{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:40:52Z","timestamp":1785904852005,"version":"3.56.0"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T00:00:00Z","timestamp":1583280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001502","name":"Department of Atomic Energy, Government of India","doi-asserted-by":"publisher","award":["CTCTMC awarded to Tata Memorial Centre"],"award-info":[{"award-number":["CTCTMC awarded to Tata Memorial Centre"]}],"id":[{"id":"10.13039\/501100001502","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0229017","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T18:25:37Z","timestamp":1583346337000},"page":"e0229017","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Cell-free chromatin particles released from dying host cells are global instigators of endotoxin sepsis in mice"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5768-3821","authenticated-orcid":true,"given":"Indraneel","family":"Mittra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Pal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namrata","family":"Pancholi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pritishkumar","family":"Tidke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophiya","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhagyeshri","family":"Rane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenevieve","family":"D\u2019souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfina","family":"Shaikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saili","family":"Parab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushma","family":"Shinde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Jadhav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soniya","family":"Shende","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorantla V.","family":"Raghuram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,3,4]]},"reference":[{"key":"pone.0229017.ref001","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S2213-2600(14)70061-X","article-title":"Assessment of the worldwide burden of critical illness: The Intensive Care Over Nations (ICON) audit","volume":"5","author":"JL Vincent","year":"2014","journal-title":"Lancet Respir Med"},{"key":"pone.0229017.ref002","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1164\/rccm.201504-0781OC","article-title":"Assessment of Global Incidence and Mortality of Hospital-treated Sepsis","volume":"193","author":"C Fleischmann","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0229017.ref003","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1056\/NEJMra021333","article-title":"The Pathophysiology and Treatment of Sepsis","volume":"348","author":"RS Hotchkiss","year":"2003","journal-title":"N Engl J Med"},{"key":"pone.0229017.ref004","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1080\/00365540310015692","article-title":"Role of apoptotic cell death in sepsis","volume":"35","author":"Tinsley KW Hotchkiss","year":"2003","journal-title":"Scand J Infect Dis"},{"key":"pone.0229017.ref005","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/MCC.0b013e328344b446","article-title":"Multiple organ failure in sepsis: Prognosis and role of systemic inflammatory response","volume":"17","author":"T. Gustot","year":"2011","journal-title":"Curr Opin Crit Care"},{"key":"pone.0229017.ref006","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.thromres.2016.11.007","article-title":"Coagulation and sepsis","volume":"149","author":"M Levi","year":"2017","journal-title":"Thromb Res"},{"key":"pone.0229017.ref007","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.ccc.2005.04.002","article-title":"Does disseminated intravascular coagulation lead to multiple organ failure?","volume":"21","author":"JL Vincent","year":"2005","journal-title":"Crit Care Clin"},{"key":"pone.0229017.ref008","first-page":"1076029618806424","article-title":"Disseminated Intravascular Coagulation: An Update on Pathogenesis, Diagnosis, and Therapeutic Strategies","volume":"8","author":"C Papageorgiou","year":"2018","journal-title":"Clin Appl Thromb"},{"key":"pone.0229017.ref009","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0140-6736(18)30696-2","article-title":"Sepsis and septic shock","volume":"392","author":"M Cecconi","year":"2018","journal-title":"Lancet"},{"key":"pone.0229017.ref010","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1001\/jama.2011.1853","article-title":"The search for effective therapy for sepsis: Back to the drawing board?","volume":"306","author":"DC Angus","year":"2011","journal-title":"JAMA"},{"key":"pone.0229017.ref011","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S1473-3099(15)70112-X","article-title":"Sepsis: A roadmap for future research","volume":"15","author":"J Cohen","year":"2015","journal-title":"Lancet Infect Dis"},{"key":"pone.0229017.ref012","doi-asserted-by":"crossref","first-page":"17015","DOI":"10.1038\/cddiscovery.2017.15","article-title":"Cell-free chromatin from dying cancer cells integrate into genomes of healthy cells to induce DNA damage and inflammation","volume":"3","author":"I Mittra","year":"2017","journal-title":"Cell Death Discov"},{"key":"pone.0229017.ref013","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s12038-015-9508-6","article-title":"Circulating nucleic acids damage DNA of healthy cells by integrating into their genomes","volume":"40","author":"I Mittra","year":"2015","journal-title":"J. Biosci"},{"key":"pone.0229017.ref014","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.mrfmmm.2016.10.002","article-title":"Evidence