{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T12:10:47Z","timestamp":1777723847087,"version":"3.51.4"},"reference-count":70,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007289","name":"Nanjing Medical University","doi-asserted-by":"publisher","award":["NMUB20220067"],"award-info":[{"award-number":["NMUB20220067"]}],"id":[{"id":"10.13039\/501100007289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.ejphar.2025.177944","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T08:31:45Z","timestamp":1752568305000},"page":"177944","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Urinary trypsin inhibitor exerts multifaceted regulation of angiopoietin 2 in septic cardiomyopathy"],"prefix":"10.1016","volume":"1003","author":[{"given":"Yi-ni","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-han","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo-cheng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-fen","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian-yin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7021-8588","authenticated-orcid":false,"given":"Feng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"15","key":"10.1016\/j.ejphar.2025.177944_bib1","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1007\/s40265-021-01605-y","article-title":"Targeting the angiopoietin\/tie pathway: prospects for treatment of retinal and respiratory disorders","volume":"81","author":"Akwii","year":"2021","journal-title":"Drugs"},{"issue":"23","key":"10.1016\/j.ejphar.2025.177944_bib2","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1161\/CIRCULATIONAHA.112.134304","article-title":"Effective treatment of edema and endothelial barrier dysfunction with imatinib","volume":"126","author":"Aman","year":"2012","journal-title":"Circulation"},{"issue":"1","key":"10.1016\/j.ejphar.2025.177944_bib3","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1186\/s13054-023-04554-y","article-title":"Prognostic and predictive value of endothelial dysfunction biomarkers in sepsis-associated acute kidney injury: risk-stratified analysis from a prospective observational cohort of pediatric septic shock","volume":"27","author":"Atreya","year":"2023","journal-title":"Crit. Care"},{"issue":"11","key":"10.1016\/j.ejphar.2025.177944_bib4","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22115880","article-title":"PCSK9 biology and its role in atherothrombosis","volume":"22","author":"Barale","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejphar.2025.177944_bib5","article-title":"Integrated single cell and bulk RNA-seq analysis revealed immunomodulatory effects of ulinastatin in sepsis: a multicenter cohort study","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ejphar.2025.177944_bib6","doi-asserted-by":"crossref","first-page":"e488","DOI":"10.1016\/j.wneu.2021.11.008","article-title":"Sigma-1 receptor and binding immunoglobulin protein interact with ulinastatin contributing to a protective effect in rat cerebral ischemia\/reperfusion","volume":"158","author":"Dai","year":"2022","journal-title":"World Neurosurg."},{"issue":"3","key":"10.1016\/j.ejphar.2025.177944_bib7","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1097\/HEP.0000000000000354","article-title":"Sepsis-induced endothelial dysfunction drives acute-on-chronic liver failure through Angiopoietin-2-HGF-C\/EBPbeta pathway","volume":"78","author":"Elias","year":"2023","journal-title":"Hepatology"},{"issue":"11","key":"10.1016\/j.ejphar.2025.177944_bib8","doi-asserted-by":"crossref","first-page":"e1063","DOI":"10.1097\/CCM.0000000000005337","article-title":"Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021","volume":"49","author":"Evans","year":"2021","journal-title":"Crit. Care Med."},{"key":"10.1016\/j.ejphar.2025.177944_bib9","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2018.00823","article-title":"Ulinastatin ameliorates pulmonary capillary endothelial permeability induced by sepsis through protection of tight junctions via inhibition of TNF-\u03b1 and related pathways","volume":"9","author":"Fang","year":"2018","journal-title":"Front. Pharmacol."