{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T20:21:52Z","timestamp":1784233312494,"version":"3.55.0"},"reference-count":200,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01GM099807"],"award-info":[{"award-number":["R01GM099807"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Sepsis and septic shock are the leading causes of death among hospitalized patients in the US. The immune response in sepsis transitions from a pro-inflammatory and pro-oxidant hyper-inflammation to an anti-inflammatory and cytoprotective hypo-inflammatory phase. While 1\/3rd sepsis-related deaths occur during hyper-, a vast majority of sepsis-mortality occurs during the hypo-inflammation. Hyper-inflammation is cytotoxic for the immune cells and cannot be sustained. As a compensatory mechanism, the immune cells transition from cytotoxic hyper-inflammation to a cytoprotective hypo-inflammation with anti-inflammatory\/immunosuppressive phase. However, the hypo-inflammation is associated with an inability to clear invading pathogens, leaving the host susceptible to secondary infections. Thus, the maladaptive immune response leads to a marked departure from homeostasis during sepsis-phases. The transition from hyper- to hypo-inflammation occurs via epigenetic programming. Sirtuins, a highly conserved family of histone deacetylators and guardians of homeostasis, are integral to the epigenetic programming in sepsis. Through their anti-inflammatory and anti-oxidant properties, the sirtuins modulate the immune response in sepsis. We review the role of sirtuins in orchestrating the interplay between the oxidative stress and epigenetic programming during sepsis.<\/jats:p>","DOI":"10.3390\/antiox11010003","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T09:50:43Z","timestamp":1640080243000},"page":"3","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Sirtuins and Sepsis: Cross Talk between Redox and Epigenetic Pathways"],"prefix":"10.3390","volume":"11","author":[{"given":"Anugraha","family":"Gandhirajan","sequence":"first","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjoy","family":"Roychowdhury","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidula","family":"Vachharajani","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Department of Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"key":"ref_1","unstructured":"Torio, C.M., and Andrews, R.M. (2006). National inpatient hospital costs: The most expensive conditions by payer, 2011: Sta-tistical brief #160, Healthcare Cost and Utilization Project (Hcup) Statistical Briefs."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1590\/S0103-507X2013000100002","article-title":"O \u00f4nus da sepse: Uma chamada em apoio ao Dia Mundial da Sepse 2013","volume":"25","author":"Reinhart","year":"2013","journal-title":"Rev. Bras. Ter. Intensiv."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1189\/jlb.3MA0114-034RR","article-title":"SIRT1 inhibition during the hypoinflammatory phenotype of sepsis enhances immunity and improves outcome","volume":"96","author":"Vachharajani","year":"2014","journal-title":"J. Leukoc. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1001\/jama.2011.1829","article-title":"Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure","volume":"306","author":"Boomer","year":"2011","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"R183","DOI":"10.1186\/cc10332","article-title":"The late phase of sepsis is characterized by an increased microbiological burden and death rate","volume":"15","author":"Otto","year":"2011","journal-title":"Crit. Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1097\/00003246-199510000-00007","article-title":"Multiple Organ Dysfunction Score","volume":"23","author":"Marshall","year":"1995","journal-title":"Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E312","DOI":"10.21037\/jtd.2016.03.47","article-title":"Balanced control of both hyper and hypo-inflammatory phases as a new treatment paradigm in sepsis","volume":"8","author":"Tsirigotis","year":"2016","journal-title":"J. Thorac. Dis."},{"key":"ref_8","unstructured":"Halliwell, B., and Gutteridge, J.M.C. (2007). Free Radicals in Biology and Medicine, Oxford University Press. [4th ed.]."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1080\/00365540310015692","article-title":"Role of apoptotic cell death in sepsis","volume":"35","author":"Hotchkiss","year":"2003","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1177\/1753425919842320","article-title":"Epigenetic and metabolic programming of innate immunity in sepsis","volume":"25","author":"Vachharajani","year":"2019","journal-title":"Innate Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"66","DOI":"10.4161\/viru.26907","article-title":"The role of mitochondrial dysfunction in sepsis-induced multi-organ failure","volume":"5","author":"Singer","year":"2013","journal-title":"Virulence"},{"key":"ref_12","first-page":"5030","article-title":"Mitochondrial mechanisms of sepsis-induced organ failure","volume":"13","author":"Exline","year":"2008","journal-title":"Front. Biosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1089\/ars.2013.5447","article-title":"Are Reactive Oxygen Species Always Detrimental to Pathogens?","volume":"20","author":"Paiva","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1159\/000485089","article-title":"Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species","volume":"44","author":"He","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1111\/ped.12698","article-title":"Oxidant and antioxidant status in neonatal proven and clinical sepsis according to selenium status","volume":"57","author":"Asci","year":"2015","journal-title":"Pediatr. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/cc10334","article-title":"Bench-to-bedside review: Sepsis\u2014From the redox point of view","volume":"15","author":"Andrades","year":"2011","journal-title":"Crit. Care"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/bja\/aeg034","article-title":"Oxidative stress and gene expression in sepsis","volume":"90","author":"Macdonald","year":"2003","journal-title":"Br. J. Anaesth."