{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T21:41:40Z","timestamp":1769118100197,"version":"3.49.0"},"reference-count":102,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009045","name":"Jagiellonian University Medical College","doi-asserted-by":"crossref","award":["N41\/DBS\/000875"],"award-info":[{"award-number":["N41\/DBS\/000875"]}],"id":[{"id":"10.13039\/100009045","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009045","name":"Jagiellonian University Medical College","doi-asserted-by":"crossref","award":["N41\/DBS\/001496"],"award-info":[{"award-number":["N41\/DBS\/001496"]}],"id":[{"id":"10.13039\/100009045","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Early prevention of pathological changes underlying gastric cancer (GC) development is a critical strategy, offering the most effective opportunity to limit malignant progression and improve patient outcomes. We have previously demonstrated that Helicobacter pylori (Hp) (cagA+vacA+) contributes to GC development by activating gastric fibroblasts toward CAF-like phenotype, eliciting aggressive, cancer stem cells (CSCs)-related malignant transformation of LGR5+ normal epithelial cells. A key mediator of these processes appears to be the NF-\u03baB\/STAT3 axis. Therefore, our aim was to investigate the protective role of hydrogen sulfide (H2S) as a potential novel strategy for counteracting Hp-induced fibroblast reprogramming. Human fibroblasts were infected with Hp (cagA+vacA+) for 120 h. The fast-releasing H2S donor NaHS (50, 100, 200 and 400 \u00b5M) was added every 24 h. Activation markers, corresponding signaling pathways, H2S release and activities of H2S-metabolizing enzymes were determined. NaHS reduced Hp-induced fibroblast activation and their pro-inflammatory, pro-tumorigenic markers, which was associated with the inhibition of NF-\u03baB\/STAT3 axis and Twist expression. Additionally, it modulated sulfur metabolism while preserving sulfur-enzyme homeostasis. NaHS limited Hp adhesion (high doses), reduced reinfection-induced activation and increased sensitivity of Hp to metronidazole. These findings suggest that H2S signaling may represent a modulatory factor of NF-\u03baB\/STAT3-driven inflammatory responses during Hp infection and warrant further investigation.<\/jats:p>","DOI":"10.3390\/cells15020167","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T08:23:56Z","timestamp":1768811036000},"page":"167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hydrogen Sulfide Inhibits H. pylori-Induced Gastric Fibroblast Activation: Implications for Cancer Prevention"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5388-9646","authenticated-orcid":false,"given":"Gracjana","family":"Krzysiek-Maczka","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aneta","family":"Targosz","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7167-8685","authenticated-orcid":false,"given":"Patrycja","family":"Bronowicka-Adamska","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Mikolaja Kopernika 7c, 31-034 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urszula","family":"Szczyrk","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malgorzata","family":"Strzalka","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubert","family":"M\u0105czka","sequence":"additional","affiliation":[{"name":"Student Research Group, Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1350-1886","authenticated-orcid":false,"given":"Mateusz","family":"Wierdak","sequence":"additional","affiliation":[{"name":"Department of Endoscopic, Metabolic and Soft Tissue Malignancies Surgery of University Hospital, Jagiellonian University, Jakubowskiego 2, 30-688 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3631-8718","authenticated-orcid":false,"given":"Izabela","family":"Rodzon","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6779-7630","authenticated-orcid":false,"given":"Jaroslaw","family":"Czyz","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5805-0065","authenticated-orcid":false,"given":"Tomasz","family":"Brzozowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0294-5185","authenticated-orcid":false,"given":"Agata","family":"Ptak-Belowska","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4342","DOI":"10.18632\/oncotarget.14027","article-title":"Outcomes of surgery for gastric cancer with distant metastases: A retrospective study from the SEER database","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57654","DOI":"10.18632\/oncotarget.14825","article-title":"Targeted therapies for gastric cancer: Failures and hopes from clinical trials","volume":"8","author":"Apicella","year":"2017","journal-title":"Oncotarget"},{"key":"ref_3","first-page":"414","article-title":"A systematic review and meta-analysis of the role of Helicobacter pylori eradication in preventing gastric cancer","volume":"30","author":"Rokkas","year":"2017","journal-title":"Ann. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1007\/s10555-023-10122-1","article-title":"Helicobacter pylori-activated fibroblasts as a silent partner in gastric cancer development","volume":"42","author":"Brzozowski","year":"2023","journal-title":"Cancer Metastasis Rev."},{"key":"ref_5","unstructured":"Menon, G., El-Nakeep, S., and Babiker, H.M. (2024). Gastric Cancer. StatPearls, StatPearls Publishing."},{"key":"ref_6","first-page":"727","article-title":"Involvement of epithelial\u2013mesenchymal transition-inducing transcription factors in the mechanism of Helicobacter pylori-induced fibroblast activation","volume":"70","author":"Targosz","year":"2019","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Krzysiek-M\u0105czka, G., Targosz, A., Szczyrk, U., Wrobel, T., Strzalka, M., Brzozowski, T., Czyz, J., and Ptak-Belowska, A. (2020). Long-Term Helicobacter pylori Infection Switches Gastric Epithelium Reprogramming Towards Cancer Stem Cell-Related Differentiation Program in Hp-Activated Gastric Fibroblast-TGF\u03b2 Dependent Manner. Microorganisms, 8.","DOI":"10.3390\/microorganisms8101519"},{"key":"ref_8","first-page":"1337","article-title":"Time-extended exposure of gastric epithelial cells to the secretome of Helicobacter pylori-activated fibroblasts induces reprogramming of gastric epithelium towards a pre-carcinogenic and pro-invasive phenotype","volume":"12","author":"Targosz","year":"2022","journal-title":"Am. J. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12964-015-0111-0","article-title":"Helicobacter pylori virulence factor CagA promotes tumorigenesis of gastric cancer via multiple signaling pathways","volume":"13","author":"Yong","year":"2015","journal-title":"Cell Commun. Signal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"G1004","DOI":"10.1152\/ajpgi.00096.2007","article-title":"Toll-like receptor (TLR)2 induced through TLR4 signaling initiated by Helicobacter pylori cooperatively amplifies iNOS induction in gastric epithelial cells","volume":"293","author":"Uno","year":"2007","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.micpath.2016.06.028","article-title":"The contribution of Toll-like receptor 2 to Helicobacter pylori activation of the NF-\u03baB signaling pathway in gastric epithelial cells","volume":"98","author":"Li","year":"2016","journal-title":"Microb. Pathog."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/s41419-020-2440-1","article-title":"Activation of STAT3 is a key event in TLR4 signaling-mediated melanoma progression","volume":"11","author":"Fu","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ham, I.-H., Lee, D., and Hur, H. (2021). Cancer-associated fibroblast-induced resistance to chemotherapy and radiotherapy in gastrointestinal cancers. Cancers, 13.","DOI":"10.3390\/cancers13051172"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.semcancer.2021.03.006","article-title":"Heterogeneity and plasticity of cancer-associated fibroblasts in the pancreatic tumor microenvironment","volume":"82","author":"Lenka","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s12943-019-0972-8","article-title":"Targeting interleukin-6 as a strategy to overcome stroma-induced resistance to chemotherapy in gastric cancer","volume":"18","author":"Ham","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.bcp.2017.11.014","article-title":"A review of hydrogen sulfide (H2S) donors: Chemistry and potential therapeutic applications","volume":"149","author":"Powell","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e13065","DOI":"10.1097\/MD.0000000000013065","article-title":"The biologic effect of hydrogen sulfide and its function in various diseases","volume":"97","author":"Xiao","year":"2018","journal-title":"Medicine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"102331","DOI":"10.1016\/j.redox.2022.102331","article-title":"Emerging roles of cystathionine \u03b2-synthase in various forms of