EDECIO CUNHA NETO

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Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/60 - Laboratório de Imunologia Clínica e Alergia, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • conferenceObject
    Immune Responses Of CVID Patients To COVID-19 Vaccines
    (2023) MEDEIROS, Giuliana Xavier de; FERREIRA, Loisi de Carvalho Pereira; MAGAWA, Jhosiene Yukari; KURAMOTO, Andreia; SASAHARA, Greyce Luri; FERREIRA, Marcelo; BARROS, Myrthes Maragna Toledo; KALIL, Jorge; MARINHO, Ana Karolina Barreto Berselli; CUNHA-NETO, Edecio; SANTOS, Keity Souza; KOKRON, Cristina
  • article 2 Citação(ões) na Scopus
    4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification
    (2023) KIYUNA, Ligia A.; CANDIDO, Darlan S.; BECHARA, Luiz R. G.; JESUS, Itamar C. G.; RAMALHO, Lisley S.; KRUM, Barbara; ALBUQUERQUE, Ruda P.; CAMPOS, Juliane C.; BOZI, Luiz H. M.; ZAMBELLI, Vanessa O.; ALVES, Ariane N.; CAMPOLO, Nicolas; MASTROGIOVANNI, Mauricio; BARTESAGHI, Silvina; LEYVA, Alejandro; DURAN, Rosario; RADI, Rafael; ARANTES, Guilherme M.; CUNHA-NETO, Edecio; MORI, Marcelo A.; CHEN, Che-Hong; YANG, Wenjin; MOCHLY-ROSEN, Daria; MACRAE, Ian J.; FERREIRA, Ludmila R. P.; FERREIRA, Julio C. B.
    Background and Aims Developing novel therapies to battle the global public health burden of heart failure remains challenging. This study investigates the underlying mechanisms and potential treatment for 4-hydroxynonenal (4-HNE) deleterious effects in heart failure.Methods Biochemical, functional, and histochemical measurements were applied to identify 4-HNE adducts in rat and human failing hearts. In vitro studies were performed to validate 4-HNE targets.Results 4-HNE, a reactive aldehyde by-product of mitochondrial dysfunction in heart failure, covalently inhibits Dicer, an RNase III endonuclease essential for microRNA (miRNA) biogenesis. 4-HNE inhibition of Dicer impairs miRNA processing. Mechanistically, 4-HNE binds to recombinant human Dicer through an intermolecular interaction that disrupts both activity and stability of Dicer in a concentration- and time-dependent manner. Dithiothreitol neutralization of 4-HNE or replacing 4-HNE-targeted residues in Dicer prevents 4-HNE inhibition of Dicer in vitro. Interestingly, end-stage human failing hearts from three different heart failure aetiologies display defective 4-HNE clearance, decreased Dicer activity, and miRNA biogenesis impairment. Notably, boosting 4-HNE clearance through pharmacological re-activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) using Alda-1 or its improved orally bioavailable derivative AD-9308 restores Dicer activity. ALDH2 is a major enzyme responsible for 4-HNE removal. Importantly, this response is accompanied by improved miRNA maturation and cardiac function/remodelling in a pre-clinical model of heart failure.Conclusions 4-HNE inhibition of Dicer directly impairs miRNA biogenesis in heart failure. Strikingly, decreasing cardiac 4-HNE levels through pharmacological ALDH2 activation is sufficient to re-establish Dicer activity and miRNA biogenesis; thereby representing potential treatment for patients with heart failure. Structured Graphical Abstract The vicious cycle of heart failure (HF). (i) Impaired aldehyde metabolism by aldehyde dehydrogenase 2 (ALDH2); (ii) accumulation of 4-hydroxynonenal (4-HNE), a reactive aldehyde by-product of mitochondrial dysfunction; (iii) direct 4-HNE inhibition of Dicer, an RNase III endonuclease essential for microRNA (miRNA) biogenesis; and (iv) overall impairment of miRNA biogenesis, which negatively impacts HF outcome. Blue and red arrows/inhibitors represent the vicious cycle of HF and the benefits of small molecule activators of ALDH2 in HF, respectively.