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"526","DOI":"10.7326\/0003-4819-107-4-526","article-title":"Oxygen Radicals and Human Disease","volume":"107","author":"Cross","year":"1987","journal-title":"Ann. Intern. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5985209","DOI":"10.1155\/2017\/5985209","article-title":"Role of Oxidative Stress and Mitochondrial Dysfunction in Sepsis and Potential Therapies","volume":"2017","author":"Mantzarlis","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6914849","DOI":"10.1155\/2019\/6914849","article-title":"Mitochondria-Derived Damage-Associated Molecular Patterns in Sepsis: From Bench to Bedside","volume":"2019","author":"Li","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/jcp.21678","article-title":"Epigenetic control","volume":"219","author":"Delcuve","year":"2009","journal-title":"J. Cell. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1161\/CIRCULATIONAHA.110.956839","article-title":"Epigenetic modifications: Basic mechanisms and role in cardiovascular disease","volume":"123","author":"Handy","year":"2011","journal-title":"Circulation"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/hdy.2010.54","article-title":"Epigenetics and gene expression","volume":"105","author":"Gibney","year":"2010","journal-title":"Heredity"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1097\/CCM.0000000000004247","article-title":"Epigenetics of Sepsis","volume":"48","author":"Binnie","year":"2020","journal-title":"Crit. Care Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/S1470-2045(13)70110-4","article-title":"Methylation of the TERT promoter and risk stratification of childhood brain tumours: An integrative genomic and molecular study","volume":"14","author":"Choufani","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13148-016-0256-8","article-title":"DNA methylation: Conducting the orchestra from exposure to phenotype?","volume":"8","author":"Leenen","year":"2016","journal-title":"Clin. Epigenet."},{"key":"ref_28","first-page":"3094","article-title":"Epigenetic modifiers reduce inflammation and modulate macrophage phenotype during endotoxemia-induced acute lung injury","volume":"128","author":"Thangavel","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Shih, C.-C., Liao, M.-H., Hsiao, T.-S., Hii, H.-P., Shen, C.-H., Chen, S.-J., Ka, S.-M., Chang, Y.-L., and Wu, C.-C. (2016). Procainamide Inhibits DNA Methylation and Alleviates Multiple Organ Dysfunction in Rats with Endotoxic Shock. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163690"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cyto.2010.10.007","article-title":"Facultative heterochromatin formation at the IL-1 beta promoter in LPS tolerance and sepsis","volume":"53","author":"Yoza","year":"2011","journal-title":"Cytokine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1038\/s41467-017-01196-x","article-title":"Coding and noncoding landscape of extracellular RNA released by human glioma stem cells","volume":"8","author":"Wei","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"273","DOI":"10.4161\/epi.6.3.14017","article-title":"Epigenetic regulation of immune cell functions during post-septic immunosuppression","volume":"6","author":"Carson","year":"2011","journal-title":"Epigenetics"},{"key":"ref_33","first-page":"5489571","article-title":"Emerging Evidence concerning the Role of Sirtuins in Sepsis","volume":"2018","author":"Li","year":"2018","journal-title":"Crit. Care Res. Pract."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1146\/annurev.pathol.4.110807.092250","article-title":"Mammalian Sirtuins: Biological Insights and Disease Relevance","volume":"5","author":"Haigis","year":"2010","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1089\/ars.2017.7290","article-title":"The Role of Sirtuins in Antioxidant and Redox Signaling","volume":"28","author":"Singh","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8167273","DOI":"10.1155\/2016\/8167273","article-title":"Sirtuins Link Inflammation and Metabolism","volume":"2016","author":"Vachharajani","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1021\/cr500457h","article-title":"Sirtuins in Epigenetic Regulation","volume":"115","author":"Jing","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1093\/nar\/gkz1127","article-title":"SIRT1\/2 orchestrate acquisition of DNA methylation and loss of histone H3 activating marks to prevent premature activation of inflammatory genes in macrophages","volume":"48","author":"Li","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"16045","DOI":"10.1038\/nrdp.2016.45","article-title":"Sepsis and septic shock","volume":"2","author":"Hotchkiss","year":"2016","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1016\/j.freeradbiomed.2009.08.019","article-title":"A systematic review of experimental treatments for mitochondrial dysfunction in sepsis and multiple organ dysfunction syndrome","volume":"47","author":"Dare","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1097\/00003246-199706000-00007","article-title":"Oxygen transport patterns in patients with sepsis syndrome or septic shock","volume":"25","author":"Hayes","year":"1997","journal-title":"Crit. Care Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0749-0704(05)70161-5","article-title":"Cytopathic Hypoxia","volume":"17","author":"Fink","year":"2001","journal-title":"Crit. Care Clin."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/bja\/aer093","article-title":"Oxidative stress and mitochondrial dysfunction in sepsis","volume":"107","author":"Galley","year":"2011","journal-title":"Br. J. Anaesth."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1097\/01.CCM.0000174478.70338.03","article-title":"Outcome measures for clinical research in sepsis: A report of the 2nd Cambridge Colloquium of the International Sepsis Forum","volume":"33","author":"Marshall","year":"2005","journal-title":"Crit. Care Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"R129","DOI":"10.1186\/cc9097","article-title":"Time course of nitric oxide synthases, nitrosative stress, and poly(ADP ribosylation) in an ovine sepsis model","volume":"14","author":"Lange","year":"2010","journal-title":"Crit. Care"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1172\/JCI119585","article-title":"Endothelial dysfunction in a rat model of endotoxic shock. Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite","volume":"100","author":"Cuzzocrea","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1136\/heart.87.6.507","article-title":"Myocardial dysfunction in sepsis: No role for NO?","volume":"87","author":"Belcher","year":"2002","journal-title":"Heart"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1023\/A:1005479920097","article-title":"Mitochondrial genome mutation in cell death and aging","volume":"31","author":"Ozawa","year":"1999","journal-title":"J. Bioenerget. Biomembr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1113\/jphysiol.2003.049478","article-title":"Mitochondrial formation of reactive oxygen species","volume":"552","author":"Turrens","year":"2003","journal-title":"J. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s11010-007-9520-8","article-title":"Mitochondria: A hub of redox activities and cellular distress control","volume":"305","author":"Kakkar","year":"2007","journal-title":"Mol. Cell. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1152\/physrev.00018.2001","article-title":"Free Radicals in the Physiological Control of Cell Function","volume":"82","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/BF02254975","article-title":"How Mitochondrial Damage Affects Cell Function","volume":"9","author":"James","year":"2002","journal-title":"J. Biomed. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1515\/hsz-2012-0119","article-title":"Mitophagy: Mechanisms, pathophysiological roles, and analysis","volume":"393","author":"Ding","year":"2012","journal-title":"Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1097\/SHK.0000000000000463","article-title":"Mitochondrial Function in Sepsis","volume":"45","author":"Arulkumaran","year":"2016","journal-title":"Shock"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.mito.2008.03.002","article-title":"Antioxidant treatment reverses mitochondrial dysfunction in a sepsis animal model","volume":"8","author":"Zapelini","year":"2008","journal-title":"Mitochondrion"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ogura, Y., Kitada, M., and Koya, D. (2021). Sirtuins and Renal Oxidative Stress. Antioxidants, 10.","DOI":"10.3390\/antiox10081198"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s10522-017-9685-9","article-title":"Sirtuins, a promising target in slowing down the ageing process","volume":"18","author":"Grabowska","year":"2017","journal-title":"Biogerontology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1074\/jbc.M114.566349","article-title":"Sequential Actions of SIRT1-RELB-SIRT3 Coordinate Nuclear-Mitochondrial Communication during Immunometabolic Adaptation to Acute Inflammation and Sepsis","volume":"290","author":"Liu","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1681\/ASN.2018111126","article-title":"Mitochondria in Sepsis-Induced AKI","volume":"30","author":"Sun","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"87","DOI":"10.14348\/molcells.2016.2318","article-title":"Sirt1 and the Mitochondria","volume":"39","author":"Tang","year":"2016","journal-title":"Mol. Cells"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.3389\/fimmu.2020.01043","article-title":"The Metabolic Basis of Immune Dysfunction Following Sepsis and Trauma","volume":"11","author":"McBride","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1152\/advan.00052.2006","article-title":"PGC-1\u03b1: A key regulator of energy metabolism","volume":"30","author":"Liang","year":"2006","journal-title":"Adv. Physiol. Educ."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.mito.2013.01.006","article-title":"Regulation of mitochondrial biogenesis and PGC-1\u03b1 under cellular stress","volume":"13","author":"Wenz","year":"2013","journal-title":"Mitochondrion"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"14447","DOI":"10.1073\/pnas.0803790105","article-title":"A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis","volume":"105","author":"Ahn","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.molcel.2011.01.002","article-title":"Sirt3 Promotes the Urea Cycle and Fatty Acid Oxidation during Dietary Restriction","volume":"41","author":"Hallows","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nature08778","article-title":"SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation","volume":"464","author":"Hirschey","year":"2010","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.tibs.2010.07.003","article-title":"Sirtuin regulation of mitochondria: Energy production, apoptosis, and signaling","volume":"35","author":"Verdin","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Finley, L.W.S., Haas, W., Desquiret-Dumas, V., Wallace, D.C., Procaccio, V., Gygi, S.P., and Haigis, M.C. (2011). Succinate Dehydrogenase Is a Direct Target of Sirtuin 3 Deacetylase Activity. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023295"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"14608","DOI":"10.1073\/pnas.1111308108","article-title":"Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production","volume":"108","author":"Jing","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.exger.2012.08.007","article-title":"SIRT3 regulation of mitochondrial oxidative stress","volume":"48","author":"Bause","year":"2013","journal-title":"Exp. Gerontol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.cmet.2010.11.015","article-title":"Calorie Restriction Reduces Oxidative Stress by SIRT3-Mediated SOD2 Activation","volume":"12","author":"Qiu","year":"2010","journal-title":"Cell Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.cell.2010.10.002","article-title":"Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction","volume":"143","author":"Someya","year":"2010","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.jss.2015.02.005","article-title":"Beneficial effect of cyclosporine A on traumatic hemorrhagic shock","volume":"195","author":"Lei","year":"2015","journal-title":"J. Surg. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"36998","DOI":"10.18632\/oncotarget.6076","article-title":"Activation of sirtuin 1\/3 improves vascular hyporeactivity in severe hemorrhagic shock by alleviation of mitochondrial damage","volume":"6","author":"Li","year":"2015","journal-title":"Oncotarget"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"914","DOI":"10.18632\/aging.100252","article-title":"Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy","volume":"2","author":"Hafner","year":"2010","journal-title":"Aging"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"33201","DOI":"10.1038\/srep33201","article-title":"Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury","volume":"6","author":"Zhao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.3389\/fphys.2018.01526","article-title":"SIRT3 Protects Against Acute Kidney Injury via AMPK\/mTOR-Regulated Autophagy","volume":"9","author":"Zhao","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.bbrc.2013.10.033","article-title":"SIRT5 desuccinylates and activates SOD1 to eliminate ROS","volume":"441","author":"Lin","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.molmed.2017.02.005","article-title":"Mitochondrial Sirtuins and Molecular Mechanisms of Aging","volume":"23","author":"Santos","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1007\/s00018-016-2180-7","article-title":"Using mitochondrial sirtuins as drug targets: Disease implications and available compounds","volume":"73","author":"Gertz","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_81","first-page":"397","article-title":"SIRT3 Silencing Sensitizes Breast Cancer Cells to Cytotoxic Treatments Through an Increment in ROS Production","volume":"118","author":"Pons","year":"2016","journal-title":"J. Cell. Biochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jaut.2017.04.006","article-title":"NAD + dependent deacetylase Sirtuin 5 rescues the innate inflammatory response of endotoxin tolerant macrophages by promoting acetylation of p65","volume":"81","author":"Qin","year":"2017","journal-title":"J. Autoimmun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.3389\/fimmu.2019.02341","article-title":"Impact of the Dual Deletion of the Mitochondrial Sirtuins SIRT3 and SIRT5 on Anti-microbial Host Defenses","volume":"10","author":"Heinonen","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3389\/fimmu.2018.00419","article-title":"Mitochondrial Sirtuin 4 Resolves Immune Tolerance in Monocytes by Rebalancing Glycolysis and Glucose Oxidation Homeostasis","volume":"9","author":"Tao","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e99292","DOI":"10.1172\/jci.insight.99292","article-title":"Pyruvate dehydrogenase complex stimulation promotes immunometabolic homeostasis and sepsis survival","volume":"3","author":"McCall","year":"2018","journal-title":"JCI Insight"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"296","DOI":"10.2741\/s27","article-title":"Current advances in identification of cancer biomarkers in saliva","volume":"1","author":"Arellano","year":"2009","journal-title":"Front. Biosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.freeradbiomed.2006.10.033","article-title":"Ascorbate inhibits NADPH oxidase subunit p47phox expression in microvascular endothelial cells","volume":"42","author":"Wu","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_88","first-page":"E1044","article-title":"Derangements in mitochondrial metabolism in intercostal and leg muscle of critically ill patients with sepsis-induced multiple organ failure","volume":"291","author":"Fredriksson","year":"2006","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1007\/s00134-003-1789-9","article-title":"Oxidative parameters and mortality in sepsis induced by cecal ligation and perforation","volume":"29","author":"Ritter","year":"2003","journal-title":"Intensiv. Care Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1124\/jpet.104.077644","article-title":"Cyclooxygenase-2 Inhibition Improves Vascular Endothelial Dysfunction in a Rat Model of Endotoxic Shock: Role of Inducible Nitric-Oxide Synthase and Oxidative Stress","volume":"312","author":"Virdis","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.freeradbiomed.2005.06.010","article-title":"Exogenous superoxide mediates pro-oxidative, proinflammatory, and procoagulatory changes in primary endothelial cell cultures","volume":"39","author":"Jacobi","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/cmi.2014.89","article-title":"NADPH oxidases: An overview from structure to innate immunity-associated pathologies","volume":"12","author":"Panday","year":"2014","journal-title":"Cell. Mol. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e94248","DOI":"10.1172\/jci.insight.94248","article-title":"Inhibition of NADPH oxidase 2 (NOX2) prevents sepsis-induced cardiomyopathy by improving calcium handling and mitochondrial function","volume":"2","author":"Joseph","year":"2017","journal-title":"JCI Insight"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1097\/01.ASN.0000031702.86799.B9","article-title":"Cyclosporine A Suppresses Cyclooxygenase-2 Expression in the Rat Kidney","volume":"13","author":"Dreher","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0300-483X(02)00286-X","article-title":"Biological reactivity and biomarkers of the neutrophil oxidant, hypochlorous acid","volume":"181-182","author":"Winterbourn","year":"2002","journal-title":"Toxicology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.matbio.2009.09.005","article-title":"Myeloperoxidase-derived oxidants selectively disrupt the protein core of the heparan sulfate proteoglycan perlecan","volume":"29","author":"Rees","year":"2010","journal-title":"Matrix Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s12272-001-1245-y","article-title":"Hypochlorous acid-induced modulation of cellular redox status in HeLa cells","volume":"31","author":"Park","year":"2008","journal-title":"Arch. Pharmacal Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.redox.2014.02.006","article-title":"Hydrogen peroxide sensing, signaling and regulation of transcription factors","volume":"2","author":"Marinho","year":"2014","journal-title":"Redox Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nrm2256","article-title":"ROS