cancer","volume":"53","author":"Szabo","year":"2022","journal-title":"Redox Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kimura, H. (2021). Hydrogen sulfide (H2S) and polysulfide (H2Sn) signaling: The first 25 years. Biomolecules, 11.","DOI":"10.3390\/biom11060896"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1515\/hsz-2020-0249","article-title":"3-Mercaptopyruvate sulfurtransferase: An enzyme at the crossroads of sulfane sulfur trafficking","volume":"402","author":"Pedre","year":"2021","journal-title":"Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2437338","DOI":"10.1080\/13510002.2024.2437338","article-title":"Emerging roles of hydrogen sulfide-metabolizing enzymes in cancer","volume":"29","author":"Dawoud","year":"2024","journal-title":"Redox Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"148338","DOI":"10.1016\/j.bbabio.2020.148338","article-title":"The multifaceted roles of sulfane sulfur species in cancer-associated processes","volume":"1862","author":"Zuhra","year":"2021","journal-title":"BBA Bioenerg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1089\/ars.2011.4351","article-title":"Hydrogen sulfide: An endogenous mediator of resolution of inflammation and injury","volume":"17","author":"Wallace","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Magierowski, M., Magierowska, K., Hubalewska-Mazgaj, M., Sliwowski, Z., Pajdo, R., Ginter, G., Kwiecien, S., and Brzozowski, T. (2017). Exogenous and endogenous hydrogen sulfide protects gastric mucosa against the formation and time-dependent development of ischemia\/reperfusion-induced acute lesions progressing into deeper ulcerations. Molecules, 22.","DOI":"10.3390\/molecules22020295"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"G288","DOI":"10.1152\/ajpgi.00324.2005","article-title":"Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation","volume":"291","author":"Ramasamy","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6717212","DOI":"10.1155\/2018\/6717212","article-title":"Hydrogen sulfide attenuates LPS-induced acute kidney injury by inhibiting inflammation and oxidative stress","volume":"2018","author":"Chen","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116595","DOI":"10.1016\/j.bcp.2024.116595","article-title":"Increased hydrogen sulfide turnover serves a cytoprotective role during the development of replicative senescence","volume":"230","author":"Chlopicki","year":"2024","journal-title":"Biochem. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sokolova, O., and Naumann, M. (2017). NF\u03baB signaling in gastric cancer. Toxins, 9.","DOI":"10.3390\/toxins9040119"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"866","DOI":"10.3390\/microorganisms3040866","article-title":"Hydrogen sulfide in physiology and diseases of the digestive tract","volume":"3","author":"Singh","year":"2015","journal-title":"Microorganisms"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.molcel.2011.10.021","article-title":"Hydrogen sulfide-linked sulfhydration of NF-\u03baB mediates its anti-apoptotic actions","volume":"45","author":"Sen","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/j.bcp.2006.04.011","article-title":"NF-\u03baB activation by reactive oxygen species: Fifteen years later","volume":"72","author":"Gloire","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10059-010-0105-0","article-title":"Reactive oxygen species in TNF\u03b1-induced signaling and cell death","volume":"30","author":"Morgan","year":"2010","journal-title":"Mol. Cells"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1161\/CIRCRESAHA.109.199919","article-title":"Hydrogen sulfide mediates cardioprotection through Nrf2 signaling","volume":"105","author":"Calvert","year":"2009","journal-title":"Circ. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejphar.2014.01.009","article-title":"Hydrogen sulfide protected gastric epithelial cells from ischemia\/reperfusion injury by Keap1 S-sulfhydration, MAPK-dependent anti-apoptosis and NF-\u03baB-dependent anti-inflammation pathways","volume":"725","author":"Guo","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1016\/j.freeradbiomed.2007.03.018","article-title":"Upregulation of thioredoxin system via Nrf2-antioxidant responsive element pathway in adaptive-retinal neuroprotection in vivo and in vitro","volume":"42","author":"Tanito","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4161\/gmic.1.2.11587","article-title":"The many roads traveled by Helicobacter pylori to NF\u03baB