{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T23:42:38Z","timestamp":1781739758854,"version":"3.54.5"},"reference-count":45,"publisher":"BMJ","issue":"4","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Gut"],"accepted":{"date-parts":[[2017,4,3]]},"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>In previous studies using oesophageal squamous cells from patients with Barrett's oesophagus (normal oesophageal squamous (NES)-B cells) and from patients without Barrett's oesophagus (NES-G cells), we showed that acid and bile salts induced caudal-related homeobox transcription factor 2 (CDX2) expression only in NES-B cells. CDX2, a transcription factor required to form intestinal epithelium, is a target of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB) signalling, which can be inhibited by aspirin. We explored mechanisms underlying differences between NES-B and NES-G cells in CDX2 expression and effects of aspirin on that CDX2 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>We exposed NES-B and NES-G cells to acid and bile salts, with and without aspirin, and evaluated effects on I\u03baB-NF-\u03baB-PKAc complex activation, p65 NF-\u03baB subunit function, and CDX2 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In both NES-B and NES-G cells, acid and bile salts activated nicotinamide adenine dinucleotide phosphate oxidase to generate H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      , which activated the I\u03baB-NF-\u03baB-PKAc complex. NES-B cells exhibited higher levels of phosphorylated I\u03baB and p65 and greater NF-\u03baB transcriptional activity than NES-G cells, indicating greater I\u03baB-NF-\u03baB-PKAc complex activation by acid and bile salts in NES-B cells, and p65 siRNA prevented their increased expression of CDX2. Aspirin blocked I\u03baB phosphorylation, p65 nuclear translocation, CDX2 promoter activation and CDX2 expression induced by acid and bile salts in NES-B cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Differences between NES-B and NES-G cells in NF-\u03baB activation by acid and bile salts can account for their differences in CDX2 expression, and their CDX2 expression can be blocked by aspirin. These findings might explain why some patients with GORD develop Barrett's oesophagus while others do not, and why aspirin might protect against development of Barrett's oesophagus.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gutjnl-2016-313584","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T20:50:15Z","timestamp":1493153415000},"page":"606-615","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Aspirin prevents NF-\u03baB activation and CDX2 expression stimulated by acid and bile salts in oesophageal squamous cells of patients with Barrett's oesophagus"],"prefix":"10.1136","volume":"67","author":[{"given":"Xiaofang","family":"Huo","sequence":"first","affiliation":[{"name":"Esophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Medicine, Center for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Esophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Medicine, Center for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Yu","sequence":"additional","affiliation":[{"name":"Esophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edaire","family":"Cheng","sequence":"additional","affiliation":[{"name":"Esophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Pediatrics, Children's Medical Center and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Esophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Medicine, Center for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry B","family":"Dunbar","sequence":"additional","affiliation":[{"name":"Esophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thai H","family":"Pham","sequence":"additional","affiliation":[{"name":"Esophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Surgery, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H","family":"Wang","sequence":"additional","affiliation":[{"name":"Esophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S","family":"Bresalier","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart J","family":"Spechler","sequence":"additional","affiliation":[{"name":"Esophageal Diseases Center, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Medicine, VA North Texas Health Care System and the University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Medicine, Center for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas, Texas, USA"},{"name":"Harold C. 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