  • conferenceObject
    Repurposed drugs acting on host mechanisms of T. cruzi invasion synergize with Benznidazole: New therapies for Chagas disease
    (2019) PANDEY, R. P.; NASCIMENTO, M. Savoia; BARRIOS, L.; GIBALDI, D.; LANNES-VIEIRA, J.; KALIL, J.; CUNHA-NETO, E.
  • article 11 Citação(ões) na Scopus
    SBC Guideline on the Diagnosis and Treatment of Patients with Cardiomyopathy of Chagas Disease-2023
    (2023) MARIN-NETO, Jose Antonio; JR, Anis Rassi; OLIVEIRA, Glaucia Maria Moraes; CORREIA, Luis Claudio Lemos; RAMOS JUNIOR, Alberto Novaes; LUQUETTI, Alejandro Ostermayer; HASSLOCHER-MORENA, Alejandro Marcel; SOUSA, Andrea Silvestre de; PAOLA, Angelo Amato Vincenzo de; SOUSA, Antonio Carlos Sobral; RIBEIRO, Antonio Luiz Pinho; CORREIA FILHO, Dalmo; SOUZA, Dilma do Socorro Moraes de; CUNHA-NETO, Edecio; RAMIRES, Felix Jose Alvarez; BACAL, Fernando; NUNES, Maria do Carmo Pereira; MARTINELLI FILHO, Martino; SCANAVACCA, Maurici Ibrahim; SARAIVA, Roberto Magalhaes; OLIVEIRA JUNIOR, Wilson Alves de; LORGA-FILHO, Adalberto Menezes; GUIMARAES, Adriana de Jesus Benevides de Almeida; BRAGA, Adriana Lopes Latado; OLIVEIRA, Adriana Sarmento de; SARABANDA, Alvaro Valentim Lima; PINTO, Ana Yece das Neves; CARMO, Andre Assis Lopes do; SCHMIDT, Andre; COSTA, Andrea Rodrigues da; IANNI, Barbara Maria; MARKMAN FILHO, Brivaldo; ROCHITT, Carlos Eduardo; MACEDO, Carolina The; MADY, Charles; CHEVILLARD, Christophe; VIRGENS, Claudio Marcelo Bittencourt das; CASTRO, Cleudson Nery de; BRITTO, Constanca Felicia De Paoli de Carvalho; PISANI, Cristiano; RASSI, Daniel do Carmo; SOBRAL FILHO, Dario Celestino; ALMEIDA, Dirceu Rodrigues de; BOCCHI, Edimar Alcides; MESQUITA, Evandro Tinoco; MENDES, Fernanda de Souza Nogueira Sardinha; GONDIM, Francisca Tatiana Pereira; SILVA, Gilberto Marcelo Sperandio da; PEIXOTO, Giselle de Lima; LIMA, Gustavo Glotz de; VELOSO, Henrique Horta; MOREIRA, Henrique Turin; LOPES, Hugo Bellotti; PINTO, Ibraim Masciarelli Francisco; FERREIRA, Joao Marcos Bemfica Barbosa; NUNES, Joao Paulo Silva; BARRETO-FILHO, Jose Augusto Soares; SARAIVA, Jose Francisco Kerr; LANNES-VIEIRA, Joseli; OLIVEIRA, Joselina Luzia Menezes; ARMAGANIJAN, Luciana Vidal; MARTINS, Luiz Claudio; SANGENIS, Luiz Henrique Conde; BARBOSA, Marco Paulo Tomaz; ALMEIDA-SANTOS, Marcos Antonio; SIMOES, Marcos Vinicius; YASUDA, Maria Aparecida Shikanai; MOREIRA, Maria da Consolacao Vieira; HIGUCHI, Maria de Lourdes; MONTEIRO, Maria Rita de Cassia Costa; MEDIANO, Mauro Felippe Felix; LIMA, Mayara Maia; OLIVEIRA, Maykon Tavares de; ROMANO, Minna Moreira Dias; ARAUJO, Nadjar Nitz Silva Lociks de; MEDEIROS, Paulo de Tarso Jorge; ALVES, Renato Vieira; TEIXEIRA, Ricardo Alkmim; PEDROSA, Roberto Coury; ARAS JUNIOR, Roque; TORRES, Rosalia Morais; POVOA, Rui Manoel dos Santos; RASSI, Sergio Gabriel; ALVES, Silvia Marinho Martins; TAVARES, Suelene Brito do Nascimento; PALMEIRA, Swamy Lima; SILVA JUNIOR, Telemaco Luiz da; RODRIGUES, Thiago da Rocha; MADRINI JUNIOR, Vagner; BRANT, Veruska Maia da Costa; DUTRA, Walderez Ornelas; DIAS, Joao Carlos Pinto
