{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:46:34Z","timestamp":1784133994292,"version":"3.55.0"},"reference-count":167,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T00:00:00Z","timestamp":1648339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Otago Vice-Chancellor\u2019s Strategic Development Fund","award":["-"],"award-info":[{"award-number":["-"]}]},{"DOI":"10.13039\/501100001518","name":"Maurice and Phyllis Paykel Trust","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100001518","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sepsis, a potentially lethal condition resulting from failure to control the initial infection, is associated with a dysregulated host defense response to pathogens and their toxins. Sepsis remains a leading cause of morbidity, mortality and disability worldwide. The pathophysiology of sepsis is very complicated and is not yet fully understood. Worse still, the development of effective therapeutic agents is still an unmet need and a great challenge. Gases, including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), are small-molecule biological mediators that are endogenously produced, mainly by enzyme-catalyzed reactions. Accumulating evidence suggests that these gaseous mediators are widely involved in the pathophysiology of sepsis. Many sepsis-associated alterations, such as the elimination of invasive pathogens, the resolution of disorganized inflammation and the preservation of the function of multiple organs and systems, are shaped by them. Increasing attention has been paid to developing therapeutic approaches targeting these molecules for sepsis\/septic shock, taking advantage of the multiple actions played by NO, CO and H2S. Several preliminary studies have identified promising therapeutic strategies for gaseous-mediator-based treatments for sepsis. In this review article, we summarize the state-of-the-art knowledge on the pathophysiology of sepsis; the metabolism and physiological function of NO, CO and H2S; the crosstalk among these gaseous mediators; and their crucial effects on the development and progression of sepsis. In addition, we also briefly discuss the prospect of developing therapeutic interventions targeting these gaseous mediators for sepsis.<\/jats:p>","DOI":"10.3390\/ijms23073669","type":"journal-article","created":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T21:27:51Z","timestamp":1648416471000},"page":"3669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Gases in Sepsis: Novel Mediators and Therapeutic Targets"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5991-3264","authenticated-orcid":false,"given":"Zhixing","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand"},{"name":"Department of Internal Medicine (Pulmonary and Critical Care Medicine), The Second Clinical Medical School of Fujian Medical University, Quanzhou 362002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Chambers","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Pulmonary and Critical Care Medicine), The Second Clinical Medical School of Fujian Medical University, Quanzhou 362002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhav","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0140-6736(18)30696-2","article-title":"Sepsis and septic shock","volume":"392","author":"Cecconi","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13054-018-2157-z","article-title":"The global burden of sepsis: Barriers and potential solutions","volume":"22","author":"Rudd","year":"2018","journal-title":"Crit. Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the global burden of disease study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1056\/NEJMp1707170","article-title":"Recognizing sepsis as a global health priority\u2014A WHO resolution","volume":"377","author":"Reinhart","year":"2017","journal-title":"New Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"re2","DOI":"10.1126\/scisignal.268re2","article-title":"Signaling by Gasotransmitters","volume":"2","author":"Mustafa","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_8","first-page":"283","article-title":"Gasotransmitters: Growing pains and joys","volume":"39","author":"Wang","year":"2018","journal-title":"Trends Biochem. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3389\/fphys.2013.00027","article-title":"Gasotransmitters: Novel regulators of ion channels and transporters","volume":"4","author":"Althaus","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.smim.2015.05.004","article-title":"Gaseous mediators in resolution of inflammation","volume":"27","author":"Wallace","year":"2015","journal-title":"Semin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"691","DOI":"10.3389\/fphys.2017.00691","article-title":"Gaseous mediators and mitochondrial function: The future of pharmacologically induced suspended animation?","volume":"8","author":"Hartmann","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nrd.2015.1","article-title":"Gasotransmitters in cancer: From pathophysiology to experimental therapy","volume":"15","author":"Szabo","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1089\/ars.2016.6909","article-title":"Gasotransmitter heterocellular signaling","volume":"26","author":"Kolluru","year":"2017","journal-title":"Antioxid. Redox Signal."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1089\/ars.2021.0213","article-title":"Sulfur dioxide: Endogenous generation, biological effects, detection, and therapeutic potential","volume":"36","author":"Huang","year":"2022","journal-title":"Antioxid. Redox Signal."