},{"issue":"11","key":"10.1016\/j.ejphar.2025.177944_bib10","doi-asserted-by":"crossref","first-page":"4150","DOI":"10.1182\/blood-2003-10-3685","article-title":"The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell weibel-palade bodies","volume":"103","author":"Fiedler","year":"2004","journal-title":"Blood"},{"issue":"11","key":"10.1016\/j.ejphar.2025.177944_bib11","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1097\/CCM.0000000000001853","article-title":"Elevated plasma Angiopoietin-2 levels are associated with fluid overload, organ dysfunction, and mortality in human septic shock","volume":"44","author":"Fisher","year":"2016","journal-title":"Crit. Care Med."},{"issue":"5","key":"10.1016\/j.ejphar.2025.177944_bib12","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1513\/AnnalsATS.202106-689OC","article-title":"Etiology of myocardial injury in critically ill patients with sepsis: a cohort study","volume":"19","author":"Frencken","year":"2022","journal-title":"Ann. Am. Thorac. Soc."},{"issue":"2","key":"10.1016\/j.ejphar.2025.177944_bib13","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/jcp.21229","article-title":"Flow-dependent regulation of angiopoietin-2","volume":"214","author":"Goettsch","year":"2008","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.ejphar.2025.177944_bib14","doi-asserted-by":"crossref","first-page":"5962","DOI":"10.1038\/ncomms6962","article-title":"Endothelial destabilization by angiopoietin-2 via integrin beta1 activation","volume":"6","author":"Hakanpaa","year":"2015","journal-title":"Nat. Commun."},{"issue":"28","key":"10.1016\/j.ejphar.2025.177944_bib15","doi-asserted-by":"crossref","first-page":"E6467","DOI":"10.1073\/pnas.1722317115","article-title":"Targeting beta1-integrin inhibits vascular leakage in endotoxemia","volume":"115","author":"Hakanpaa","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"335","key":"10.1016\/j.ejphar.2025.177944_bib16","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aad9260","article-title":"Amelioration of sepsis by TIE2 activation-induced vascular protection","volume":"8","author":"Han","year":"2016","journal-title":"Sci. Transl. Med."},{"issue":"4","key":"10.1016\/j.ejphar.2025.177944_bib17","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1080\/00325481.2022.2136390","article-title":"Trends and recent developments in pharmacotherapy of acute pancreatitis","volume":"135","author":"Hey-Hadavi","year":"2023","journal-title":"Postgrad. Med. J."},{"issue":"10","key":"10.1016\/j.ejphar.2025.177944_bib18","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.119.012260","article-title":"Myocardial strain and cardiac output are preferable measurements for cardiac dysfunction and can predict mortality in septic mice","volume":"8","author":"Hoffman","year":"2019","journal-title":"J. Am. Heart Assoc."},{"issue":"6","key":"10.1016\/j.ejphar.2025.177944_bib19","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/s41569-020-00492-2","article-title":"Pathophysiology of sepsis-induced cardiomyopathy","volume":"18","author":"Hollenberg","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"issue":"5","key":"10.1016\/j.ejphar.2025.177944_bib20","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1182\/blood.V99.5.1646","article-title":"Thrombin induces increased expression and secretion of angiopoietin-2 from human umbilical vein endothelial cells","volume":"99","author":"Huang","year":"2002","journal-title":"Blood"},{"issue":"10","key":"10.1016\/j.ejphar.2025.177944_bib21","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1080\/13543784.2019.1667333","article-title":"Tie-2\/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease","volume":"28","author":"Hussain","year":"2019","journal-title":"Expet Opin. Invest. Drugs"},{"issue":"12","key":"10.1016\/j.ejphar.2025.177944_bib22","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1158\/1078-0432.CCR-17-1775","article-title":"Phase I study of MEDI3617, a selective Angiopoietin-2 inhibitor alone and combined with carboplatin\/paclitaxel, paclitaxel, or bevacizumab for advanced solid tumors","volume":"24","author":"Hyman","year":"2018","journal-title":"Clin. Cancer Res."