285915700_B24","doi-asserted-by":"publisher","first-page":"S583","DOI":"10.1245\/s10434-013-3043-1","article-title":"Oxidative DNA damage in Barrett mucosa: correlation with telomeric dysfunction and p53 mutation","volume":"20","author":"Cardin","year":"2013","journal-title":"Ann. Surg. Oncol."},{"key":"2021111618285915700_B25","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1053\/jhep.2002.36088","article-title":"Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited","volume":"36","author":"Paumgartner","year":"2002","journal-title":"Hepatology"},{"key":"2021111618285915700_B26","doi-asserted-by":"publisher","first-page":"8770","DOI":"10.3748\/wjg.v19.i46.8770","article-title":"Meta-analysis of Barrett's esophagus in China","volume":"19","author":"Dong","year":"2013","journal-title":"World J. Gastroenterol."}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20160124\/428386\/bsr036e357.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20160124\/428386\/bsr036e357.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T18:57:08Z","timestamp":1637089028000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/36\/4\/e00357\/56399\/Controlled-bile-acid-exposure-to-oesophageal"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,8]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,8,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20160124","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,8]]},"article-number":"e00357"}}