{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T15:20:15Z","timestamp":1770996015932,"version":"3.50.1"},"reference-count":87,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec>\n            <jats:title>Objectives:<\/jats:title>\n            <jats:p>Recent evidence from the fields of microbiology and immunology, as well as a small number of human sepsis studies, suggest that epigenetic regulation may play a central role in the pathogenesis of sepsis. The term \u201cepigenetics\u201d refers to regulatory mechanisms that control gene expression but are not related to changes in DNA sequence. These include DNA methylation, histone modifications, and regulation of transcription via non-coding RNAs. Epigenetic modifications, occurring in response to external stressors, lead to changes in gene expression, and thus lie at the intersection between genetics and the environment. In this review, we examine data from in vitro studies, animal studies, and the existing human sepsis studies in epigenetics to demonstrate that epigenetic mechanisms are likely central to the pathogenesis of sepsis and that epigenetic therapies may have potential in the treatment of sepsis and its associated organ failures.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Data Sources:<\/jats:title>\n            <jats:p>Online search of published scientific literature via Pubmed using the term \u201cepigenetics\u201d in combination with the terms \u201csepsis\u201d, \u201cinfection\u201d, \u201cbacterial infection\u201d, \u201cviral infection\u201d, \u201ccritical illness\u201d, \u201cacute respiratory distress syndrome\u201d, and \u201cacute lung injury\u201d.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Study Selection:<\/jats:title>\n            <jats:p>Articles were chosen for inclusion based on their relevance to sepsis, acute inflammation, sepsis-related immune suppression, and sepsis-related organ failure. Reference lists were reviewed to identify additional relevant articles.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Data Extraction:<\/jats:title>\n            <jats:p>Relevant data was extracted and synthesized for narrative review.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Data Synthesis:<\/jats:title>\n            <jats:p>Epigenetic regulation is a key determinant of gene expression in sepsis. At the onset of infection, host-pathogen interactions often result in epigenetic alterations to host cells that favor pathogen survival. In parallel, the host inflammatory response is characterized by epigenetic modifications in key regulatory genes, including <jats:italic toggle=\"yes\">tumor necrosis factor<\/jats:italic> and interleukin-1\u03b2. In human sepsis patients, multiple epigenetic modifying enzymes show differential expression in early sepsis, suggesting a role for epigenetics in coordinating the response to infection. In the later stages of sepsis, epigenetic modifications accompany endotoxin tolerance and the immune-suppressed state. In animal models, treatment with epigenetic modifiers can mitigate the effects of sepsis and improve survival as well as reverse sepsis-associated organ injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Epigenetic modifications are associated with key phases of sepsis, from the host-pathogen interaction, to acute inflammation, to immune suppression. Epigenetic markers show promise in the diagnosis and prognosis of sepsis and epigenetic modifying agents show promise as therapeutic tools in animal models of sepsis. Human studies in the area of epigenetics are sorely lacking and should be a priority for sepsis researchers.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ccm.0000000000004247","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T04:51:46Z","timestamp":1582260706000},"page":"745-756","source":"Crossref","is-referenced-by-count":67,"title":["Epigenetics of Sepsis"],"prefix":"10.1097","volume":"48","author":[{"given":"Alexandra","family":"Binnie","sequence":"first","affiliation":[{"name":"William Osler Health System, Brampton, ON, Canada."},{"name":"Algarve Biomedical Center, Campus Gambelas, Edificio 2, Faro, Portugal."}]},{"given":"Jennifer L. Y.","family":"Tsang","sequence":"additional","affiliation":[{"name":"Department of Medicine, McMaster University, Hamilton, ON, Canada."},{"name":"Niagara Health, St. Catharines, ON, Canada."}]},{"given":"Pingzhao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada."}]},{"given":"Gabriela","family":"Carrasqueiro","sequence":"additional","affiliation":[{"name":"Algarve Biomedical Center, Campus Gambelas, Edificio 2, Faro, Portugal."},{"name":"Centre for Biomedical Research, University of Algarve, Faro, Portugal."},{"name":"Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal."}]},{"given":"Pedro","family":"Castelo-Branco","sequence":"additional","affiliation":[{"name":"Algarve Biomedical Center, Campus Gambelas, Edificio 2, Faro, Portugal."},{"name":"Centre for Biomedical Research, University of Algarve, Faro, Portugal."},{"name":"Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal."}]},{"given":"Claudia C.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Keenan and Li Ka Shing Knowledge Institute of Saint Michael\u2019s Hospital, Toronto, ON, Canada."},{"name":"Institute of Medical Sciences and Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada."}]}],"member":"276","reference":[{"key":"R1-20231015","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":"R2-20231015","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/SHK.0000000000000473","article-title":"The endothelium in sepsis.","volume":"45","author":"Ince","year":"2016","journal-title":"Shock"},{"key":"R3-20231015","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1084\/jem.20111354","article-title":"A genomic storm in critically injured humans.","volume":"208","author":"Xiao","year":"2011","journal-title":"J Exp Med"},{"key":"R4-20231015","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJM198803243181202","article-title":"Genetic and environmental influences on premature death in adult adoptees.","volume":"318","author":"S\u00f8rensen","year":"1988","journal-title":"N Engl J Med"},{"key":"R5-20231015","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S2213-2600(14)70290-5","article-title":"Genome-wide association study of survival from sepsis due to pneumonia: An observational cohort study.","volume":"3","author":"Rautanen","year":"2015","journal-title":"Lancet Respir Med"},{"key":"R6-20231015","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1007\/s00134-006-0327-y","article-title":"A systematic review of the quality of genetic association studies in human sepsis.","volume":"32","author":"Clark","year":"2006","journal-title":"Intensive Care Med"},{"key":"R7-20231015","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/sj.gene.6364162","article-title":"Heritability estimates of innate immunity: An extended twin study.","volume":"6","author":"de Craen","year":"2005","journal-title":"Genes Immun"},{"key":"R8-20231015","doi-asserted-by":"crossref","first-page":"e10603","DOI":"10.1371\/journal.pone.0010603","article-title":"Genetic influences on incidence and case-fatality of infectious disease.","volume":"5","author":"Petersen","year":"2010","journal-title":"PLoS One"},{"key":"R9-20231015","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrg3114","article-title":"Human genetic susceptibility to infectious disease.","volume":"13","author":"Chapman","year":"2012","journal-title":"Nat Rev Genet"},{"key":"R10-20231015","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":"R11-20231015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-61779-316-5_1","article-title":"Advances in epigenetic technology.","volume":"791","author":"Tollefsbol","year":"2011","journal-title":"Methods Mol Biol"},{"key":"R12-20231015","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/490171a","article-title":"Epigenetics: Stress makes its molecular mark.","volume":"490","author":"Nestler","year":"2012","journal-title":"Nature"},{"key":"R13-20231015","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.tig.2007.05.008","article-title":"Epigenetics and aging: The targets and the marks.","volume":"23","author":"Fraga","year":"2007","journal-title":"Trends Genet"},{"key":"R14-20231015","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1177\/0193945912453685","article-title":"Validation of DNA methylation patterns: Potential biomarker for heritable risk of preeclampsia.","volume":"34","author":"Wright","year":"2012","journal-title":"West J Nurs Res"},{"key":"R15-20231015","doi-asserted-by":"crossref","first-page":"e1001212","DOI":"10.1371\/journal.pgen.1001212","article-title":"Altered DNA methylation in leukocytes with trisomy 21.","volume":"6","author":"Kerkel","year":"2010","journal-title":"PLoS Genet"},{"key":"R16-20231015","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1002\/ibd.21912","article-title":"Genome-wide methylation profiling in Crohn\u2019s disease identifies altered epigenetic regulation of key host defense mechanisms including the Th17 pathway.","volume":"18","author":"Nimmo","year":"2012","journal-title":"Inflamm Bowel Dis"},{"key":"R17-20231015","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/nature14125","article-title":"An epigenome-wide association study of total serum immunoglobulin E concentration.","volume":"520","author":"Liang","year":"2015","journal-title":"Nature"},{"key":"R18-20231015","doi-asserted-by":"crossref","first-page":"82","DOI":"10.18632\/aging.100715","article-title":"Identification of a DNA methylation signature in blood cells from persons with down syndrome.","volume":"7","author":"Bacalini","year":"2015","journal-title":"Aging (Albany NY)"},{"key":"R19-20231015","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrc1045","article-title":"The power and the promise of DNA methylation markers.","volume":"3","author":"Laird","year":"2003","journal-title":"Nat Rev Cancer"},{"key":"R20-20231015","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":"Castelo-Branco","year":"2013","journal-title":"Lancet Oncol"},{"key":"R21-20231015","doi-asserted-by":"crossref","first-page":"12484","DOI":"10.18632\/oncotarget.14226","article-title":"Epigenetic therapy in urologic cancers: An update on clinical trials.","volume":"8","author":"Faleiro","year":"2017","journal-title":"Oncotarget"},{"key":"R22-20231015","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/nrg.2016.93","article-title":"Targeting the cancer epigenome for therapy.","volume":"17","author":"Jones","year":"2016","journal-title":"Nat Rev Genet"},{"key":"R23-20231015","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1146\/annurev-med-111314-035900","article-title":"Epigenetic therapeutics: A new weapon in the war against cancer.","volume":"67","author":"Ahuja","year":"2016","journal-title":"Annu Rev Med"},{"key":"R24-20231015","doi-asserted-by":"crossref","first-page":"17046","DOI":"10.1073\/pnas.0806560105","article-title":"Persistent epigenetic differences associated with prenatal exposure to famine in humans.","volume":"105","author":"Heijmans","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R25-20231015","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1111\/j.1471-0528.2008.01822.x","article-title":"Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life.","volume":"115","author":"Painter","year":"2008","journal-title":"BJOG"},{"key":"R26-20231015","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13148-018-0522-z","article-title":"Paternal sepsis induces alterations of the sperm methylome and dampens offspring immune responses-an animal study.","volume":"10","author":"Bomans","year":"2018","journal-title":"Clin Epigenetics"},{"key":"R27-20231015","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nrg3230","article-title":"Functions of DNA methylation: Islands, start sites, gene bodies and beyond.","volume":"13","author":"Jones","year":"2012","journal-title":"Nat Rev Genet"},{"key":"R28-20231015","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":"R29-20231015","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":"Castelo-Branco","year":"2016","journal-title":"Oncotarget"},{"key":"R30-20231015","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":"R31-20231015","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cell.2007.02.006","article-title":"Epigenetics: A landscape takes shape.","volume":"128","author":"Goldberg","year":"2007","journal-title":"Cell"},{"key":"R32-20231015","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.1093\/nar\/gkq147","article-title":"Chromatin methylation activity of Dnmt3a and Dnmt3a\/3L is guided by interaction of the ADD domain with the histone H3 tail.","volume":"38","author":"Zhang","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"R33-20231015","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1073\/pnas.0909344107","article-title":"Histone modification levels are predictive for gene expression.","volume":"107","author":"Karli\u0107","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R34-20231015","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":"R35-20231015","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.bbrc.2009.08.003","article-title":"Helicobacter pylori causes runx3 gene methylation and its loss of expression in gastric epithelial cells, which is mediated by nitric oxide produced by macrophages.","volume":"388","author":"Katayama","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"key":"R36-20231015","doi-asserted-by":"crossref","first-page":"5771","DOI":"10.1158\/0008-5472.CAN-07-0529","article-title":"Expression of DNA methyltransferase 1 is activated by hepatitis B virus X protein via a regulatory circuit involving the p16INK4a-cyclin D1-CDK 4\/6-pRb-E2F1 pathway.","volume":"67","author":"Jung","year":"2007","journal-title":"Cancer Res"},{"key":"R37-20231015","doi-asserted-by":"crossref","first-page":"13467","DOI":"10.1073\/pnas.0702729104","article-title":"Histone modifications induced by a family of bacterial toxins.","volume":"104","author":"Hamon","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R38-20231015","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1111\/j.1462-5822.2011.01640.x","article-title":"The pathogenic Escherichia coli type III secreted protease NleC degrades the host acetyltransferase p300.","volume":"13","author":"Shames","year":"2011","journal-title":"Cell Microbiol"},{"key":"R39-20231015","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/ni1423","article-title":"An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses.","volume":"8","author":"Arbibe","year":"2007","journal-title":"Nat Immunol"},{"key":"R40-20231015","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.tim.2010.07.003","article-title":"Epigenetic reprogramming of host genes in viral and microbial pathogenesis.","volume":"18","author":"Paschos","year":"2010","journal-title":"Trends Microbiol"},{"key":"R41-20231015","doi-asserted-by":"crossref","first-page":"E1012","DOI":"10.1073\/pnas.1706928115","article-title":"MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape.","volume":"115","author":"Menachery","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R42-20231015","doi-asserted-by":"crossref","first-page":"e01174","DOI":"10.1128\/mBio.01174-14","article-title":"Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses.","volume":"5","author":"Menachery","year":"2014","journal-title":"mBio"},{"key":"R43-20231015","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature10892","article-title":"Suppression of the antiviral response by an influenza histone mimic.","volume":"483","author":"Marazzi","year":"2012","journal-title":"Nature"},{"issue":"Suppl 1","key":"R44-20231015","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/01.shk.0000191384.34066.85","article-title":"Evaluation of endotoxin models for the study of sepsis.","volume":"24","author":"Remick","year":"2005","journal-title":"Shock"},{"key":"R45-20231015","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1073\/pnas.1401965111","article-title":"Genomic responses in mouse models greatly