},{"issue":"4","key":"10.1016\/j.ejphar.2025.177944_bib23","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1517\/13543781003649533","article-title":"Urinary trypsin inhibitor as a therapeutic option for endotoxin-related inflammatory disorders","volume":"19","author":"Inoue","year":"2010","journal-title":"Expet Opin. Invest. Drugs"},{"issue":"1","key":"10.1016\/j.ejphar.2025.177944_bib24","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1186\/s12967-022-03841-6","article-title":"KPNA2 promotes angiogenesis by regulating STAT3 phosphorylation","volume":"20","author":"Jia","year":"2022","journal-title":"J. Transl. Med."},{"issue":"3","key":"10.1016\/j.ejphar.2025.177944_bib25","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1164\/rccm.201910-1911TR","article-title":"Endothelial responses in sepsis","volume":"202","author":"Joffre","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"issue":"6","key":"10.1016\/j.ejphar.2025.177944_bib26","doi-asserted-by":"crossref","first-page":"549","DOI":"10.3109\/00365519109104564","article-title":"Distribution and elimination of intravenously injected urinary trypsin inhibitor","volume":"51","author":"Jonsson-Berling","year":"1991","journal-title":"Scand. J. Clin. Lab. Invest."},{"issue":"6","key":"10.1016\/j.ejphar.2025.177944_bib27","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1007\/s00134-014-3278-8","article-title":"Intravenous administration of ulinastatin (human urinary trypsin inhibitor) in severe sepsis: a multicenter randomized controlled study","volume":"40","author":"Karnad","year":"2014","journal-title":"Intensive Care Med."},{"issue":"20","key":"10.1016\/j.ejphar.2025.177944_bib28","doi-asserted-by":"crossref","first-page":"20126","DOI":"10.1074\/jbc.M500292200","article-title":"Oligomerization and multimerization are critical for angiopoietin-1 to bind and phosphorylate Tie2","volume":"280","author":"Kim","year":"2005","journal-title":"J. Biol. Chem."},{"issue":"2","key":"10.1016\/j.ejphar.2025.177944_bib29","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1007\/s11033-022-08117-2","article-title":"Molecular and pathobiological insights of bikunin\/UTI in cancer","volume":"50","author":"Lepedda","year":"2023","journal-title":"Mol. Biol. Rep."},{"issue":"1","key":"10.1016\/j.ejphar.2025.177944_bib30","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s40360-022-00585-3","article-title":"Real-world safety of ulinastatin: a post-marketing surveillance of 11,252 patients in China","volume":"23","author":"Li","year":"2022","journal-title":"BMC Pharmacol. Toxicol."},{"issue":"8","key":"10.1016\/j.ejphar.2025.177944_bib31","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1038\/aps.2017.143","article-title":"Ulinastatin attenuates LPS-induced inflammation in mouse macrophage RAW264.7 cells by inhibiting the JNK\/NF-kappaB signaling pathway and activating the PI3K\/Akt\/Nrf2 pathway","volume":"39","author":"Li","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"issue":"4","key":"10.1016\/j.ejphar.2025.177944_bib32","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1159\/000521648","article-title":"Ulinastatin improves renal microcirculation by protecting endothelial cells and inhibiting autophagy in a septic rat model","volume":"47","author":"Li","year":"2022","journal-title":"Kidney Blood Press. Res."},{"issue":"31","key":"10.1016\/j.ejphar.2025.177944_bib33","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1093\/eurheartj\/ehv132","article-title":"Cardiac endothelium-myocyte interaction: clinical opportunities for new heart failure therapies regardless of ejection fraction","volume":"36","author":"Lim","year":"2015","journal-title":"Eur. Heart J."},{"issue":"3","key":"10.1016\/j.ejphar.2025.177944_bib34","doi-asserted-by":"crossref","first-page":"925","DOI":"10.3892\/ijmm.2020.4662","article-title":"Neuregulin-1, a microvascular endothelial-derived protein, protects against myocardial ischemia-reperfusion injury","volume":"46","author":"Lin","year":"2020","journal-title":"Int. J. Mol. Med."