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Abstract(s)
As evidências recentes mostram uma relação entre a doença cardiovascular, a periodontite crónica e a diabetes tipo II, contudo, os mecanismos moleculares e respetivas proteínas que se encontram alterados nestas doenças ainda não estão bem estabelecidos. O envelhecimento da população trouxe como uma das suas consequências pacientes com fenótipos complexos, decorrentes do acumular de múltiplas doenças, tornando o diagnóstico e o tratamento destas doenças um enorme desafio. Conhecer como as proteínas se alteram e como estão implicadas em indivíduos multicomprometidos constitui um desafio adicional.
É objetivo deste trabalho identificar as proteínas cuja expressão se encontra alterada por recurso a estratégias bioinformáticas, no sentido de poderem ser identificados os mecanismos moleculares que se encontram alterados e adicionalmente constituir informação importante para a proposta de potenciais biomarcadores em indivíduos multicomprometidos com conjugações diversas de doença cardiovascular, periodontite crónica e diabetes tipo II. Nesse sentido foi criada, no âmbito da presente tese, a primeira coleção de amostras de saliva de doentes multicomprometidos com combinações diversas da doença cardiovascular, periodontite crónica e diabetes tipo II. Uma vez estabelecida a referida coleção será possível no futuro a quantificação das diversas proteínas em amostras de saliva. A identificação das proteínas alteradas nas diferentes patologias em estudo, descrita na bibliografia, permitiu a atualização da base de dados OralOme. Com a informação disponível foram realizados estudos funcionais recorrendo às ferramentas bioinformáticas PANTHER e Cytoscape, no sentido de serem identificadas, a partir da informação sobre as proteínas alteradas, quais os mecanismos moleculares que se encontram comprometidos. Com os resultados obtidos foi possível verificar que seriam necessários mais estudos de quantificação de proteínas em saliva, para cada uma das patologias em estudo e principalmente os estudos serem estendidos a pacientes multicomprometidos para que o diagnóstico destes pacientes possa ser mais efetivo.
Recent evidence demonstrates a relation between cardiovascular disease, chronic periodontitis and type II diabetes mellitus. However, the molecular mechanisms and altered proteins in these diseases are not well established yet. Ageing is a process that consequently develops complex phenotypes resulting from the accumulation of multiple diseases, making the diagnostic and treatment of the clinical situations harder. To know how proteins are altered and how they interact in multi compromised individuals poses an additional challenge. This work aims to identify proteins with altered expression, using bioinformatics tools, to identify the molecular mechanisms compromised. Additionally, the creation of important information in order to propose potential biomarkers in individuals with two or more of these diseases is also a goal. For that purpose, a collection of saliva samples was created from individuals with different combinations of cardiovascular disease, chronic periodontitis and type II diabetes. Once this collection is created the future quantification of the different proteins present in these sample is possible. The identification of the proteins altered in the different diseases in study, describe in literature, allowed the update of the OralOme database. With all the information present in the OralOme for the three diseases, a functional analysis of the proteins was made using the bioinformatics tools PANTHER and Cytoscape in order to find the proteins altered in saliva and the molecular mechanisms in which they participate. With the results obtained it was possible to suggest the need of more quantification studies of salivary proteins, for each disease and above all the quantification of salivary proteins in patients with the association of cardiovascular, diabetes melitus type 2 and periodontal disease to improve the differential diagnostic.
Recent evidence demonstrates a relation between cardiovascular disease, chronic periodontitis and type II diabetes mellitus. However, the molecular mechanisms and altered proteins in these diseases are not well established yet. Ageing is a process that consequently develops complex phenotypes resulting from the accumulation of multiple diseases, making the diagnostic and treatment of the clinical situations harder. To know how proteins are altered and how they interact in multi compromised individuals poses an additional challenge. This work aims to identify proteins with altered expression, using bioinformatics tools, to identify the molecular mechanisms compromised. Additionally, the creation of important information in order to propose potential biomarkers in individuals with two or more of these diseases is also a goal. For that purpose, a collection of saliva samples was created from individuals with different combinations of cardiovascular disease, chronic periodontitis and type II diabetes. Once this collection is created the future quantification of the different proteins present in these sample is possible. The identification of the proteins altered in the different diseases in study, describe in literature, allowed the update of the OralOme database. With all the information present in the OralOme for the three diseases, a functional analysis of the proteins was made using the bioinformatics tools PANTHER and Cytoscape in order to find the proteins altered in saliva and the molecular mechanisms in which they participate. With the results obtained it was possible to suggest the need of more quantification studies of salivary proteins, for each disease and above all the quantification of salivary proteins in patients with the association of cardiovascular, diabetes melitus type 2 and periodontal disease to improve the differential diagnostic.
Description
Keywords
Doença cardiovascular Doença periodontal Diabetes tipo II Diagnóstico em saliva Multicomprometidos Cardiovascular disease Periodontal disease Type II diabetes Salivary diagnostic Multi compromised
