{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:52:50Z","timestamp":1792641170652,"version":"4.5.0"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100004699","name":"Chung Shan Medical University Hospital","doi-asserted-by":"publisher","award":["CSMU-INT-102-06"],"award-info":[{"award-number":["CSMU-INT-102-06"]}],"id":[{"id":"10.13039\/501100004699","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003711","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["103-2320-B-040-001-MY3"],"award-info":[{"award-number":["103-2320-B-040-001-MY3"]}],"id":[{"id":"10.13039\/501100003711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jmmc-online.com","clinicalkey.jp","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Molecular and Cellular Cardiology"],"published-print":{"date-parts":[[2016,10]]},"DOI":"10.1016\/j.yjmcc.2016.08.004","type":"journal-article","created":{"date-parts":[[2016,8,6]],"date-time":"2016-08-06T11:41:41Z","timestamp":1470483701000},"page":"113-122","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":40,"special_numbering":"C","title":["Lumbrokinase attenuates myocardial ischemia-reperfusion injury by inhibiting TLR4 signaling"],"prefix":"10.1016","volume":"99","author":[{"given":"Yi-Hsin","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Min","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping-Sung","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Chan","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsing-Hui","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Shiou","family":"Jan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Wei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dah-Yuu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Tsung","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuan-Miaw","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghua Tsai","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiang-Suo","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.yjmcc.2016.08.004_bb0005","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.carpath.2005.03.006","article-title":"Myocardial ischemia and reperfusion injury","volume":"14","author":"Buja","year":"2005","journal-title":"Cardiovasc. Pathol."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0010","first-page":"180","article-title":"Mechanisms of load dependency of myocardial ischemia reperfusion injury","volume":"3","author":"Mozaffari","year":"2013","journal-title":"Am J Cardiovasc Dis."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0015","series-title":"Shock (Augusta, Ga)","first-page":"463","article-title":"Neutrophils\u2014a key component of ischemia-reperfusion injury","volume":"40","author":"Schofield","year":"2013"},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0020","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1056\/NEJMra071667","article-title":"Myocardial reperfusion injury","volume":"357","author":"Yellon","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0025","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1097\/FJC.0b013e3182a50c45","article-title":"Balance of nitric oxide and reactive oxygen species in myocardial reperfusion injury and protection","volume":"62","author":"Folino","year":"2013","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0030","series-title":"Shock (Augusta, Ga)","first-page":"401","article-title":"The role of the complement system in ischemia-reperfusion injury","volume":"21","author":"Arumugam","year":"2004"},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0035","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.imbio.2012.07.024","article-title":"The complement system in ischemia-reperfusion injuries","volume":"217","author":"Gorsuch","year":"2012","journal-title":"Immunobiology"},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0040","series-title":"Shock (Augusta, Ga)","first-page":"4","article-title":"Toll-like receptors in ischemia-reperfusion injury","volume":"32","author":"Arumugam","year":"2009"},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0045","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/nm.2507","article-title":"Ischemia and reperfusion\u2013from mechanism to translation","volume":"17","author":"Eltzschig","year":"2011","journal-title":"Nat. Med."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0050","doi-asserted-by":"crossref","first-page":"461","DOI":"10.2170\/jjphysiol.41.461","article-title":"A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus","volume":"41","author":"Mihara","year":"1991","journal-title":"The Japanese journal of physiology."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0055","first-page":"199","article-title":"Purification and characterization of six fibrinolytic serine-proteases from earthworm Lumbricus rubellus","volume":"37","author":"Cho","year":"2004","journal-title":"J. Biochem. Mol. Biol."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0060","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.drudis.2010.09.004","article-title":"Unearthing a source of medicinal molecules","volume":"15","author":"Cooper","year":"2010","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0065","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.pep.2004.05.018","article-title":"Codon optimization, expression, and characterization of recombinant lumbrokinase in goat milk","volume":"37","author":"Hu","year":"2004","journal-title":"Protein Expr. Purif."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0070","first-page":"213","article-title":"Changes in coagulation and tissue plasminogen activator after the treatment of cerebral infarction with lumbrokinase","volume":"23","author":"Jin","year":"2000","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0075","doi-asserted-by":"crossref","first-page":"4060","DOI":"10.3760\/cma.j.issn.0366-6999.20131332","article-title":"Oral fibrinogen-depleting agent lumbrokinase for secondary ischemic stroke prevention: results from a multicenter, randomized, parallel-group and controlled clinical trial","volume":"126","author":"Cao","year":"2013","journal-title":"Chin. Med. J."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0080","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1089\/acm.2008.0506","article-title":"Improved myocardial perfusion in stable angina pectoris by oral lumbrokinase: a pilot study","volume":"15","author":"Kasim","year":"2009","journal-title":"J. Altern. Complement. Med."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0085","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1161\/01.CIR.0000101921.93016.1C","article-title":"Toll-like receptor-2 modulates ventricular remodeling after myocardial infarction","volume":"108","author":"Shishido","year":"2003","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0090","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1161\/01.CIR.0000112575.66565.84","article-title":"Reduced myocardial ischemia-reperfusion injury in toll-like receptor 4-deficient mice","volume":"109","author":"Oyama","year":"2004","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0095","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1089\/ars.2010.3723","article-title":"Toll-like receptors: new players in myocardial ischemia\/reperfusion injury","volume":"15","author":"Ha","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0100","doi-asserted-by":"crossref","unstructured":"Liao PH, Hung LM, Chen YH, Kuan YH, Zhang FB, Lin RH, et al. Cardioprotective effects of luteolin during ischemia-reperfusion injury in rats. Circ. J. (official journal of the Japanese Circulation Society). 2011;75:443\u201350.","DOI":"10.1253\/circj.CJ-10-0381"},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0105","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.pharmthera.2013.04.008","article-title":"The Lambeth conventions (II): guidelines for the study of animal and human ventricular and supraventricular arrhythmias","volume":"139","author":"Curtis","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0110","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1093\/cvr\/22.7.447","article-title":"The Lambeth conventions: guidelines for the study of arrhythmias in ischaemia infarction, and reperfusion","volume":"22","author":"Walker","year":"1988","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0115","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0022-510X(99)00303-2","article-title":"Marked increase of matrix metalloproteinase 9 in cerebrospinal fluid of patients with fungal or tuberculous meningoencephalitis","volume":"173","author":"Matsuura","year":"2000","journal-title":"J. Neurol. Sci."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0120","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1016\/j.yjmcc.2010.02.020","article-title":"Cardiomyocyte toll-like receptor 4 is involved in heart dysfunction following septic shock or myocardial ischemia","volume":"48","author":"Fallach","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0125","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1089\/ars.2010.3728","article-title":"Toll-like receptor 4 stimulation initiates an inflammatory response that decreases cardiomyocyte contractility","volume":"15","author":"Avlas","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0130","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1111\/j.1582-4934.2009.00798.x","article-title":"Deficiency in TLR4 signal transduction ameliorates cardiac injury and cardiomyocyte contractile dysfunction during ischemia","volume":"13","author":"Zhao","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0135","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/sj.bjp.0707344","article-title":"Acute actions and novel targets of matrix metalloproteinases in the heart and vasculature","volume":"152","author":"Chow","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0140","doi-asserted-by":"crossref","first-page":"H21","DOI":"10.1152\/ajpheart.00292.2009","article-title":"Myocardial TLR4 is a determinant of neutrophil infiltration after global myocardial ischemia: mediating KC and MCP-1 expression induced by extracellular HSC70","volume":"297","author":"Ao","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0145","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.cardiores.2006.09.011","article-title":"Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-kappaB dependent inflammatory response","volume":"72","author":"Boyd","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0150","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1097\/ALN.0b013e31820a4d5b","article-title":"Toll-like receptor 4 signaling confers cardiac protection against ischemic injury via inducible nitric oxide synthase- and soluble guanylate cyclase-dependent mechanisms","volume":"114","author":"Wang","year":"2011","journal-title":"Anesthesiology"},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0155","doi-asserted-by":"crossref","first-page":"31308","DOI":"10.1074\/jbc.M111.246124","article-title":"Myocardial ischemia activates an injurious innate immune signaling via cardiac heat shock protein 60 and toll-like receptor 4","volume":"286","author":"Li","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0160","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.bbrc.2005.10.068","article-title":"Blocking the MyD88-dependent pathway protects the myocardium from ischemia\/reperfusion injury in rat hearts","volume":"338","author":"Hua","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0165","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2015.10.027","article-title":"Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-kappaB pathway","author":"Jiang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0170","doi-asserted-by":"crossref","first-page":"Ra100-9","DOI":"10.12659\/MSM.881709","article-title":"Toll-like receptor and its roles in myocardial ischemic\/reperfusion injury","volume":"17","author":"Fang","year":"2011","journal-title":"Med. Sci. Monit."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0175","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/S0891-5849(01)00626-8","article-title":"Grape seed proanthocyanidin reduces cardiomyocyte apoptosis by inhibiting ischemia\/reperfusion-induced activation of JNK-1 and C-JUN","volume":"31","author":"Sato","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0180","doi-asserted-by":"crossref","first-page":"928954","DOI":"10.1155\/2012\/928954","article-title":"Role of mitogen-activated protein kinases in myocardial ischemia-reperfusion injury during heart transplantation","volume":"2012","author":"Vassalli","year":"2012","journal-title":"J. Transplant."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0185","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S1054-3589(08)60669-9","article-title":"Inducible cyclooxygenase and nitric oxide synthase","volume":"33","author":"Wu","year":"1995","journal-title":"Adv. Pharmacol."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0190","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1161\/01.CIR.103.17.2181","article-title":"Matrixdependent mechanism of neutrophil-mediated release and activation of matrix metalloproteinase 9 in myocardial ischemia\/reperfusion","volume":"103","author":"Lindsey","year":"2001","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0195","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0008-6363(02)00254-7","article-title":"Myocardial protection from ischemia\/reperfusion injury by targeted deletion of matrix metalloproteinase-9","volume":"54","author":"Romanic","year":"2002","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0200","doi-asserted-by":"crossref","first-page":"H601","DOI":"10.1152\/ajpheart.2000.279.2.H601","article-title":"Matrix metalloproteinases and collagen ultrastructure in moderate myocardial ischemia and reperfusion in vivo","volume":"279","author":"Lu","year":"2000","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0205","first-page":"57","article-title":"Lumbrokinase \u2013 a potent and stable fibrin\u2013specific plasminogen activator","volume":"3","author":"Verma","year":"2011","journal-title":"Int. J. Biosci. Biotechnol."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0210","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1006\/jmcc.2000.1261","article-title":"Cytotoxic T lymphocytes are activated following myocardial infarction and can recognize and kill healthy myocytes in vitro","volume":"32","author":"Varda-Bloom","year":"2000","journal-title":"J. Mol. Cell. Cardiol."},{"key":"10.1016\/j.yjmcc.2016.08.004_bb0215","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0053110","article-title":"Cloning, expression and characterization of a gene from earthworm Eisenia fetida encoding a blood-clot dissolving protein","volume":"7","author":"Li","year":"2012","journal-title":"PLoS One"}],"container-title":["Journal of Molecular and Cellular Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022282816302346?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022282816302346?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T15:44:58Z","timestamp":1749051898000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022282816302346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":43,"alternative-id":["S0022282816302346"],"URL":"https:\/\/doi.org\/10.1016\/j.yjmcc.2016.08.004","relation":{},"ISSN":["0022-2828"],"issn-type":[{"value":"0022-2828","type":"print"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Lumbrokinase attenuates myocardial ischemia-reperfusion injury by inhibiting TLR4 signaling","name":"articletitle","label":"Article Title"},{"value":"Journal of Molecular and Cellular Cardiology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.yjmcc.2016.08.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}