  • conferenceObject
    Endothelial inflammatory activation is related to myocardial perfusion disturbance in experimental chronic Chagas disease
    (2022) TANAKA, D. M.; FABRICIO, C. G.; MARIN-NETO, J. A.; BARROS-FILHO, A. C. L.; LOPES, C. D.; OLIVEIRA, L. F. L.; MEJIA, J.; ALMEIDA, R. R.; BATAH, S. S.; NEKOLLA, S. G.; HIGUCHI, M. L.; CUNHA-NETO, E.; FABRO, A. T.; ROMANO, M. M.; SIMOES, M. V.
  • article 1 Citação(ões) na Scopus
    Evaluation of the therapeutic effects of oestradiol on the systemic inflammatory response and on lung injury caused by the occlusion of the proximal descending aorta in male rats
    (2023) SOUSA, Marcelo Nunes de; ANUNCIACAO, Lucas Ferreira da; FREITAS, Pedro Luiz Zonta de; RICARDO-DA-SILVA, Fernanda Yamamoto; MOREIRA, Luiz Felipe Pinho; CORREIA, Cristiano Jesus; BREITHAUPT-FALOPPA, Ana Cristina
    OBJECTIVES: Ischaemia and reperfusion-induced microvascular dysfunction is a serious problem encountered during a variety surgical procedures, leading to systemic inflammation and affecting remote organs, specially the lungs. 17 beta-Oestradiol reduces pulmonary repercussions from various acute lung injury forms. Here, we focused on the 17 beta-oestradiol therapeutic effects after aortic ischaemia and reperfusion (I/R) by evaluating lung inflammation. METHODS: Twenty-four Wistar rats were submitted to I/R by insufflation of a 2-F catheter in thoracic aorta for 20 min. Reperfusion took 4 h and 17 beta-oestradiol (280 mg/kg, i.v.) was administered after 1 h of reperfusion. Sham-operated rats were controls. Bronchoalveolar lavage was performed and lung samples were prepared for histopathological analysis and tissue culture (explant). Interleukin (IL)-1 beta, IL-10 and tumour necrosis factor-a were quantified. RESULTS: After I/R, higher number of leukocytes in bronchoalveolar lavage were reduced by 17 beta-oestradiol. The treatment also decreased leukocytes in lung tissue. I/R increased lung myeloperoxidase expression, with reduction by 17 beta-oestradiol. Serum cytokine-induced neutrophil chemoattractant 1 and IL-1 beta increased after I/R and 17 beta-oestradiol decreased cytokine-induced neutrophil chemoattractant 1. I/R increased IL-1 beta and IL-10 in lung explants, reduced by 17 beta-oestradiol. CONCLUSIONS: Our results showed that 17 beta-oestradiol treatment performed in the period of reperfusion, modulated the systemic response and the lung repercussions of I/R by thoracic aortic occlusion. Thus, we can suggest that 17 beta-oestradiol might be a supplementary approach leading the lung deterioration after aortic clamping in surgical procedures.
