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Sci.","Medical Sciences"],"abstract":"<jats:p>Background: Radiation-induced sepsis resulting from intestinal inflammation and injury is a severe complication of high-dose radiation exposure. High-dose radiation compromises the integrity of the intestinal lining, causing bacterial translocation, systemic inflammation, and sepsis. Extracellular cold-inducible RNA-binding protein (eCIRP), a damage-associated molecular pattern, plays a pivotal role in the pathogenesis of inflammatory diseases and contributes to organ injury. C23, a small molecular peptide antagonist of eCIRP, has demonstrated anti-inflammatory and organ-protective effects during organ-injury indications. However, its role in radiation-induced inflammation and injury is not known. The objective of this study is to evaluate whether C23 mitigates inflammation and injury, leading to improved survival in a murine model of partial-body irradiation (PBI) combined with sepsis. Methods: Mice were exposed to 10 Gy PBI, and at 48 h, they were subjected to cecal ligation and puncture (CLP), a well-established model of sepsis. C23 (8 mg\/kg body weight [BW]) or vehicle (saline) was administered subcutaneously at 24 h and 48 h after PBI. Blood and intestinal tissue samples were collected 20 h after CLP (i.e., 68 h post-PBI) for various analyses. In another set of mice after PBI\u2013sepsis, intestinal permeability was also assessed. In an additional cohort of mice subjected to the same experimental procedure, 10-day survival was monitored. Results: Our findings demonstrate that administration of C23 attenuated systemic inflammatory responses, intestinal permeability, intestinal injury, and apoptosis; increased crypt cell proliferation and improved survival after PBI\u2013sepsis. Conclusions: These results reveal a novel protective role of the eCIRP antagonist, C23, in mitigating PBI\u2013sepsis-induced inflammation and injury and represents a promising therapeutic candidate for the treatment of radiation combined injury with sepsis.<\/jats:p>","DOI":"10.3390\/medsci14050539","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:31:13Z","timestamp":1788251473000},"page":"539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of eCIRP Attenuates Inflammation and Gut Injury After Radiation Combined Injury with Sepsis"],"prefix":"10.3390","volume":"14","author":[{"given":"Fangming","family":"Zhang","sequence":"first","affiliation":[{"name":"Center for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Gaifeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Hui","family":"Jin","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8280-8999","authenticated-orcid":false,"given":"Asha","family":"Jacob","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Departments of Surgery and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8010-148X","authenticated-orcid":false,"given":"Max","family":"Brenner","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Departments of Surgery and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1557-0394","authenticated-orcid":false,"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Departments of Surgery and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/jrr\/rrac108","article-title":"Comparison between external and internal doses to the thyroid after the Fukushima Daiichi Nuclear Power Plant accident","volume":"64","author":"Ishikawa","year":"2023","journal-title":"J. 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