as signalling molecules: Mechanisms that generate specificity in ROS homeostasis","volume":"8","author":"Toledano","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1056\/NEJM199704103361506","article-title":"Nuclear Factor-\u03baB\u2014A Pivotal Transcription Factor in Chronic Inflammatory Diseases","volume":"336","author":"Barnes","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"23863","DOI":"10.1074\/jbc.M803072200","article-title":"Dynein Light Chain LC8 Negatively Regulates NF-\u03baB through the Redox-dependent Interaction with I\u03baB\u03b1","volume":"283","author":"Jung","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1128\/IAI.68.4.1942-1945.2000","article-title":"Predictive Value of Nuclear Factor \u03baB Activity and Plasma Cytokine Levels in Patients with Sepsis","volume":"68","author":"Arnalich","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1172\/JCI119648","article-title":"Role of NFkappaB in the mortality of sepsis","volume":"100","author":"Qiu","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"945","DOI":"10.2174\/138955706777934937","article-title":"Naturally Occurring NF-\u03baB Inhibitors","volume":"6","author":"Nam","year":"2006","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4541","DOI":"10.1016\/j.febslet.2005.06.078","article-title":"Reactive oxygen species-linked regulation of the multidrug resistance transporter P-glycoprotein in Nox-1 overexpressing prostate tumor spheroids","volume":"579","author":"Wartenberg","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.hlc.2006.10.006","article-title":"Early-phase Endotoxic Shock-induced Myocardial Injury Increases iNOS and Selectin Expression in Macaque Primate","volume":"16","author":"Yin","year":"2007","journal-title":"Heart Lung Circ."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/jlb.57.1.36","article-title":"Im-munohistochemical expression of inducible nitric oxide synthase (inos) in reversible endotoxic shock studied by a novel monoclonal antibody against rat inos","volume":"57","author":"Sato","year":"1995","journal-title":"J. Leukoc. Biol."},{"key":"ref_108","first-page":"71","article-title":"Evidence of increased nitric oxide production in patients with the sepsis syndrome","volume":"41","author":"Evans","year":"1993","journal-title":"Circ. Shock."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1172\/JCI25790","article-title":"Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis","volume":"116","author":"Thimmulappa","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1006\/bbrc.2000.4106","article-title":"Nrf2-Dependent Activation of the Antioxidant Responsive Element by tert-Butylhydroquinone Is Independent of Oxidative Stress in IMR-32 Human Neuroblastoma Cells","volume":"280","author":"Lee","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"27694","DOI":"10.1074\/jbc.M004729200","article-title":"Mechanism of Heme Oxygenase-1 Gene Activation by Cadmium in MCF-7 Mammary Epithelial Cells","volume":"275","author":"Alam","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"18399","DOI":"10.1074\/jbc.M100103200","article-title":"Hemin-induced Activation of the Thioredoxin Gene by Nrf2","volume":"276","author":"Kim","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1016\/j.bbamcr.2008.05.024","article-title":"Heterodimerization with small Maf proteins enhances nuclear retention of Nrf2 via masking the NESzip motif","volume":"1783","author":"Li","year":"2008","journal-title":"Biochim. Biophys. Acta (BBA) Bioenerg."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"569","DOI":"10.4049\/jimmunol.0902315","article-title":"NADPH Oxidase-Dependent Reactive Oxygen Species Mediate Amplified TLR4 Signaling and Sepsis-Induced Mortality in Nrf2-Deficient Mice","volume":"185","author":"Kong","year":"2010","journal-title":"J. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"4796","DOI":"10.1182\/blood-2010-10-314526","article-title":"Plant homologue constitutive photomorphogenesis 9 (COP9) signalosome subunit CSN5 regulates innate immune responses in macrophages","volume":"117","author":"Deng","year":"2011","journal-title":"Blood"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1172\/JCI28111","article-title":"Oxidative stress in sepsis: A redox redux","volume":"116","author":"Kolls","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.freeradbiomed.2013.01.004","article-title":"Redox-regulating sirtuins in aging, caloric restriction, and exercise","volume":"58","author":"Radak","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/S0891-5849(01)00480-4","article-title":"Redox environment of the cell as viewed through the redox state of the glutathione disulfide\/glutathione couple","volume":"30","author":"Schafer","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s10753-018-0881-9","article-title":"Cysteine thiol oxidation on SIRT2 regulates inflammation in obese mice with sepsis","volume":"42","author":"Wang","year":"2018","journal-title":"Inflammation"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"11005","DOI":"10.1038\/s41598-017-11388-6","article-title":"The Oxidative State of Cysteine Thiol 144 Regulates the SIRT6 Glucose Homeostat","volume":"7","author":"Long","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1038\/sj.emboj.7600244","article-title":"Modulation of NF-\u03baB-dependent transcription and cell survival by the SIRT1 deacetylase","volume":"23","author":"Yeung","year":"2004","journal-title":"EMBO J."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4251","DOI":"10.1242\/jcs.073783","article-title":"SIRT2 regulates NF-\u03baB-dependent gene expression through deacetylation of p65 Lys310","volume":"123","author":"Rothgiesser","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"6853","DOI":"10.1038\/sj.onc.1203239","article-title":"Activators and target genes of Rel\/NF-kappaB transcription factors","volume":"18","author":"Pahl","year":"1999","journal-title":"Oncogene"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Gao, R., Chen, J., Hu, Y., Li, Z., Wang, S., Shetty, S., and Fu, J. (2014). Sirt1 Deletion Leads to Enhanced Inflammation and Aggravates Endotoxin-Induced Acute Kidney Injury. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098909"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1002\/oby.21086","article-title":"Resveratrol attenuates microvascular inflammation in sepsis via SIRT-1-Induced modulation of adhesion molecules in ob\/ob mice","volume":"23","author":"Wang","year":"2015","journal-title":"Obesity"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e0162560","DOI":"10.1371\/journal.pone.0162560","article-title":"Correction: Sirtuin-2 Regulates Sepsis Inflammation in ob\/ob Mice","volume":"11","author":"Wang","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e4020","DOI":"10.1371\/journal.pone.0004020","article-title":"Phosphorylation Regulates SIRT1 Function","volume":"3","author":"Sasaki","year":"2008","journal-title":"PLoS ONE"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Shih, L.-J., Wang, J.-Y., Jheng, J.-Y., Siao, A.-C., Lin, Y.-Y., Tsuei, Y.-W., Kuo, Y.-C., Chuu, C.-P., and Kao, Y.-H. (2020). Betel Nut Arecoline Induces Different Phases of Growth Arrest between Normal and Cancerous Prostate Cells through the Reactive Oxygen Species Pathway. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239219"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.freeradbiomed.2021.07.037","article-title":"Oxidized GAPDH transfers S-glutathionylation to a nuclear protein Sirtuin-1 leading to apoptosis","volume":"174","author":"Rizvi","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"7293","DOI":"10.1074\/jbc.M113.520403","article-title":"A Redox-resistant Sirtuin-1 Mutant Protects against Hepatic Metabolic and Oxidant Stress","volume":"289","author":"Shao","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_131","first-page":"1094","article-title":"GAPDH mediates nitrosylation of nuclear proteins","volume":"12","author":"Kornberg","year":"2010","journal-title":"Nature"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Jung, S.-B., Kim, C.-S., Kim, Y.-R., Naqvi, A., Yamamori, T., Kumar, S., Kumar, A., and Irani, K. (2013). Redox Factor-1 Activates Endothelial SIRTUIN1 through Reduction of Conserved Cysteine Sulfhydryls in Its Deacetylase Domain. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065415"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"9831825","DOI":"10.1155\/2016\/9831825","article-title":"Potential Modulation of Sirtuins by Oxidative Stress","volume":"2016","author":"Santos","year":"2015","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/nature06500","article-title":"DBC1 is a negative regulator of SIRT1","volume":"451","author":"Kim","year":"2008","journal-title":"Nature"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.molcel.2007.08.030","article-title":"Active Regulator of SIRT1 Cooperates with SIRT1 and Facilitates Suppression of p53 Activity","volume":"28","author":"Kim","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1101\/gad.188482.112","article-title":"Regulation of SIRT1 activity by genotoxic stress","volume":"26","author":"Yuan","year":"2012","journal-title":"Genes Dev."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1172\/JCI88574","article-title":"Sirtuin 2 regulates cellular iron homeostasis via deacetylation of transcription factor NRF2","volume":"127","author":"Yang","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1002\/1873-3468.12236","article-title":"SIRT2 mediates NADH-induced increases in Nrf2, GCL, and glutathione by modulating Akt phosphorylation in PC12 cells","volume":"590","author":"Cao","year":"2016","journal-title":"FEBS Lett."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbr.2016.04.045","article-title":"Nrf2\/antioxidant defense pathway is involved in the neuroprotective effects of Sirt1 against focal cerebral ischemia in rats after hyperbaric oxygen preconditioning","volume":"309","author":"Xue","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/cr.2016.4","article-title":"SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2","volume":"26","author":"Pan","year":"2016","journal-title":"Cell Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1474-9726.2007.00304.x","article-title":"SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction","volume":"6","author":"Wang","year":"2007","journal-title":"Aging Cell"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.redox.2015.06.019","article-title":"Redox regulation of FoxO transcription factors","volume":"6","author":"Klotz","year":"2015","journal-title":"Redox Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nature01036","article-title":"Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress","volume":"419","author":"Kops","year":"2002","journal-title":"Nature"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"4776","DOI":"10.1038\/ncomms5776","article-title":"Site-specific mapping and quantification of protein S-sulphenylation in cells","volume":"5","author":"Yang","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.3892\/or.2015.4477","article-title":"SIRT6 suppresses glioma cell growth via induction of apoptosis, inhibition of oxidative stress and suppression of JAK2\/STAT3 signaling pathway activation","volume":"35","author":"Feng","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"7914","DOI":"10.1093\/nar\/gkz528","article-title":"SIRT6 promotes transcription of a subset of NRF2 targets by mono-ADP-ribosylating BAF170","volume":"47","author":"Rezazadeh","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.cell.2005.11.044","article-title":"Genomic Instability and Aging-like Phenotype in the Absence of Mammalian SIRT6","volume":"124","author":"Mostoslavsky","year":"2006","journal-title":"Cell"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.tig.2013.11.004","article-title":"Mining cancer methylomes: Prospects and challenges","volume":"30","author":"Stirzaker","year":"2014","journal-title":"Trends Genet."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA Methylation and Its Basic Function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/ng1089","article-title":"Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals","volume":"33","author":"Jaenisch","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Guede, A., Vera, O., and Ib\u00e1\u00f1ez-De-Caceres, I. (2020). When Oxidative Stress Meets Epigenetics: Implications in Cancer Development. Antioxidants, 9.","DOI":"10.3390\/antiox9060468"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"57726","DOI":"10.18632\/oncotarget.10639","article-title":"A cancer specific hypermethylation signature of the TERT promoter predicts biochemical relapse in prostate cancer: A retrospective cohort study","volume":"7","author":"Lipman","year":"2016","journal-title":"Oncotarget"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/0045-6039(88)90070-X","article-title":"The histones of the sperm of Spisula solidissima include a novel, cysteine-containing H-1 histone","volume":"23","author":"Ausio","year":"1988","journal-title":"Cell Differ."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/nbt.1685","article-title":"Epigenetic modifications and human disease","volume":"28","author":"Portela","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of chromatin by histone modifications","volume":"21","author":"Bannister","year":"2011","journal-title":"Cell Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1073\/pnas.1012798108","article-title":"Histone code pathway involving H3 S28 phosphorylation and K27 acetylation activates transcription and antagonizes polycomb silencing","volume":"108","author":"Lau","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/nature08448","article-title":"JAK2 phosphorylates histone H3Y41 and excludes HP1\u03b1 from chromatin","volume":"461","author":"Dawson","year":"2009","journal-title":"Nature"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.molcel.2006.12.012","article-title":"DNA-Independent PARP-1 Activation by Phosphorylated ERK2 Increases Elk1 Activity: A Link to Histone Acetylation","volume":"25","author":"Visochek","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"33","DOI":"10.21037\/acs.2017.01.03","article-title":"Cost effectiveness of robotic mitral valve surgery","volume":"6","author":"Moss","year":"2017","journal-title":"Ann. Cardiothorac. Surg."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.gde.2005.07.004","article-title":"Something about SUMO inhibits transcription","volume":"15","author":"Gill","year":"2005","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S1097-2765(04)00060-7","article-title":"SUMO Promotes HDAC-Mediated Transcriptional Repression","volume":"13","author":"Yang","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.dnarep.2015.09.016","article-title":"Histone ubiquitylation and its roles in transcription and DNA damage response","volume":"36","author":"Meas","year":"2015","journal-title":"DNA Repair"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.cell.2009.02.027","article-title":"RAD6-Mediated Transcription-Coupled H2B Ubiquitylation Directly Stimulates H3K4 Methylation in Human Cells","volume":"137","author":"Kim","year":"2009","journal-title":"Cell"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1517\/14728222.12.10.1301","article-title":"Chromatin-modifying enzymes as therapeutic targets\u2014Part 1","volume":"12","author":"Keppler","year":"2008","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nrg2540","article-title":"Linking DNA methylation and histone modification: Patterns and paradigms","volume":"10","author":"Cedar","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/nrg3074","article-title":"Non-coding RNAs in human disease","volume":"12","author":"Esteller","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1038\/nature03985","article-title":"A network-based analysis of systemic inflammation in humans","volume":"437","author":"Calvano","year":"2005","journal-title":"Nature"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1016\/j.cell.2016.09.034","article-title":"\u03b2-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance","volume":"167","author":"Novakovic","year":"2016","journal-title":"Cell"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.drudis.2011.03.009","article-title":"Histone acetyltransferases are crucial regulators in NF-\u03baB mediated inflammation","volume":"16","author":"Ghizzoni","year":"2011","journal-title":"Drug Discov. Today"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1183\/09031936.05.00117504","article-title":"Histone acetylation and deacetylation: Importance in inflammatory lung diseases","volume":"25","author":"Barnes","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"a018762","DOI":"10.1101\/cshperspect.a018762","article-title":"Writers and Readers of Histone Acetylation: Structure, Mechanism, and Inhibition","volume":"6","author":"Marmorstein","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"8797206","DOI":"10.1155\/2016\/8797206","article-title":"HDAC Inhibitors as Epigenetic Regulators of the Immune System: Impacts on Cancer Therapy and Inflammatory Diseases","volume":"2016","author":"Hull","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1074\/jbc.M109.067330","article-title":"Dynamic and Selective Nucleosome Repositioning during Endotoxin Tolerance","volume":"285","author":"Liu","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"5147","DOI":"10.1128\/MCB.02429-06","article-title":"Epigenetic Regulation of Tumor Necrosis Factor Alpha","volume":"27","author":"Sullivan","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.3389\/fimmu.2018.01620","article-title":"Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome","volume":"9","author":"Hopp","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"4925","DOI":"10.1210\/en.2014-1595","article-title":"Inhibiting DNA Methylation by 5-Aza-2\u2032-deoxycytidine Ameliorates Atherosclerosis Through Suppressing Macrophage Inflammation","volume":"155","author":"Cao","year":"2014","journal-title":"Endocrinology"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"685333","DOI":"10.3389\/fmed.2021.685333","article-title":"Epigenetic Regulation in Sepsis, Role in Pathophysiology and Therapeutic Perspective","volume":"8","author":"Brunialti","year":"2021","journal-title":"Front. Med."