MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia Intensiva

Detalhes bibliográficos
Autor(a) principal: Souza-Siqueira, Talita
Data de Publicação: 2020
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da Universidade Cruzeiro do Sul
Texto Completo: https://repositorio.cruzeirodosul.edu.br/handle/123456789/922
Resumo: Apesar dos estudos já realizados sobre microRNAs (miRNAs) durante a sepse, pouco se sabe sobre a expressão desses após a alta hospitalar. Esse estudo teve como objetivo avaliar proteínas e miRNAs nas vesículas extracelulares (VEs) plasmáticas de pacientes sépticos em seis fases: a) fase aguda (entre o primeiro e o 4º dia de internação), b) no momento de alta da Unidade de Terapia Intensiva (UTI) e c) após 3 meses da alta da UTI, d) 6 meses, e) 12 meses, e f) 3 anos. Os dados dos miRNAs das VEs foram correlacionados com aqueles da concentração plasmática de citocinas (pró- e anti-inflamatórias). Os pacientes desenvolveram um estado basal crônico de inflamação de baixa intensidade, quando comparados ao grupo controle, com valores ligeiramente aumentados de IL-6, IL-8 e proteína C reativa no plasma mesmo após 3 anos da alta. As VEs plasmáticas isoladas por ultracentrifugação apresentaram tamanho e composição de proteínas características. A composição proteica variou entre os estados saudável e de sepse além de também ser diferente entre os pacientes que sobreviveram e os que foram a óbito. Baseado nos dados da proteômica, as VEs são oriundas do sistema linfóide, linfócitos B e baço, medula óssea e hepatócitos. Quinze miRNAs foram encontrados nas VEs plasmáticas dos pacientes sépticos e controles: miRNAs miR-15b-5p, -16- 5p, -20a-5p, -21-5p, -25-3p, -27a-3p, -29a-3p, -30d-5p, -93-5p, -126-3p -146a-5p, - 148a-3p, -191-5p, -195-5p e -223-3p. A redução da expressão de treze miRNAs (miR-15b-5p, -16-5p, -20a-5p, -25-3p, -27a-3p, -29a-3p, -30d-5p, -93-5p, -146a-5p, - 148a-3p, -191-5p, -195-5p e -223-3p) na fase aguda da sepse (internação na UTI) foi mais intensa nos pacientes que foram a óbito do que nos sobreviventes. Isso indica que esses 13 miRNAs podem ser usados como biomarcadores plasmáticos de prognóstico de sobrevida na sepse. A redução na expressão dos miRNAs -15b-5p, - 16-5p, -25-3p, -27a-3p, -29a-3p, -30d-5p, -93-5p, -195-5p e -223-3p durante a fase aguda se manteve até um ano após a alta da UTI, mas houve reversão após três anos, retornando aos valores dos controles. Esses nove miRNAs podem ser utilizados como biomarcadores plasmáticos da evolução e recuperação dos pacientes sépticos após alta hospitalar.