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zuhra, K., and Szabo, C. (2021). The two faces of cyanide: An environmental toxin and a potential novel mammalian gasotransmitter. FEBS J.","DOI":"10.1111\/febs.16135"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.3389\/fphys.2019.01244","article-title":"Methane production and bioactivity-a link to oxido-reductive stress","volume":"10","author":"Boros","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/4627308","article-title":"Gasotransmitters in biology and medicine: Molecular mechanisms and drug targets","volume":"2016","author":"Yang","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.coph.2019.07.001","article-title":"Gasotransmitters in health and disease: A mitochondria-centered view","volume":"45","author":"Hendriks","year":"2019","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13054-017-1782-2","article-title":"Markers of nitric oxide are associated with sepsis severity: An observational study","volume":"21","author":"Winkler","year":"2017","journal-title":"Crit. Care"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"L1387","DOI":"10.1152\/ajplung.00311.2015","article-title":"Carbon monoxide in the treatment of sepsis","volume":"309","author":"Nakahira","year":"2015","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"653601","DOI":"10.3389\/fphys.2021.653601","article-title":"Hydrogen sulfide attenuated sepsis-induced myocardial dysfunction through TLR4 pathway and endoplasmic reticulum stress","volume":"12","author":"Chen","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_22","first-page":"629","article-title":"Organ dysfunction in sepsis: An ominous trajectory from infection to death","volume":"92","author":"Caraballo","year":"2019","journal-title":"Yale J. Biol Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ccc.2017.08.003","article-title":"Mechanisms of organ dysfunction in sepsis","volume":"34","author":"Pool","year":"2018","journal-title":"Crit. Care Clin."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41581-018-0005-7","article-title":"Mechanisms and treatment of organ failure in sepsis","volume":"14","author":"Lelubre","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Huang, M., Cai, S., and Su, J. (2019). The pathogenesis of sepsis and potential therapeutic targets. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215376"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/imr.12499","article-title":"The immune system\u2019s role in sepsis progression, resolution, and long-term outcome","volume":"274","author":"Delano","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ccc.2017.08.002","article-title":"Immune activation in sepsis","volume":"34","author":"Wilson","year":"2018","journal-title":"Crit. Care Clin."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"691234","DOI":"10.3389\/fphar.2021.691234","article-title":"Pro-Oncogenic c-Met\/EGFR, biomarker signatures of the tumor microenvironment are clinical and therapy response prognosticators in colorectal cancer, and therapeutic targets of 3-Phenyl-2H-benzo[e][1,3]-Oxazine-2,4(3H)-Dione derivatives","volume":"12","author":"Lawal","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00281-017-0639-8","article-title":"Cytokine storm and sepsis disease pathogenesis","volume":"39","author":"Chousterman","year":"2017","journal-title":"Semin. Immunopathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"628302","DOI":"10.3389\/fmed.2021.628302","article-title":"Sepsis\u2014Pathophysiology and therapeutic concepts","volume":"8","author":"Jarczak","year":"2021","journal-title":"Front. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"i1585","DOI":"10.1136\/bmj.i1585","article-title":"Sepsis: Pathophysiology and clinical management","volume":"353","author":"Gotts","year":"2016","journal-title":"BMJ"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/jcb.27547","article-title":"Recent advances in endotoxin tolerance","volume":"120","author":"Liu","year":"2019","journal-title":"J. Cell Biochem."},{"key":"ref_33","first-page":"426","article-title":"Sepsis-induced immunoparalysis: Mechanisms, markers, and treatment options","volume":"81","author":"Hamers","year":"2014","journal-title":"Minerva Anestesiol"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrneph.2017.165","article-title":"Advances in the understanding and treatment of sepsis-induced immunosuppression","volume":"14","author":"Venet","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"718089","DOI":"10.3389\/fphar.2021.718089","article-title":"Immune intervention in sepsis","volume":"12","author":"Chen","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101550","DOI":"10.1016\/j.redox.2020.101550","article-title":"Nitric oxide in cellular adaptation and disease","volume":"34","author":"Gantner","year":"2020","journal-title":"Redox Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kr\u00f3l, M., and Kepinska, M. (2020). Human nitric oxide Synthase\u2014Its functions, polymorphisms, and inhibitors in the context of inflammation, diabetes and cardiovascular diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010056"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/med.21599","article-title":"Inducible nitric oxide synthase: Regulation, structure, and inhibition","volume":"40","author":"Cinelli","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.tips.2005.02.005","article-title":"Mitochondrial nitric oxide