{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T23:20:45Z","timestamp":1785885645843,"version":"3.56.0"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Chronic <jats:italic>Helicobacter pylori<\/jats:italic> infection causes gastric cancer via the progression of precancerous chronic atrophic gastritis (CAG). Therefore, repairing gastric atrophy could be a useful strategy in preventing <jats:italic>H. pylori<\/jats:italic>\u2013associated gastric carcinogenesis. Although eradication of the bacterial pathogen offers one solution to this association, this study was designed to evaluate an alternative approach using mesenchymal stem cells to treat CAG and prevent carcinogenesis. Here, we used human placenta-derived mesenchymal stem cells (PD-MSCs) and their conditioned medium (CM) to treat <jats:italic>H. pylori<\/jats:italic>\u2013associated CAG in a mice\/cell model to explore their therapeutic effects and elucidate their molecular mechanisms. We compared the changes in the fecal microbiomes in response to PD-MSC treatments, and chronic <jats:italic>H. pylori<\/jats:italic>\u2013infected mice were given ten treatments with PD-MSCs before being sacrificed for end point assays at around 36\u00a0weeks of age. These animals presented with significant reductions in the mean body weights of the control group, which were eradicated following PD-MSC treatment (<jats:italic>p &amp;lt; 0.01<\/jats:italic>). Significant changes in various pathological parameters including inflammation, gastric atrophy, erosions\/ulcers, and dysplastic changes were noted in the control group (<jats:italic>p &amp;lt; 0.01<\/jats:italic>), but these were all significantly reduced in the PD-MSC\/CM-treated groups. Lgr5+, Ki-67, H<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>-ATPase, and Musashi-1 expressions were all significantly increased in the treated animals, while inflammatory mediators, MMP, and apoptotic executors were significantly decreased in the PD-MSC group compared to the control group (<jats:italic>p &amp;lt; 0.001<\/jats:italic>). Our model showed that <jats:italic>H. pylori<\/jats:italic>\u2013initiated, high-salt diet\u2013promoted gastric atrophic gastritis resulted in significant changes in the fecal microbiome at the phylum\/genus level and that PD-MSC\/CM interventions facilitated a return to more normal microbial communities. In conclusion, administration of PD-MSCs or their conditioned medium may present a novel rejuvenating agent in preventing the progression of <jats:italic>H. pylori<\/jats:italic>\u2013associated premalignant lesions.<\/jats:p>","DOI":"10.3389\/fphar.2021.675443","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T08:19:38Z","timestamp":1629274778000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Rejuvenation of Helicobacter pylori\u2013Associated Atrophic Gastritis Through Concerted Actions of Placenta-Derived Mesenchymal Stem Cells Prevented Gastric Cancer"],"prefix":"10.3389","volume":"12","author":[{"given":"Jong Min","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Min","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Baik","family":"Hahm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"12767","DOI":"10.3748\/wjg.v20.i36.12767","article-title":"Effect ofHelicobacter Pylorion Gastric Epithelial Cells","volume":"20","author":"Alzahrani","year":"2014","journal-title":"World. J. Gasteroentrol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3164\/jcbn.19-10","article-title":"Dietary Intake of Probiotic Kimchi Ameliorated IL-6-driven Cancer Cachexia","volume":"65","author":"An","year":"2019","journal-title":"J. Clin. Biochem. Nutr."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1016\/j.ajpath.2020.01.021","article-title":"Constitutive STAT3 Serine Phosphorylation Promotes Helicobacter-Mediated Gastric Disease","volume":"190","author":"Balic","year":"2020","journal-title":"Am. J. Pathol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1111\/j.1600-065X.2011.01041.x","article-title":"Molecular Mechanisms of Inflammasome Activation during Microbial Infections","volume":"243","author":"Broz","year":"2011","journal-title":"Immunol. Rev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1089\/scd.2017.0104","article-title":"From \"Bench to Bedside\": Current Advancement on Large-Scale Production of Mesenchymal Stem Cells","volume":"26","author":"Bunpetch","year":"2017","journal-title":"Stem Cell Develop."