{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T10:29:31Z","timestamp":1794479371446,"version":"4.9.1"},"reference-count":54,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010937","name":"St. John's University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010937","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1R16GM145586"],"award-info":[{"award-number":["1R16GM145586"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","em-consulte.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomedicine & Pharmacotherapy"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.biopha.2026.119403","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T14:18:47Z","timestamp":1776521927000},"page":"119403","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["The FDA-approved excipient N,N-dimethylacetamide improves survival and attenuates inflammatory pathways in a murine model of endotoxemia"],"prefix":"10.1016","volume":"199","author":[{"given":"Zhihui","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2415-0159","authenticated-orcid":false,"given":"Sean","family":"Carrig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6272-7198","authenticated-orcid":false,"given":"Sandra E.","family":"Reznik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"8","key":"10.1016\/j.biopha.2026.119403_bib1","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"},{"issue":"7","key":"10.1016\/j.biopha.2026.119403_bib2","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2020.6004","article-title":"Assessment of health care exposures and outcomes in adult patients with sepsis and septic shock","volume":"3","author":"Fay","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"10.1016\/j.biopha.2026.119403_bib3","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."},{"issue":"3","key":"10.1016\/j.biopha.2026.119403_bib4","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1097\/TA.0b013e31829de6cd","article-title":"Acute kidney injury is surprisingly common and a powerful predictor of mortality in surgical sepsis","volume":"75","author":"White","year":"2013","journal-title":"J. Trauma Acute Care Surg."},{"issue":"8","key":"10.1016\/j.biopha.2026.119403_bib5","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1001\/jama.2017.0131","article-title":"Management of sepsis and septic shock","volume":"317","author":"Howell","year":"2017","journal-title":"JAMA"},{"issue":"1","key":"10.1016\/j.biopha.2026.119403_bib6","first-page":"53","article-title":"Sepsis and septic shock: current treatment strategies and new approaches","volume":"49","author":"Polat","year":"2017","journal-title":"Eurasia J. Med."},{"issue":"13","key":"10.1016\/j.biopha.2026.119403_bib7","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1200\/JCO.2006.08.8807","article-title":"J. Boss, Cytotoxicity of dimethylacetamide and pharmacokinetics in children receiving intravenous busulfan","volume":"25","author":"Hempel","year":"2007","journal-title":"J. Clin. Oncol."},{"issue":"5a","key":"10.1016\/j.biopha.2026.119403_bib8","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/S1083-8791(00)70064-4","article-title":"Acute safety and pharmacokinetics of intravenous busulfan when used with oral busulfan and cyclophosphamide as pretransplantation conditioning therapy: a phase I study","volume":"6","author":"Andersson","year":"2000","journal-title":"Biol. Blood Marrow Transpl."},{"issue":"5","key":"10.1016\/j.biopha.2026.119403_bib9","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s002800050404","article-title":"Formulation and stability of busulfan for intravenous administration in high-dose chemotherapy","volume":"37","author":"Bhagwatwar","year":"1996","journal-title":"Cancer Chemother. Pharm."},{"issue":"2","key":"10.1016\/j.biopha.2026.119403_bib10","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.ajpath.2013.05.006","article-title":"N,N-dimethylacetamide regulates the proinflammatory response associated with endotoxin and prevents preterm birth","volume":"183","author":"Sundaram","year":"2013","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.biopha.2026.119403_bib11","doi-asserted-by":"crossref","first-page":"42108","DOI":"10.1038\/srep42108","article-title":"a drug excipient that acts as bromodomain ligand for osteoporosis treatment","volume":"7","author":"Ghayor","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.biopha.2026.119403_bib12","doi-asserted-by":"crossref","first-page":"747","DOI":"10.2119\/molmed.2016.00017","article-title":"N,N-dimethylacetamide significantly attenuates LPS- and TNFalpha-induced proinflammatory responses via inhibition of the nuclear factor kappa B pathway","volume":"22","author":"Pekson","year":"2016","journal-title":"Mol. Med."