synthase","volume":"26","author":"Ghafourifar","year":"2005","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1093\/eurheartj\/ehr304","article-title":"Nitric oxide synthases: Regulation and function","volume":"33","author":"Sessa","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1111\/febs.15090","article-title":"The mitochondrial NO-synthase\/guanylate cyclase\/protein kinase G signaling system underpins the dual effects of nitric oxide on mitochondrial respiration and opening of the permeability transition pore","volume":"287","author":"Dynnik","year":"2019","journal-title":"FEBS J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/bph.14484","article-title":"Nitrite and nitrate chemical biology and signalling","volume":"176","author":"DeMartino","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1124\/pr.120.019240","article-title":"The noncanonical pathway for in vivo nitric oxide generation: The nitrate-nitrite-nitric oxide pathway","volume":"72","author":"Kapil","year":"2020","journal-title":"Pharmacol. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Nowaczyk, A., Kowalska, M., Nowaczyk, J., and Grze\u015bk, G. (2021). Carbon monoxide and nitric oxide as examples of the youngest class of transmitters. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116029"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1161\/CIRCRESAHA.113.301577","article-title":"The identification of nitric oxide as endothelium-derived relaxing factor","volume":"113","author":"Loscalzo","year":"2013","journal-title":"Circ. Res."},{"key":"ref_46","first-page":"4021","article-title":"Nitric oxide and hydrogen sulfide: The gasotransmitter paradigm of the vascular system","volume":"174","author":"Cirino","year":"2017","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/nrcardio.2017.224","article-title":"Nitric oxide signalling in cardiovascular health and disease","volume":"15","author":"Farah","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"C254","DOI":"10.1152\/ajpcell.00315.2016","article-title":"Nitric oxide: What\u2019s new to NO?","volume":"312","author":"Ghimire","year":"2017","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Shah, S., Karathanasi, A., Revythis, A., Ioannidou, E., and Boussios, S. (2021). Cancer-Associated thrombosis: A new light on an old story. Diseases, 9.","DOI":"10.3390\/diseases9020034"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ejphar.2018.07.026","article-title":"Gasotransmitters and the immune system: Mode of action and novel therapeutic targets","volume":"834","author":"Fagone","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.freeradbiomed.2021.01.010","article-title":"Nitric oxide and hydrogen sulfide: Sibling rivalry in the family of epigenetic regulators","volume":"170","author":"Kuschman","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"McGinity, C., Palmieri, E., Somasundaram, V., Bhattacharyya, D., Ridnour, L., Cheng, R., Ryan, A., Glynn, S., Thomas, D., and Miranda, K. (2021). Nitric oxide modulates metabolic processes in the tumor immune microenvironment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137068"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/aos.13384","article-title":"Nitric oxide in the pathophysiology of retinopathy: Evidences from preclinical and clinical researches","volume":"96","author":"Opatrilova","year":"2018","journal-title":"Acta Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.niox.2021.04.001","article-title":"A brief history of carbon monoxide and its therapeutic origins","volume":"111-112","author":"Hopper","year":"2021","journal-title":"Nitric. Oxide"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1124\/pr.57.4.3","article-title":"Carbon monoxide: Endogenous production, physiological functions, and pharmacological applications","volume":"57","author":"Wu","year":"2005","journal-title":"Pharmacol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Duvigneau, J.C., Esterbauer, H., and Kozlov, A.V. (2019). Role of heme oxygenase as a modulator of heme-mediated pathways. Antioxidants, 8.","DOI":"10.3390\/antiox8100475"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cbi.2014.08.005","article-title":"Carbon monoxide is not always a poison gas for human organism: Physiological and pharmacological features of CO","volume":"222","author":"Olas","year":"2014","journal-title":"Chem. Interact."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S496","DOI":"10.1097\/01.CCM.0000185501.92983.EC","article-title":"Carbon monoxide","volume":"33","author":"Sethi","year":"2005","journal-title":"Crit. Care Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/biof.192","article-title":"CO metabolism, sensing, and signaling","volume":"38","author":"Gullotta","year":"2011","journal-title":"BioFactors"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.pharmthera.2009.05.005","article-title":"Actions and interactions of nitric oxide, carbon monoxide and hydrogen sulphide in the cardiovascular system and in inflammation\u2014a tale of three gases!","volume":"123","author":"Li","year":"2009","journal-title":"Pharmacol. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"L1270","DOI":"10.1152\/ajplung.00145.2003","article-title":"Low-dose carbon monoxide reduces airway hyperresponsiveness in mice","volume":"285","author":"Ameredes","year":"2003","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"G\u0142owacka, U., Brzozowski, T., and Magierowski, M. (2020). Synergisms, discrepancies and interactions between hydrogen sulfide and carbon monoxide in the gastrointestinal and digestive system physiology, pathophysiology and pharmacology. Biomolecules, 10.","DOI":"10.3390\/biom10030445"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"C302","DOI":"10.1152\/ajpcell.00360.2016","article-title":"Biological signaling by carbon monoxide and carbon monoxide-releasing molecules","volume":"312","author":"Motterlini","year":"2017","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s00134-009-1575-4","article-title":"Beneficial effects of the heme oxygenase-1\/carbon monoxide system in patients with severe sepsis\/septic shock","volume":"36","author":"Takaki","year":"2010","journal-title":"Intensive Care Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"C211","DOI":"10.1152\/ajpcell.00022.2017","article-title":"Carbon monoxide in lung cell physiology and disease","volume":"314","author":"Ryter","year":"2018","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.clinbiochem.2010.07.011","article-title":"Endogenous carbon monoxide production in disease","volume":"43","author":"Owens","year":"2010","journal-title":"Clin. Biochem."},{"key":"ref_67","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_68","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.bcp.2017.09.010","article-title":"A timeline of hydrogen sulfide (H2S) research: From environmental toxin to biological mediator","volume":"149","author":"Szabo","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.bcp.2017.12.010","article-title":"H2S and polysulfide metabolism: Conventional and unconventional pathways","volume":"149","author":"Olson","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1089\/ars.2013.5339","article-title":"Enzymology of H2S Biogenesis, Decay and Signaling","volume":"20","author":"Kabil","year":"2014","journal-title":"Antioxidants Redox Signal."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1126\/science.1162667","article-title":"H2S as a physiologic vasorelaxant: Hypertension in mice with deletion of cystathionine gamma-lyase","volume":"322","author":"Yang","year":"2008","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1113\/expphysiol.2011.057455","article-title":"Hydrogen sulfide: Its production and functions","volume":"96","author":"Kimura","year":"2011","journal-title":"Exp. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.niox.2014.01.002","article-title":"The physiological role of hydrogen sulfide and beyond","volume":"41","author":"Kimura","year":"2014","journal-title":"Nitric Oxide"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1007\/s00018-016-2406-8","article-title":"H2S biosynthesis and catabolism: New insights from molecular studies","volume":"74","author":"Rose","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1089\/ars.2009.2927","article-title":"Hydrogen sulfide and substance P in inflammation","volume":"12","author":"Bhatia","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Kimura, H. (2021). Hydrogen sulfide (H(2)S) and polysulfide (H(2)S(n)) signaling: The first 25 years. Biomolecules, 11.","DOI":"10.3390\/biom11060896"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1152\/physrev.00017.2011","article-title":"Physiological implications of hydrogen sulfide: A whiff exploration that blossomed","volume":"92","author":"Wang","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/ki.2009.221","article-title":"Hydrogen sulfide: A new EDRF","volume":"76","author":"Wang","year":"2009","journal-title":"Kidney Int."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/apha.12475","article-title":"Hydrogen sulphide induces vasoconstriction of rat coronary artery via activation of Ca 2+ influx","volume":"214","author":"Ping","year":"2015","journal-title":"Acta Physiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/sj.bjp.0706906","article-title":"Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulphide?","volume":"149","author":"Ali","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jare.2020.05.007","article-title":"Hydrogen sulfide and vascular regulation\u2013An update","volume":"27","author":"Lv","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Khattak, S., Zhang, Q.-Q., Sarfraz, M., Muhammad, P., Ngowi, E., Khan, N., Rauf, S., Wang, Y.-Z., Qi, H.-W., and Wang, D. (2021). The role of hydrogen sulfide in respiratory diseases. Biomolecules, 11.","DOI":"10.3390\/biom11050682"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"L710","DOI":"10.1152\/ajplung.00134.2015","article-title":"The H2S-generating enzymes cystathionine \u03b2-synthase and cystathionine \u03b3-lyase play a role in vascular development during normal lung alveolarization","volume":"309","author":"Madurga","year":"2015","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"105119","DOI":"10.1016\/j.phrs.2020.105119","article-title":"Hydrogen sulfide: An endogenous regulator of the immune system","volume":"161","author":"Dilek","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/1873962","article-title":"Antioxidant and cell-signaling functions of hydrogen sulfide in the central nervous system","volume":"2018","author":"Shefa","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/978-981-16-0991-6_6","article-title":"Hydrogen sulfide and its interaction with other players in inflammation","volume":"1315","author":"Manandhar","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/imm.13253","article-title":"The role of hydrogen sulphide signalling in macrophage activation","volume":"162","author":"Sun","year":"2021","journal-title":"Immunology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"588","DOI":"10.3389\/fphar.2017.00588","article-title":"Role