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Browsing by Author "Bicho, M"

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  • Analysis of Genes Involved in Oxidative Stress and Iron Metabolism in Heart Failure: A Step Forward in Risk Stratification
    Publication . Silva, PX; Aguiar, L; Gaspar, M; Faustino, P; Falcão, LM; Barbosa, M; Bicho, M; Inácio, Â
    Introduction: Heart failure (HF) is a clinical syndrome characterized by cardinal symptoms that may be accompanied by signs. It results from structural and/or functional abnormalities of the heart leading to elevated intracardiac pressures and/or inadequate cardiac output at rest and/or during exercise. The prevalence of iron deficiency and anemia justifies the current guidelines recommendation of screening. Genes HP, ACE, MTHFR, HFE, and CYBA are involved in oxidative mechanisms, iron metabolism, and hematologic homeostasis. This study investigates the contribution of variants Hp1/2 (HP), I/D (ACE), C677T (MTHFR), C282Y and H63D (HFE), and C242T (CYBA) to the development of HF, either independently or in epistasis. Methods: We used a database of 389 individuals, 143 HF patients, and 246 healthy controls. Genotypes were characterized through PAGE electrophoresis, PCR, PCR-RFLP, and multiplex-ARMS. Data analysis was performed with the SPSS® 26.0 software (IBM Corp., Armonk, NY). Results: We observed a significant association between the MTHFR gene and HF predisposition. The presence of allele T and genotype CT constituted risk, while genotype CC granted protection. Epistatic interactions revealed risk between genotype II of the ACE gene and genotypes CC (C282Y) or HH (H63D) of the HFE gene. Risk was also observed for interactions between genotype CC (CYBA)and genotypes 2-2 (HP), CT (MTHFR), or HH (HFE-H63D). Conclusion: We concluded that genes HP, ACE, MTHFR, HFE, and CYBA contribute to the susceptibility for HF, individually or in epistasis. This study contributes to the clarification of the role that genes involved in oxidative mechanisms and iron metabolism play in the physiopathology of HF. It is, therefore, a step forward in risk stratification and personalized medicine.
    2024Journal article Open access Show more
  • Can Classic Biomarkers be Prognosticators in Heart Failure? - Data from the REFERENCE study
    Publication . Barbosa, M; Matos, A; Bicho, M; Falcão, LM
    2019Conference object Open access Show more
  • Complete blood count parameters as biomarkers of retinopathy of prematurity: a Portuguese multicenter study
    Publication . Fevereiro-Martins, M; Santos, AC; Marques-Neves, C; Guimarães, H; Bicho, M; Afonso, C; Ferreira, J; Espírito Santo, R; Teixeira, F; Rosa, R; Carneiro, CV; Ferreira, M; Matos, T; Neiva, L; Pereira, S; Aires, S; Parreira, R; Melnik, Z; Faria, J; Teixeira, J; Barros, P; Almeida, J; Malheiro, B; Rodrigues, PC; Albuquerque, L; Freitas, A; Barros, P; Kotchekova, N; Freitas, R; Silveira, AC; Ferreira, A; Morais, B; Teixeira, S; Mota, M; Guerra, M; Coimbra, L; Gigante, J; Ferreira, M; Lapa, P; Monteiro, M; Alfaiate, M; Rodrigues, T; Pina, T; Rosário, M; Silva, R; Breda, J; Bazenga, F; Pinto, JA
    Purpose: To evaluate complete blood count (CBC) parameters in the first week of life as predictive biomarkers for the development of retinopathy of prematurity (ROP). Methods: Multicenter, prospective, observational study of a cohort of preterm infants born with gestational age (GA) < 32 weeks or birth weight < 1500 g in eight Portuguese neonatal intensive care units. All demographic, clinical, and laboratory data from the first week of life were collected. Univariate logistic regression was used to assess risk factors for ROP and then multivariate regression was performed. Results: A total of 455 infants were included in the study. The median GA was 29.6 weeks, and the median birth weight was 1295 g. One hundred and seventy-two infants (37.8%) developed ROP. Median values of erythrocytes (p < 0.001), hemoglobin (p < 0.001), hematocrit (p < 0.001), mean corpuscular hemoglobin concentration (p < 0.001), lymphocytes (p = 0.035), and platelets (p = 0.003) of the group of infants diagnosed with ROP any stage were lower than those without ROP. Mean corpuscular volume (MCV) (p = 0.044), red blood cell distribution width (RDW) (p < 0.001), erythroblasts (p < 0.001), neutrophils (p = 0.030), neutrophils-lymphocytes ratio (p = 0.028), and basophils (p = 0.003) were higher in the ROP group. Higher values of MCV, erythroblasts, and basophils remained significantly associated with ROP after multivariate regression. Conclusion: In our cohort, the increase in erythroblasts, MCV, and basophils in the first week of life was significantly and independently associated with the development of ROP. These CBC parameters may be early predictive biomarkers for ROP.