},{"issue":"1","key":"10.1016\/j.ejphar.2025.177944_bib35","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13613-022-01089-3","article-title":"Association of sepsis-induced cardiomyopathy and mortality: a systematic review and meta-analysis","volume":"12","author":"Lin","year":"2022","journal-title":"Ann. Intensive Care"},{"issue":"4","key":"10.1016\/j.ejphar.2025.177944_bib36","article-title":"Inflammatory risk stratification individualizes anti-inflammatory pharmacotherapy for acute type A aortic dissection","volume":"4","author":"Liu","year":"2023","journal-title":"Innovation"},{"issue":"9","key":"10.1016\/j.ejphar.2025.177944_bib37","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1038\/s12276-024-01298-9","article-title":"STAT3 promotes NLRP3 inflammasome activation by mediating NLRP3 mitochondrial translocation","volume":"56","author":"Luo","year":"2024","journal-title":"Exp. Mol. Med."},{"issue":"4","key":"10.1016\/j.ejphar.2025.177944_bib38","doi-asserted-by":"crossref","DOI":"10.1186\/cc12848","article-title":"A high angiopoietin-2\/angiopoietin-1 ratio is associated with a high risk of septic shock in patients with febrile neutropenia","volume":"17","author":"Luz Fiusa","year":"2013","journal-title":"Crit. Care"},{"key":"10.1016\/j.ejphar.2025.177944_bib39","first-page":"30","article-title":"Pathophysiology of sepsis-induced myocardial dysfunction","volume":"3","author":"Lv","year":"2016","journal-title":"Mil. Med. Res."},{"issue":"9","key":"10.1016\/j.ejphar.2025.177944_bib40","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.116.003820","article-title":"Cardiac electrical and structural changes during bacterial infection: an instructive model to study cardiac dysfunction in sepsis","volume":"5","author":"Makara","year":"2016","journal-title":"J. Am. Heart Assoc."},{"issue":"4","key":"10.1016\/j.ejphar.2025.177944_bib41","article-title":"Pharmacological interventions for acute pancreatitis","volume":"4","author":"Moggia","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"issue":"10","key":"10.1016\/j.ejphar.2025.177944_bib42","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1111\/jth.13441","article-title":"Coagulation and non-coagulation effects of thrombin","volume":"14","author":"Posma","year":"2016","journal-title":"J. Thromb. Haemostasis"},{"issue":"1","key":"10.1016\/j.ejphar.2025.177944_bib43","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00005-023-00688-7","article-title":"Expression of Angiopoietin-2 in lung tissue of juvenile SD rats with lipopolysaccharide-induced acute lung injury and the role of ulinastatin","volume":"71","author":"Qiao","year":"2023","journal-title":"Arch. Immunol. Ther. Exp."},{"issue":"4","key":"10.1016\/j.ejphar.2025.177944_bib44","doi-asserted-by":"crossref","DOI":"10.3892\/mmr.2021.12369","article-title":"Ulinastatin protects against sepsis-induced myocardial injury by inhibiting NLRP3 inflammasome activation","volume":"24","author":"Qiu","year":"2021","journal-title":"Mol. Med. Rep."},{"issue":"8","key":"10.1016\/j.ejphar.2025.177944_bib45","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1111\/jth.13376","article-title":"Angiopoietin-2 mediates thrombin-induced monocyte adhesion and endothelial permeability","volume":"14","author":"Rathnakumar","year":"2016","journal-title":"J. Thromb. Haemostasis"},{"issue":"11","key":"10.1016\/j.ejphar.2025.177944_bib46","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1007\/s00134-018-5328-0","article-title":"Plasma angiopoietin-2 as a potential causal marker in sepsis-associated ARDS development: evidence from Mendelian randomization and mediation analysis","volume":"44","author":"Reilly","year":"2018","journal-title":"Intensive Care Med."},{"issue":"9","key":"10.1016\/j.ejphar.2025.177944_bib47","doi-asserted-by":"crossref","first-page":"e874","DOI":"10.1097\/PCC.0000000000002508","article-title":"Associations of plasma Angiopoietins-1 and -2 and Angiopoietin-2\/-1 ratios with measures of organ injury and clinical outcomes in children with sepsis: a preliminary report","volume":"21","author":"Richter","year":"2020","journal-title":"Pediatr. Crit. Care Med."