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spelling 2020-08-25T18:57:25Z2020-06-292020-08-25T18:57:25Z2020-04-27SOUZA-SIQUEIRA, T. MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia Intensiva. 2020. 99 f. Tese (Doutorado Interdisciplinar em Ciências da Saúde) - Universidade Cruzeiro do Sul, São Paulo – 2020.https://repositorio.cruzeirodosul.edu.br/handle/123456789/922Apesar dos estudos já realizados sobre microRNAs (miRNAs) durante a sepse, pouco se sabe sobre a expressão desses após a alta hospitalar. Esse estudo teve como objetivo avaliar proteínas e miRNAs nas vesículas extracelulares (VEs) plasmáticas de pacientes sépticos em seis fases: a) fase aguda (entre o primeiro e o 4º dia de internação), b) no momento de alta da Unidade de Terapia Intensiva (UTI) e c) após 3 meses da alta da UTI, d) 6 meses, e) 12 meses, e f) 3 anos. Os dados dos miRNAs das VEs foram correlacionados com aqueles da concentração plasmática de citocinas (pró- e anti-inflamatórias). Os pacientes desenvolveram um estado basal crônico de inflamação de baixa intensidade, quando comparados ao grupo controle, com valores ligeiramente aumentados de IL-6, IL-8 e proteína C reativa no plasma mesmo após 3 anos da alta. As VEs plasmáticas isoladas por ultracentrifugação apresentaram tamanho e composição de proteínas características. A composição proteica variou entre os estados saudável e de sepse além de também ser diferente entre os pacientes que sobreviveram e os que foram a óbito. Baseado nos dados da proteômica, as VEs são oriundas do sistema linfóide, linfócitos B e baço, medula óssea e hepatócitos. Quinze miRNAs foram encontrados nas VEs plasmáticas dos pacientes sépticos e controles: miRNAs miR-15b-5p, -16- 5p, -20a-5p, -21-5p, -25-3p, -27a-3p, -29a-3p, -30d-5p, -93-5p, -126-3p -146a-5p, - 148a-3p, -191-5p, -195-5p e -223-3p. A redução da expressão de treze miRNAs (miR-15b-5p, -16-5p, -20a-5p, -25-3p, -27a-3p, -29a-3p, -30d-5p, -93-5p, -146a-5p, - 148a-3p, -191-5p, -195-5p e -223-3p) na fase aguda da sepse (internação na UTI) foi mais intensa nos pacientes que foram a óbito do que nos sobreviventes. Isso indica que esses 13 miRNAs podem ser usados como biomarcadores plasmáticos de prognóstico de sobrevida na sepse. A redução na expressão dos miRNAs -15b-5p, - 16-5p, -25-3p, -27a-3p, -29a-3p, -30d-5p, -93-5p, -195-5p e -223-3p durante a fase aguda se manteve até um ano após a alta da UTI, mas houve reversão após três anos, retornando aos valores dos controles. Esses nove miRNAs podem ser utilizados como biomarcadores plasmáticos da evolução e recuperação dos pacientes sépticos após alta hospitalar.Despite the studies already carried out on plasma microRNAs (miRNAs) in sepsis, they are not well known about changes in their expression after hospital discharge. This study aimed to evaluate septic individuals extracellular plasma vesicles (EVs) proteins and miRNAs in six phases: a) acute phase (between the first and the 4th day of hospitalization), b) at the time of Intensive Care Unit (ICU) discharge and c) 3 months after ICU discharge, d) 6 months, e) 12 months, and f) 3 years. The miRNA's results were correlated with the cytokines (pro- and anti-inflammatory) plasma concentrations. The patients developed a low-level baseline chronic inflammation state as compared to the control group with slightly increased plasma levels of IL-6, IL-8 and C reactive protein even 3 months after ICU discharge. Plasma EVs isolated by ultracentrifugation had the size and protein composition expected. The protein composition was different between the states of health and sepsis and between the survivors and the ones who died. According to the proteomics, the plasma EVs originated from the lymphoid system, B lymphocytes and spleen, bone morrow, and hepatocytes. The following 15 miRNAs were found in the plasma EVs from septic patients and controls: miR-15b-5p, -16-5p, -20a-5p, -25-3p, -27a-3p, -29a-3p, -30d- 5p, -93-5p, -146a-5p, -148a -3p, -191-5p, -195-5p, and -223-3p. The reduction in the expression of thirteen