    2023Journal article Open access Show more
  • Disruption of balance of oxidative stress-associated angiogenesis in heart failure
    Publication . Matos, A; Barbosa, M; Bicho, M; Falcão, LM
    2019Conference object Open access Show more
  • Fatores angiogénicos modulados pelo perfil de plaquetas na insuficiência cardíaca
    Publication . Matos, A; Barbosa, M; Sequeira, T; Santos, AC; Bicho, M; Falcão, LM
    2019Conference object Open access Show more
  • Fetal Hemoglobin as a Predictive Biomarker for Retinopathy of Prematurity: A Prospective Multicenter Cohort Study in Portugal
    Publication . Fevereiro-Martins, M; Aguiar, L; Inácio, Â; Cardoso, C; Santos, AC; Marques-Neves, C; Guimarães, H; Pinto, R; Bicho, M
    Background/Objectives: Retinopathy of prematurity (ROP) is a leading cause of vision impairment in preterm infants, with its pathogenesis linked to oxygen exposure. Red blood cell (RBC) transfusions, commonly performed in neonatal intensive care units (NICUs), reduce fetal hemoglobin (HbF) fraction, altering oxygen dynamics and potentially contributing to ROP. We aimed to investigate the relationship between RBC transfusions, HbF percentage, and ROP, evaluating HbF as a potential predictive biomarker. Methods: A multicenter, prospective study was conducted across eight Portuguese NICUs, involving infants born at <32 weeks gestational age (GA) or <1500 g. ROP staging followed the International Classification of ROP (ICROP2). Clinical data were collected during hospitalization, and HbF fractions were measured from blood samples in the first four weeks of life using standardized methods. Infants were stratified by ROP presence and treatment requirement. Statistical analysis was performed using SPSS 28.0, with p < 0.05. Results: Eighty-two infants (mean GA: 28.1 ± 2.1 weeks, birth weight: 1055.8 ± 258.3 g) were included. Among them, 29 (35.4%) presented ROP and 4 (4.9%) required treatment. Infants with ROP had more RBC transfusions and lower HbF percentages than those without ROP (p < 0.05). Lower HbF was associated with more RBC transfusions (p < 0.001). Kaplan-Meier survival curves showed a higher ROP risk in infants with reduced HbF (p < 0.05). Conclusions: Low HbF percentage in the first four weeks of life may increase ROP risk in preterm infants. HbF could serve as a biomarker for ROP prediction. Interventions preserving HbF may reduce ROP risk. Further studies are needed to validate HbF as a biomarker and refine prevention strategies.
