Percorrer por autor "Saraiva, Joana"
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- Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical studyPublication . Febra, Claúdia; Saraiva, Joana; Vaz, Fátima; Soares, Nelson; Penque, PenqueBackground: Venous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE. Methods: This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was D-glutamine and D-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3',5'-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68). Conclusions: Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.
- Discriminative Protein Markers of Second-Hand Smoke Exposure Identified by Shotgun ProteomicsPublication . Neves, Sofia; Pacheco, Solange A.; Vaz, Fátima; Saraiva, Joana; James, Peter; Simões, Tânia; Penque, DeborahObjective: Chronic exposure to second-hand smoke (SHS) increases the risk of developing tobacco-related pathologies such as lung cancer and cardiovascular diseases. This study aimed to identify potential protein biomarkers for response and risk assessment of SHS exposure. Methods: A shotgun proteomics approach was employed to analyse protein expression profiles in nasal epithelium and plasma samples from healthy, non-smoking restaurant workers who were either exposed or not exposed to SHS in the workplace. A label-free quantification strategy was used to measure differential protein expression between the two groups. Logistic regression modelling was applied to identify the proteins that best discriminated exposed individuals from non-exposed controls, with the goal of establishing an expression profile indicative of SHS-related response. Results: In the nasal epithelium, SHS exposure was associated with modulation of proteins involved in HIF1α-regulated glycolytic pathways, xenobiotic metabolism, cell proliferation, and differentiation. In plasma, differentially expressed proteins were related to systemic inflammation and atherosclerosis. Among these, three plasma proteins—Histidine-rich glycoprotein (HRG), Vitamin D-binding protein (GC), and Leucine-rich alpha-2-glycoprotein (LRG1)—showed a significant discriminatory potential between SHS-exposed and non-exposed individuals. Conclusions: The identified proteins, particularly HRG, GC, and LRG1, are promising response biomarkers for SHS exposure. Their expression profiles may support the development of molecular tools for individual response assessment associated with environmental tobacco smoke.
- Impacto do fumo do cigarro passivo no proteoma humano: em busca de biomarcadores precoces de risco para a saúdePublication . Neves, Sofia; Pacheco, Solange A.; Vaz, Fátima; Valentim-Coelho, Cristina; Saraiva, Joana; James, Peter; Simões, Tânia; Penque, DeborahOs não-fumadores expostos ao fumo do cigarro passivo ou, simplesmente fumo passivo (FP), apresentam um risco acrescido de desenvolver diversas doenças graves. No entanto, os mecanismos moleculares que explicam estes efeitos continuam pouco esclarecidos, o que reforça a necessidade de identificar biomarcadores capazes de avaliar o risco associado a esta exposição. Neste estudo, analisámos o proteoma do epitélio nasal e do plasma de indivíduos não-fumadores saudáveis expostos ao FP no local de trabalho, num contexto ainda enquadrado pela Lei n.º 37/2007, utilizando uma abordagem proteómica ‘shotgun’ por espectrometria de massa. No epitélio nasal, observámos um aumento de proteínas envolvidas em vias centrais do metabolismo energético, como a Gliceraldeído-3-fosfato desidrogenase (GAPDH) e a Triosefosfato isomerase (TPI1), sugerindo uma possível reprogramação metabólica induzida pela exposição. Identificámos também uma diminuição da tubulina beta-4B (TUBB4B), relacionada com a organização do citoesqueleto, e um aumento da proteína anti-apoptótica SERPINB3, apontando para alterações em processos de morte e sobrevivência celular. No plasma, destacaram-se o aumento da Butirilcolinesterase (BChE) e a diminuição da Proteína de ligação à vitamina D (GC), ambas associadas à resposta a xenobióticos e a processos de lesão tecidular. Foram ainda detetadas alterações em proteínas reguladoras da inflamação sistémica, como C1R, C1QC, HRG e PROS1. A expressão diferencial de APOA4 e SERPINF2 sugere, adicionalmente, a ativação de mecanismos relacionados com risco aterotrombótico. Em conjunto, estes resultados contribuem para aprofundar a compreensão das vias biológicas que ligam a exposição ao fumo passivo ao risco acrescido de cancro e de doenças cardiovasculares, e apresentam um conjunto promissor de potenciais biomarcadores para avaliação do risco associado à exposição ao FP.