miRNAs (miR-15b-5p, -16-5p, -20a-5p, -25-3p, -27a-3p, -29a- 3p, -30d-5p, -93-5p, -146a-5p, -148a-3p, -191-5p, -195-5p e -223-3p) during the acute phase (ICU internment) was more pronounced in the patients who died than in the survivors. These 13 miRNAs maybe used as plasma biomarkers of survival prognosis in sepsis. The reduction in expression of the miRNAs -15b-5p, -16-5p, -25- 3p, -27a-3p, -29a-3p, -30d-5p, -93-5p, -195-5p, and -223-3p during the acute phase remained for up to one year after ICU discharge but it was abolished after three years, reaching the control levels. These 9 miRNAs can then be used as plasma biomarkers of evolution and recovery of septic patients after hospital discharge.porUniversidade Cruzeiro do SulPrograma de Pós Graduação Interdisciplinar em Ciências da SaúdeCruzeiro do SulBrasilCNPQ::CIENCIAS DA SAUDEInflamaçãomiR-15b-5pmiR-146a-5pmiR-223-3pmiR-195-5pSepticemia.MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia IntensivaCirculating Extracellular Vesicle MicroRNAs as survival Biomarkers in Septic Patients after Intensive Care Unit Dischargeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisSoriano, Francisco Garcia04768281800http://lattes.cnpq.br/897978139013533206601333930http://lattes.cnpq.br/Souza-Siqueira, TalitaA NAHID, Md; SATOH, M.; CHAN, E Kl. MicroRNA in TLR signaling and endotoxin tolerance. Cellular & Molecular Immunology, [s.l.], v. 8, n. 5, p.388-403, 8 ago. 2011. Springer Science and Business Media LLC. 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Springer Nature.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Cruzeiro do Sulinstname:Universidade Cruzeiro do Sul (UNICSUL)instacron:UNICSULORIGINALTalita Souza Siqueira.pdfTalita Souza Siqueira.pdfteseapplication/pdf849445http://dev.siteworks.com.br:8080/jspui/bitstream/123456789/922/1/Talita%20Souza%20Siqueira.pdfb5009e319d2a3813e641af03e327d926MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://dev.siteworks.com.br:8080/jspui/bitstream/123456789/922/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52123456789/9222020-08-25 15:59:16.389oai:repositorio.cruzeirodosul.edu.br: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Repositório InstitucionalPRIhttps://repositorio.cruzeirodosul.edu.br/oai/requestmary.pela@unicid.edu.bropendoar:2020-08-25T18:59:16Repositório Institucional da Universidade Cruzeiro do Sul - Universidade Cruzeiro do Sul (UNICSUL)false
dc.title.pt_BR.fl_str_mv MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia Intensiva
dc.title.alternative.pt_BR.fl_str_mv Circulating Extracellular Vesicle MicroRNAs as survival Biomarkers in Septic Patients after Intensive Care Unit Discharge
title MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia Intensiva
spellingShingle MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia Intensiva
Souza-Siqueira, Talita
CNPQ::CIENCIAS DA SAUDE
Inflamação
miR-15b-5p
miR-146a-5p
miR-223-3p
miR-195-5p
Septicemia.
title_short MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia Intensiva
title_full MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia Intensiva
title_fullStr MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia Intensiva
title_full_unstemmed MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia Intensiva
title_sort MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia Intensiva
author Souza-Siqueira, Talita
author_facet Souza-Siqueira, Talita
author_role author
dc.contributor.advisor1.fl_str_mv Soriano, Francisco Garcia
dc.contributor.advisor1ID.fl_str_mv 04768281800
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/8979781390135332
dc.contributor.authorID.fl_str_mv 06601333930
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/
dc.contributor.author.fl_str_mv Souza-Siqueira, Talita
contributor_str_mv Soriano, Francisco Garcia
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE
topic CNPQ::CIENCIAS DA SAUDE
Inflamação
miR-15b-5p
miR-146a-5p
miR-223-3p
miR-195-5p
Septicemia.
dc.subject.por.fl_str_mv Inflamação
miR-15b-5p
miR-146a-5p
miR-223-3p
miR-195-5p
Septicemia.