},{"key":"10.1016\/j.biopha.2026.119403_bib13","doi-asserted-by":"crossref","first-page":"499","DOI":"10.26502\/fjhs.076","article-title":"FDA-approved excipient N,N-dimethylacetamide attenuates inflammatory bowel disease in in vitro and in vivo models","volume":"5","author":"Koya","year":"2022","journal-title":"Fortune J. Health Sci."},{"key":"10.1016\/j.biopha.2026.119403_bib14","doi-asserted-by":"crossref","first-page":"8234","DOI":"10.1038\/s41598-025-93282-0","article-title":"N,N-dimethylacetamide blocks inflammation-induced preterm birth and remediates maternal systemic immune responses","volume":"15","author":"Reznik","year":"2025","journal-title":"Sci. Rep."},{"key":"10.1016\/j.biopha.2026.119403_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbadis.2025.167822","article-title":"Improving the safety of N,N-dimethylacetamide (DMA) as a potential treatment for preterm birth in a pregnant mouse model using a vaginal nanoformulation","volume":"1871","author":"Mir","year":"2025","journal-title":"BBA Mol. Basis Dis."},{"issue":"1","key":"10.1016\/j.biopha.2026.119403_bib16","doi-asserted-by":"crossref","first-page":"7077","DOI":"10.1038\/s41598-023-34355-w","article-title":"N,N-dimethylacetamide targets neuroinflammation in Alzheimer's disease in in vitro and ex vivo models","volume":"13","author":"Wei","year":"2023","journal-title":"Sci. Rep."},{"key":"10.1016\/j.biopha.2026.119403_bib17","doi-asserted-by":"crossref","first-page":"3.20.1","DOI":"10.1002\/0471142735.im0320s110","article-title":"Isolation of mouse neutrophils","volume":"110","author":"Swamydas","year":"2015","journal-title":"Curr. Protoc. Immunol."},{"issue":"1","key":"10.1016\/j.biopha.2026.119403_bib18","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1186\/s13054-021-03736-w","article-title":"Initial antimicrobial management of sepsis","volume":"25","author":"Niederman","year":"2012","journal-title":"Crit. Care"},{"issue":"7","key":"10.1016\/j.biopha.2026.119403_bib19","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1001\/jamainternmed.2024.0581","article-title":"Mortality of patients with sepsis administered piperacillin-tazobactam vs cefepime","volume":"184","author":"Chanderraj","year":"2024","journal-title":"JAMA Intern. Med."},{"issue":"9","key":"10.1016\/j.biopha.2026.119403_bib20","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1001\/jamasurg.2022.2761","article-title":"Association between time to source control in sepsis and 90-day mortality","volume":"157","author":"Reitz","year":"2022","journal-title":"JAMA Surg."},{"issue":"6","key":"10.1016\/j.biopha.2026.119403_bib21","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1056\/NEJMoa2212663","article-title":"Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network, Early restrictive or liberal fluid management for sepsis-induced hypotension","volume":"388","author":"National Heart","year":"2023","journal-title":"N. Engl. J. Med."},{"issue":"1","key":"10.1016\/j.biopha.2026.119403_bib22","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13613-022-01021-9","article-title":"Timing of vasoactive agents and corticosteroid initiation in septic shock","volume":"12","author":"Ammar","year":"2022","journal-title":"Ann. Intensive Care"},{"key":"10.1016\/j.biopha.2026.119403_bib23","article-title":"Corticosteroids for treating sepsis in children and adults","author":"Annane","year":"2025","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.biopha.2026.119403_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2022.104318","article-title":"Current sepsis therapeutics","volume":"86","author":"Vincent","year":"2022","journal-title":"eBioMedicine"},{"issue":"3","key":"10.1016\/j.biopha.2026.119403_bib25","doi-asserted-by":"crossref","DOI":"10.1186\/cc9019","article-title":"The impact of IL-1 modulation on the development of lipopolysaccharide-induced cognitive dysfunction","volume":"14","author":"Terrando","year":"2010","journal-title":"Crit. Care"},{"issue":"4","key":"10.1016\/j.biopha.2026.119403_bib26","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1590\/S1807-59322007000400017","article-title":"Characterization of an animal model of severe sepsis associated with respiratory dysfunction","volume":"62","author":"de Azevedo","year":"2007","journal-title":"Clin. (Sao Paulo)"},{"issue":"3","key":"10.1016\/j.biopha.2026.119403_bib27","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.neuint.2007.08.006","article-title":"TNF is a key mediator of septic encephalopathy acting through its receptor, TNF receptor-1","volume":"52","author":"Alexander","year":"2008","journal-title":"Neurochem. Int."},{"issue":"2","key":"10.1016\/j.biopha.2026.119403_bib28","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1006\/jsre.1999.5584","article-title":"Kupffer cells are responsible for producing inflammatory cytokines and hepatocellular dysfunction during early sepsis","volume":"83","author":"Koo","year":"1999","journal-title":"J. Surg. Res."