{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T00:41:36Z","timestamp":1793580096107,"version":"4.5.0"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370659"],"award-info":[{"award-number":["82370659"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172167"],"award-info":[{"award-number":["82172167"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Acute pancreatitis can lead to systemic inflammation and multiple organ damage. Increased endothelial permeability is a hallmark of systemic inflammation. Several studies have demonstrated that cold-inducible RNA-binding protein (CIRP) functions as a proinflammatory factor in various diseases. However, its role in endothelial barrier dysfunction during acute pancreatitis remains unknown. To study this, acute pancreatitis was induced by two hourly intraperitoneal injections of 4.0\u2009g\/kg <jats:sc>l<\/jats:sc>-arginine in wild-type (WT) or CIRP knockout mice. Our results showed that CIRP levels in the pancreas, small intestine, lung, and liver were upregulated at 72\u2009h after the induction of acute pancreatitis in WT mice. CIRP deficiency significantly attenuated tissue injury, edema, and extravasation of Evans blue in the pancreas, small intestine, lung, and liver at 72\u2009h after <jats:sc>l<\/jats:sc>-arginine injection. Administration of C23, a specific antagonist of CIRP, at 2\u2009h after the last injection of <jats:sc>l<\/jats:sc>-arginine also produced similar protective effects as CIRP knockout in mice. In vitro studies showed that recombinant CIRP caused a significant reduction in transcellular electric resistance in HUVEC monolayers. Immunocytochemical analysis of endothelial cells exposed to CIRP revealed an increased formation of actin stress fibers. VE-cadherin and \u03b2-catenin staining showed intercellular gaps were formed in CIRP-stimulated cells. Western blot analysis showed that CIRP induced SRC phosphorylation at TYR416. Exposure to the SRC inhibitor PP2 reduced CIRP-induced endothelial barrier dysfunction in HUVEC monolayers. In conclusion, blocking CIRP mitigates acute pancreatitis-induced multiple organ damage by alleviating endothelial hyperpermeability. Targeting CIRP may be a potential therapeutic option for acute pancreatitis.<\/jats:p>","DOI":"10.1038\/s42003-025-07772-y","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T19:20:31Z","timestamp":1741634431000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["CIRP contributes to multiple organ damage in acute pancreatitis by increasing endothelial permeability"],"prefix":"10.1038","volume":"8","author":[{"given":"Wuming","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek H.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzhou","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0993-4531","authenticated-orcid":false,"given":"Rongqian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"7772_CR1","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1136\/gutjnl-2011-300771","volume":"62","author":"M Sendler","year":"2013","unstructured":"Sendler, M. et al. Tumour necrosis factor \u03b1 secretion induces protease activation and acinar cell necrosis in acute experimental pancreatitis in mice. Gut 62, 430\u2013439 (2013).","journal-title":"Gut"},{"key":"7772_CR2","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.1053\/j.gastro.2009.04.023","volume":"136","author":"H. Y Gaisano","year":"2009","unstructured":"Gaisano, H. Y. & Gorelick, F. S. New insights into the mechanisms of pancreatitis. Gastroenterology 136, 2040\u20132044 (2009).","journal-title":"Gastroenterology"},{"key":"7772_CR3","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1001\/jama.2020.20317","volume":"325","author":"M. A Mederos","year":"2021","unstructured":"Mederos, M. A., Reber, H. A. & Girgis, M. D. Acute pancreatitis: a review. Jama 325, 382\u2013390 (2021).","journal-title":"Jama"},{"key":"7772_CR4","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0140-6736(14)60649-8","volume":"386","author":"P. G Lankisch","year":"2015","unstructured":"Lankisch, P. G., Apte, M. & Banks, P. A. Acute pancreatitis. Lancet386, 85\u201396 (2015).","journal-title":"Lancet"},{"key":"7772_CR5","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1053\/gast.2002.30348","volume":"122","author":"T