  • article 3 Citação(ões) na Scopus
    MiRNA-30d and miR-770-5p as potential clinical risk predictors of Vasoplegic Syndrome in Patients undergoing on-pump coronary artery bypass grafting
    (2023) MEJIA, Omar Asdrubal Vilca; SOUZA, Renato Cesar de; SANTOS, Aritania S.; MENEGHINI, Bianca; SILVA, Ana Carolina Carvalho; BRASIL, Guilherme Visconde; RIGAUD, Vagner Oliveira Carvalho; DALLAN, Luis Roberto Palma; MOREIRA, Luiz Felipe Pinho; LISBOA, Luiz Augusto Ferreira; DALLAN, Luis Alberto Oliveira; KALIL, Jorge; CUNHA-NETO, Edecio; FERREIRA, Ludmila Rodrigues Pinto; JATENE, Fabio Biscegli
    The aims of this study were to perform pre-surgery miRNA profiling of patients who develop Vasoplegic syndrome (VS) after coronary artery bypass grafting (CABG) and identify those miRNAs that could be used as VS prognostic tools and biomarkers. The levels of 754 microRNAs (miRNAs) were measured in whole blood samples from a cohort of patients collected right before the coronary artery bypass grafting (CABG) surgery. We compared the miRNA levels of those who developed VS (VASO group) with those who did not (NONVASO group) after surgery. Six miRNAs (hsa-miR-548c-3p, -199b-5p, -383-5p -571 -183-3p, -30d-5p) were increased and two (hsa-1236-3p, and hsa-miR770-5p) were decreased in blood of VASO compared to NONVASO groups. Receiver Operating Characteristic (ROC) curve analysis revealed that a combination of the miRNAs, hsa-miR-30d-5p and hsa-miR-770-5p can be used as VS predictors (AUC = 0.9615, p < 0.0001). The computational and functional analyses were performed to gain insights into the potential role of these dysregulated miRNAs in VS and have identified the ""Apelin Liver Signaling Pathway"" as the canonical pathway containing the most target genes regulated by these miRNAs. The expression of the combined miRNAs hsa-miR-30d and hsa-miR-770-5p allowed the ability to distinguish between patients who could and could not develop VS, representing a potential predictive biomarker of VS.
  • article 5 Citação(ões) na Scopus
    Immunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escape
    (2023) OLIVEIRA, Jamille Ramos; RUIZ, Cesar Manuel Remuzgo; MACHADO, Rafael Rahal Guaragna; MAGAWA, Jhosiene Yukari; DAHER, Isabela Pazotti; URBANSKI, Alysson Henrique; SCHMITZ, Gabriela Justamante Haendel; ARCURI, Helen Andrade; FERREIRA, Marcelo Alves; SASAHARA, Greyce Luri; MEDEIROS, Giuliana Xavier de; JR, Roberto Carlos Vieira Silva; DURIGON, Edison Luiz; BOSCARDIN, Silvia Beatriz; ROSA, Daniela Santoro; SCHECHTMAN, Deborah; NAKAYA, Helder. I. I.; CUNHA-NETO, Edecio; GADERMAIER, Gabriele; KALIL, Jorge; COELHO, Veronica; SANTOS, Keity Souza
    IntroductionConsidering the likely need for the development of novel effective vaccines adapted to emerging relevant CoV-2 variants, the increasing knowledge of epitope recognition profile among convalescents and afterwards vaccinated with identification of immunodominant regions may provide important information. MethodsWe used an RBD peptide microarray to identify IgG and IgA binding regions in serum of 71 COVID-19 convalescents and 18 vaccinated individuals. ResultsWe found a set of immunodominant RBD antibody epitopes, each recognized by more than 30% of the tested cohort, that differ among the two different groups and are within conserved regions among betacoronavirus. Of those, only one peptide, P44 (S415-429), recognized by 68% of convalescents, presented IgG and IgA antibody reactivity that positively correlated with nAb titers, suggesting that this is a relevant RBD region and a potential target of IgG/IgA neutralizing activity. DiscussionThis peptide is localized within the area of contact with ACE-2 and harbors the mutation hotspot site K417 present in gamma (K417T), beta (K417N), and omicron (K417N) variants of concern. The epitope profile of vaccinated individuals differed from convalescents, with a more diverse repertoire of immunodominant peptides, recognized by more than 30% of the cohort. Noteworthy, immunodominant regions of recognition by vaccinated coincide with mutation sites at Omicron BA.1, an important variant emerging after massive vaccination. Together, our data show that immune pressure induced by dominant antibody responses may favor hotspot mutation sites and the selection of variants capable of evading humoral response.
