{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:29:42Z","timestamp":1790364582516,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T00:00:00Z","timestamp":1639699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81750110551"],"award-info":[{"award-number":["81750110551"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073075"],"award-info":[{"award-number":["82073075"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Helicobacter pylori infection and alcohol intake are independent risk factors in gastric carcinogenesis; however, until now, the combined effect of H. pylori infection and alcohol consumption and the specific mechanism is still problematic. Here, we developed a series of mouse models that progress from chronic gastritis to gastric cancer, induced by infecting H. pylori combined with chronic alcohol consumption and then determining the molecular mechanism of the progression by flow cytometry, western blotting, qPCR, Mito Traker assay in the gastric cancer and T-cell lines. Interleukin-10 (IL-10) knockout mice was used to determine whether IL-10 deficiency directly contributes to H. pylori and alcohol induced gastric tumorigenesis. Alcohol consumption, together with H. pylori infection, causes gastric cancer; IL-10 downregulation and mitochondrial metabolic dysfunction in CD8+ cells are also involved. IL-10 knockout accelerates tumor development in mice with either H. pylori infection or alcohol induced gastric cancer or both. IL-10 inhibits glucose uptake and glycolysis and promotes oxidative phosphorylation with lactate inhibition. Consequently, in the absence of IL-10 signaling, CD8+ cells accumulate damaged mitochondria in a mouse model of gastric cancer induced with the combination of alcohol plus H. pylori infection, and this results in mitochondrial dysfunction and production of IL-1\u03b2. IL-1\u03b2 promotes H. pylori infection and reduces NKX6.3 gene expression, resulting in increased cancer cell survival and proliferation. Gastric cancer can be induced by the combination of H. pylori infection and chronic alcohol consumption through IL-10 inhibition induced CD8+ cells dysfunction and NKX6.3 suppression.<\/jats:p>","DOI":"10.1093\/carcin\/bgab114","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T12:07:36Z","timestamp":1637928456000},"page":"126-139","source":"Crossref","is-referenced-by-count":29,"title":["Gastric tumorigenesis induced by combining <i>Helicobacter pylori<\/i> infection and chronic alcohol through IL-10 inhibition"],"prefix":"10.1093","volume":"43","author":[{"given":"Faisal","family":"Aziz","sequence":"first","affiliation":[{"name":"The China\u2013US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR China"},{"name":"The Hormel Institute, University of Minnesota, Austin, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijit","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"The Hormel Institute, University of Minnesota, Austin, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangdong","family":"Liu","sequence":"additional","affiliation":[{"name":"The China\u2013US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR China"},{"name":"Department of Pathophysiology, School of Basic Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, Henan, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianshun","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Hormel Institute, University of Minnesota, Austin, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"The China\u2013US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR China"},{"name":"Department of Pathophysiology, School of Basic Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, Henan, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijuan","family":"Du","sequence":"additional","affiliation":[{"name":"The China\u2013US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR China"},{"name":"Department of Pathophysiology, School of Basic Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, Henan, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"Monts","sequence":"additional","affiliation":[{"name":"The Hormel Institute, University of Minnesota, Austin, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Xu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghan","family":"Li","sequence":"additional","affiliation":[{"name":"The China\u2013US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihua","family":"Bai","sequence":"additional","affiliation":[{"name":"Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, Henan, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4174-4028","authenticated-orcid":false,"given":"Zigang","family":"Dong","sequence":"additional","affiliation":[{"name":"The China\u2013US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, PR China"},{"name":"Department of Pathophysiology, School of Basic Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou, Henan, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"2022032516110650200_CIT0001","first-page":"1273","article-title":"Unidentified curved bacilli on gastric epithelium in active chronic gastritis.","volume":"1","author":"Warren","year":"1983","journal-title":"Lancet"},{"key":"2022032516110650200_CIT0002","doi-asserted-by":"crossref","first-page":"12767","DOI":"10.3748\/wjg.v20.i36.12767","article-title":"Effect of Helicobacter pylori on gastric epithelial cells.","volume":"20","author":"Alzahrani","year":"2014","journal-title":"World J. 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Biotechnol."},{"key":"2022032516110650200_CIT0004","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/0016-5085(90)90957-3","article-title":"Urea protects Helicobacter (Campylobacter) pylori from the bactericidal effect of acid.","volume":"99","author":"Marshall","year":"1990","journal-title":"Gastroenterology"},{"key":"2022032516110650200_CIT0005","doi-asserted-by":"crossref","first-page":"142980","DOI":"10.1155\/2014\/142980","article-title":"Prevalence and correlation with clinical diseases of Helicobacter pylori cagA and vacA genotype among gastric patients from Northeast China.","volume":"2014","author":"Aziz","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"2022032516110650200_CIT0006","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.3892\/mmr.2015.3692","article-title":"A method for establishing human primary gastric epithelial cell culture from fresh surgical gastric tissues.","volume":"12","author":"Aziz","year":"2015","journal-title":"Mol. 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