},{"key":"B6","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1007\/s10120-015-0462-7","article-title":"Helicobacter pylori Eradication Cannot Reduce the Risk of Gastric Cancer in Patients with Intestinal Metaplasia and Dysplasia: Evidence from a Meta-Analysis","volume":"19","author":"Chen","year":"2016","journal-title":"Gastric Cancer"},{"key":"B7","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1186\/s13287-019-1503-7","article-title":"Menstrual Blood-Derived Stem Cells: toward Therapeutic Mechanisms, Novel Strategies, and Future Perspectives in the Treatment of Diseases","volume":"10","author":"Chen","year":"2019","journal-title":"Stem Cel Res Ther"},{"key":"B8","doi-asserted-by":"publisher","first-page":"7361","DOI":"10.3748\/wjg.v19.i42.7361","article-title":"Role of Cyclooxygenase-2 in Gastric Cancer Development and Progression","volume":"19","author":"Cheng","year":"2013","journal-title":"World. J. Gasteroentrol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1056\/NEJMoa1909666","article-title":"Family History of Gastric Cancer and Helicobacter pylori Treatment","volume":"382","author":"Choi","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1056\/NEJMoa1708423","article-title":"Helicobacter pylori Therapy for the Prevention of Metachronous Gastric Cancer","volume":"378","author":"Choi","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.pedneo.2020.05.012","article-title":"Human Placenta-Derived Mesenchymal Stem Cells Attenuate Established Hyperoxia-Induced Lung Injury in Newborn Rats","volume":"61","author":"Chou","year":"2020","journal-title":"Pediatr. Neonatal."},{"key":"B12","doi-asserted-by":"publisher","first-page":"4157","DOI":"10.1128\/IAI.00524-10","article-title":"Invasion and Multiplication of Helicobacter pylori in Gastric Epithelial Cells and Implications for Antibiotic Resistance","volume":"78","author":"Chu","year":"2010","journal-title":"Infect. Immun."},{"key":"B13","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s13045-020-00936-9","article-title":"Crosstalks between Inflammasome and Autophagy in Cancer","volume":"13","author":"Chung","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1111\/j.1440-1746.2010.06251.x","article-title":"Rejuvenation of Atrophic Gastritis in the Elderly","volume":"25","author":"Chung","year":"2010","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1136\/gutjnl-2017-314281","article-title":"Mucosal Microbiome Dysbiosis in Gastric Carcinogenesis","volume":"67","author":"Coker","year":"2018","journal-title":"Gut"},{"key":"B16","first-page":"59","article-title":"Helicobacter pylori Infection and Gastric Adenocarcinoma","volume":"7","author":"Correa","year":"2011","journal-title":"US Gastroenterol. Hepatol. Rev."},{"key":"B17","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.gtc.2013.01.002","article-title":"Gastric Cancer","volume":"42","author":"Correa","year":"2013","journal-title":"Gastroenterol. Clin. North America"},{"key":"B18","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/j.dld.2008.02.035","article-title":"Natural History of Helicobacter pylori Infection","volume":"40","author":"Correa","year":"2008","journal-title":"Dig. Liver Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/j.1751-2980.2011.00550.x","article-title":"The Gastric Precancerous cascade","volume":"13","author":"Correa","year":"2012","journal-title":"J. Dig. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1523-5378.2007.00475.x","article-title":"The Detection, Surveillance and Treatment of Premalignant Gastric Lesions Related to Helicobacter pylori Infection","volume":"12","author":"de Vries","year":"2007","journal-title":"Helicobacter"},{"key":"B21","doi-asserted-by":"publisher","first-page":"639","DOI":"10.4161\/auto.23782","article-title":"The Impact of Autophagic Processes on the Intracellular Fate ofHelicobacter Pylori","volume":"9","author":"Deen","year":"2013","journal-title":"Autophagy"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1111\/j.1572-0241.1998.01407.x","article-title":"Reversal of Gastric Atrophy after Helicobacter pylori Eradication: Is it Possible or