activation","volume":"1","author":"Lamb","year":"2010","journal-title":"Gut Microbes"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/nri2423","article-title":"New regulators of NF-\u03baB in inflammation","volume":"8","author":"Ghosh","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cytogfr.2009.11.005","article-title":"Dangerous liaisons: STAT3 and NF-\u03baB collaboration and crosstalk in cancer","volume":"21","author":"Grivennikov","year":"2010","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"17771","DOI":"10.1074\/jbc.270.30.17771","article-title":"Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori: Association of specific vacA types with cytotoxin production and peptic ulceration","volume":"270","author":"Atherton","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e12538","DOI":"10.1111\/hel.12538","article-title":"Role of Helicobacter pylori infection in cancer-associated fibroblast-induced epithelial\u2013mesenchymal transition in vitro","volume":"23","author":"Targosz","year":"2018","journal-title":"Helicobacter"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative CT method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bronowicka-Adamska, P., Wrobel, M., Magierowski, M., Magierowska, K., Kwiecien, S., and Brzozowski, T. (2017). Hydrogen sulfide production in healthy and ulcerated gastric mucosa of rats. Molecules, 22.","DOI":"10.3390\/molecules22040530"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e71929","DOI":"10.7554\/eLife.71929","article-title":"Cystathionine-\u03b2-synthase is essential for AKT-induced senescence and suppresses the development of gastric cancers with PI3K\/AKT activation","volume":"11","author":"Zhu","year":"2022","journal-title":"eLife"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Szlezak, D., Bronowicka-Adamska, P., Hutsch, T., Ufnal, M., and Wrobel, M. (2021). Hypertension and aging affect liver sulfur metabolism in rats. Cells, 10.","DOI":"10.3390\/cells10051238"},{"key":"ref_45","first-page":"113","article-title":"Cystathionine \u03b3-lyase (EC 4.4.1.1): An enzymatic assay of \u03b1-ketobutyrate using lactate dehydrogenase","volume":"44","author":"Czubak","year":"2002","journal-title":"Acta Biol. Crac. Ser. Zool."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0009-8981(74)90031-X","article-title":"3-Mercaptopyruvate sulfurtransferase (EC 2.8.1.2): A simple assay adapted to human blood cells","volume":"51","author":"Valentine","year":"1974","journal-title":"Clin. Chim. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/15376520490434683","article-title":"Sulfurtransferases and cyanide detoxification in mouse liver, kidney and brain","volume":"14","author":"Wrobel","year":"2004","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Makobongo, M.O., Einck, L., Peek, R.M., and Merrell, D.S. (2013). In Vitro Characterization of the Anti-Bacterial Activity of SQ109 against Helicobacter pylori. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068917"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lee, Z.W., Zhou, J., Chen, C.S., Zhao, Y., Tan, C.H., Li, L., Moore, P.K., and Deng, L.W. (2011). The slow-releasing hydrogen sulfide donor, GYY4137, exhibits novel anti-cancer effects in vitro and in vivo. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021077"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1006\/jsre.1996.0020","article-title":"The effects of hyperosmolarity on the viability and function of endothelial cells","volume":"60","author":"Luh","year":"1996","journal-title":"J. Surg. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1089\/ten.tea.2009.0001","article-title":"Medium osmolarity and pericellular matrix development improves chondrocyte survival when photoencapsulated in poly(ethylene glycol) hydrogels at low densities","volume":"15","author":"Villanueva","year":"2009","journal-title":"Tissue Eng. Part A"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1121064","DOI":"10.1155\/2022\/1121064","article-title":"Effects of changes in osmolarity on the biological activity of human normal nucleus pulposus mesenchymal stem cells","volume":"2022","author":"Zhang","year":"2022","journal-title":"Stem Cells Int."