- Investigating the impact of COVID-19 vaccines on the red blood cell immune function by omics-based approachesPublication . Saraiva, Joana; Coelho, Cristina Valentim; Vaz, Fátima; Antunes, Marilia; Neves, Sofia; Ricardo, Peliano; Andrade, Odília; Miranda, Armandina; Melo, Aryse; Roque, Carla; Guiomar, Raquel; Mohammad, Hamza; Soares, Nelson; Penque, DeborahThe role of red blood cells (RBC) in the immune system is increasingly recognized. However, RBC-derived molecules with an immunomodulatory role in health and disease, as well as in vaccine immunogenicity are still poorly investigated. Taking as a model the emergent COVID-19 vaccines, we aimed to investigate whether vaccines induce proteome and/or metabolome changes in RBCs able to affect T-cell immune activity, as a mechanistic test for vaccine immunization regulated by RBCs. Our ultimate goal is to identify RBC immunomodulators as potential co-adjuvants in the formulation of next-generation vaccines with bolstered efficacy and duration. A biobank of blood samples collected longitudinally under ‘omics’ quality control from subjects (n=39) that underwent vaccination for COVID-19 between April and September 2021 was created. This biobank is associated with extensive clinical data, including demographic data, COVID-19 PCR diagnosis, hematological and vaccine effectivity data. Linear Mixed Models, were used to evaluate the association between biometrical characteristics, health related habits, vaccine technology and vaccine effectivity and hematological parameters, along the different time-points (t0-t4) under study, i.e, before and after (24-72h or 30 days) of the first and second dose of vaccine. Statistical analyses were performed using R software version 4.1.2. Results showed significant differences (p<0.05) before/after vaccination in a set of hematological variables (e.g., hemoglobin, lymphocytes and monocytes values), as well in terms of vaccine effectivity and vaccine technology (mRNA or adenovirus – based vaccines). Preliminary data from proteomics and metabolomics analysis of RBCs along the different time-points (t0-4) of immunization response will be also presented and discussed. The knowledge gained with this project can generate important evidence-based recommendations intended to optimize vaccine immunization, by recognizing the impact of blood cells such RBCs in the immune system regulation.
- Multiomics profiling of Red Blood Cells (RBCs) combined with Deep Machine Learning analysis – reveals potential Diagnostic Biomarkers for Acute Venous ThromboembolismPublication . Febra, Cláudia; Saraiva, Joana; AlKhnbashi, Omer; Vaz, Fátima; Macedo, João; Uddin, Mohammed J.; Penque, Deborah; Soares, Nelson C.Background and aims: Venous Thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is still based on complex imaging exams due to the lack of biomarkers. However, studies assessing the diagnostic capacity of novel metabolomics biomarkers in VTE are scarce. Our aim was to determine whether patients with acute VTE exhibit differences in proteomic and metabolomic profiles.
- Multiomics screening of red blood cells (RBCs) reveals new candidate diagnostic biomarkers for acute venous thrombosisPublication . Febra, Cláudia; Saraiva, Joana; AlKhnbashi, Omer; Pinto, Frederico G.; Vaz, Fátima; Macedo, João; Uddin, Mohammed J.; Goswami, Nandu; Penque, Deborah; Soares, Nelson C.Venous Thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is still based on complex imaging exams due to the lack of biomarkers. However, studies assessing the diagnostic capacity of novel biomarkers in VTE are scarce. We aimed to determine if patients with acute VTE have differences in the proteomics/metabolomic profile. This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis (DVT) or pulmonary embolism (PE) admitted to the emergency room (ER).