},{"issue":"6","key":"10.1016\/j.biopha.2026.119403_bib29","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1097\/00024382-199612000-00008","article-title":"Modulation of Kupffer cell activity by gadolinium chloride in endotoxemic rats","volume":"6","author":"Vollmar","year":"1996","journal-title":"Shock"},{"key":"10.1016\/j.biopha.2026.119403_bib30","article-title":"PPARgamma alleviates sepsis-induced liver injury by inhibiting hepatocyte pyroptosis via inhibition of the ROS\/TXNIP\/NLRP3 signaling pathway","author":"Li","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"issue":"2","key":"10.1016\/j.biopha.2026.119403_bib31","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0014-5793(89)80476-4","article-title":"Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes","volume":"242","author":"Castell","year":"1989","journal-title":"FEBS Lett."},{"issue":"5","key":"10.1016\/j.biopha.2026.119403_bib32","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1002\/hep.1840120517","article-title":"Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6","volume":"12","author":"Castell","year":"1990","journal-title":"Hepatology"},{"issue":"7","key":"10.1016\/j.biopha.2026.119403_bib33","doi-asserted-by":"crossref","first-page":"4470","DOI":"10.4049\/jimmunol.172.7.4470","article-title":"CD14 is an acute-phase protein","volume":"172","author":"Bas","year":"2004","journal-title":"J. Immunol."},{"issue":"5","key":"10.1016\/j.biopha.2026.119403_bib34","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.jcrc.2013.04.010","article-title":"Coagulopathy, catecholamines, and biomarkers of endothelial damage in experimental human endotoxemia and in patients with severe sepsis: a prospective study","volume":"28","author":"Ostrowski","year":"2013","journal-title":"J. Crit. Care"},{"key":"10.1016\/j.biopha.2026.119403_bib35","doi-asserted-by":"crossref","first-page":"S42","DOI":"10.1097\/00003246-200107001-00016","article-title":"Hepatic response to sepsis: interaction between coagulation and inflammatory processes","volume":"29","author":"Dhainaut","year":"2001","journal-title":"Crit. Care Med."},{"issue":"1","key":"10.1016\/j.biopha.2026.119403_bib36","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.cardiores.2005.05.010","article-title":"C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation","volume":"68","author":"Cirillo","year":"2005","journal-title":"Cardiovasc. Res."},{"issue":"2","key":"10.1016\/j.biopha.2026.119403_bib37","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1006\/bbrc.2000.2143","article-title":"A novel function of serum amyloid A: a potent stimulus for the release of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-8 by human blood neutrophil","volume":"268","author":"Furlaneto","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"6","key":"10.1016\/j.biopha.2026.119403_bib38","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1189\/jlb.3VMR0315-080R","article-title":"Emerging functions of serum amyloid A in inflammation","volume":"98","author":"Ye","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"10.1016\/j.biopha.2026.119403_bib39","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/8356645","article-title":"Lipopolysaccharide-induced transcriptional changes in LBP-deficient rat and its possible implications for liver dysregulation during sepsis","author":"He","year":"2021","journal-title":"J. Immunol. Res."},{"issue":"6-7","key":"10.1016\/j.biopha.2026.119403_bib40","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.ejcb.2011.09.008","article-title":"Hepatic acute phase proteins\u2014regulation by IL-6- and IL-1-type cytokines involving STAT3 and its crosstalk with NF-kappaB-dependent signaling","volume":"91","author":"Bode","year":"2012","journal-title":"Eur. J. Cell Biol."},{"issue":"1","key":"10.1016\/j.biopha.2026.119403_bib41","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/imr.12499","article-title":"The immune system's role in sepsis progression, resolution, and long-term outcome","volume":"274","author":"Delano","year":"2016","journal-title":"Immunol. Rev."},{"issue":"2","key":"10.1016\/j.biopha.2026.119403_bib42","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/0168-8278(95)80433-1","article-title":"Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge","volume":"22","author":"Knolle","year":"1995","journal-title":"J. Hepatol."},{"issue":"7","key":"10.1016\/j.biopha.2026.119403_bib43","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.4049\/jimmunol.167.7.3919","article-title":"Critical role of Kupffer cell-derived IL-10 for host defense in septic peritonitis","volume":"167","author":"Emmanuilidis","year":"2001","journal-title":"J. Immunol."