{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:32:54Z","timestamp":1790400774377,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T00:00:00Z","timestamp":1577404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31201893"],"award-info":[{"award-number":["31201893"]}],"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":["81673673"],"award-info":[{"award-number":["81673673"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Helicobacter"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>It has been documented that <jats:italic>Helicobacter hepaticus<\/jats:italic> (<jats:italic>H\u00a0hepaticus<\/jats:italic>) infection is linked to chronic hepatitis and liver cancer. However, our understanding of the molecular mechanisms underlying progression of the <jats:italic>H\u00a0hepaticus\u2010<\/jats:italic>induced hepatic inflammation to cellular hepatocarcinoma is still limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>In our study, male BALB\/c mice were infected by <jats:italic>H\u00a0hepaticus<\/jats:italic> for 8, 12, 16, 20, and 24\u00a0weeks. Histopathology, <jats:italic>H\u00a0hepaticus<\/jats:italic> colonization dynamics, select signaling pathways, and expression of key inflammatory cytokines in the liver were examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that <jats:italic>H\u00a0hepaticus<\/jats:italic> was detectible in feces of mice at 7\u00a0days postinfection (DPI) by PCR, but it was not detected in the livers by PCR until 8\u00a0weeks postinfection (WPI). In addition, abundance of colonic and hepatic <jats:italic>H\u00a0hepaticus<\/jats:italic> was progressively increased over the infection duration. <jats:italic>H\u00a0hepaticus<\/jats:italic>\u2010induced hepatic inflammation and fibrosis were aggravated over the infection duration, and necrosis or cirrhosis developed in the infected liver at 24 WPI <jats:italic>H\u00a0hepaticus<\/jats:italic> infection increased levels of alanine aminotransferase and aspartate aminotransferase. Moreover, mRNA levels of <jats:italic>Il\u20106<\/jats:italic> and <jats:italic>Tnf\u2010\u03b1<\/jats:italic> were significantly elevated in the livers of <jats:italic>H\u00a0hepaticus<\/jats:italic>\u2010infected mice compared to uninfected control from 8 WPI to 24 WPI. Furthermore, Stat3, nuclear factor\u2010\u03baB (p65), and MAPK (Erk1\/2 and p38) were activated by <jats:italic>H\u00a0hepaticus<\/jats:italic> infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data demonstrated that male BALB\/c mice can be used as a new mouse model of <jats:italic>H\u00a0hepaticus<\/jats:italic>\u2010induced liver diseases and that the <jats:italic>H\u00a0hepaticus<\/jats:italic>\u2010induced liver injury is triggered by NF\u2010\u03baB, Jak\u2010Stat, and MAPK signaling pathways.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hel.12677","type":"journal-article","created":{"date-parts":[[2019,12,28]],"date-time":"2019-12-28T00:30:00Z","timestamp":1577493000000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["<i>Helicobacter hepaticus<\/i> infection induces chronic hepatitis and fibrosis in male BALB\/c mice via the activation of NF\u2010\u03baB, Stat3, and MAPK signaling pathways"],"prefix":"10.1111","volume":"25","author":[{"given":"Shuyang","family":"Cao","sequence":"first","affiliation":[{"name":"Institute of Comparative Medicine College of Veterinary Medicine Yangzhou University Yangzhou Jiangsu China"},{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou University Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine College of Veterinary Medicine Yangzhou University Yangzhou Jiangsu China"},{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou University Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Feng","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine College of Veterinary Medicine Yangzhou University Yangzhou Jiangsu China"},{"name":"Shanghai Lab Animal Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine College of Veterinary Medicine Yangzhou University Yangzhou Jiangsu China"},{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou University Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yin","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine College of Veterinary Medicine Yangzhou University Yangzhou Jiangsu China"},{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou University Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Xu","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology Jiangsu Institute of Parasitic Diseases Wuxi Jiangsu Province China"},{"name":"Public Health Research Center Jiangnan University Wuxi Jiangsu Province China"},{"name":"Center for Global Health School of Public Health Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Yang","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology Jiangsu Institute of Parasitic Diseases Wuxi Jiangsu Province China"},{"name":"Public Health Research Center Jiangnan University Wuxi Jiangsu Province China"},{"name":"Center for Global Health School of Public Health Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzheng","family":"Huang","sequence":"additional","affiliation":[{"name":"National Health Commission Key Laboratory of Parasitic Disease Control and Prevention Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology Jiangsu Institute of Parasitic Diseases Wuxi Jiangsu Province China"},{"name":"Public Health Research Center Jiangnan University Wuxi Jiangsu Province China"},{"name":"Center for Global Health School of Public Health Nanjing Medical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6389-6500","authenticated-orcid":false,"given":"Quan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Comparative Medicine College of Veterinary Medicine Yangzhou University Yangzhou Jiangsu China"},{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou University Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/hel.12135"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2008.03.011"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2010.61"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099713"},{"issue":"6","key":"e_1_2_7_6_1","first-page":"1160","article-title":"Immune responses to bile\u2010tolerant helicobacter species in patients with chronic liver diseases, a randomized population group, and healthy blood donors","volume":"9","author":"Ananieva O","year":"2002","journal-title":"Clin Diagn Lab Immunol"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i35.12462"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23917"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00939.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0014-7"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230590522365"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfl173"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfq009"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623308322312"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.12.8449-8452.2005"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsps.2016.04.015"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25500"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.33.11.2968-2972.1995"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.6.3559-3567.2005"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.39.7.2598-2602.2001"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12184"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.1040752"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-013-2084-3"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-1009-0"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.64.5.1548-1558.1996"},{"issue":"4","key":"e_1_2_7_27_1","first-page":"959","article-title":"Chronic active hepatitis in mice caused by Helicobacter hepaticus","volume":"145","author":"Ward JM","year":"1994","journal-title":"Am J Pathol"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.65.8.3126-3131.1997"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.025"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00401-08"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01044-07"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106764"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid0104.950404"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230490524247"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/86.16.1222"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep45846"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.020479-0"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.7.3142-3148.1998"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.12-0304"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.5152\/tjg.2018.17330"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20071723"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1934"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6FO01873D"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20173"},{"issue":"3","key":"e_1_2_7_45_1","first-page":"2013","article-title":"Effect of JAK2\/STAT3 signaling pathway on liver injury associated with severe acute pancreatitis in rats","volume":"16","author":"Li M","year":"2018","journal-title":"Exp Ther Med"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15521-3"}],"container-title":["Helicobacter"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hel.12677","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hel.12677","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hel.12677","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T09:43:09Z","timestamp":1694079789000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hel.12677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,27]]},"references-count":45,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1111\/hel.12677"],"URL":"https:\/\/doi.org\/10.1111\/hel.12677","archive":["Portico"],"relation":{},"ISSN":["1083-4389","1523-5378"],"issn-type":[{"value":"1083-4389","type":"print"},{"value":"1523-5378","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,27]]},"assertion":[{"value":"2019-07-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12677"}}