of hydrogen sulfide in retinal diseases","volume":"8","author":"Du","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7866992","DOI":"10.1155\/2021\/7866992","article-title":"The antiviral roles of hydrogen sulfide by blocking the interaction between SARS-CoV-2 and its potential cell surface receptors","volume":"2021","author":"Dai","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1007\/s12272-009-1806-9","article-title":"Subtle interplay of endogenous bioactive gases (NO, CO and H2S) in inflammation","volume":"32","author":"Pae","year":"2009","journal-title":"Arch. Pharmacal Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/112_2017_7","article-title":"Gaseous signaling molecules in cardiovascular function: From mechanisms to clinical translation","volume":"174","author":"Lee","year":"2018","journal-title":"Rev. Physiol. Biochem. Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1016\/j.lfs.2007.01.058","article-title":"Synergism between hydrogen sulfide (H2S) and nitric oxide (NO) in vasorelaxation induced by stonustoxin (SNTX), a lethal and hypotensive protein factor isolated from stonefish Synanceja horrida venom","volume":"80","author":"Liew","year":"2007","journal-title":"Life Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.bbrc.2006.02.154","article-title":"Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide","volume":"343","author":"Whiteman","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0076-6879(08)01218-4","article-title":"Interactive relations between nitric oxide (NO) and carbon monoxide (CO): Heme oxygenase-1\/CO pathway is a key modulator in NO-mediated antiapoptosis and anti-inflammation","volume":"441","author":"Chung","year":"2008","journal-title":"Methods Enzym."},{"key":"ref_95","first-page":"1","article-title":"A review on Hemeoxygenase-2: Focus on cellular protection and oxygen response","volume":"2014","year":"2014","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"8579","DOI":"10.1074\/jbc.M113.507533","article-title":"NO* binds human cystathionine \u03b2-synthase quickly and tightly","volume":"289","author":"Vicente","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1111\/bph.12171","article-title":"Selectivity of commonly used pharmacological inhibitors for cystathionine \u03b2 synthase (CBS) and cystathionine \u03b3 lyase (CSE)","volume":"169","author":"Asimakopoulou","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"6008","DOI":"10.1093\/emboj\/20.21.6008","article-title":"The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener","volume":"20","author":"Zhao","year":"2001","journal-title":"Embo. J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1111\/bph.12674","article-title":"Beneficial effects of diminished production of hydrogen sulfide or carbon monoxide on hypertension and renal injury induced by NO withdrawal","volume":"172","author":"Wesseling","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"9161","DOI":"10.1073\/pnas.1202916109","article-title":"Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation","volume":"109","author":"Coletta","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"44807","DOI":"10.1038\/srep44807","article-title":"H2S regulates endothelial nitric oxide synthase protein stability by promoting microRNA-455-3p expression","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"24932","DOI":"10.1074\/jbc.M115.660316","article-title":"Selective irreversible inhibition of neuronal and inducible nitric-oxide synthase in the combined presence of hydrogen sulfide and nitric oxide","volume":"290","author":"Heine","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.lfs.2013.10.007","article-title":"Cardioprotection of H2S by downregulating iNOS and upregulating HO-1 expression in mice with CVB3-induced myocarditis","volume":"93","author":"Hua","year":"2013","journal-title":"Life Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.bbrc.2006.05.002","article-title":"Hydrogen sulfide potentiates interleukin-1beta-induced nitric oxide production via enhancement of extracellular signal-regulated kinase activation in rat vascular smooth muscle cells","volume":"345","author":"Jeong","year":"2006","journal-title":"Biochem. Biophys Res. Commun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1586\/ers.09.39","article-title":"Bench-to-bedside review: The role of nitric oxide in sepsis","volume":"3","author":"Kenyon","year":"2009","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/cc7706","article-title":"Bench-to-bedside review: Nitric oxide in critical illness\u2013update 2008","volume":"13","author":"Hollenberg","year":"2009","journal-title":"Crit. Care"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1164\/ajrccm.158.5.9803112","article-title":"Diaphragm Sarcolemmal injury is induced by sepsis and alleviated by nitric oxide synthase inhibition","volume":"158","author":"Lin","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.lfs.2015.08.007","article-title":"Thymoquinone modulates nitric oxide production and improves organ dysfunction of sepsis","volume":"143","author":"Alkharfy","year":"2015","journal-title":"Life Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"110083","DOI":"10.1016\/j.biopha.2020.110083","article-title":"Tubeimoside I improves survival of mice in sepsis by inhibiting inducible nitric oxide synthase expression","volume":"126","author":"Luo","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.intimp.2018.07.024","article-title":"Prognostic value of the biomarkers serum amyloid A and nitric oxide in patients with sepsis","volume":"62","author":"Yu","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40635-019-0274-x","article-title":"Bench to bedside review: Therapeutic modulation of nitric oxide in sepsis\u2014an update","volume":"7","author":"Lambden","year":"2019","journal-title":"Intensiv. Care Med. Exp."