DEBORA LEVY
Projetos de Pesquisa
Unidades Organizacionais
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina
13 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 13
conferenceObject BONE MARROW MESENCHYMAL STEM CELLS DERIVED FROM HEALTHY DONORS BUT NOT THOSE DERIVED FROM ACUTE MYELOID LEUKEMIA PATIENTS ARE ABLE TO AFFECT PROLIFERATION AND DEATH OF LEUKEMIC CELL LINEAGES K562 AND K562 LUCENA(2021) FREITAS, F. A.; LEVY, D.; REICHERT, C. O.; LIMA-BARROS, P.; SAMPAIO-SILVA, J.; ROKITA-ROSA, L.; BYDLOWSKI, S. P.conferenceObject ONE STEP TECHNIQUETM IS EFFICIENT IN HARVESTING MESENCHYMAL STEM CELLS FROM HUMAN ADIPOSE TISSUE(2021) LEVY, D.; MELLO, L.; GIGLIO, P. N.; CENTURION, P.; VASQUEZ, M. W. M.; LOPES, L. A.; BYDLOWSKI, S. P.; DEMANGE, M. K.- Immune Senescence-Related Gene Expression Profile in CD4+T-Lymphocytes of HTLV-1 Asymptomatic Carriers and Patients with Adult T-Cell Leukemia/Lymphoma (ATLL): A Brazilian Preliminary Study(2021) ASSIS FILHO, Jose Roberto; CULLER, Hebert Fabricio; LEVY, Debora; OLIVEIRA, Karolliny Silva de; NOGUEIRA, Daniel Silva; ALMEIDA, Lis Vilela de; ROCHA, Vanderson; NUKUI, Youko; LAGE, Luis Alberto de Padua Covas; PEREIRA, Juliana
- Circulating Cell-Free DNA (ccfDNA) Isolation from Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Comparative Analysis of Commercial Kits(2021) OLIVEIRA, Karolliny Silva de; CULLER, Hebert Fabricio; LEVY, Debora; ASSIS FILHO, Jose Roberto; NOGUEIRA, Daniel Silva; ALMEIDA, Lis Vilela de; SILVA, Luiz Henrique da; FONSECA, Fernando Luiz Affonso; ALVES, Sarah Isabel Pinto Monteiro do Nascimento; LAGE, Luis Alberto de Padua Covas; PEREIRA, Juliana
- Oxysterols and mesenchymal stem cell biology(2021) REICHERT, Cadiele Oliana; FREITAS, Fabio Alessandro De; LEVY, Debora; BYDLOWSKI, Sergio PauloMesenchymal stem cells have the ability to differentiate into several cell types when exposed to determined substances, including oxysterols. Oxysterols are cholesterol products derived from its auto-oxidation by reactive species or from enzymatic action. They are present in the body in low quantities under physiological conditions and exhibit several physiological and pharmacological actions according to both the types of oxysterol and tissue. Some of them are cytotoxic while others have been shown to promote cell differentiation through the action on several different receptors, such as nuclear LXR receptors and Smoothened receptor ligands. Here, we review the main pathways by which oxysterols have been associated with cell differentiation and death of mesenchymal stem cells.
- High Toxicity and Poor Survival with Association CHOP Plus Etoposide Compared to CHOP Regimen in 124 Brazilian Patients with Nodal PTCL Lymphomas (nPTCL): A Real-Life Experience(2021) LAGE, Luis Alberto de Padua Covas; BRITO, Claudio Vinicius; BARRETO, Guilherme Carneiro; REICHERT, Cadiele Oliana; LEVY, Debora; CULLER, Hebert Fabricio; ZERBINI, Maria Claudia Nogueira; ROCHA, Vanderson; PEREIRA, Juliana
- Antioxidant Properties and Cytoprotective Effect of Pistacia lentiscus L. Seed Oil against 7 beta-Hydroxycholesterol-Induced Toxicity in C2C12 Myoblasts: Reduction in Oxidative Stress, Mitochondrial and Peroxisomal Dysfunctions and Attenuation of Cell Death(2021) GHZAIEL, Imen; ZARROUK, Amira; NURY, Thomas; LIBERGOLI, Michela; FLORIO, Francesca; HAMMOUDA, Souha; MENETRIER, Franck; AVOSCAN, Laure; YAMMINE, Aline; SAMADI, Mohammad; LATRUFFE, Norbert; BIRESSI, Stefano; LEVY, Debora; BYDLOWSKI, Sergio Paulo; HAMMAMI, Sonia; VEJUX, Anne; HAMMAMI, Mohamed; LIZARD, GerardAging is characterized by a progressive increase in oxidative stress, which favors lipid peroxidation and the formation of cholesterol oxide derivatives, including 7 beta-hydroxycholesterol (7 beta-OHC). This oxysterol, which is known to trigger oxidative stress, inflammation, and cell death, could contribute to the aging process and age-related diseases, such as sarcopenia. Identifying molecules or mixtures of molecules preventing the toxicity of 7 beta-OHC is therefore an important issue. This study consists of determining the chemical composition of Tunisian Pistacia lentiscus L. seed oil (PLSO) used in the Tunisian diet and evaluating its ability to counteract the cytotoxic effects induced by 7 beta-OHC in murine C2C12 myoblasts. The effects of 7 beta-OHC (50 mu M; 24 h), associated or not with PLSO, were studied on cell viability, oxidative stress, and on mitochondrial and peroxisomal damages induction. alpha-Tocopherol (400 mu M) was used as the positive control for cytoprotection. Our data show that PLSO is rich in bioactive compounds; it contains polyunsaturated fatty acids, and several nutrients with antioxidant properties: phytosterols, alpha-tocopherol, carotenoids, flavonoids, and phenolic compounds. When associated with PLSO (100 mu g/mL), the 7 beta-OHC-induced cytotoxic effects were strongly attenuated. The cytoprotection was in the range of those observed with alpha-tocopherol. This cytoprotective effect was characterized by prevention of cell death and organelle dysfunction (restoration of cell adhesion, cell viability, and plasma membrane integrity; prevention of mitochondrial and peroxisomal damage) and attenuation of oxidative stress (reduction in reactive oxygen species overproduction in whole cells and at the mitochondrial level; decrease in lipid and protein oxidation products formation; and normalization of antioxidant enzyme activities: glutathione peroxidase (GPx) and superoxide dismutase (SOD)). These results provide evidence that PLSO has similar antioxidant properties than alpha-tocopherol used at high concentration and contains a mixture of molecules capable to attenuate 7 beta-OHC-induced cytotoxic effects in C2C12 myoblasts. These data reinforce the interest in edible oils associated with the Mediterranean diet, such as PLSO, in the prevention of age-related diseases, such as sarcopenia.