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Pellegrina, D.V.D.S., Severino, P., Barbeiro, H.V., De Souza, H.P., Machado, M.C.C., Pinheiro-Da-Silva, F., and Reis, E.M. (2017). Insights into the Function of Long Noncoding RNAs in Sepsis Revealed by Gene Co-Expression Network Analysis. Non-Coding RNA, 3.","DOI":"10.3390\/ncrna3010005"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"e58597","DOI":"10.7554\/eLife.58597","article-title":"The leukocyte non-coding RNA landscape in critically ill patients with sepsis","volume":"9","author":"Scicluna","year":"2020","journal-title":"eLife"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.it.2009.07.009","article-title":"Endotoxin tolerance: New mechanisms, molecules and clinical significance","volume":"30","author":"Biswas","year":"2009","journal-title":"Trends Immunol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.immuni.2015.02.001","article-title":"Human Monocytes Undergo Functional Re-programming during Sepsis Mediated by Hypoxia-Inducible Factor-1\u03b1","volume":"42","author":"Shalova","year":"2015","journal-title":"Immunity"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"32198","DOI":"10.1074\/jbc.M803446200","article-title":"G9a and HP1 Couple Histone and DNA Methylation to TNF\u03b1 Transcription Silencing during Endotoxin Tolerance","volume":"283","author":"Yoza","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"461","DOI":"10.4049\/jimmunol.175.1.461","article-title":"Endotoxin Tolerance Disrupts Chromatin Remodeling and NF-\u03baB Transactivation at the IL-1\u03b2 Promoter","volume":"175","author":"Chan","year":"2005","journal-title":"J. Immunol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"20940","DOI":"10.1074\/jbc.M110.115063","article-title":"MicroRNAs Distinguish Translational from Transcriptional Silencing during Endotoxin Tolerance","volume":"285","author":"McCall","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1189\/jlb.0211074","article-title":"MicroRNA-146a regulates both transcription silencing and translation disruption of TNF-\u03b1 during TLR4-induced gene reprogramming","volume":"90","author":"Church","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/JLB.3HI0918-373R","article-title":"Frontline Science: Monocytes sequentially rewire metabolism and bioenergetics during an acute inflammatory response","volume":"105","author":"Zhu","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"25758","DOI":"10.1074\/jbc.M112.362343","article-title":"NAD+-dependent Sirtuin 1 and 6 Proteins Coordinate a Switch from Glucose to Fatty Acid Oxidation during the Acute Inflammatory Response","volume":"287","author":"Liu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"9856","DOI":"10.1074\/jbc.M110.196790","article-title":"NAD+-dependent SIRT1 Deacetylase Participates in Epigenetic Reprogramming during Endotoxin Tolerance","volume":"286","author":"Liu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"2402593","DOI":"10.1155\/2018\/2402593","article-title":"Sirtuin1 Targeting Reverses Innate and Adaptive Immune Tolerance in Septic Mice","volume":"2018","author":"Martin","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Lyn-Kew, K., Rich, E., Zeng, X., Wen, H., Kunkel, S.L., Newstead, M.W., Bhan, U., and Standiford, T.J. (2010). IRAK-M Regulates Chromatin Remodeling in Lung Macrophages during Experimental Sepsis. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011145"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1128\/MCB.01862-08","article-title":"Chromatin-Specific Remodeling by HMGB1 and Linker Histone H1 Silences Proinflammatory Genes during Endotoxin Tolerance","volume":"29","author":"Yoza","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1159\/000314077","article-title":"Gene-Specific Epigenetic Regulation in Serious Infections with Systemic Inflammation","volume":"2","author":"McCall","year":"2010","journal-title":"J. Innate Immun."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"26857","DOI":"10.1074\/jbc.M704584200","article-title":"Epigenetic Silencing of Tumor Necrosis Factor \u03b1 during Endotoxin Tolerance","volume":"282","author":"Yoza","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1238858","DOI":"10.1126\/science.1238858","article-title":"A Role for SIRT2-Dependent Histone H3K18 Deacetylation in Bacterial Infection","volume":"341","author":"Eskandarian","year":"2013","journal-title":"Science"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.celrep.2018.03.116","article-title":"Infection Reveals a Modification of SIRT2 Critical for Chromatin Association","volume":"23","author":"Pereira","year":"2018","journal-title":"Cell Rep."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s10059-013-0297-1","article-title":"Regulation of SIRT1 by MicroRNAs","volume":"36","author":"Choi","year":"2013","journal-title":"Mol. Cells"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fphys.2012.00068","article-title":"MicroRNA Regulation of SIRT1","volume":"3","author":"Yamakuchi","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1159\/000492988","article-title":"MicroRNA-138 Aggravates Inflammatory Responses of Macrophages by Targeting SIRT1 and Regulating the NF-\u03baB and AKT Pathways","volume":"49","author":"Bai","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.3389\/fimmu.2020.01829","article-title":"MicroRNA-34a Inhibition Alleviates Lung Injury in Cecal Ligation and Puncture Induced Septic Mice","volume":"11","author":"Chen","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"C449","DOI":"10.1152\/ajpcell.00173.2017","article-title":"Acute downregulation of miR-199a attenuates sepsis-induced acute lung injury by targeting SIRT1","volume":"314","author":"Liu","year":"2018","journal-title":"Am. J. Physiol. Physiol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/1\/3\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:50:23Z","timestamp":1760169023000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/1\/3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,21]]},"references-count":200,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["antiox11010003"],"URL":"https:\/\/doi.org\/10.3390\/antiox11010003","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,21]]}}}