    2025Journal article Open access Show more
  • Gal-3 y ST2 como biomarcadores: un paso al frente en el pronóstico de la Insuficiencia Cardíaca
    Publication . Barbosa, M; Matos, A; Bicho, M; Falcão, LM
    Aims: The American College of Cardiology (ACA)/ American Heart Association (AHA) granted Galectin-3 (Gal-3) and Suppression of Tumorigenicity 2 (ST2) evaluation a class II recommendation for HF prognosis, as an adjunctive to conventional clinical risk factors and natriuretic peptides dosing in 2013. However, in Europe this endorsement is not valid. The purpose of this study was to study the association of Gal-3 and ST2 collected at-admission with early (defined as the period of 90 days post-discharge) rehospitalization and overall mortality, and end of follow-up overall mortality in HF patients. Additionally, aminoterminal B-type natriuretic peptide (NT-proBNP) at admission was considered to test if a multi-marker strategy could yield supplementary information. Material and Methods: Gal-3, ST2 and NT-proBNP were assessed in patients hospitalized with acute decompensated HF in class III or IV of New York Heart Association (NYHA). Univariate Cox proportional hazard model was used to assess the relationship between variables and outcomes. Since there are no standardized cut-offs for Gal-3 and ST2, the multiclass Area Under the Curve Receiver-Operator Characteristic (AUCROC) as defined by Hand and Till was used to evaluate the overall performance of each biomarker as a predictor of the outcomes. Results: We followed 65 patients for a median of 13.7 (Q1-Q3 6.7-18.9) months. Gal-3 correlated with short-term rehospitalization (HR: 9.886, 95% CI: 2.027-48.214, P-value=0.005), short-term mortality (HR: 13.731, 95% CI: 1.650-114.276, P value=0.015) and end of follow-up mortality (HR: 4.492, 95% CI: 1.594-12.656, P-value=0.004). The association of elevated NT-proBNP determinations increased the risk of short-term rehospitalization (HR: 11.985, 95% CI: 1.962-73.218, P value=0.007) and end of follow-up mortality (HR: 78.025, 95% CI: 7.592-801.926, P-value<0.001). ST2 correlated with end of follow-up mortality (HR: 4.846, 95% CI: 1.396-16.825, P-value=0.013). The risk further increased if NT-proBNP (HR: 5.953, 95% CI: 1.683- 21.055, P-value=0.006) or Gal-3 determinations (HR: 6.209, 95% CI: 2.393-16.114, P-value<0.001) were added. Conclusions: Elevated Gal-3 concentrations correlated with short-term rehospitalization, short-term mortality and end of follow-up mortality; whereas ST2 prognosticated end of follow-up mortality. Collective analysis with elevated NT-proBNP values further increased the outcomes’ risk. These results corroborate the assumption that promising novel biomarkers Gal-3 and ST2 could be valuable for HF risk stratification. We highlight that a multi-marker strategy added information, as a synergism between myocardial fibrosis biomarkers and the myocardial stretch peptide was observed.
    2021Journal article Open access Show more
  • Genetic Modulation of the Erythrocyte Phenotype Associated with Retinopathy of Prematurity—A Multicenter Portuguese Cohort Study
    Publication . Fevereiro-Martins, M; Santos, AC; Marques-Neves, C; Guimarães, H; Bicho, M
    The development of retinopathy of prematurity (ROP) may be influenced by anemia or a low fetal/adult hemoglobin ratio. We aimed to analyze the association between DNA methyltransferase 3 β (DNMT3B) (rs2424913), methylenetetrahydrofolate reductase (MTHFR) (rs1801133), and lysine-specific histone demethylase 1A (KDM1A) (rs7548692) polymorphisms, erythrocyte parameters during the first week of life, and ROP. In total, 396 infants (gestational age < 32 weeks or birth weight < 1500 g) were evaluated clinically and hematologically. Genotyping was performed using a MicroChip DNA on a platform employing iPlex MassARRAY®. Multivariate regression was performed after determining risk factors for ROP using univariate regression. In the group of infants who developed ROP red blood cell distribution width (RDW), erythroblasts, and mean corpuscular volume (MCV) were higher, while mean hemoglobin and mean corpuscular hemoglobin concentration (MCHC) were lower; higher RDW was associated with KDM1A (AA), MTHFR (CC and CC + TT), KDM1A (AA) + MTHFR (CC), and KDM1A (AA) + DNMT3B (allele C); KDM1A (AA) + MTHFR (CC) were associated with higher RDW, erythroblasts, MCV, and mean corpuscular hemoglobin (MCH); higher MCV and MCH were also associated with KDM1A (AA) + MTHFR (CC) + DNMT3B (allele C). We concluded that the polymorphisms studied may influence susceptibility to ROP by modulating erythropoiesis and gene expression of the fetal/adult hemoglobin ratio.