Keck","year":"2002","unstructured":"Keck, T. et al. Matrix metalloproteinase-9 promotes neutrophil migration and alveolar capillary leakage in pancreatitis-associated lung injury in the rat. Gastroenterology 122, 188\u2013201 (2002).","journal-title":"Gastroenterology"},{"key":"7772_CR6","doi-asserted-by":"publisher","first-page":"6653","DOI":"10.3748\/wjg.v25.i45.6653","volume":"25","author":"Y. F Ren","year":"2019","unstructured":"Ren, Y. F. et al. Irisin attenuates intestinal injury, oxidative and endoplasmic reticulum stress in mice with l-arginine-induced acute pancreatitis. World J. Gastroenterol. 25, 6653\u20136667 (2019).","journal-title":"World J. Gastroenterol."},{"key":"7772_CR7","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-022-00308-0","volume":"19","author":"F. R Walter","year":"2022","unstructured":"Walter, F. R. et al. Blood\u2013brain barrier dysfunction in L-ornithine induced acute pancreatitis in rats and the direct effect of L-ornithine on cultured brain endothelial cells. Fluids barriers CNS 19, 16 (2022).","journal-title":"Fluids barriers CNS"},{"key":"7772_CR8","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.724514","volume":"12","author":"L Kong","year":"2021","unstructured":"Kong, L. et al. AICAR, an AMP-activated protein kinase activator, ameliorates acute pancreatitis-associated liver injury partially through Nrf2-mediated antioxidant effects and inhibition of NLRP3 inflammasome activation. Front. Pharmacol. 12, 724514 (2021).","journal-title":"Front. Pharmacol."},{"key":"7772_CR9","first-page":"1190","volume":"10","author":"S van Brunschot","year":"2012","unstructured":"van Brunschot, S. et al. Treatment of necrotizing pancreatitis. Clin. Gastroenterol. Hepatology Off. Clin. Pract. J. Am. Gastroenterol. Assoc. 10, 1190\u20131201 (2012).","journal-title":"Clin. Gastroenterol. Hepatology Off. Clin. Pract. J. Am. Gastroenterol. Assoc."},{"key":"7772_CR10","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1097\/MPA.0000000000000435","volume":"45","author":"Y. F Chen","year":"2016","unstructured":"Chen, Y. F. et al. Cartilage oligomeric matrix protein-angiopoietin-1 has a protective effect of vascular endothelial barrier in rat with acute necrotizing pancreatitis. Pancreas 45, 142\u2013147 (2016).","journal-title":"Pancreas"},{"key":"7772_CR11","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1159\/000212100","volume":"9","author":"O Mann","year":"2009","unstructured":"Mann, O. et al. Therapeutic small-volume resuscitation preserves pancreatic microcirculation in acute experimental pancreatitis of graded severity in rats. Pancreatol. Off. J. Int. Assoc. Pancreatol.9, 652\u2013661 (2009).","journal-title":"Pancreatol. Off. J. Int. Assoc. Pancreatol."},{"key":"7772_CR12","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1038\/nm.3368","volume":"19","author":"X Qiang","year":"2013","unstructured":"Qiang, X. et al. Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis. Nat. Med. 19, 1489\u20131495 (2013).","journal-title":"Nat. Med."},{"key":"7772_CR13","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1002\/JLB.3MIR1118-443R","volume":"106","author":"M Aziz","year":"2019","unstructured":"Aziz, M., Brenner, M. & Wang, P. Extracellular CIRP (eCIRP) and inflammation. J. Leukoc. Biol. 106, 133\u2013146 (2019).","journal-title":"J. Leukoc. Biol."},{"key":"7772_CR14","doi-asserted-by":"publisher","first-page":"2536","DOI":"10.3389\/fimmu.2019.02536","volume":"10","author":"N. L Denning","year":"2019","unstructured":"Denning, N. L., Aziz, M., Gurien, S. D. & Wang, P. DAMPs and NETs in Sepsis. Front. Immunol. 10, 2536 (2019).","journal-title":"Front. Immunol."},{"key":"7772_CR15","doi-asserted-by":"crossref","unstructured":"K\u00fcbler M., et al. The absence of extracellular cold-inducible RNA-binding protein (eCIRP) promotes pro-angiogenic microenvironmental conditions and angiogenesis in muscle tissue ischemia. Int. J. Mol. Sci. 22, 9484 (2021).","DOI":"10.3390\/ijms22179484"},{"key":"7772_CR16","doi-asserted-by":"publisher","first-page":"3628","DOI":"10.1007\/s12035-021-02368-z","volume":"58","author":"A Sharma","year":"2021","unstructured":"Sharma, A., Brenner, M., Jacob, A., Marambaud, P. & Wang, P. Extracellular CIRP activates the IL-6R\u03b1\/STAT3\/Cdk5 pathway in neurons. Mol. Neurobiol. 