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/sj.ki.5002340","article-title":"Nitric oxide in shock","volume":"72","author":"Cauwels","year":"2007","journal-title":"Kidney Int."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1007\/s00134-007-0814-9","article-title":"Neuronal nitric oxide synthase deficiency decreases survival in bacterial peritonitis and sepsis","volume":"33","author":"Cui","year":"2007","journal-title":"Intensiv. Care Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.freeradbiomed.2017.12.032","article-title":"Nitric oxide synthase 2 enhances the survival of mice during Salmonella Typhimurium infection-induced sepsis by increasing reactive oxygen species, inflammatory cytokines and recruitment of neutrophils to the peritoneal cavity","volume":"116","author":"Yadav","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1089\/ars.2007.1762","article-title":"Carbon monoxide in sepsis","volume":"9","author":"Hoetzel","year":"2007","journal-title":"Antioxid. Redox Signal."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1053\/gast.2001.23249","article-title":"Carbon monoxide from heme catabolism protects against hepatobiliary dysfunction in endotoxin-treated rat liver","volume":"120","author":"Kyokane","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1172\/JCI32730","article-title":"Heme oxygenase-1\u2013derived carbon monoxide enhances the host defense response to microbial sepsis in mice","volume":"118","author":"Chung","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1124\/mol.109.055137","article-title":"Heme-Oxygenase-1 Induction and Carbon Monoxide-Releasing Molecule Inhibit Lipopolysaccharide (LPS)-Induced High-Mobility Group Box 1 Release in Vitro and Improve Survival of Mice in LPS- and Cecal Ligation and Puncture-Induced Sepsis Model in Vivo","volume":"76","author":"Tsoyi","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"108973","DOI":"10.1016\/j.cbi.2020.108973","article-title":"Carbon monoxide and its donors-Chemical and biological properties","volume":"318","author":"Adach","year":"2020","journal-title":"Chem. Interact."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s00395-017-0603-8","article-title":"Carbon monoxide releasing molecule-3 improves myocardial function in mice with sepsis by inhibiting NLRP3 inflammasome activation in cardiac fibroblasts","volume":"112","author":"Zhang","year":"2017","journal-title":"Basic Res. Cardiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e920668-1","DOI":"10.12659\/MSM.920668","article-title":"Carbon monoxide inhibits the expression of proteins associated with intestinal mucosal Pyroptosis in a rat model of sepsis induced by Cecal ligation and puncture","volume":"26","author":"Wang","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4926","DOI":"10.1172\/JCI72853","article-title":"Macrophages sense and kill bacteria through carbon monoxide\u2013dependent inflammasome activation","volume":"124","author":"Wegiel","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"20595","DOI":"10.3390\/ijms160920595","article-title":"Exogenous carbon monoxide decreases sepsis-induced acute kidney injury and inhibits NLRP3 inflammasome activation in rats","volume":"16","author":"Wang","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1124\/jpet.108.148049","article-title":"Carbon monoxide rescues mice from lethal sepsis by supporting mitochondrial energetic metabolism and activating mitochondrial biogenesis","volume":"329","author":"Lancel","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1164\/rccm.201106-1152OC","article-title":"Activation of mitochondrial biogenesis by heme oxygenase-1-mediated NF-E2-related factor-2 induction rescues mice from lethal Staphylococcus aureus sepsis","volume":"185","author":"MacGarvey","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/j.bbrc.2017.12.020","article-title":"The down-regulation of cardiac contractile proteins underlies myocardial depression during sepsis and is mitigated by carbon monoxide","volume":"495","author":"Unuma","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Qin, W., Zhang, J., Lv, W., Wang, X., and Sun, B. (2013). Effect of carbon monoxide-releasing molecules II-liberated CO on suppressing inflammatory response in sepsis by interfering with nuclear factor kappa B activation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075840"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/imm.12375","article-title":"Carbon monoxide down-modulates Toll-like receptor 4\/MD2 expression on innate immune cells and reduces endotoxic shock susceptibility","volume":"144","author":"Riquelme","year":"2015","journal-title":"Immunology"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"23653","DOI":"10.1038\/srep23653","article-title":"Suppressive effect of exogenous carbon monoxide on endotoxin-stimulated platelet over-activation via the glycoprotein-mediated PI3K-Akt-GSK3\u03b2 pathway","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00011-015-0834-9","article-title":"Nrf2 is essential for the anti-inflammatory effect of carbon monoxide in LPS-induced inflammation","volume":"64","author":"Qin","year":"2015","journal-title":"Inflamm. Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e1236","DOI":"10.1097\/CCM.0000000000001999","article-title":"Carbon monoxide improves efficacy of mesenchymal stromal cells during sepsis by production of specialized proresolving lipid mediators*","volume":"44","author":"Tsoyi","year":"2016","journal-title":"Crit. Care Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00134-002-1269-7","article-title":"Increased endogenous carbon monoxide production in severe sepsis","volume":"28","author":"Zegdi","year":"2002","journal-title":"Intensiv. Care Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s005950300005","article-title":"Inhibition of heme oxygenase ameliorates sepsis-induced liver dysfunction in rats","volume":"33","author":"Iwasashi","year":"2003","journal-title":"Surg. Today"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0163-4453(03)00043-4","article-title":"Changes in arterial hydrogen sulfide (H2S) content during septic shock and endotoxin shock in rats","volume":"47","author":"Hui","year":"2003","journal-title":"J. Infect."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"L1193","DOI":"10.1152\/ajplung.00489.2005","article-title":"Role of hydrogen sulfide in cecal ligation and puncture-induced sepsis in the mouse","volume":"290","author":"Zhang","year":"2006","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"L960","DOI":"10.1152\/ajplung.00388.2006","article-title":"Hydrogen sulfide acts as an inflammatory mediator in cecal ligation and puncture-induced sepsis in mice by upregulating the production of cytokines and chemokines via NF-kappaB","volume":"292","author":"Zhang","year":"2007","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1189\/jlb.0407237","article-title":"Endogenous hydrogen sulfide regulates leukocyte trafficking in cecal ligation and puncture-induced sepsis","volume":"82","author":"Zhang","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"4320","DOI":"10.4049\/jimmunol.181.6.4320","article-title":"Endogenous hydrogen sulfide regulates inflammatory response by activating the ERK pathway in polymicrobial sepsis","volume":"181","author":"Zhang","year":"2008","journal-title":"J. Immunol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.4049\/jimmunol.179.6.4153","article-title":"Hydrogen sulfide up-regulates substance P in polymicrobial sepsis-associated lung injury","volume":"179","author":"Zhang","year":"2007","journal-title":"J. Immunol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/CCM.0b013e3181c0df00","article-title":"Hydrogen sulfide promotes transient receptor potential vanilloid 1-mediated neurogenic inflammation in polymicrobial sepsis*","volume":"38","author":"Ang","year":"2010","journal-title":"Crit. Care Med."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Ang, S.F., Moochhala, S.M., MacAry, P.A., and Bhatia, M. (2011). Hydrogen sulfide and neurogenic inflammation in polymicrobial sepsis: Involvement of substance P and ERK-NF-\u03baB signaling. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024535"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.4049\/jimmunol.1101559","article-title":"Hydrogen Sulfide Upregulates Cyclooxygenase-2 and Prostaglandin E Metabolite in Sepsis-Evoked Acute Lung Injury via Transient Receptor Potential Vanilloid Type 1 Channel Activation","volume":"187","author":"Ang","year":"2011","journal-title":"J. Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s12038-016-9598-9","article-title":"Cystathionine-\u03b3-lyase gene silencing with siRNA in monocytes\/macrophages attenuates inflammation in cecal ligation and puncture-induced sepsis in the mouse","volume":"41","author":"Badiei","year":"2016","journal-title":"J. Biosci."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"G1070","DOI":"10.1152\/ajpgi.00395.2012","article-title":"Hydrogen sulfide modulates sinusoidal constriction and contributes to hepatic microcirculatory dysfunction during endotoxemia","volume":"304","author":"Norris","year":"2013","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jhep.2016.07.009","article-title":"Liver sinusoidal endothelial cells: Physiology and role in liver diseases","volume":"66","author":"Poisson","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Gaddam, R.R., Fraser, R., Badiei, A., Chambers, S., Cogger, V.C., Le Couteur, D.G., Ishii, I., and Bhatia, M. (2016). Cystathionine-Gamma-Lyase Gene Deletion Protects Mice against Inflammation and Liver Sieve Injury following Polymicrobial Sepsis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160521"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Gaddam, R.R., Chambers, S., Fraser, R., Cogger, V.C., Le Couteur, D.G., Ishii, I., and Bhatia, M. (2019). Cystathionine-Gamma-Lyase-Derived hydrogen sulfide-regulated substance P modulates liver sieve fenestrations in Caecal ligation and puncture-induced sepsis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133191"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.bcp.2017.10.010","article-title":"Endogenous hydrogen sulfide regulates histone demethylase JMJD3-mediated inflammatory response in LPS-stimulated macrophages and in a mouse model of LPS-induced septic shock","volume":"149","author":"Liu","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.jinf.2017.07.005","article-title":"Circulating levels of hydrogen sulfide and substance P in patients with sepsis","volume":"75","author":"Gaddam","year":"2017","journal-title":"J. Infect."