Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.

<h4>Background</h4>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.<h4>Methodology/prin...

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Autores principales:	Amanda Ribeiro Dos Santos, Aline Dionizio, Mileni da Silva Fernandes, Marília Afonso Rabelo Buzalaf, Beatriz Pereira, Débora de Fátima Almeida Donanzam, Sergio Marrone Ribeiro, Anamaria Mello Miranda Paniago, Ricardo de Souza Cavalcante, Rinaldo Poncio Mendes, James Venturini
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/f3e936d065af485eae5940c4c0ea23ae
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spelling	oai:doaj.org-article:f3e936d065af485eae5940c4c0ea23ae2021-12-02T20:24:16ZProteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.1935-27271935-273510.1371/journal.pntd.0009714https://doaj.org/article/f3e936d065af485eae5940c4c0ea23ae2021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009714https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>Development of severe PS is related to increased expression of proteins involved in glycolytic pathway and oxygen exchange), 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.Amanda Ribeiro Dos SantosAline DionizioMileni da Silva FernandesMarília Afonso Rabelo BuzalafBeatriz PereiraDébora de Fátima Almeida DonanzamSergio Marrone RibeiroAnamaria Mello Miranda PaniagoRicardo de Souza CavalcanteRinaldo Poncio MendesJames VenturiniPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 8, p e0009714 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Amanda Ribeiro Dos Santos Aline Dionizio Mileni da Silva Fernandes Marília Afonso Rabelo Buzalaf Beatriz Pereira Débora de Fátima Almeida Donanzam Sergio Marrone Ribeiro Anamaria Mello Miranda Paniago Ricardo de Souza Cavalcante Rinaldo Poncio Mendes James Venturini Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>Development of severe PS is related to increased expression of proteins involved in glycolytic pathway and oxygen exchange), 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.
format	article
author	Amanda Ribeiro Dos Santos Aline Dionizio Mileni da Silva Fernandes Marília Afonso Rabelo Buzalaf Beatriz Pereira Débora de Fátima Almeida Donanzam Sergio Marrone Ribeiro Anamaria Mello Miranda Paniago Ricardo de Souza Cavalcante Rinaldo Poncio Mendes James Venturini
author_facet	Amanda Ribeiro Dos Santos Aline Dionizio Mileni da Silva Fernandes Marília Afonso Rabelo Buzalaf Beatriz Pereira Débora de Fátima Almeida Donanzam Sergio Marrone Ribeiro Anamaria Mello Miranda Paniago Ricardo de Souza Cavalcante Rinaldo Poncio Mendes James Venturini
author_sort	Amanda Ribeiro Dos Santos
title	Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.
title_short	Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.
title_full	Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.
title_fullStr	Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.
title_full_unstemmed	Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.
title_sort	proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/f3e936d065af485eae5940c4c0ea23ae
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Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.

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