58, 3628\u20133640 (2021).","journal-title":"Mol. Neurobiol."},{"key":"7772_CR17","doi-asserted-by":"publisher","first-page":"11310","DOI":"10.1111\/jcmm.17062","volume":"25","author":"W Liu","year":"2021","unstructured":"Liu, W. et al. Normothermic machine perfusion attenuates hepatic ischaemia-reperfusion injury by inhibiting CIRP-mediated oxidative stress and mitochondrial fission. J. Cell. Mol. Med. 25, 11310\u201311321 (2021).","journal-title":"J. Cell. Mol. Med."},{"key":"7772_CR18","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.655372","volume":"12","author":"Q Xu","year":"2021","unstructured":"Xu, Q. et al. Emodin alleviates severe acute pancreatitis-associated acute lung injury by inhibiting the cold-inducible RNA-binding protein (CIRP)-mediated activation of the NLRP3\/IL-1\u03b2\/CXCL1 signaling. Front. Pharmacol. 12, 655372 (2021).","journal-title":"Front. Pharmacol."},{"key":"7772_CR19","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.mvr.2008.10.002","volume":"77","author":"G Hu","year":"2009","unstructured":"Hu, G. & Minshall, R. D. Regulation of transendothelial permeability by Src kinase. Microvasc. Res. 77, 21\u201325 (2009).","journal-title":"Microvasc. Res."},{"key":"7772_CR20","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1016\/j.apsb.2021.09.017","volume":"12","author":"Y Wu","year":"2022","unstructured":"Wu, Y. et al. Ruscogenin alleviates LPS-triggered pulmonary endothelial barrier dysfunction through targeting NMMHC IIA to modulate TLR4 signaling. Acta Pharma. Sin. B 12, 1198\u20131212 (2022).","journal-title":"Acta Pharma. Sin. B"},{"key":"7772_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107043","volume":"26","author":"W Liu","year":"2023","unstructured":"Liu, W. et al. Targeting extracellular CIRP with an X-aptamer shows therapeutic potential in acute pancreatitis. iScience 26, 107043 (2023).","journal-title":"iScience"},{"key":"7772_CR22","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/S0140-6736(20)31310-6","volume":"396","author":"L Boxhoorn","year":"2020","unstructured":"Boxhoorn, L. et al. Acute pancreatitis. Lancet396, 726\u2013734 (2020).","journal-title":"Lancet"},{"key":"7772_CR23","doi-asserted-by":"publisher","first-page":"e0117588","DOI":"10.1371\/journal.pone.0117588","volume":"10","author":"B Kui","year":"2015","unstructured":"Kui, B. et al. New insights into the methodology of L-arginine-induced acute pancreatitis. PLoS One 10, e0117588 (2015).","journal-title":"PLoS One"},{"key":"7772_CR24","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1002\/bjs.1800831113","volume":"83","author":"X. D Wang","year":"1996","unstructured":"Wang, X. D., Wang, Q., Andersson, R. & Ihse, I. Alterations in intestinal function in acute pancreatitis in an experimental model. Br. J. Surg. 83, 1537\u20131543 (1996).","journal-title":"Br. J. Surg."},{"key":"7772_CR25","doi-asserted-by":"publisher","first-page":"899","DOI":"10.3892\/etm.2014.1810","volume":"8","author":"B Qi","year":"2014","unstructured":"Qi, B. et al. Effects of hypoxia-inducible factor-1\u03b1 and matrix metalloproteinase-9 on alveolar-capillary barrier disruption and lung edema in rat models of severe acute pancreatitis-associated lung injury. Exp. Ther. Med. 8, 899\u2013906 (2014).","journal-title":"Exp. Ther. Med."},{"key":"7772_CR26","doi-asserted-by":"publisher","first-page":"4140","DOI":"10.1182\/blood-2013-03-491423","volume":"122","author":"J Han","year":"2013","unstructured":"Han, J. et al. A critical role for Lyn kinase in strengthening endothelial integrity and barrier function. Blood 122, 4140\u20134149 (2013).","journal-title":"Blood"},{"key":"7772_CR27","doi-asserted-by":"publisher","first-page":"e136277","DOI":"10.1172\/jci.insight.136277","volume":"5","author":"J Bi","year":"2020","unstructured":"Bi, J. et al. Exercise hormone irisin mitigates endothelial barrier dysfunction and microvascular leakage-related diseases. JCI Insight 5, e136277 (2020).","journal-title":"JCI Insight"},{"key":"7772_CR28","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1046\/j.1365-2168.2002.01991.x","volume":"89","author":"M Dib","year":"2002","unstructured":"Dib, M., Zhao, X., Wang, X. D. & Andersson, R. Role of mast cells in the development of pancreatitis-induced multiple organ dysfunction. Br. J. Surg. 89, 172\u2013178 (2002).","journal-title":"Br. J. Surg."