mimic human inflammatory diseases.","volume":"112","author":"Takao","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R46-20231015","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13054-015-0783-2","article-title":"Human metabolic response to systemic inflammation: Assessment of the concordance between experimental endotoxemia and clinical cases of sepsis\/SIRS.","volume":"19","author":"Kamisoglu","year":"2015","journal-title":"Crit Care"},{"key":"R47-20231015","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":"R48-20231015","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":"R49-20231015","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":"El Gazzar","year":"2010","journal-title":"J Biol Chem"},{"key":"R50-20231015","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":"R51-20231015","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":"R52-20231015","doi-asserted-by":"crossref","first-page":"4925","DOI":"10.1210\/en.2014-1595","article-title":"Inhibiting DNA methylation by 5-aza-2\u2019-deoxycytidine ameliorates atherosclerosis through suppressing macrophage inflammation.","volume":"155","author":"Cao","year":"2014","journal-title":"Endocrinology"},{"key":"R53-20231015","doi-asserted-by":"crossref","first-page":"e0163690","DOI":"10.1371\/journal.pone.0163690","article-title":"Procainamide inhibits DNA methylation and alleviates multiple organ dysfunction in rats with endotoxic shock.","volume":"11","author":"Shih","year":"2016","journal-title":"PLoS One"},{"key":"R54-20231015","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/nri3552","article-title":"Sepsis-induced immunosuppression: From cellular dysfunctions to immunotherapy.","volume":"13","author":"Hotchkiss","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"R55-20231015","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1186\/cc13110","article-title":"Pathophysiology of endotoxin tolerance: Mechanisms and clinical consequences.","volume":"17","author":"L\u00f3pez-Collazo","year":"2013","journal-title":"Crit Care"},{"key":"R56-20231015","doi-asserted-by":"crossref","first-page":"32198","DOI":"10.1074\/jbc.M803446200","article-title":"G9a and HP1 couple histone and DNA methylation to TNFalpha transcription silencing during endotoxin tolerance.","volume":"283","author":"El Gazzar","year":"2008","journal-title":"J Biol Chem"},{"key":"R57-20231015","doi-asserted-by":"crossref","first-page":"461","DOI":"10.4049\/jimmunol.175.1.461","article-title":"Endotoxin tolerance disrupts chromatin remodeling and NF-kappaB transactivation at the IL-1beta promoter.","volume":"175","author":"Chan","year":"2005","journal-title":"J Immunol"},{"key":"R58-20231015","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":"El Gazzar","year":"2010","journal-title":"J Biol Chem"},{"key":"R59-20231015","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":"El Gazzar","year":"2011","journal-title":"J Leukoc Biol"},{"key":"R60-20231015","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":"R61-20231015","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":"R62-20231015","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":"R63-20231015","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1586\/1744666X.2014.943192","article-title":"Epigenetic coordination of acute systemic inflammation: Potential therapeutic targets.","volume":"10","author":"Vachharajani","year":"2014","journal-title":"Expert Rev Clin Immunol"},{"key":"R64-20231015","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.3892\/mmr.2013.1405","article-title":"Genome-wide analysis of DNA methylation in rat lungs with lipopolysaccharide-induced acute lung injury.","volume":"7","author":"Zhang","year":"2013","journal-title":"Mol Med Rep"},{"key":"R65-20231015","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/adb.12037","article-title":"Genome-wide DNA methylation analysis in alcohol dependence.","volume":"18","author":"Zhang","year":"2013","journal-title":"Addict Biol"},{"key":"R66-20231015","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.biopha.2016.09.072","article-title":"Decitabine and 5-azacitidine both alleviate LPS induced ARDS through anti-inflammatory\/antioxidant activity and protection of glycocalyx and inhibition of MAPK pathways in mice.","volume":"84","author":"Huang","year":"2016","journal-title":"Biomed Pharmacother"},{"key":"R67-20231015","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1165\/rcmb.2014-0327OC","article-title":"Regulatory T cell DNA methyltransferase inhibition accelerates resolution of lung inflammation.","volume":"52","author":"Singer","year":"2015","journal-title":"Am J Respir Cell Mol Biol"},{"key":"R68-20231015","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1007\/s00268-010-0493-5","article-title":"Histone deacetylase inhibitors attenuate acute lung injury during cecal ligation and puncture-induced polymicrobial sepsis.","volume":"34","author":"Zhang","year":"2010","journal-title":"World J Surg"},{"key":"R69-20231015","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.4161\/epi.26645","article-title":"DNA methylation pattern of CALCA in preterm neonates with bacterial sepsis as a putative epigenetic biomarker.","volume":"8","author":"Tendl","year":"2013","journal-title":"Epigenetics"},{"key":"R70-20231015","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.gdata.2014.11.004","article-title":"Comparison