for cell-free nucleic acids as continuously arising endogenous DNA mutagens","volume":"793\u2013794","author":"R Basak","year":"2016","journal-title":"Mutat Res\u2014Fundam Mol Mech Mutagen"},{"key":"pone.0229017.ref015","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.mrfmmm.2018.02.002","article-title":"Is inflammation a direct response to dsDNA breaks?","volume":"808","author":"S. Chaudhary","year":"2018","journal-title":"Mutat Res\u2014Fundam Mol Mech Mutagen"},{"key":"pone.0229017.ref016","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s12038-019-9849-7","article-title":"Cell-free chromatin: A newly described mediator of systemic inflammation","volume":"44","author":"S. Chaudhary","year":"2019","journal-title":"J Biosci"},{"key":"pone.0229017.ref017","doi-asserted-by":"crossref","first-page":"407","DOI":"10.3390\/genes10060407","article-title":"Illegitimate and Repeated Genomic Integration of Cell-Free Chromatin in the Aetiology of Somatic Mosaicism, Ageing, Chronic Diseases and Cancer","volume":"10","author":"R. V. Gorantla","year":"2019","journal-title":"Genes"},{"key":"pone.0229017.ref018","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2119\/molmed.2010.00001.commentary","article-title":"\u201cMerinoff Symposium 2010: Sepsis\u201d\u2014Speaking with One Voice","volume":"17","author":"J. C Christopher","year":"2011","journal-title":"Mol Med"},{"key":"pone.0229017.ref019","doi-asserted-by":"crossref","first-page":"6328","DOI":"10.1016\/j.biomaterials.2013.05.019","article-title":"Pullulan-histone antibody nanoconjugates for the removal of chromatin fragments from systemic circulation","volume":"34","author":"MR Rekha","year":"2013","journal-title":"Biomaterials"},{"key":"pone.0229017.ref020","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1093\/annonc\/mdx318","article-title":"Prevention of chemotherapy toxicity by agents that neutralize or degrade cell-free chromatin","volume":"28","author":"I. Mittra","year":"2017","journal-title":"Ann Oncol"},{"key":"pone.0229017.ref021","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ifset.2009.07.002","article-title":"Antioxidant properties of resveratrol: A structure-activity insight","volume":"11","author":"I G\u00fcl\u00e7in","year":"2010","journal-title":"Innov Food Sci Emerg Technol"},{"key":"pone.0229017.ref022","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1016\/S0960-894X(98)00585-X","article-title":"Resveratrol as a new type of DNA-cleaving agent","volume":"8","author":"K Fukuhara","year":"1998","journal-title":"Bioorganic Med Chem Lett"},{"key":"pone.0229017.ref023","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1042\/BST0351156","article-title":"Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications","volume":"35","author":"C. A. de la Lastra","year":"2007","journal-title":"Biochem Soc Trans"},{"key":"pone.0229017.ref024","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.12688\/f1000research.7202.1","article-title":"A paradoxical relationship between Resveratrol and copper (II) with respect to degradation of DNA and RNA","volume":"4","author":"S. Subramaniam","year":"2015","journal-title":"F1000Res"},{"key":"pone.0229017.ref025","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/s41419-018-1181-x","article-title":"Prevention of radiation-induced bystander effects by agents that inactivate cell-free chromatin released from irradiated dying cells","volume":"9","author":"S Kirolikar","year":"2018","journal-title":"Cell Death Dis"},{"key":"pone.0229017.ref026","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1172\/JCI117842","article-title":"Involvement of reactive oxygen intermediates in cyclooxygenase-2 expression induced by interleukin-1, tumor necrosis factor-a, and lipopolysaccharide","volume":"95","author":"L Feng","year":"1995","journal-title":"J. Clin. Invest"},{"key":"pone.0229017.ref027","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1128\/CDLI.12.1.60-67.2005","article-title":"Inflammation and the Host Response to Injury Investigators. Acute inflammatory response to endotoxin in mice and humans","volume":"12","author":"S Copeland","year":"2005","journal-title":"Clin Diagn Lab Immunol"},{"key":"pone.0229017.ref028","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1128\/IAI.58.11.3743-3750.1990","article-title":"Cytokine induction by lipopolysaccharide (LPS) corresponds to lethal toxicity and is inhibited by nontoxic Rhodobacter capsulatus LPS","volume":"58","author":"H Loppnow","year":"1990","journal-title":"Infect Immun"},{"key":"pone.0229017.ref029","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1080\/00365540310015692","article-title":"Role of apoptotic cell death in sepsis","volume":"35","author":"RS Hotchkiss","year":"2003","journal-title":"Scand J Infect Dis"},{"key":"pone.0229017.ref030","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/00024382-199504000-00003","article-title":"The induction of accelerated thymic programmed cell death during polymicrobial sepsis: control by corticosteroids but not tumor necrosis factor","volume":"3","author":"A Ayala","year":"1995","journal-title":"Shock"},{"key":"pone.0229017.ref031","doi-asserted-by":"crossref","first-page":"646","DOI":"10.4103\/0377-4929.72013","article-title":"Apoptosis of peripheral blood mononuclear cells in patients with sepsis","volume":"53","author":"Z Jadali","year":"2010","journal-title":"Indian J Pathol Microbiol"},{"key":"pone.0229017.ref032","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1097\/MCC.0b013e328344b446","article-title":"Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response","volume":"17","author":"T