Not?","volume":"93","author":"Domell\u00f6f","year":"1998","journal-title":"Am. J. Gastroenterol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1111\/cas.12901","article-title":"Inflammation in Gastric Cancer: Interplay of the COX\u20102\/prostaglandin E 2 and Toll\u2010like receptor\/MyD88 Pathways","volume":"107","author":"Echizen","year":"2016","journal-title":"Cancer Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"4358","DOI":"10.1073\/pnas.0800668105","article-title":"Helicobacter pylori Evolution during Progression from Chronic Atrophic Gastritis to Gastric Cancer and its Impact on Gastric Stem Cells","volume":"105","author":"Giannakis","year":"2008","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1152\/physrev.00019.2015","article-title":"Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue","volume":"96","author":"Golpanian","year":"2016","journal-title":"Physiol. Rev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"633","DOI":"10.3892\/mmr.2019.10286","article-title":"Comparison of Biological Characteristics of Mesenchymal Stem Cells Derived from the Human Umbilical Cord and Decidua Parietalis","volume":"20","author":"Guan","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"B27","first-page":"65","article-title":"Tissue Stem Cells and Cancer Stem Cells: Potential Implications for Gastric Cancer","volume":"50","author":"Gumucio","year":"2008","journal-title":"Panminerva Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"66606","DOI":"10.18632\/oncotarget.11261","article-title":"Suppressed Helicobacter Pylori-Associated Gastric Tumorigenesis in Fat-1 Transgenic Mice Producing Endogenous \u03c9-3 Polyunsaturated Fatty Acids","volume":"7","author":"Han","year":"2016","journal-title":"Oncotarget"},{"key":"B29","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s13287-017-0559-5","article-title":"The Efficacy of Human Placenta-Derived Mesenchymal Stem Cells on Radiation Enteropathy along with Proteomic Biomarkers Predicting a Favorable Response","volume":"8","author":"Han","year":"2017","journal-title":"Stem Cel Res Ther"},{"key":"B30","doi-asserted-by":"publisher","first-page":"100","DOI":"10.3390\/biomedicines6040100","article-title":"Gastric Stem Cell and Cellular Origin of Cancer","volume":"6","author":"Hata","year":"2018","journal-title":"Biomedicines"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1111\/jcmm.13492","article-title":"Preconditioning Influences Mesenchymal Stem Cell Properties In Vitro and In Vivo","volume":"22","author":"Hu","year":"2018","journal-title":"J. Cel. Mol. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"8315","DOI":"10.1111\/jcmm.15565","article-title":"Autophagy Regulation Is an Effective Strategy to Improve the Prognosis of Chemically Induced Acute Liver Injury Based on Experimental Studies","volume":"24","author":"Hu","year":"2020","journal-title":"J. Cel Mol Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s13287-019-1225-x","article-title":"Modulating Autophagy in Mesenchymal Stem Cells Effectively Protects against Hypoxia- or Ischemia-Induced Injury","volume":"10","author":"Hu","year":"2019","journal-title":"Stem Cel Res Ther"},{"key":"B34","doi-asserted-by":"publisher","first-page":"141030","DOI":"10.1016\/j.scitotenv.2020.141030","article-title":"A Gut Dysbiotic Microbiota-Based Hypothesis of Human-To-Human Transmission of Non-communicable Diseases","volume":"745","author":"Huang","year":"2020","journal-title":"Sci. Total Environ."},{"key":"B35","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1111\/hel.12229","article-title":"Dietary Intervention ofArtemisiaand Green Tea Extracts to RejuvenateHelicobacter Pylori-Associated Chronic Atrophic Gastritis and to Prevent Tumorigenesis","volume":"21","author":"Jeong","year":"2016","journal-title":"Helicobacter"},{"key":"B36","doi-asserted-by":"publisher","first-page":"29513","DOI":"10.18632\/oncotarget.4897","article-title":"Dietary Prevention of Helicobacter Pylori-Associated Gastric Cancer with Kimchi","volume":"6","author":"Jeong","year":"2015","journal-title":"Oncotarget"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1002\/stem.1396","article-title":"Human Placenta-Derived Mesenchymal Stem Cells Promote Hepatic Regeneration in CCl4-Injured Rat Liver Model via Increased Autophagic Mechanism","volume":"31","author":"Jung","year":"2013","journal-title":"Stem Cells"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1101\/gad.1565707","article-title":"Autophagy Mitigates Metabolic Stress and Genome Damage in Mammary Tumorigenesis","volume":"21","author":"Karantza-Wadsworth","year":"2007","journal-title":"Genes Develop."