},{"issue":"15","key":"10.1016\/j.ejphar.2025.177944_bib48","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.155010","article-title":"Glycocalyx heparan sulfate cleavage promotes endothelial cell angiopoietin-2 expression by impairing shear stress-related AMPK\/FoxO1 signaling","volume":"7","author":"Richter","year":"2022","journal-title":"JCI Insight"},{"issue":"1","key":"10.1016\/j.ejphar.2025.177944_bib49","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nprot.2008.214","article-title":"Immunodesign of experimental sepsis by cecal ligation and puncture","volume":"4","author":"Rittirsch","year":"2009","journal-title":"Nat. Protoc."},{"issue":"5","key":"10.1016\/j.ejphar.2025.177944_bib50","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1161\/01.ATV.0000209501.56852.6c","article-title":"Dynamics and plasticity of weibel-palade bodies in endothelial cells","volume":"26","author":"Rondaij","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"issue":"1","key":"10.1016\/j.ejphar.2025.177944_bib51","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1186\/s13054-023-04525-3","article-title":"Early plasma angiopoietin-2 is prognostic for ARDS and mortality among critically ill patients with sepsis","volume":"27","author":"Rosenberger","year":"2023","journal-title":"Crit. Care"},{"issue":"6","key":"10.1016\/j.ejphar.2025.177944_bib52","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1042\/CS20120334","article-title":"Early functional and transcriptomic changes in the myocardium predict outcome in a long-term rat model of sepsis","volume":"124","author":"Rudiger","year":"2013","journal-title":"Clin. Sci. (Lond.)"},{"issue":"3","key":"10.1016\/j.ejphar.2025.177944_bib53","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.cell.2017.10.009","article-title":"SnapShot: angiopoietins and their functions","volume":"171","author":"Saharinen","year":"2017","journal-title":"Cell"},{"issue":"1","key":"10.1016\/j.ejphar.2025.177944_bib54","doi-asserted-by":"crossref","DOI":"10.1002\/ctm2.266","article-title":"Activation of toll-like receptor 7 provides cardioprotection in septic cardiomyopathy-induced systolic dysfunction","volume":"11","author":"Saiyang","year":"2021","journal-title":"Clin. Transl. Med."},{"issue":"6","key":"10.1016\/j.ejphar.2025.177944_bib55","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S0008-6363(96)00025-9","article-title":"Paracrine modulation of heart cell function by endothelial cells","volume":"31","author":"Shah","year":"1996","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.ejphar.2025.177944_bib56","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2023.1200441","article-title":"Sepsis-induced myocardial dysfunction: heterogeneity of functional effects and clinical significance","volume":"10","author":"Shvilkina","year":"2023","journal-title":"Front. Cardiovasc. Med."},{"issue":"8","key":"10.1016\/j.ejphar.2025.177944_bib57","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":"6","key":"10.1016\/j.ejphar.2025.177944_bib58","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1083\/jcb.201404140","article-title":"ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation","volume":"208","author":"Tornavaca","year":"2015","journal-title":"JCB (J. Cell Biol.)"},{"issue":"1","key":"10.1016\/j.ejphar.2025.177944_bib59","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1165\/rcmb.2019-0377OC","article-title":"Serine protease imbalance in the small airways and development of centrilobular emphysema in chronic obstructive pulmonary disease","volume":"63","author":"Uemasu","year":"2020","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"issue":"1","key":"10.1016\/j.ejphar.2025.177944_bib60","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/CCM.0000000000000553","article-title":"International study on microcirculatory shock occurrence in acutely ill patients","volume":"43","author":"Vellinga","year":"2015","journal-title":"Crit. Care Med."},{"key":"10.1016\/j.ejphar.2025.177944_bib61","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1223014","article-title":"Baricitinib protects mice from sepsis-induced cardiac dysfunction and multiple-organ failure","volume":"14","author":"Verra","year":"2023","journal-title":"Front. Immunol."},{"issue":"2","key":"10.1016\/j.ejphar.2025.177944_bib62","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1161\/ATVBAHA.107.158014","article-title":"VE-cadherin - the major endothelial adhesion molecule controlling cellular junctions and blood vessel formation","volume":"28","author":"Vestweber","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"issue":"8","key":"10.1016\/j.ejphar.2025.177944_bib63","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1002\/ptr.7802","article-title":"Ginkgolide A targets forkhead box O1 to protect against lipopolysaccharide-induced septic cardiomyopathy","volume":"37","author":"Wang","year":"2023","journal-title":"Phytother Res."},{"issue":"19","key":"10.1016\/j.ejphar.2025.177944_bib64","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.120.017544","article-title":"Endothelial cell cystathionine gamma-Lyase expression level modulates exercise capacity, vascular function, and myocardial ischemia reperfusion injury","volume":"9","author":"Xia","year":"2020","journal-title":"J. Am. Heart Assoc."},{"issue":"5","key":"10.1016\/j.ejphar.2025.177944_bib65","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1006\/jmbi.1997.1582","article-title":"The crystal structure of bikunin from the inter-\u03b1-inhibitor complex:: a serine protease inhibitor with two kunitz domains","volume":"276","author":"Xu","year":"1998","journal-title":"J. Mol. Biol."},{"issue":"2","key":"10.1016\/j.ejphar.2025.177944_bib66","doi-asserted-by":"crossref","DOI":"10.3390\/antiox13020214","article-title":"Integrative multiomics profiling unveils the protective function of ulinastatin against dextran sulfate sodium-induced colitis","volume":"13","author":"Yu","year":"2024","journal-title":"Antioxidants"},{"issue":"1","key":"10.1016\/j.ejphar.2025.177944_bib67","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s13054-021-03474-z","article-title":"Angiopoietin-2 outperforms other endothelial biomarkers associated with severe acute kidney injury in patients with severe sepsis and respiratory failure","volume":"25","author":"Yu","year":"2021","journal-title":"Crit. Care"},{"issue":"18","key":"10.1016\/j.ejphar.2025.177944_bib68","doi-asserted-by":"crossref","first-page":"7205","DOI":"10.1073\/pnas.1216890110","article-title":"Structural basis for angiopoietin-1-mediated signaling initiation","volume":"110","author":"Yu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"5","key":"10.1016\/j.ejphar.2025.177944_bib69","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.3892\/ijmm.2017.2920","article-title":"Ulinastatin protects against lipopolysaccharide-induced cardiac microvascular endothelial cell dysfunction via downregulation of lncRNA MALAT1 and EZH2 in sepsis","volume":"39","author":"Yu","year":"2017","journal-title":"Int. J. Mol. Med."},{"issue":"24","key":"10.1016\/j.ejphar.2025.177944_bib70","doi-asserted-by":"crossref","first-page":"4988","DOI":"10.1111\/bph.16477","article-title":"Ulinastatin attenuated cardiac ischaemia\/reperfusion injury by suppressing activation of the tissue kallikrein-kinin system","volume":"181","author":"Zhang","year":"2024","journal-title":"Br. J. Pharmacol."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925006983?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925006983?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:38:16Z","timestamp":1777459096000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299925006983"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":70,"alternative-id":["S0014299925006983"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.177944","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Urinary trypsin inhibitor exerts multifaceted regulation of angiopoietin 2 in septic cardiomyopathy","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.177944","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"177944"}}