    2023Journal article Open access Show more
  • Influence of Functional Variations in Genes of Neurotrophins and Neurotransmitter Systems on the Development of Retinopathy of Prematurity
    Publication . Fevereiro-Martins, M; Santos, AC; Marques-Neves, C; Guimarães, H; Bicho, M
    first_pagesettingsOrder Article Reprints Open AccessArticle Influence of Functional Variations in Genes of Neurotrophins and Neurotransmitter Systems on the Development of Retinopathy of Prematurity by Mariza Fevereiro-Martins 1,2,3,4,*,Ana Carolina Santos 1,2ORCID,Carlos Marques-Neves 1,2,5,Hercília Guimarães 6ORCID,Manuel Bicho 1,2,3ORCID andon behalf of the GenE-ROP Study Group † 1 Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal 2 Grupo Ecogenética e Saúde Humana, Instituto de Saúde Ambiental-ISAMB, Laboratório Associado Terra, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal 3 Instituto de Investigação Científica Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisboa, Portugal 4 Departamento de Oftalmologia, Hospital Cuf Descobertas, Rua Mário Botas, 1998-018 Lisboa, Portugal 5 Centro de Estudos das Ciências da Visão, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, Piso 1C, 1649-028 Lisboa, Portugal 6 Departamento de Ginecologia-Obstetrícia e Pediatria, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal * Author to whom correspondence should be addressed. † Collaborators of the study group are included in the Acknowledgments. Int. J. Mol. Sci. 2025, 26(3), 898; https://doi.org/10.3390/ijms26030898 Submission received: 7 December 2024 / Revised: 20 January 2025 / Accepted: 20 January 2025 / Published: 22 January 2025 (This article belongs to the Special Issue Molecular Aspects of Retinopathy and Protection) Downloadkeyboard_arrow_down Browse Figure Review Reports Versions Notes Abstract Retinal neurodevelopment, vascularization, homeostasis, and stress response are influenced by factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH), and erythropoietin (EPO). As retinopathy of prematurity (ROP) is a neurovascular retinal disease, this study analyzed the contributions of NGF (rs6330), BDNF (rs7934165), TH (rs10770141), and EPO (rs507392) genetic functional polymorphisms to the modulation of hematological and biochemical parameters of the first week of life and their association with ROP development. A multicenter cohort of 396 preterm infants (gestational age < 32 weeks or birth weight < 1500 g) was genotyped using MicroChip DNA and iPlex MassARRAY® platform. Multivariate regression followed univariate assessment of ROP risk factors. NGF (GG) genotype was associated with a higher ROP risk (OR = 1.79), which increased further (OR = 2.38) when epistatic interactions with TH (allele C) and BDNF (allele G) were present. Significant circulating biomarker differences, including bilirubin, erythrocytes, monocytes, neutrophils, lymphocytes, and platelet markers, were found between ROP and non-ROP groups, with variations depending on the polymorphism. These findings suggest that NGF (rs6330) and its interactions with related genes contribute to ROP risk, providing valuable insights into the genetic and biological mechanisms underlying the disease and identifying potential predictive biomarkers.
    2025Journal article Open access Show more
  • Insights from the pREdictors oF Early REadmission iN Chronic hEart failure (REFERENCE) Study
    Publication . Barbosa, M; Matos, A; Bicho, M; Falcão, LM
    2019Conference object Open access Show more