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Han, S., Li, Y., and Gao, H. (2022). Generation and physiology of hydrogen sulfide and reactive sulfur species in bacteria. Antioxidants, 11.","DOI":"10.3390\/antiox11122487"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.lfs.2017.04.006","article-title":"Toll-like receptor 2: An important immunomodulatory molecule during Helicobacter pylori infection","volume":"178","author":"Nemati","year":"2017","journal-title":"Life Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1158\/0008-5472.CAN-08-1191","article-title":"Helicobacter pylori CagA activates the signal transducer and activator of transcription 3 (STAT3) pathway in vitro and in vivo","volume":"69","author":"Terebiznik","year":"2009","journal-title":"Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"32031","DOI":"10.18632\/oncotarget.8672","article-title":"STAT3 and NF-\u03baB cooperatively control in vitro spontaneous apoptosis and poor chemo-responsiveness in patients with chronic lymphocytic leukemia","volume":"7","author":"Liu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"20741","DOI":"10.18632\/oncotarget.15119","article-title":"IL-6 secreted by cancer-associated fibroblasts promotes epithelial\u2013mesenchymal transition and metastasis of gastric cancer via JAK2\/STAT3 signaling pathway","volume":"8","author":"Wu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"16975","DOI":"10.1073\/pnas.1315862110","article-title":"STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor","volume":"110","author":"Wang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e12653","DOI":"10.1111\/hel.12653","article-title":"Helicobacter pylori-activated gastric fibroblasts induce epithelial\u2013mesenchymal transition of gastric epithelial cells in vitro in a TGF-\u03b2-dependent manner","volume":"24","author":"Wrobel","year":"2019","journal-title":"Helicobacter"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13086","DOI":"10.1073\/pnas.0603290103","article-title":"Dynamic redox control of NF-\u03baB through glutaredoxin-regulated S-glutathionylation of inhibitory \u03baB kinase \u03b2","volume":"103","author":"Reynaert","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.2174\/1570159X20666220302101854","article-title":"Hydrogen sulfide (H2S) signaling as a protective mechanism against endogenous and exogenous neurotoxicants","volume":"20","author":"Aschner","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1152\/physrev.00056.2006","article-title":"Cellular response to hyperosmotic stresses","volume":"87","author":"Burg","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_63","first-page":"65","article-title":"Hypertonic stress response","volume":"569","author":"Dmitrieva","year":"2005","journal-title":"Mutat. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1152\/physrev.1998.78.1.247","article-title":"Functional significance of cell volume regulatory mechanisms","volume":"78","author":"Lang","year":"1998","journal-title":"Physiol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S1569-2582(96)80061-4","article-title":"Cell volume regulation","volume":"4","year":"1996","journal-title":"Princ. Med. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8615","DOI":"10.3748\/wjg.v21.i28.8615","article-title":"TLR4 upregulates CBS expression through NF-\u03baB activation in a rat model of irritable bowel syndrome with chronic visceral hypersensitivity","volume":"21","author":"Yuan","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2263936","DOI":"10.1080\/19490976.2023.2263936","article-title":"Targeting hypoxia-inducible factor-1 alpha suppresses Helicobacter pylori-induced gastric injury via attenuation of both cag-mediated microbial virulence and proinflammatory host responses","volume":"15","author":"Noto","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"12679","DOI":"10.1073\/pnas.1308487110","article-title":"Oxygen-sensitive mitochondrial accumulation of cystathionine \u03b2-synthase mediated by Lon protease","volume":"110","author":"Teng","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"13528","DOI":"10.1021\/bi0615644","article-title":"Human cystathionine \u03b2-synthase is a target for sumoylation","volume":"45","author":"Kabil","year":"2006","journal-title":"Biochemistry"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Zuhra, K., Augsburger, F., Majtan, T., and Szabo, C. (2020). Cystathionine-\u03b2-synthase: Molecular regulation and pharmacological inhibition. Biomolecules, 10.","DOI":"10.3390\/biom10050697"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5741","DOI":"10.1158\/0008-5472.CAN-16-3480","article-title":"Upregulation of cystathionine-\u03b2-synthase in colonic epithelia