{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:10:54Z","timestamp":1788401454799,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","doi-asserted-by":"publisher","award":["2014\/470221-3"],"award-info":[{"award-number":["2014\/470221-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Funda\u00e7\u00e3o da Universidade Federal do Mato Grosso do Sul, UFMS\/MEC","award":["2014\/470221-3"],"award-info":[{"award-number":["2014\/470221-3"]}]},{"name":"Funda\u00e7\u00e3o da Universidade Federal do Mato Grosso do Sul, UFMS\/MEC","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"BRASIL","award":["2014\/470221-3"],"award-info":[{"award-number":["2014\/470221-3"]}]},{"name":"BRASIL","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","award":["2014\/470221-3"],"award-info":[{"award-number":["2014\/470221-3"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Paracoccidioidomycosis (PCM), which mainly affects rural workers, is a systemic mycosis caused by the Paracoccidioides genus that induces pulmonary sequelae in most adult patients, causing serious disability and impairing their quality of life. Silymarin is herbal medicine with an effective antifibrotic activity. Considering that in PCM, antifibrotic treatment is still not available in pulmonary fibrosis, we aimed to evaluate combined silymarin and cotrimoxazole (CMX) therapy via the intratracheal route in BALB\/c mice infected with P.\u00a0brasiliensis yeast. After 12 weeks of treatment, the lungs were collected for the determination of fungal burden, production of OH-proline, deposition of collagen fibers, pulmonary concentrations of cytokines, and expression of fibronectin, \u03b1-SMA, MMP-2, MMP-9, and TIMP-2. Spleen cell cultures were also performed. Our results showed that infected mice treated with combined silymarin\/CMX showed lower deposition of collagen fibers in the lungs and lower pulmonary concentrations of hydroxyproline than the placebo groups. Decreased levels of TGF-\u03b21 and fibronectin and high levels of MMP-2 and IFN-\u03b3 were also observed in this group of mice. Collectively, our findings indicate that the combination of antifungal treatment with silymarin has a potent antifibrotic effect associated with an immunomodulatory effect that potentializes the antifungal immune response.<\/jats:p>","DOI":"10.3390\/jof8101010","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T01:51:49Z","timestamp":1664329909000},"page":"1010","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Combined Silymarin and Cotrimoxazole Therapy Attenuates Pulmonary Fibrosis in Experimental Paracoccidioidomycosis"],"prefix":"10.3390","volume":"8","author":[{"given":"Victor Quinholes","family":"Resende","sequence":"first","affiliation":[{"name":"Faculdade de Ci\u00eancias, Universidade Estadual Paulista (UNESP), Bauru 17033-360, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karoline Hagata","family":"Reis-Goes","sequence":"additional","affiliation":[{"name":"Faculdade de Ci\u00eancias, Universidade Estadual Paulista (UNESP), Bauru 17033-360, SP, Brazil"},{"name":"Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu 18618-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela Carolina","family":"Finato","sequence":"additional","affiliation":[{"name":"Faculdade de Ci\u00eancias, Universidade Estadual Paulista (UNESP), Bauru 17033-360, SP, Brazil"},{"name":"Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu 18618-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7570-6337","authenticated-orcid":false,"given":"D\u00e9bora","family":"de F\u00e1tima Almeida-Donanzam","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande 79070-900, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Ribeiro","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande 79070-900, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonatas","family":"Perico","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu 18618-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara Casella","family":"Amorim","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande 79070-900, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0035-2439","authenticated-orcid":false,"given":"James","family":"Venturini","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande 79070-900, MS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ympev.2009.04.005","article-title":"Phylogenetic analysis reveals a high level of speciation in the Paracoccidioides genus","volume":"52","author":"Teixeira","year":"2009","journal-title":"Mol. 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