Gustot","year":"2011","journal-title":"Curr Opin Crit Care"},{"key":"pone.0229017.ref033","doi-asserted-by":"crossref","first-page":"27","DOI":"10.21037\/jeccm.2017.09.04","article-title":"Sepsis-induced multi-organ dysfunction syndrome\u2014a mechanistic approach","volume":"1","author":"DS Herbert","year":"2017","journal-title":"J Emerg Crit Care Med"},{"key":"pone.0229017.ref034","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40560-015-0105-4","article-title":"Lactate kinetics in sepsis and septic shock: a review of the literature and rationale for further research","volume":"3","author":"J Chertoff","year":"2015","journal-title":"J Intensive Care"},{"key":"pone.0229017.ref035","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/ACO.0000000000000163","article-title":"The coagulopathy of acute sepsis","volume":"28","author":"J Simmons","year":"2015","journal-title":"Curr. Opin. Anaesthesiol"},{"key":"pone.0229017.ref036","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.ccm.2008.06.006","article-title":"The coagulant response in sepsis","volume":"29","author":"M Levi","year":"2008","journal-title":"Clin Chest Med"},{"key":"pone.0229017.ref037","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s40560-014-0051-6","article-title":"Efficacy of antithrombin in preclinical and clinical applications for sepsis-associated disseminated intravascular coagulation","volume":"2","author":"I Toshiaki","year":"2014","journal-title":"J Intensive Care"},{"key":"pone.0229017.ref038","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s11908-007-1008-x","article-title":"The role of protein C in sepsis","volume":"3","author":"MR Looney","year":"2007","journal-title":"Curr Infect Dis Rep"},{"key":"pone.0229017.ref039","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0168-8278(02)00324-0","article-title":"Bacterial lipopolysaccharide decreases thrombomodulin expression in the sinusoidal endothelial cells of rats\u2014a possible mechanism of intrasinusoidal microthrombus formation and liver dysfunction","volume":"38","author":"M Kume","year":"2003","journal-title":"J Hepatol"},{"key":"pone.0229017.ref040","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1177\/1076029613492875","article-title":"Thrombin generation mediators and markers in sepsis-associated coagulopathy and their modulation by recombinant thrombomodulin","volume":"20","author":"D Hoppensteadt","year":"2014","journal-title":"Clin Appl Thromb Hemost"},{"key":"pone.0229017.ref041","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s13613-017-0337-7","article-title":"Blood platelets and sepsis pathophysiology: A new therapeutic prospect in critical ill patients?","volume":"7","author":"A Dewitte","year":"2017","journal-title":"Ann Intensive Care"},{"key":"pone.0229017.ref042","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1097\/01.CCM.0000074719.40109.95","article-title":"Elevated nucleosome levels in systemic inflammation and sepsis","volume":"31","author":"S Zeerleder","year":"2003","journal-title":"Crit Care Med"},{"key":"pone.0229017.ref043","doi-asserted-by":"crossref","first-page":"e558","DOI":"10.1016\/j.ijid.2012.03.007","article-title":"Circulating nucleosomes as a predictor of sepsis and organ dysfunction in critically ill patients","volume":"16","author":"Q Chen","year":"2012","journal-title":"Int J Infect Dis"},{"key":"pone.0229017.ref044","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1038\/nm.2053","article-title":"Extracellular histones are major mediators of death in sepsis","volume":"15","author":"J Xu","year":"2009","journal-title":"Nat Med"},{"key":"pone.0229017.ref045","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1164\/rccm.201206-1037OC","article-title":"Circulating histones are mediators of trauma-associated lung injury","volume":"187","author":"ST Abrams","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0229017.ref046","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.4049\/jimmunol.1003930","article-title":"Extracellular Histones Are Mediators of Death through TLR2 and TLR4 in Mouse Fatal Liver Injury","volume":"187","author":"J Xu","year":"2011","journal-title":"J Immunol"},{"key":"pone.0229017.ref047","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1097\/SHK.0000000000000221","article-title":"Neutrophil extracellular traps in sepsis","volume":"42","author":"G Camicia","year":"2014","journal-title":"Shock"},{"key":"pone.0229017.ref048","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3389\/fvets.2018.00291","article-title":"A Comparative Review of Neutrophil Extracellular Traps in Sepsis","volume":"5","author":"HLL Ronald","year":"2018","journal-title":"Front Vet Sci"},{"key":"pone.0229017.ref049","doi-asserted-by":"crossref","first-page":"e21055","DOI":"10.7554\/eLife.21055","article-title":"Peripherally administered orexin improves survival of mice with endotoxin shock","volume":"5","author":"Y Ogawa","year":"2016","journal-title":"Elife"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0229017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T14:10:09Z","timestamp":1614694209000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0229017"}},"subtitle":[],"editor":[{"given":"Partha","family":"Mukhopadhyay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,3,4]]},"references-count":49,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0229017","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,4]]}}}