  • article 0 Citação(ões) na Scopus
    Follow-up of young adult monozygotic twins after simultaneous critical coronavirus disease 2019: a case report (vol 9, 1008585, 2022)
    (2023) CASTRO, Mateus V. de; SILVA, Monize V. R.; SOARES, Flavia B.; CORIA, Vivian R.; NASLAVSKY, Michel S.; SCLIAR, Marilia O.; CASTELLI, Erick C.; OLIVEIRA, Jamile R. de; MEDEIROS, Giuliana X. de; SASAHARA, Greyce L.; SANTOS, Keity S.; CUNHA-NETO, Edecio; KALIL, Jorge; ZATZ, Mayana
  • article 0 Citação(ões) na Scopus
    Immunological evaluation of young unvaccinated patients with Turner syndrome after COVID-19
    (2023) CASTRO, Mateus V. de; SILVA, Monize V. R.; OLIVEIRA, Luana de M.; GOZZI-SILVA, Sarah C.; NASLAVSKY, Michel S.; SCLIAR, Marilia O.; MAGALHAES, Monize L.; ROCHA, Katia M. da; NUNES, Kelly; CASTELLI, Erick C.; MAGAWA, Jhosiene Y.; SANTOS, Keity S.; CUNHA-NETO, Edecio; SATO, Maria N.; ZATZ, Mayana
    Objectives: The X-chromosome contains the largest number of immune-related genes, which play a major role in COVID-19 symptomatology and susceptibility. Here, we had a unique opportunity to investigate, for the first time, COVID-19 outcomes in six unvaccinated young Brazilian patients with Turner syndrome (TS; 45, X0), including one case of critical illness in a child aged 10 years, to evaluate their immune response according to their genetic profile. Methods: A serological analysis of humoral immune response against SARS-CoV-2, phenotypic character-ization of antiviral responses in peripheral blood mononuclear cells after stimuli, and the production of cytotoxic cytokines of T lymphocytes and natural killer cells were performed in blood samples collected from the patients with TS during the convalescence period. Whole exome sequencing was also performed.Results: Our volunteers with TS showed a delayed or insufficient humoral immune response to SARS-CoV-2 (particularly immunoglobulin G) and a decrease in interferon-gamma production by cluster of differentiation (CD)4 + and CD8 + T lymphocytes after stimulation with toll-like receptors 7/8 agonists. In contrast, we observed a higher cytotoxic activity in the volunteers with TS than the volunteers without TS after phor-bol myristate acetate/ionomycin stimulation, particularly granzyme B and perforin by CD8 + and natural killer cells. Interestingly, two volunteers with TS carry rare genetic variants in genes that regulate type I and III interferon immunity.Conclusion: Following previous reports in the literature for other conditions, our data showed that pa-tients with TS may have an impaired immune response against SARS-CoV-2. Furthermore, other medical conditions associated with TS could make them more vulnerable to COVID-19.(c) 2023 The Author(s).