{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:54:38Z","timestamp":1767182078558,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pntd.0009714","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000}}],"reference-count":100,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["CNPq; Grant #470221\/2014-3"],"award-info":[{"award-number":["CNPq; Grant #470221\/2014-3"]}],"id":[{"id":"10.13039\/501100003593","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":["Finance Code 001- Master Scholarship"],"award-info":[{"award-number":["Finance Code 001- Master Scholarship"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Funda\u00e7\u00e3o da Universidade Federal do Mato Grosso do Sul, UFMS\/MEC, BRASIL"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pulmonary sequelae (PS) in patients with chronic paracoccidioidomycosis (PCM) typically include pulmonary fibrosis and emphysema. Knowledge of the molecular pathways involved in PS of PCM is required for treatment and biomarker identification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology\/Principal findings<\/jats:title>\n                    <jats:p>This non-concurrent cohort study included 29 patients with pulmonary PCM that were followed before and after treatment. From this group, 17 patients evolved to mild\/ moderate PS and 12 evolved severe PS. Sera from patients were evaluated before treatment and at clinical cure, serological cure, and apparent cure. A nanoACQUITY UPLC-Xevo QT MS system and PLGS software were used to identify serum differentially expressed proteins, data are available via ProteomeXchange with identifier PXD026906. Serum differentially expressed proteins were then categorized using Cytoscape software and the Reactome pathway database. Seventy-two differentially expressed serum proteins were identified in patients with severe PS compared with patients with mild\/moderate PS. Most proteins altered in severe PS were involved in wound healing, inflammatory response, and oxygen transport pathways. Before treatment and at clinical cure, signaling proteins participating in wound healing, complement cascade, cholesterol transport and retinoid metabolism pathways were downregulated in patients with severe PS, whereas signaling proteins in gluconeogenesis and gas exchange pathways were upregulated. At serological cure, the pattern of protein expression reversed. At apparent cure pathways related with tissue repair (fibrosis) became downregulated, and pathway related oxygen transport became upregulated. Additionally, we identified 15 proteins as candidate biomarkers for severe PS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions\/Significance<\/jats:title>\n                    <jats:p>\n                      Development of severe PS is related to increased expression of proteins involved in glycolytic pathway and oxygen exchange\n                      <jats:strike>)<\/jats:strike>\n                      , indicative of the greater cellular activity and replication associated with early dysregulation of wound healing and aberrant tissue repair. Our findings provide new targets to study mechanisms of PS in PCM, as well as potential biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0009714","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T13:57:20Z","timestamp":1629727040000},"page":"e0009714","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5577-4498","authenticated-orcid":true,"given":"Amanda Ribeiro dos","family":"Santos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline","family":"Dionizio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6125-6697","authenticated-orcid":true,"given":"Mileni da Silva","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5985-3951","authenticated-orcid":true,"given":"Mar\u00edlia Afonso Rabelo","family":"Buzalaf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5446-2671","authenticated-orcid":true,"given":"Beatriz","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7570-6337","authenticated-orcid":true,"given":"D\u00e9bora de F\u00e1tima Almeida","family":"Donanzam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0732-2814","authenticated-orcid":true,"given":"Sergio Marrone","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8925-7712","authenticated-orcid":true,"given":"Anamaria Mello Miranda","family":"Paniago","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo de Souza","family":"Cavalcante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0661-5917","authenticated-orcid":true,"given":"Rinaldo Poncio","family":"Mendes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0035-2439","authenticated-orcid":true,"given":"James","family":"Venturini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"pntd.0009714.ref001","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":"MM Teixeira","year":"2009","journal-title":"Mol Phylogenet Evol"},{"key":"pntd.0009714.ref002","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1590\/S0074-02762009000300019","article-title":"Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006","volume":"104","author":"M Prado","year":"2009","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"pntd.0009714.ref003","doi-asserted-by":"crossref","DOI":"10.2174\/1874285801711010224","article-title":"Paracoccidioidomycosis: Current Perspectives from Brazil.","volume":"11","author":"RP Mendes","year":"2017","journal-title":"Open Microbiol J."},{"key":"pntd.0009714.ref004","article-title":"Brazilian guidelines for the clinical management of paracoccidioidomycosis.","author":"MA Shikanai-Yasuda","year":"2017","journal-title":"Rev Soc Bras Med Trop."},{"key":"pntd.0009714.ref005","doi-asserted-by":"crossref","first-page":"441","DOI":"10.6061\/clinics\/2013(04)02","article-title":"The lung in paracoccidioidomycosis: new insights into old problems","volume":"68","author":"AN Costa","year":"2013","journal-title":"Clin Sao Paulo Braz"},{"key":"pntd.0009714.ref006","unstructured":"ALINE FERREIRA DOS SANTOS. 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