- Rare Pathogenic Variants in Mitochondrial and Inflammation-Associated Genes May Lead to Inflammatory Cardiomyopathy in Chagas Disease(2021) OUARHACHE, Maryem; MARQUET, Sandrine; FRADE, Amanda Farage; FERREIRA, Ariela Mota; IANNI, Barbara; ALMEIDA, Rafael Ribeiro; NUNES, Joao Paulo Silva; FERREIRA, Ludmila Rodrigues Pinto; RIGAUD, Vagner Oliveira-Carvalho; CANDIDO, Darlan; MADY, Charles; ZANIRATTO, Ricardo Costa Fernandes; BUCK, Paula; TORRES, Magali; GALLARDO, Frederic; ANDRIEUX, Pauline; BYDLOWSKY, Sergio; LEVY, Debora; ABEL, Laurent; CARDOSO, Clareci Silva; SANTOS-JUNIOR, Omar Ribeiro; OLIVEIRA, Lea Campos; OLIVEIRA, Claudia Di Lorenzo; NUNES, Maria Do Carmo; COBAT, Aurelie; KALIL, Jorge; RIBEIRO, Antonio Luiz; SABINO, Ester Cerdeira; CUNHA-NETO, Edecio; CHEVILLARD, ChristopheCardiomyopathies are an important cause of heart failure and sudden cardiac death. Little is known about the role of rare genetic variants in inflammatory cardiomyopathy. Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory cardiomyopathy prevalent in Latin America, developing in 30% of the 6 million patients chronically infected by the protozoan Trypanosoma cruzi, while 60% remain free of heart disease (asymptomatic (ASY)). The cytokine interferon-gamma and mitochondrial dysfunction are known to play a major pathogenetic role. Chagas disease provides a unique model to probe for genetic variants involved in inflammatory cardiomyopathy. Methods We used whole exome sequencing to study nuclear families containing multiple cases of Chagas disease. We searched for rare pathogenic variants shared by all family members with CCC but absent in infected ASY siblings and in unrelated ASY. Results We identified heterozygous, pathogenic variants linked to CCC in all tested families on 22 distinct genes, from which 20 were mitochondrial or inflammation-related - most of the latter involved in proinflammatory cytokine production. Significantly, incubation with IFN-gamma on a human cardiomyocyte line treated with an inhibitor of dihydroorotate dehydrogenase brequinar (enzyme showing a loss-of-function variant in one family) markedly reduced mitochondrial membrane potential (Delta psi M), indicating mitochondrial dysfunction. Conclusion Mitochondrial dysfunction and inflammation may be genetically determined in CCC, driven by rare genetic variants. We hypothesize that CCC-linked genetic variants increase mitochondrial susceptibility to IFN-gamma-induced damage in the myocardium, leading to the cardiomyopathy phenotype in Chagas disease. This mechanism may also be operative in other inflammatory cardiomyopathies.
- Impairment of Multiple Mitochondrial Energy Metabolism Pathways in the Heart of Chagas Disease Cardiomyopathy Patients(2021) TEIXEIRA, Priscila Camillo; DUCRET, Axel; LANGEN, Hanno; NOGOCEKE, Everson; SANTOS, Ronaldo Honorato Barros; NUNES, Joao Paulo Silva; BENVENUTI, Luiz; LEVY, Debora; BYDLOWSKI, Sergio Paulo; BOCCHI, Edimar Alcides; TAKARA, Andreia Kuramoto; FIORELLI, Alfredo Inacio; STOLF, Noedir Antonio; POMERANZEFF, Pablo; CHEVILLARD, Christophe; KALIL, Jorge; CUNHA-NETO, EdecioChagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients' myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.
- Paraoxonase Role in Human Neurodegenerative Diseases(2021) REICHERT, Cadiele Oliana; LEVY, Debora; BYDLOWSKI, Sergio P.The human body has biological redox systems capable of preventing or mitigating the damage caused by increased oxidative stress throughout life. One of them are the paraoxonase (PON) enzymes. The PONs genetic cluster is made up of three members (PON1, PON2, PON3) that share a structural homology, located adjacent to chromosome seven. The most studied enzyme is PON1, which is associated with high density lipoprotein (HDL), having paraoxonase, arylesterase and lactonase activities. Due to these characteristics, the enzyme PON1 has been associated with the development of neurodegenerative diseases. Here we update the knowledge about the association of PON enzymes and their polymorphisms and the development of multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD).