{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T06:37:01Z","timestamp":1773729421587,"version":"3.50.1"},"reference-count":62,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010435","name":"Universidade Federal Fluminense","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010435","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011919","name":"Universidade Federal do Estado do Rio de Janeiro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011919","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E\u201026\/010.000983\/2019"],"award-info":[{"award-number":["E\u201026\/010.000983\/2019"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E\u201026\/201.448\/2021"],"award-info":[{"award-number":["E\u201026\/201.448\/2021"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E\u201026\/2010.592\/2019"],"award-info":[{"award-number":["E\u201026\/2010.592\/2019"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E\u201026\/203.290\/2017"],"award-info":[{"award-number":["E\u201026\/203.290\/2017"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011919","name":"Universidade Federal do Estado do Rio de Janeiro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011919","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100024786","name":"Instituto Oswaldo Cruz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100024786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis, a leading cause of death globally, lacks targeted and effective treatment. Its pathophysiology involves unbalanced inflammation, marked by a high release of inflammatory mediators, leukocyte recruitment, vascular changes and dysfunction of the nervous and respiratory systems. Src family tyrosine kinases (SFK) play a critical role in immune responses, and their inhibition can modulate excessive inflammation. This study investigates the potential of bosutinib, an SFK inhibitor, as a treatment for sepsis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical signs, survival rates, systemic and neuronal inflammatory responses, cell recruitment, lung function and cerebral microcirculation were analysed in mice treated with bosutinib (3\u2009mg\/kg) or DMSO\/saline followed by cecal ligation and puncture (CLP)\u2010induced sepsis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bosutinib treatment reduced the severity of sepsis, improved survival rates and reduced the levels of pro\u2010inflammatory cytokines and chemokines in peritoneal lavage, plasma and brain tissue. It also reduced cellular infiltration and bacterial growth at the infection site and protected lung function by reducing diffuse alveolar damage. Using intravital microscopy and laser speckle techniques, bosutinib improved capillary density and blood perfusion and reduced leukocyte recruitment and adhesion in the cerebral microcirculation of septic animals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Bosutinib pretreatment attenuated dysregulated inflammatory responses and neurovascular changes in experimental sepsis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.70055","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T07:14:46Z","timestamp":1745824486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Bosutinib mitigates inflammation in experimental sepsis"],"prefix":"10.1111","volume":"55","author":[{"given":"C. M. C.","family":"Cunha","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"},{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Biom\u00e9dico, Universidade Federal Do Estado Do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. H. P.","family":"Abreu","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"},{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Biom\u00e9dico, Universidade Federal Do Estado Do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Estato","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. M. V.","family":"Soares","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"},{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Biom\u00e9dico, Universidade Federal Do Estado Do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. P. T.","family":"Moraes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"},{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Biom\u00e9dico, Universidade Federal Do Estado Do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. P.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Pulmonary Investigation Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. D.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Pulmonary Investigation Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. L.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Pulmonary Investigation Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Immler","sequence":"additional","affiliation":[{"name":"Walter Brendel Centre, Department of Cardiovascular Physiology and Pathophysiology Klinikum der Universit\u00e4t, Ludwig Maximilians University M\u00fcnchen  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. R.","family":"Rocco","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7689-3613","authenticated-orcid":false,"given":"M.","family":"Sperandio","sequence":"additional","affiliation":[{"name":"Walter Brendel Centre, Department of Cardiovascular Physiology and Pathophysiology Klinikum der Universit\u00e4t, Ludwig Maximilians University M\u00fcnchen  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. R.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8349-9529","authenticated-orcid":false,"given":"P. T.","family":"Bozza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. C.","family":"Castro\u2010Faria\u2010Neto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4458-3055","authenticated-orcid":false,"given":"C. F.","family":"Gon\u00e7alves\u2010de\u2010Albuquerque","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Oswaldo Cruz, FIOCRUZ  Rio de Janeiro Brazil"},{"name":"Laborat\u00f3rio de Imunofarmacologia Instituto Biom\u00e9dico, Universidade Federal Do Estado Do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-017-0622-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1707170"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.45"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-1701-3"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-020-00270-5"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.1043859"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201910-1911TR"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431x20207851"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/512926"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.222208"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a002352"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20132496"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200407-981OC"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00901"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-0082-8"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20141165"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.07.070"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.36"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107476"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.158.1.9708031"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1985.59.3.732"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1365-z"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12825"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.87a.18143"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201810128"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S173867"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431x20198595"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-018-0005-7"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.74.7162"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1466294"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.334"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-020-00862-1"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.278.5.R1140"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2012.05.006"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-011-2151-2"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.6.4053"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.225722"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01364"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1447901"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6053492"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000520"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1159\/000503775"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc9205"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1368"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18822801"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/84675"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.01268"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00028"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10877-016-9945-2"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00008"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(03)00251-0"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-5-7"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep33123"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.4046\/trd.2016.79.2.53"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000702"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0069-0"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1159\/000430325"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.07-0420"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03696-8"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2015.01.018"}],"container-title":["European Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/eci.70055","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/eci.70055","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/eci.70055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T21:07:18Z","timestamp":1769720838000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/eci.70055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,28]]},"references-count":62,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/eci.70055"],"URL":"https:\/\/doi.org\/10.1111\/eci.70055","archive":["Portico"],"relation":{},"ISSN":["0014-2972","1365-2362"],"issn-type":[{"value":"0014-2972","type":"print"},{"value":"1365-2362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,28]]},"assertion":[{"value":"2025-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70055"}}