},{"key":"7772_CR29","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1038\/s41366-018-0125-y","volume":"42","author":"C Ye","year":"2018","unstructured":"Ye, C., Wang, R., Wang, M., Huang, Z. & Tang, C. Leptin alleviates intestinal mucosal barrier injury and inflammation in obese mice with acute pancreatitis. Int. J. Obes.42, 1471\u20131479 (2018).","journal-title":"Int. J. Obes."},{"key":"7772_CR30","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1038\/s41419-021-04227-0","volume":"12","author":"L Kong","year":"2021","unstructured":"Kong, L. et al. Sitagliptin activates the p62-Keap1-Nrf2 signalling pathway to alleviate oxidative stress and excessive autophagy in severe acute pancreatitis-related acute lung injury. Cell Death Dis. 12, 928 (2021).","journal-title":"Cell Death Dis."},{"key":"7772_CR31","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1053\/j.gastro.2018.12.041","volume":"156","author":"P. K Garg","year":"2019","unstructured":"Garg, P. K. & Singh, V. P. Organ failure due to systemic injury in acute pancreatitis. Gastroenterology 156, 2008\u20132023 (2019).","journal-title":"Gastroenterology"},{"key":"7772_CR32","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.mehy.2008.09.007","volume":"72","author":"H Sha","year":"2009","unstructured":"Sha, H., Ma, Q. & Jha, R. K. Trypsin is the culprit of multiple organ injury with severe acute pancreatitis. Med. Hypotheses 72, 180\u2013182 (2009).","journal-title":"Med. Hypotheses"},{"key":"7772_CR33","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1161\/HYPERTENSIONAHA.122.19465","volume":"80","author":"C De Ciuceis","year":"2023","unstructured":"De Ciuceis, C., Rizzoni, D. & Palatini, P. Microcirculation and physical exercise in hypertension. Hypertension80, 730\u2013739 (2023).","journal-title":"Hypertension"},{"key":"7772_CR34","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1002\/bjs.5316","volume":"93","author":"C. M Cuthbertson","year":"2006","unstructured":"Cuthbertson, C. M. & Christophi, C. Disturbances of the microcirculation in acute pancreatitis. Br. J. Surg. 93, 518\u2013530 (2006).","journal-title":"Br. J. Surg."},{"key":"7772_CR35","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1146\/annurev-pathol-011110-130158","volume":"6","author":"M. A Matthay","year":"2011","unstructured":"Matthay, M. A. & Zemans, R. L. The acute respiratory distress syndrome: pathogenesis and treatment. Annu. Rev. Pathol. 6, 147\u2013163 (2011).","journal-title":"Annu. Rev. Pathol."},{"key":"7772_CR36","doi-asserted-by":"publisher","first-page":"3765","DOI":"10.1182\/blood-2002-06-1887","volume":"101","author":"W. C Aird","year":"2003","unstructured":"Aird, W. C. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 101, 3765\u20133777 (2003).","journal-title":"Blood"},{"key":"7772_CR37","doi-asserted-by":"publisher","first-page":"7947","DOI":"10.1038\/sj.onc.1208161","volume":"23","author":"A. B Reynolds","year":"2004","unstructured":"Reynolds, A. B. & Roczniak-Ferguson, A. Emerging roles for p120-catenin in cell adhesion and cancer. Oncogene 23, 7947\u20137956 (2004).","journal-title":"Oncogene"},{"key":"7772_CR38","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1091\/mbc.e16-06-0459","volume":"28","author":"B. A Nanes","year":"2017","unstructured":"Nanes, B. A. et al. p120-catenin regulates VE-cadherin endocytosis and degradation induced by the Kaposi sarcoma-associated ubiquitin ligase K5. Mol. Biol. cell 28, 30\u201340 (2017).","journal-title":"Mol. Biol. cell"},{"key":"7772_CR39","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/84675","volume":"7","author":"R Paul","year":"2001","unstructured":"Paul, R. et al. Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke. Nat. Med. 7, 222\u2013227 (2001).","journal-title":"Nat. Med."},{"key":"7772_CR40","doi-asserted-by":"crossref","unstructured":"Fang Z., et al. An MD2-perturbing peptide has therapeutic effects in rodent and rhesus monkey models of stroke. Sci. Transl. Med. 13, eabb6716 (2021).","DOI":"10.1126\/scitranslmed.abb6716"},{"key":"7772_CR41","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.721970","volume":"12","author":"S Bolourani","year":"2021","unstructured":"Bolourani, S., Sari, E., Brenner, M. & Wang, P. Extracellular CIRP induces an inflammatory phenotype in pulmonary fibroblasts via TLR4. Front. Immunol. 12, 721970 (2021).","journal-title":"Front. Immunol."},{"key":"7772_CR42","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1038\/s41374-020-0469-5","volume":"100","author":"J Linders","year":"2020","unstructured":"Linders, J. et al. Extracellular cold-inducible RNA-binding protein regulates neutrophil extracellular trap formation and tissue damage in acute pancreatitis. Lab. Investig. J. Tech. Methods Pathol. 100, 1618\u20131630 (2020).","journal-title":"Lab. Investig. J. Tech. Methods Pathol."},{"key":"7772_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13139-z","volume":"8","author":"F Zhang","year":"2018","unstructured":"Zhang, F., Brenner, M., Yang, W. L. & Wang, P. A cold-inducible RNA-binding protein (CIRP)-derived peptide attenuates inflammation and organ injury in septic mice. Sci. Rep. 8, 3052 (2018).","journal-title":"Sci. Rep."},{"key":"7772_CR44","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1097\/SHK.0000000000000988","volume":"49","author":"J McGinn","year":"2018","unstructured":"McGinn, J. et al. The protective effect of a short peptide derived from cold-inducible RNA-binding protein in renal ischemia-reperfusion injury. Shock49, 269\u2013276 (2018).","journal-title":"Shock"},{"key":"7772_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176462","volume":"969","author":"W Liu","year":"2024","unstructured":"Liu, W. et al. MFG-E8 induces epithelial-mesenchymal transition and anoikis resistance to promote the metastasis of pancreatic cancer cells. Eur. J. Pharmacol. 969, 176462 (2024).","journal-title":"Eur. J. Pharmacol."},{"key":"7772_CR46","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1097\/00000658-199201000-00007","volume":"215","author":"J Schmidt","year":"1992","unstructured":"Schmidt, J. et al. A better model of acute pancreatitis for evaluating therapy. Ann. Surg. 215, 44\u201356 (1992).","journal-title":"Ann. Surg."},{"key":"7772_CR47","doi-asserted-by":"publisher","first-page":"936","DOI":"10.3389\/fphar.2018.00936","volume":"9","author":"M Zhang","year":"2018","unstructured":"Zhang, M. et al. Isoliquiritigenin protects against pancreatic injury and intestinal dysfunction after severe acute pancreatitis via Nrf2 signaling. Front. Pharmacol. 9, 936 (2018).","journal-title":"Front. Pharmacol."},{"key":"7772_CR48","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1097\/SLA.0b013e3181961d43","volume":"249","author":"J Yang","year":"2009","unstructured":"Yang, J. et al. Human adrenomedullin and its binding protein attenuate organ injury and reduce mortality after hepatic ischemia-reperfusion. Ann. Surg. 249, 310\u2013317 (2009).","journal-title":"Ann. Surg."},{"key":"7772_CR49","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1136\/gut.43.2.232","volume":"43","author":"M. O Osman","year":"1998","unstructured":"Osman, M. O. et al. A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits. Gut 43, 232\u2013239 (1998).","journal-title":"Gut"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-07772-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-07772-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-07772-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T19:20:35Z","timestamp":1741634435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-07772-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,10]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["7772"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-07772-y","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,10]]},"assertion":[{"value":"9 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors have read and agreed with the final manuscript. No conflicts of interest were disclosed by the authors of this research.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was approved by the Ethics Committee of the First Affiliated Hospital of Xi\u2019an Jiaotong University and all study participants signed the informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"403"}}