- Red blood cell proteomic profiling in mild and severe obstructive sleep apnea patients before and after positive airway pressure treatmentPublication . Valentim-Coelho, Cristina; Saraiva, Joana; Osório, Hugo; Antunes, Marília; Vaz, Fátima; Neves, Sofia; Pinto, Paula; Bárbara, Cristina; Penque, DeborahObstructive Sleep Apnea (OSA) is characterized by recurrent-episodes of apneas/hypopneas during sleep, leading to recurrent intermittent-hypoxia and sleep fragmentation. Non-treated OSA can result in cardiometabolic diseases. In this study, we applied a shotgun-proteomics strategy to deeper investigate the red blood cell-(RBC) homeostasis regulation in the context of OSA-severity and their response to six months of positive airway pressure (PAP)-treatment. RBC-samples from patients with Mild/Severe-OSA before/after-PAP treatment and patients as simple-snoring controls were selected. The mass-spectrometry raw-data was analysed by MaxQuant for protein identification/quantification followed by statistical Linear Models-(LM) and Linear Mixed Models-(LMM) to investigate OSA-severity effect and interaction with PAP, respectively. The functional/biological network analysis were performed by DAVID-platform. The results indicated that key-enzymes of the Embden-Meyerhof-Parnas (EMP)-glycolysis and pentose phosphate pathway-(PPP) were differentially changed in Severe-OSA, suggesting that the O2-dependent metabolic flux through EMP and PPP maybe compromised in these cells due to severe intermittent hypoxia/reoxygenation-induced oxidative-stress events in these patients. The Rapoport-Luebering-glycolytic shunt showed a significant downregulation across OSA-severity maybe to increase hemoglobin-O2 affinity to adapt to O2 low availability in the lung, although EMP-glycolysis showed decreased only in Severe-OSA. Proteins of the immunoproteasome were upregulated in Severe-OSA maybe to respond to severe oxidative-stress. In Mild-OSA, proteins related to the ubiquitination/neddylation-(Ub/Ned)-dependent proteasome system were upregulated. After PAP, proteins of Glycolysis and Ub/Ned-dependent proteasome system showed reactivated in Severe-OSA. In Mild-OSA, PAP induced upregulation of immunoproteasome proteins, suggesting that this treatment may increase oxidative-stress in these patients. Once validated these proteins maybe candidate biomarkers for OSA or OSA-therapy response.
- Second-hand smoke exposure modulates plasma proteins linked to detoxification, inflammation and atherothrombosisPublication . Neves, Sofia; Pacheco, Solange A.; Vaz, Fátima; Valentim-Coelho, Cristina; Saraiva, Joana; James, Peter; Simões, Tânia; Penque, DeborahChronic exposure to second-hand smoke (SHS) contributes to the development of health issues, including cancer and cardiovascular diseases. Molecular mechanisms underlying SHS-related diseases remain poorly understood, highlighting the need for reliable risk assessment biomarkers. Herein, we demonstrate that the plasma proteome of individuals exposed to SHS undergoes significant modulation. Butyrylcholinesterase (BChE) and Vitamin D-binding protein (GC) that are involved in the physiological response to circulating toxic substances, as well as key mediators of systemic inflammation, including Complement C1r subcomponent (C1R), Complement C1q subcomponent subunit C (C1QC), Histidine-rich glycoprotein (HRG), and Vitamin K-dependent protein S (PROS1), were found to be significantly modulated in SHS-exposed individuals. Moreover, strong indicators of a pro-atherothrombotic response such Apolipoprotein A-IV (APOA4) and Alpha-2-antiplasmin (SERPINF2), were also differentially expressed. These findings provide novel insights into the biological pathways linking SHS-exposure to cardiovascular risks, and suggest a panel of candidate proteins with potential utility as SHS-risk assessment biomarkers.