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3018","DOI":"10.3390\/cancers3033018","article-title":"Detouring the Undesired Route of Helicobacter Pylori-Induced Gastric Carcinogenesis","volume":"3","author":"Kim","year":"","journal-title":"Cancers"},{"key":"B40","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s00535-003-1282-9","article-title":"Histopathology and Expression of Ki-67 and Cyclooxygenase-2 in Childhood Helicobacter pylori Gastritis","volume":"39","author":"Kim","year":"2004","journal-title":"J. Gastroenterol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s00441-011-1249-8","article-title":"Human Chorionic-Plate-Derived Mesenchymal Stem Cells and Wharton's Jelly-Derived Mesenchymal Stem Cells: a Comparative Analysis of Their Potential as Placenta-Derived Stem Cells","volume":"346","author":"Kim","year":"","journal-title":"Cell Tissue Res"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1111\/jgh.14646","article-title":"Chemoprevention of Gastric Cancer byHelicobacter Pylorieradication and its Underlying Mechanism","volume":"34","author":"Kim","year":"2019","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"195","DOI":"10.3164\/jcbn.10-03","article-title":"Progression from Chronic Atrophic Gastritis to Gastric Cancer; Tangle, Toggle, Tackle with Korea Red Ginseng","volume":"46","author":"Kim","year":"2010","journal-title":"J. Clin. Biochem. Nutr."},{"key":"B44","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41573-020-0064-x","article-title":"Next-generation Stem Cells - Ushering in a new era of Cell-Based Therapies","volume":"19","author":"Kimbrel","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"B45","doi-asserted-by":"publisher","first-page":"665","DOI":"10.4251\/wjgo.v11.i9.665","article-title":"Premalignant Lesions and Gastric Cancer: Current Understanding","volume":"11","author":"Koulis","year":"2019","journal-title":"World. J. Gasteroentrol. Oncol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1007\/s11894-020-00775-1","article-title":"Current Perspectives in Atrophic Gastritis","volume":"22","author":"Lahner","year":"2020","journal-title":"Curr. Gastroenterol. Rep."},{"key":"B47","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.intimp.2012.03.024","article-title":"Comparison of Immunomodulatory Effects of Placenta Mesenchymal Stem Cells with Bone Marrow and Adipose Mesenchymal Stem Cells","volume":"13","author":"Lee","year":"2012","journal-title":"Int. Immunopharmacology"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1002\/jcb.22873","article-title":"Anti-fibrotic Effect of Chorionic Plate-Derived Mesenchymal Stem Cells Isolated from Human Placenta in a Rat Model of CCl4-Injured Liver: Potential Application to the Treatment of Hepatic Diseases","volume":"111","author":"Lee","year":"2010","journal-title":"J. Cel. Biochem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"303","DOI":"10.4166\/kjg.2015.66.6.303","article-title":"Unpleasant Journey fromHelicobacter Pylori-Associated Gastritis to Gastric Cancer: Cancer Prevention by Taking a Detour","volume":"66","author":"Lee","year":"2015","journal-title":"Korean J. Gastroenterol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1038\/s41467-017-01341-6","article-title":"HGF\/R-spondin1 Rescues Liver Dysfunction through the Induction of Lgr5+ Liver Stem Cells","volume":"8","author":"Lin","year":"2017","journal-title":"Nat. Commun."