},{"issue":"5","key":"10.1016\/j.biopha.2026.119403_bib44","first-page":"6357","article-title":"Kupffer cell depletion by gadolinium chloride aggravates liver injury after brain death in rats","volume":"17","author":"Zhu","year":"2018","journal-title":"Mol. Med. Rep."},{"issue":"3","key":"10.1016\/j.biopha.2026.119403_bib45","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1089\/wound.2013.0512","article-title":"SERPINE1: a molecular switch in the proliferation-migration dichotomy in wound-activated keratinocytes","volume":"3","author":"Simone","year":"2014","journal-title":"Adv. Wound Care"},{"issue":"11","key":"10.1016\/j.biopha.2026.119403_bib46","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1159\/000516195","article-title":"Research progress on the SERPINE1 protein and chronic inflammatory diseases of the upper respiratory tract: a literature review","volume":"182","author":"Chen","year":"2021","journal-title":"Int. Arch. Allergy Immunol."},{"issue":"3","key":"10.1016\/j.biopha.2026.119403_bib47","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1161\/01.ATV.17.3.465","article-title":"Notoginsenoside R1 counteracts endotoxin-induced activation of endothelial cells in vitro and endotoxin-induced lethality in mice in vivo","volume":"17","author":"Zhang","year":"1997","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"issue":"4","key":"10.1016\/j.biopha.2026.119403_bib48","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/onc.2013.568","article-title":"A link between inflammation and metastasis: serum amyloid A1 and A3 induce metastasis, and are targets of metastasis-inducing S100A4","volume":"34","author":"Hansen","year":"2015","journal-title":"Oncogene"},{"key":"10.1016\/j.biopha.2026.119403_bib49","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1007\/s00134-001-1139-8","article-title":"Activation of the fibrinolytic system and utilization of the coagulation inhibitors in sepsis: comparison with severe sepsis and septic shock","volume":"27","author":"Mavrommatis","year":"2001","journal-title":"Intensive Care Med"},{"issue":"2","key":"10.1016\/j.biopha.2026.119403_bib50","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1055\/s-0037-1612976","article-title":"The tissue factor and plasminogen activator inhibitor type-1 response in pediatric sepsis-induced multiple organ failure","volume":"87","author":"Green","year":"2002","journal-title":"Thromb. Haemost."},{"issue":"Suppl. 1","key":"10.1016\/j.biopha.2026.119403_bib51","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.3109\/1354750X.2011.587893","article-title":"Biomarkers of endothelial dysfunction: can they help us deciphering systemic inflammation and sepsis?","volume":"16","author":"Paulus","year":"2011","journal-title":"Biomarkers"},{"issue":"1","key":"10.1016\/j.biopha.2026.119403_bib52","doi-asserted-by":"crossref","DOI":"10.1186\/cc9412","article-title":"Plasma soluble vascular endothelial growth factor receptor-1 levels predict outcomes of pneumonia-related septic shock patients: a prospective observational study","volume":"15","author":"Yang","year":"2011","journal-title":"Crit. Care"},{"issue":"9178","key":"10.1016\/j.biopha.2026.119403_bib53","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/S0140-6736(99)02220-5","article-title":"4G\/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease","volume":"354","author":"Hermans","year":"1999","journal-title":"Lancet"},{"issue":"6","key":"10.1016\/j.biopha.2026.119403_bib54","article-title":"Time-resolved single-cell transcriptomics reveals the landscape and dynamics of hepatic cells in sepsis-induced acute liver dysfunction","volume":"5","author":"Chen","year":"2023","journal-title":"JHEP Rep."}],"container-title":["Biomedicine & Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332226004385?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332226004385?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T09:53:59Z","timestamp":1794477239000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0753332226004385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":54,"alternative-id":["S0753332226004385"],"URL":"https:\/\/doi.org\/10.1016\/j.biopha.2026.119403","relation":{},"ISSN":["0753-3322"],"issn-type":[{"value":"0753-3322","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The FDA-approved excipient N,N-dimethylacetamide improves survival and attenuates inflammatory pathways in a murine model of endotoxemia","name":"articletitle","label":"Article Title"},{"value":"Biomedicine & Pharmacotherapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biopha.2026.119403","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"119403"}}