Browsing by Author "Penque, Deborah"
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- 2-DIGE of Red Blood Cells from Sickle-Cell Disease Patients with Severe Vaso-Occlusion.Publication . Vaz, Fátima; Charro, Nuno; Morais, Anabela; Lavinha, João; Penque, Deborah
- Analytical techniques for multiplex analysis of protein biomarkersPublication . Van Gool, Alain; Corrales, Fernado; Čolović, Mirjana; Krstić, Danijela; Oliver-Martos, Begona; Martínez-Cáceres, Eva; Jakasa, Ivone; Gajski, Goran; Brun, Virginie; Kyriacou, Kyriacos; Burzynska-Pedziwiatr, Izabela; Wozniak, Lucyna Alicja; Nierkens, Stephan; Pascual García, César; Katrlik, Jaroslav; Bojic-Trbojevic, Zanka; Vacek, Jan; Llorente, Alicia; Antohe, Felicia; Suica, Viorel; Suarez, Guillaume; t’Kindt, Ruben; Martin, Petra; Penque, Deborah; Martins, Ines Lanca; Bodoki, Ede; Iacob, Bogdan-Cezar; Aydindogan, Eda; Timur, Suna; Allinson, John; Sutton, Christopher; Luider, Theo; Wittfooth, Saara; Sammar, MareiThe importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways. Hence, capabilities to analyze multiple protein biomarkers in one assay are highly interesting for biomedical research.
- Annual Scientific Report of the Center for Toxicogenomics and Human HealthPublication . Penque, Deborah; Vieira, Luis; Gonçalves, João; Louro, Henriqueta; Silva, Maria João
- Biomonitoring the genetic effects of environmental tobacco smoke exposure in restaurant workersPublication . Vital, Nádia; Louro, Henriqueta; Antunes, Susana; Penque, Deborah; Simões, Tânia; Silva, Maria JoãoEnvironmental tobacco smoke (ETS) is recognized as one of the most common indoor pollutants worldwide. Portuguese legislation prohibits smoking in most indoor public spaces. However, in some restaurants/bars smoking is still allowed, representing a potential risk factor for the workers health, particularly for chronic respiratory diseases and cancer onset.The aim of this study was to characterize early signs of ETS-associated adverse systemic effects in workers from restaurants with smoking permission in comparison with workers from smoke-free spaces, considering the modulating effects of genetic susceptibility.The ETS-exposed workers did not display differences in the frequencies of SCEs, cells with high frequency of SCEs (HFCs), MN or DNA strand breaks, as assessed by the comet assay, when compared to non-ETS workers. Smoking workers presented a significantly increased level of HFCs as compared to non-smokers. Interestingly, the ex vivo challenge of leukocytes with EMS resulted in a lower level of DNA breaks in ETS-exposed as compared to non-exposed workers (P<0,0001), suggesting an increased DNA repair capacity associated to ETS-exposure. Regarding the genetic polymorphisms studied, GSTM1 null genotype carriers presented increased frequencies of SCEs and HFCs associated with ETS exposure, suggesting an increased susceptibility to this environmental stressor. On the contrary, XRCC1-399 wild type carriers presented a lower level of MN than the variant allele carriers, in response to ETS exposure. Finally, among the ETS-exposed subjects, those carrying the hOGG1 variant alleles presented a lower level of ex vivo EMS-induced DNA damage comparatively to the wild type subjects, suggesting a higher DNA repair capacity.The study of ETS exposure in an occupational setting in Lisbon restaurants revealed that the exposed workers did not display systemic genetic effects detectable by the biomarkers analysed. However, the results of the ex vivo challenge comet assay, suggests that ETS may have a more subtle modulating effect on the DNA repair response of blood cells to a genotoxic insult. In addition, the association between some genetic polymorphisms and increased genotoxic effects in subsets of individuals, highlights the possibility of increased health risks in susceptible individuals exposed to ETS, that should be further investigated.
- Bottom up proteomics data analysis strategies to explore protein modifications and genomic variantPublication . Carvalho, Ana; Matthiesen, Rune; Penque, DeborahThe quest to understand biological systems requires further attention of the scientific community to the challenges faced in proteomics. In fact the complexity of the proteome reaches uncountable orders of magnitudes. This means that significant technical and data-analytic innovations will be needed for the full understanding of biology. Current state of art mass spectrometry (MS) is probably our best choice for studying protein complexity and exploring new ways to use MS and MS derived data should be given higher priority. We present here a brief overview of visualization and statistical analyzes strategies for quantitative peptide values on an individual protein basis. These analysis strategies can help pinpoint protein modifications, splice and genomic variants of biological relevance. We demonstrated the application of these data analysis strategies using a bottom-up proteomics data set obtained in a drug profiling experiment. Furthermore, we have also observed that the presented methods are useful for studying peptide distributions from clinical proteomics samples from a large number of individuals. We expect that the presented data analysis strategy will be useful in the future to define functional protein variants in biological model systems and disease studies. Therefore robust software implementing these strategies is urgently needed.