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.3748\/wjg.v22.i3.1311","article-title":"Helicobacter Pyloriassociated Gastric Intestinal Metaplasia: Treatment and Surveillance","volume":"22","author":"Liu","year":"2016","journal-title":"World. J. Gasteroentrol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.gpb.2013.09.002","article-title":"Clinical Therapy Using iPSCs: Hopes and Challenges","volume":"11","author":"Lu","year":"2013","journal-title":"Genomics, Proteomics & Bioinformatics"},{"key":"B53","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.cell.2004.11.046","article-title":"Growth Factor Regulation of Autophagy and Cell Survival in the Absence of Apoptosis","volume":"120","author":"Lum","year":"2005","journal-title":"Cell"},{"key":"B54","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13287-018-1104-x","article-title":"Comparative Analysis of Mesenchymal Stem Cells Derived from Amniotic Membrane, Umbilical Cord, and Chorionic Plate under Serum-free Condition","volume":"10","author":"Ma","year":"2019","journal-title":"Stem Cel Res Ther"},{"key":"B55","doi-asserted-by":"publisher","first-page":"118002","DOI":"10.1016\/j.lfs.2020.118002","article-title":"Adult Mesenchymal Stem Cells and Their Exosomes: Sources, Characteristics, and Application in Regenerative Medicine","volume":"256","author":"Maqsood","year":"2020","journal-title":"Life Sci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1053\/j.gastro.2010.12.001","article-title":"Gastric Epithelial Stem Cells","volume":"140","author":"Mills","year":"2011","journal-title":"Gastroenterology"},{"key":"B57","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.jcmgh.2016.12.001","article-title":"The Clinical Evidence Linking Helicobacter pylori to Gastric Cancer","volume":"3","author":"Moss","year":"2017","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"e14170","DOI":"10.14814\/phy2.14170","article-title":"Current Status of Diagnosis and Mesenchymal Stem Cells Therapy for Acute Pancreatitis","volume":"7","author":"Munir","year":"2019","journal-title":"Physiol. Rep."},{"key":"B59","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/s10620-007-9858-5","article-title":"Helicobacter pylori Infection Induces Candidate Stem Cell Marker Musashi-1 in the Human Gastric Epithelium","volume":"53","author":"Murata","year":"2008","journal-title":"Dig. Dis. Sci."},{"key":"B60","doi-asserted-by":"publisher","first-page":"8105","DOI":"10.1158\/1078-0432.CCR-04-0896","article-title":"The Selective Cyclooxygenase-2 Inhibitor Nimesulide Prevents Helicobacter Pylori-Associated Gastric Cancer Development in a Mouse Model","volume":"10","author":"Nam","year":"","journal-title":"Clin. Cancer Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1136\/gut.2003.030684","article-title":"Decreased Helicobacter pylori Associated Gastric Carcinogenesis in Mice Lacking Inducible Nitric Oxide Synthase","volume":"53","author":"Nam","year":"","journal-title":"Gut"},{"key":"B62","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.mib.2005.12.013","article-title":"Interactions between Gastric Epithelial Stem Cells and Helicobacter pylori in the Setting of Chronic Atrophic Gastritis","volume":"9","author":"Oh","year":"2006","journal-title":"Curr. Opin. Microbiol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"e12547","DOI":"10.1111\/hel.12547","article-title":"Evaluation of Gastric Microbiome and Metagenomic Function in Patients with Intestinal Metaplasia Using 16S rRNA Gene Sequencing","volume":"24","author":"Park","year":"2019","journal-title":"Helicobacter"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/712363","article-title":"Omega-3 Polyunsaturated Fatty Acids Intake to RegulateHelicobacter Pylori-Associated Gastric Diseases as Nonantimicrobial Dietary Approach","volume":"2015","author":"Park","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"B65","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1111\/hel.12121","article-title":"Special Licorice Extracts Containing Lowered Glycyrrhizin and Enhanced Licochalcone A PreventedHelicobacter Pylori-Initiated, Salt Diet-Promoted Gastric Tumorigenesis","volume":"19","author":"Park","year":"2014","journal-title":"Helicobacter"},{"key":"B66","doi-asserted-by":"publisher","first-page":"192","DOI":"10.25100\/cm.v44i3.1263","article-title":"Gastric C\u00e1ncer: Overview","volume":"44","author":"Piazuelo","year":"2013","journal-title":"Colomb Med. (Cali)"},{"key":"B67","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/j.idc.2010.07.010","article-title":"Gastric Cancer: an Infectious Disease","volume":"24","author":"Piazuelo","year":"2010","journal-title":"Infect. Dis. Clin. North America"},{"key":"B68","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.chom.2017.12.017","article-title":"Intestinal Epithelial Cell Autophagy Is Required to Protect against TNF-Induced Apoptosis during Chronic Colitis in Mice","volume":"23","author":"Pott","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B69","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/2001-1326-3-15","article-title":"Clinical Potentials of Human Pluripotent Stem Cells in Lung Diseases","volume":"3","author":"Quan","year":"2014","journal-title":"Clin. Translational Med."