of genomic DNA methylation pattern among septic and non-septic newborns - an epigenome wide association study.","volume":"3","author":"Dhas","year":"2015","journal-title":"Genom Data"},{"key":"R71-20231015","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1097\/CCM.0000000000004097","article-title":"Epigenetic profiling in severe sepsis: A pilot study of DNA methylation profiles in critical illness.","volume":"48","author":"Binnie","year":"2020","journal-title":"Crit Care Med"},{"key":"R72-20231015","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3389\/fimmu.2017.00118","article-title":"Circulating microRNAs as potential biomarkers of infectious disease.","volume":"8","author":"Correia","year":"2017","journal-title":"Front Immunol"},{"key":"R73-20231015","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1097\/CCM.0000000000000131","article-title":"Levels of circulating miR-133a are elevated in sepsis and predict mortality in critically ill patients.","volume":"42","author":"Tacke","year":"2014","journal-title":"Crit Care Med"},{"key":"R74-20231015","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.bbrc.2010.02.145","article-title":"Serum miR-146a and miR-223 as potential new biomarkers for sepsis.","volume":"394","author":"Wang","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"R75-20231015","doi-asserted-by":"crossref","first-page":"e38885","DOI":"10.1371\/journal.pone.0038885","article-title":"Serum microRNA signatures identified by solexa sequencing predict sepsis patients\u2019 mortality: A prospective observational study.","volume":"7","author":"Wang","year":"2012","journal-title":"PLoS One"},{"key":"R76-20231015","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3390\/ijms17010078","article-title":"Circulating microRNAs as biomarkers for sepsis.","volume":"17","author":"Benz","year":"2016","journal-title":"Int J Mol Sci"},{"key":"R77-20231015","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.surg.2010.05.003","article-title":"Surviving lethal septic shock without fluid resuscitation in a rodent model.","volume":"148","author":"Li","year":"2010","journal-title":"Surgery"},{"key":"R78-20231015","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.surg.2012.06.036","article-title":"Creating a \u201cpro-survival\u201d phenotype through epigenetic modulation.","volume":"152","author":"Li","year":"2012","journal-title":"Surgery"},{"key":"R79-20231015","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.coph.2017.05.006","article-title":"Epigenetic modulation in cancer immunotherapy.","volume":"35","author":"Gallagher","year":"2017","journal-title":"Curr Opin Pharmacol"},{"key":"R80-20231015","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1080\/13543784.2019.1557634","article-title":"New developments in investigational HDAC inhibitors for the potential multimodal treatment of cachexia.","volume":"28","author":"Penna","year":"2019","journal-title":"Expert Opin Investig Drugs"},{"key":"R81-20231015","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1038\/s41467-017-01645-7","article-title":"Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival.","volume":"8","author":"Segatto","year":"2017","journal-title":"Nat Commun"},{"key":"R82-20231015","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1007\/s00213-018-4947-z","article-title":"A translational perspective on histone acetylation modulators in psychiatric disorders.","volume":"235","author":"Ganguly","year":"2018","journal-title":"Psychopharmacology (Berl)"},{"key":"R83-20231015","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s13148-017-0378-7","article-title":"Translating epigenetics into clinic: Focus on lupus.","volume":"9","author":"Wang","year":"2017","journal-title":"Clin Epigenetics"},{"key":"R84-20231015","doi-asserted-by":"crossref","first-page":"baw159","DOI":"10.1093\/database\/baw159","article-title":"HEDD: The human epigenetic drug database.","volume":"2016","author":"Qi","year":"2016","journal-title":"Database (Oxford)"},{"key":"R85-20231015","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/S1074-7613(00)80642-1","article-title":"Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation.","volume":"9","author":"Agarwal","year":"1998","journal-title":"Immunity"},{"key":"R86-20231015","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/ni887","article-title":"Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process.","volume":"4","author":"Bruniquel","year":"2003","journal-title":"Nat Immunol"},{"key":"R87-20231015","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S2213-2600(16)00046-1","article-title":"Genomic landscape of the individual host response and outcomes in sepsis: A prospective cohort study.","volume":"4","author":"Davenport","year":"2016","journal-title":"Lancet Respir Med"}],"container-title":["Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/CCM.0000000000004247","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T08:14:00Z","timestamp":1697357640000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/CCM.0000000000004247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5]]},"references-count":87,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.1097\/ccm.0000000000004247","relation":{},"ISSN":["0090-3493"],"issn-type":[{"value":"0090-3493","type":"print"}],"subject":[],"published":{"date-parts":[[2020,5]]}}}