- Chronic Obstructive Pulmonary Disease and Proteomics: A Match for Success?Publication . Alexandre, Bruno; Penque, DeborahChronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation that is not fully reversible even under bronchodilators effect, caused by a mixture of small airway disease and parenchymal destruction. COPD is a major cause of morbidity and mortality in adults, and it is now the fourth leading death cause in the world. Cigarette smoking is the main risk factor for COPD but not all smokers will suffer from COPD, suggesting that genetic and other environmental factors are involved in this pathology. Current diagnosis is based on spirometry, but there is recurrent debate on fixed spirometric thresholds in use that lead to misdiagnosis and/or classification of COPD. The available treatments are not effective to reduce or suppress the progression of COPD. Hence, there is an urgent need to better understand the molecular mechanisms of COPD pathogenesis to provide clinicians with reliable diagnosis and treatment tools for COPD. Proteomics, defined by the comprehensive study of the proteome, has the potential to respond to this need by providing protein profiles of a particular disease and, at the same time, by identifying specific biomarkers that can be used to better understand, diagnose and manage the disease. Here, we shortly review COPD history and pathology and how proteomics can match COPD for success.
- Clinical proteomics stretch goals: EuPA 2012 roundtable reportPublication . O'Neil, S.E.; Palviainen, M.J.; Ten Have, S.; Penque, Deborah; Baker, M.S.The field of clinical proteomics is faced with multiple challenges which need to be overcome in order to improve our understanding of human diseases and provide management solutions. Researchers interested in clinical proteomics assembled for a roundtable discussion at the European Association for Proteomics (EuPA) conference held in Glasgow in July 2012, to discuss these challenges and highlight the key areas for successful clinical proteomic studies. This report shares topics of discussion and the resulting stretch goals of clinical proteomics for researchers to strive towards.
- Diabetes mellitus tipo 2 (DMT2) associada a Sindrome de Apneia Obstrutiva do Sono (SAOS): um estudo proteómicoPublication . Vaz, Fátima; Valentim-Coelho, Cristina; Neves, Sofia; Penque, Deborah; Barbara, CristinaIntrodução: A prevalência da SAOS é elevada em doentes com DMT2. O não tratamento da SAOS pode levar ao agravamento ou desenvolvimento da DMT2. Temos vindo a demonstrar que a SAOS altera o proteoma do glóbulo vermelho (GV). A SAOS aumenta a overoxidação da peroxirredoxina 2 (PRDX2) (enzima antioxidante), o que pode levar à desregulação da homeostasia do GV e ao desenvolvimento de doenças metabólicas. Após tratamento com ventilação não invasiva (PAP), esta overoxidação diminuiu seguida de um aumento de PRDX2 decamérica overoxidada com funções chaperone na proteção celular (Feliciano et al. 2017). No presente estudo, fomos investigar o estado redox/oligomérico da PRDX2 em doentes DMT2 com SAOS, antes/após PAP, para melhor compreender a interligação entre estas patologias. Material e métodos: Amostras de GVs de controles (n=22 sendo 3 DMT2) e doentes SAOS antes/após 6 meses de tratamento com PAP (n=29 sendo 8 DMT2) foram analisadas por western-blot não reduzido, com anticorpo para a PRDX2 e PRDXSO2/3 (overoxidada). Os grupos foram comparados estatisticamente e correlacionados com dados clínicos e bioquímicos. Resultados: Nos GVs de doentes DMT2/SAOS, o nível de monómeros da PRDX2 mostrou-se aumentado e diminuía após PAP. Contudo, o nível destes monómeros PRDXSO2/3 estava diminuído e não se alterou com o tratamento. Após PAP, o nível de decâmeros PRDX2SO2/3 foi também menor nestes doentes. Os níveis de monómeros PRDX2 e PRDX2SO2/3 correlacionaram-se negativamente com os níveis de insulina/triglicéridos e HbA1C, respetivamente. Após PAP, os níveis de decâmeros PRDX2SO2/3 correlacionou-se positivamente com os níveis de adrenalina. Conclusões: O estado redox/oligomérico da PRDX2 do GV é diferencialmente modulado nos doentes DTM2/SAOS em comparação com doentes SAOS. Decâmeros PRDXSO2/3 induzidos pelo tratamento e associadas à função protetora “chaperone” estão diminuídos em doentes DMT2/SAOS. O impacto clínico destas descobertas, necessita de mais investigação e validação.
- Diagnostic and prognostic biomarker discovery strategies for autoimmune disordersPublication . Gibson, David S.; Banha, João; Penque, Deborah; Costa, Luciana; Conrads, Thomas P.; Cahill, Dolores J.; O'Brien, John K.; Rooney, Madeleine E.Current clinical, laboratory or radiological parameters cannot accurately diagnose or predict disease outcomes in a range of autoimmune disorders. Biomarkers which can diagnose at an earlier time point, predict outcome or help guide therapeutic strategies in autoimmune diseases could improve clinical management of this broad group of debilitating disorders. Additionally, there is a growing need for a deeper understanding of multi-factorial autoimmune disorders. Proteomic platforms offering a multiplex approach are more likely to reflect the complexity of autoimmune disease processes. Findings from proteomic based studies of three distinct autoimmune diseases are presented and strategies compared. It is the authors' view that such approaches are likely to be fruitful in the movement of autoimmune disease treatment away from reactive decisions and towards a preventative stand point.