},{"key":"B70","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1111\/apt.15650","article-title":"Systematic Review: Gastric Microbiota in Health and Disease","volume":"51","author":"Rajilic-Stojanovic","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B71","doi-asserted-by":"publisher","first-page":"45","DOI":"10.2741\/e6","article-title":"Nuclear Factor-Kappa B Links Carcinogenic and Chemopreventive Agents","volume":"1","author":"Ralhan","year":"2009","journal-title":"Front. Biosci."},{"key":"B72","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/j.1523-5378.2011.00879.x","article-title":"Gastric Cancer: Basic Aspects","volume":"16","author":"Resende","year":"2011","journal-title":"Helicobacter"},{"key":"B73","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.bpg.2012.12.007","article-title":"Precancerous Lesions in the Stomach: from Biology to Clinical Patient Management","volume":"27","author":"Rugge","year":"2013","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.jmb.2017.10.003","article-title":"Emerging Insights into Noncanonical Inflammasome Recognition of Microbes","volume":"430","author":"Russo","year":"2018","journal-title":"J. Mol. Biol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13578-020-00433-z","article-title":"Perspective of Placenta Derived Mesenchymal Stem Cells in Acute Liver Failure","volume":"10","author":"Saleh","year":"2020","journal-title":"Cell Biosci"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13287-019-1471-y","article-title":"Alteration of Fatty Acid Oxidation by Increased CPT1A on Replicative Senescence of Placenta-Derived Mesenchymal Stem Cells","volume":"11","author":"Seok","year":"","journal-title":"Stem Cel Res Ther"},{"key":"B77","doi-asserted-by":"publisher","first-page":"591","DOI":"10.3390\/antiox9070591","article-title":"Placenta-Derived Mesenchymal Stem Cells Restore the Ovary Function in an Ovariectomized Rat Model via an Antioxidant Effect","volume":"9","author":"Seok","year":"","journal-title":"Antioxidants"},{"key":"B78","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.jmb.2017.11.006","article-title":"Checks and Balances between Autophagy and Inflammasomes during Infection","volume":"430","author":"Seveau","year":"2018","journal-title":"J. Mol. Biol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"151097","DOI":"10.1016\/j.ejcb.2020.151097","article-title":"Mesenchymal Stromal Cells (MSCs) for Neurodegenerative Disease: A Promising Frontier","volume":"99","author":"Shariati","year":"2020","journal-title":"Eur. J. Cel Biol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1038\/s41556-019-0339-9","article-title":"R-spondin-3 Induces Secretory, Antimicrobial Lgr5+ Cells in the Stomach","volume":"21","author":"Sigal","year":"2019","journal-title":"Nat. Cel Biol"},{"key":"B81","first-page":"S79","article-title":"Intestinal Metaplasia, Atrophic Gastritis and Stomach Cancer: Trends over Time","author":"Sipponen","year":"1994","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1080\/19490976.2020.1762520","article-title":"The Role of Gastric Microbiota in Gastric Cancer","volume":"11","author":"Stewart","year":"2020","journal-title":"Gut Microbes"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1136\/gutjnl-2015-309252","article-title":"Kyoto Global Consensus Report onHelicobacter Pylorigastritis","volume":"64","author":"Sugano","year":"2015","journal-title":"Gut"},{"key":"B84","doi-asserted-by":"publisher","first-page":"34","DOI":"10.7150\/ijbs.28879","article-title":"E-cadherin Is Required for the Homeostasis of Lgr5+ Gastric Antral Stem Cells","volume":"15","author":"Tang","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"B85","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s10555-011-9312-1","article-title":"Cyclooxygenase-2 and Gastric Cancer","volume":"30","author":"Thiel","year":"2011","journal-title":"Cancer Metastasis Rev."