reprograms metabolism and promotes carcinogenesis","volume":"77","author":"Phillips","year":"2017","journal-title":"Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s12935-022-02512-2","article-title":"Overexpression of CBS\/H2S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44","volume":"22","author":"Zhang","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41416-019-0660-x","article-title":"Activation of the reverse transsulfuration pathway through NRF2\/CBS confers erastin-induced ferroptosis resistance","volume":"122","author":"Liu","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Bhattacharyya, S., Saha, S., Giri, K., Lanza, I.R., Nair, K.S., Jennings, N.B., Rodriguez-Aguayo, C., Lopez-Berestein, G., Basal, E., and Weaver, A.L. (2013). Cystathionine \u03b2-synthase (CBS) contributes to advanced ovarian cancer progression and drug resistance. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079167"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"104083","DOI":"10.1016\/j.phrs.2018.11.034","article-title":"Potential role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H2S) pathway in cancer cells","volume":"154","author":"Augsburger","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.bcp.2017.10.007","article-title":"Drug resistance induces the upregulation of H2S-producing enzymes in HCT116 colon cancer cells","volume":"149","author":"Untereiner","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Zhang, X., Chen, M., Ni, X., Wang, Y., Zheng, X., Zhang, H., Xu, S., and Yang, C.-T. (2020). Metabolic reprogramming of sulfur in hepatocellular carcinoma and sulfane sulfur-triggered anti-cancer strategy. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.571143"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"30792","DOI":"10.1074\/jbc.M110.151183","article-title":"Mitochondrial enzyme rhodanese is essential for 5S ribosomal RNA import into human mitochondria","volume":"285","author":"Smirnov","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Ascen\u00e7\u00e3o, K., Dilek, N., Zuhra, K., M\u00f3dis, K., Sato, T., and Szabo, C. (2022). Sequential accumulation of \u201cdriver\u201d pathway mutations induces the upregulation of hydrogen-sulfide-producing enzymes in human colonic epithelial cell organoids. Antioxidants, 11.","DOI":"10.3390\/antiox11091823"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.12659\/MSM.893234","article-title":"Roles of sulfur metabolism and rhodanese in detoxification and anti-oxidative stress functions in the liver: Responses to radiation exposure","volume":"21","author":"Nakajima","year":"2015","journal-title":"Med. Sci. Monit."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"103595","DOI":"10.1016\/j.redox.2025.103595","article-title":"Thiosulphate sulfurtransferase: Biological roles and disease associations","volume":"82","author":"Luo","year":"2025","journal-title":"Redox Biol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Gri\u00f1\u00e1n-Ferr\u00e9, C., Servin-Mu\u00f1oz, I.V., Palomera-\u00c1valos, V., Mart\u00ednez-Fern\u00e1ndez, C., Companys-Alemany, J., Mu\u00f1oz-Villanova, A., Ortu\u00f1o-Sahag\u00fan, D., Pall\u00e0s, M., and Bellver-Sanchis, A. (2024). Changes in gene expression profile with age in SAMP8: Identifying transcripts involved in cognitive decline and sporadic Alzheimer\u2019s disease. Genes, 15.","DOI":"10.3390\/genes15111411"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.bbrc.2020.05.014","article-title":"Tst gene mediates protection against palmitate-induced inflammation in 3T3-L1 adipocytes","volume":"527","author":"Carter","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"102965","DOI":"10.1016\/j.redox.2023.102965","article-title":"Thiosulfate sulfurtransferase deficiency promotes oxidative distress and aberrant NRF2 function in the brain","volume":"68","author":"Luo","year":"2023","journal-title":"Redox Biol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Gonciarz, W., Krupa, A., Hinc, K., Obuchowski, M., Moran, A.P., Gajewski, A., and Chmiela, M. (2019). The effect of Helicobacter pylori infection and different H. pylori components on the proliferation and apoptosis of gastric epithelial cells and fibroblasts. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0220636"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1038\/s41419-017-0011-x","article-title":"Helicobacter pylori VacA induces autophagic cell death in gastric epithelial cells via the endoplasmic reticulum stress pathway","volume":"8","author":"Zhu","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Lin, Y., Liu, K., Lu, F., Zhai, C., and Cheng, F. (2024). Programmed cell death in Helicobacter pylori infection and related gastric cancer. Front. Cell. Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1416819"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS function in redox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41580-020-0230-3","article-title":"Reactive oxygen species (ROS) as pleiotropic physiological signalling agents","volume":"21","author":"Sies","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Han, L., Shu, X., and Wang, J. (2022). Helicobacter pylori-mediated oxidative stress and gastric diseases: A review. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.811258"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3515","DOI":"10.4161\/cc.9.17.12928","article-title":"Autophagy in cancer-associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NF\u03baB activation in the tumor stromal microenvironment","volume":"9","author":"Trimmer","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/sj.cdd.4401838","article-title":"Good cop, bad cop: The different faces of NF-\u03baB","volume":"13","author":"Perkins","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"155771","DOI":"10.1016\/j.metabol.2023.155771","article-title":"Cooperative STAT3\u2013NF\u03baB signaling modulates mitochondrial dysfunction and metabolic profiling in hepatocellular carcinoma","volume":"152","author":"Bawankule","year":"2024","journal-title":"Metabolism"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"11046","DOI":"10.1038\/srep11046","article-title":"Suppression of cell division-associated genes by Helicobacter pylori attenuates proliferation of RAW264.7 monocytic macrophage cells","volume":"5","author":"Tan","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"115739","DOI":"10.1016\/j.bcp.2023.115739","article-title":"Senescence in cancer: Advances in detection and treatment modalities","volume":"215","author":"Billimoria","year":"2023","journal-title":"Biochem. Pharmacol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41420-024-01868-w","article-title":"The potential role of hydrogen sulfide in cancer cell apoptosis","volume":"10","author":"Gao","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1002\/jimd.12232","article-title":"Pathogenic variants in SQOR encoding sulfide:quinone oxidoreductase are a potentially treatable cause of Leigh disease","volume":"43","author":"Friederich","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3296","DOI":"10.1093\/hmg\/ddaa214","article-title":"Coenzyme Q10 modulates sulfide metabolism and links the mitochondrial respiratory chain to pathways associated to one carbon metabolism","volume":"29","author":"Mascaraque","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"11844","DOI":"10.18632\/aging.102454","article-title":"Hydrogen sulfide attenuates mitochondrial dysfunction-induced cellular senescence and apoptosis in alveolar epithelial cells by upregulating sirtuin 1","volume":"11","author":"Guan","year":"2019","journal-title":"Aging"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Khattak, S., Rauf, M.A., Khan, N.H., Zhang, Q.-Q., Chen, H.-J., Muhammad, P., Ansari, M.A., Alomary, M.N., Jahangir, M., and Zhang, C.-Y. (2022). Hydrogen sulfide biology and its role in cancer. Molecules, 27.","DOI":"10.3390\/molecules27113389"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/embr.201338213","article-title":"S-sulfhydration of MEK1 leads to PARP-1 activation and DNA damage repair","volume":"15","author":"Zhao","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"7296874","DOI":"10.1155\/2023\/7296874","article-title":"Exogenous hydrogen sulfide activates PI3K\/Akt\/eNOS pathway to improve replicative senescence in human umbilical vein endothelial cells","volume":"2023","author":"Niu","year":"2023","journal-title":"Cardiol. Res. Pract."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/2\/167\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T05:19:04Z","timestamp":1769059144000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/2\/167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":102,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["cells15020167"],"URL":"https:\/\/doi.org\/10.3390\/cells15020167","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]}}}