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"e327","DOI":"10.1097\/PCC.0000000000001223","article-title":"Hydrogen sulfide in exhaled gases from ventilated septic neonates and children: A preliminary report","volume":"18","author":"Bee","year":"2017","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1164\/rccm.200907-1145OC","article-title":"Hydrogen sulfide improves neutrophil migration and survival in sepsis via K+ATP channel activation","volume":"182","author":"Spiller","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1097\/SHK.0000000000000589","article-title":"Delayed Treatment with sodium hydrosulfide improves regional blood flow and alleviates Cecal ligation and puncture (CLP)-Induced septic shock","volume":"46","author":"Ahmad","year":"2016","journal-title":"Shock"},{"key":"ref_153","first-page":"3270","article-title":"Hydrogen sulfide prevents diaphragm weakness in Cecal ligation puncture-induced sepsis by preservation of mitochondrial function","volume":"9","author":"Zhang","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"119192","DOI":"10.1016\/j.lfs.2021.119192","article-title":"GYY4137 alleviates sepsis-induced acute lung injury in mice by inhibiting the PDGFR\u03b2\/Akt\/NF-\u03baB\/NLRP3 pathway","volume":"271","author":"Li","year":"2021","journal-title":"Life Sci."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.molimm.2021.12.003","article-title":"Hydrogen sulfide attenuates ferroptosis and stimulates autophagy by blocking mTOR signaling in sepsis-induced acute lung injury","volume":"141","author":"Li","year":"2021","journal-title":"Mol. Immunol."},{"key":"ref_156","first-page":"2851","article-title":"Inhibition of endogenous hydrogen sulfide production exacerbates the inflammatory response during urine-derived sepsis-induced kidney injury","volume":"16","author":"Qiu","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Renieris, G., Droggiti, D.-E., Katrini, K., Koufargyris, P., Gkavogianni, T., Karakike, E., Antonakos, N., Damoraki, G., Karageorgos, A., and Sabracos, L. (2021). Host cystathionine-\u03b3 lyase derived hydrogen sulfide protects against Pseudomonas aeruginosa sepsis. PLOS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009473"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Aslami, H., Pulskens, W.P., Kuipers, M.T., Bos, A.P., Van Kuilenburg, A.B.P., Wanders, R.J.A., Roelofsen, J., Roelofs, J., Kerindongo, R.P., and Beurskens, C.J.P. (2013). Hydrogen sulfide donor NaHS reduces organ injury in a rat model of pneumococcal pneumosepsis, associated with improved bio-energetic status. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063497"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"e21710","DOI":"10.1096\/fj.202100074R","article-title":"GYY4137 protected the integrity of the blood-brain barrier via activation of the Nrf2\/ARE pathway in mice with sepsis","volume":"35","author":"Cui","year":"2021","journal-title":"FASEB J."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"3543","DOI":"10.2174\/138161206778343000","article-title":"Therapeutic use of nitric oxide scavengers in shock and sepsis","volume":"12","author":"Harbrecht","year":"2006","journal-title":"Curr. Pharm. Des."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"110","DOI":"10.4037\/ajcc2015570","article-title":"Inhaled nitric oxide to improve oxygenation for safe critical care transport of adults with severe hypoxemia","volume":"24","author":"Teman","year":"2015","journal-title":"Am. J. Crit. Care"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1097\/CCM.0000000000000549","article-title":"Randomized Controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis*","volume":"42","author":"Trzeciak","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3233\/CH-160207","article-title":"Tetrahydrobiopterin improves microcirculation in experimental sepsis","volume":"67","author":"Dumbarton","year":"2017","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/01.CCM.0000105581.01815.C6","article-title":"Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: Effect on survival in patients with septic shock*","volume":"32","author":"Lorente","year":"2004","journal-title":"Crit. Care Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/01.CCM.0000105118.66983.19","article-title":"Administration of the nitric oxide synthase inhibitor NG-methyl-l-arginine hydrochloride (546C88) by intravenous infusion for up to 72 hours can promote the resolution of shock in patients with severe sepsis: Results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002)*","volume":"32","author":"Bakker","year":"2004","journal-title":"Crit. Care Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"584","DOI":"10.5483\/BMBRep.2010.43.9.584","article-title":"Maintenance of cellular tetrahydrobiopterin homeostasis","volume":"43","author":"Kim","year":"2010","journal-title":"BMB Rep."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1172\/jci.insight.124039","article-title":"A phase I trial of low-dose inhaled carbon monoxide in sepsis-induced ARDS","volume":"3","author":"Fredenburgh","year":"2018","journal-title":"JCI Insight"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3669\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:44:21Z","timestamp":1760136261000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,27]]},"references-count":167,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ijms23073669"],"URL":"https:\/\/doi.org\/10.3390\/ijms23073669","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,27]]}}}