},{"key":"B86","doi-asserted-by":"publisher","first-page":"e12415","DOI":"10.1111\/hel.12415","article-title":"Effect on Helicobacter pylori Eradication Therapy against Gastric Cancer in Japan","volume":"22","author":"Tsuda","year":"2017","journal-title":"Helicobacter"},{"key":"B87","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1002\/jcb.21375","article-title":"Helicobacter pylori as a Class I Carcinogen: Physiopathology and Management Strategies","volume":"102","author":"Vogiatzi","year":"2007","journal-title":"J. Cel. Biochem."},{"key":"B88","doi-asserted-by":"publisher","first-page":"558471","DOI":"10.3389\/fphar.2020.558471","article-title":"A Combined Phytochemistry and Network Pharmacology Approach to Reveal the Effective Substances and Mechanisms of Wei-Fu-Chun Tablet in the Treatment of Precancerous Lesions of Gastric Cancer","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"171","DOI":"10.3181\/0808-RM-252","article-title":"The Autophagic Induction in Helicobacter Pylori-Infected Macrophage","volume":"234","author":"Wang","year":"2009","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"B90","doi-asserted-by":"publisher","first-page":"997","DOI":"10.3389\/fmicb.2020.00997","article-title":"Changes of the Gastric Mucosal Microbiome Associated with Histological Stages of Gastric Carcinogenesis","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Microbiol."},{"key":"B91","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1136\/gutjnl-2014-307650","article-title":"Helicobacter Pyloritargets Cancer-Associated Apical-Junctional Constituents in Gastroids and Gastric Epithelial Cells","volume":"64","author":"Wroblewski","year":"2015","journal-title":"Gut"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/7131532","article-title":"Comparison of the Proliferation and Differentiation Potential of Human Urine-, Placenta Decidua Basalis-, and Bone Marrow-Derived Stem Cells","volume":"2018","author":"Wu","year":"2018","journal-title":"Stem Cell Int."},{"key":"B93","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s12328-009-0130-8","article-title":"Premalignant Lesions in Gastric Cancer","volume":"3","author":"Yashima","year":"2010","journal-title":"Clin. J. Gastroenterol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"e12713","DOI":"10.1111\/hel.12713","article-title":"Changes in the Human Gut Microbiota Composition Caused by Helicobacter pylori Eradication Therapy: A Systematic Review and Meta\u2010analysis","volume":"25","author":"Ye","year":"2020","journal-title":"Helicobacter"},{"key":"B95","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.jcmgh.2018.01.007","article-title":"Regulation of Gastric Lgr5+ve Cell Homeostasis by Bone Morphogenetic Protein (BMP) Signaling and Inflammatory Stimuli","volume":"5","author":"Ye","year":"2018","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"110036","DOI":"10.1016\/j.biopha.2020.110036","article-title":"Dysbiosis of Gut Microbiota Is Associated with Gastric Carcinogenesis in Rats","volume":"126","author":"Yu","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"B97","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.3892\/mmr.2020.11231","article-title":"Placenta derived Mesenchymal Stem Cells Ameliorate Lipopolysaccharideinduced Inflammation in RAW264.7 Cells and Acute Lung Injury in Rats","volume":"22","author":"Yuan","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"B98","doi-asserted-by":"publisher","first-page":"6221","DOI":"10.3892\/ol.2019.10976","article-title":"Molecular Mechanism of Helicobacterpyloriinduced Autophagy in Gastric Cancer (Review)","volume":"18","author":"Zhang","year":"2019","journal-title":"Oncol. Lett."},{"key":"B99","doi-asserted-by":"publisher","first-page":"3427","DOI":"10.1038\/s41388-020-1241-4","article-title":"Gastric Cancer: Genome Damaged by Bugs","volume":"39","author":"Zhao","year":"2020","journal-title":"Oncogene"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.675443\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T08:19:47Z","timestamp":1629274787000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.675443\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,18]]},"references-count":99,"alternative-id":["10.3389\/fphar.2021.675443"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.675443","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,18]]},"article-number":"675443"}}