description Apesar dos estudos já realizados sobre microRNAs (miRNAs) durante a sepse, pouco se sabe sobre a expressão desses após a alta hospitalar. Esse estudo teve como objetivo avaliar proteínas e miRNAs nas vesículas extracelulares (VEs) plasmáticas de pacientes sépticos em seis fases: a) fase aguda (entre o primeiro e o 4º dia de internação), b) no momento de alta da Unidade de Terapia Intensiva (UTI) e c) após 3 meses da alta da UTI, d) 6 meses, e) 12 meses, e f) 3 anos. Os dados dos miRNAs das VEs foram correlacionados com aqueles da concentração plasmática de citocinas (pró- e anti-inflamatórias). Os pacientes desenvolveram um estado basal crônico de inflamação de baixa intensidade, quando comparados ao grupo controle, com valores ligeiramente aumentados de IL-6, IL-8 e proteína C reativa no plasma mesmo após 3 anos da alta. As VEs plasmáticas isoladas por ultracentrifugação apresentaram tamanho e composição de proteínas características. A composição proteica variou entre os estados saudável e de sepse além de também ser diferente entre os pacientes que sobreviveram e os que foram a óbito. Baseado nos dados da proteômica, as VEs são oriundas do sistema linfóide, linfócitos B e baço, medula óssea e hepatócitos. Quinze miRNAs foram encontrados nas VEs plasmáticas dos pacientes sépticos e controles: miRNAs miR-15b-5p, -16- 5p, -20a-5p, -21-5p, -25-3p, -27a-3p, -29a-3p, -30d-5p, -93-5p, -126-3p -146a-5p, - 148a-3p, -191-5p, -195-5p e -223-3p. A redução da expressão de treze miRNAs (miR-15b-5p, -16-5p, -20a-5p, -25-3p, -27a-3p, -29a-3p, -30d-5p, -93-5p, -146a-5p, - 148a-3p, -191-5p, -195-5p e -223-3p) na fase aguda da sepse (internação na UTI) foi mais intensa nos pacientes que foram a óbito do que nos sobreviventes. Isso indica que esses 13 miRNAs podem ser usados como biomarcadores plasmáticos de prognóstico de sobrevida na sepse. A redução na expressão dos miRNAs -15b-5p, - 16-5p, -25-3p, -27a-3p, -29a-3p, -30d-5p, -93-5p, -195-5p e -223-3p durante a fase aguda se manteve até um ano após a alta da UTI, mas houve reversão após três anos, retornando aos valores dos controles. Esses nove miRNAs podem ser utilizados como biomarcadores plasmáticos da evolução e recuperação dos pacientes sépticos após alta hospitalar.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-08-25T18:57:25Z
dc.date.available.fl_str_mv 2020-06-29
2020-08-25T18:57:25Z
dc.date.issued.fl_str_mv 2020-04-27
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv SOUZA-SIQUEIRA, T. MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia Intensiva. 2020. 99 f. Tese (Doutorado Interdisciplinar em Ciências da Saúde) - Universidade Cruzeiro do Sul, São Paulo – 2020.
dc.identifier.uri.fl_str_mv https://repositorio.cruzeirodosul.edu.br/handle/123456789/922
identifier_str_mv SOUZA-SIQUEIRA, T. MicroRNAs de vesículas extracelulares circulantes como biomarcadores de sobrevida de pacientes sépticos pós alta da Unidade de Terapia Intensiva. 2020. 99 f. Tese (Doutorado Interdisciplinar em Ciências da Saúde) - Universidade Cruzeiro do Sul, São Paulo – 2020.
url https://repositorio.cruzeirodosul.edu.br/handle/123456789/922
dc.language.iso.fl_str_mv por
language por
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Cruzeiro do Sul
dc.publisher.program.fl_str_mv Programa de Pós Graduação Interdisciplinar em Ciências da Saúde
dc.publisher.initials.fl_str_mv Cruzeiro do Sul
dc.publisher.country.fl_str_mv Brasil
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reponame_str Repositório Institucional da Universidade Cruzeiro do Sul
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bitstream.url.fl_str_mv http://dev.siteworks.com.br:8080/jspui/bitstream/123456789/922/1/Talita%20Souza%20Siqueira.pdf
http://dev.siteworks.com.br:8080/jspui/bitstream/123456789/922/2/license.txt
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repository.name.fl_str_mv Repositório Institucional da Universidade Cruzeiro do Sul - Universidade Cruzeiro do Sul (UNICSUL)
repository.mail.fl_str_mv mary.pela@unicid.edu.br
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