DEBORA LEVY
Projetos de Pesquisa
Unidades Organizacionais
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
conferenceObject POTENTIAL IMMUNOLOGICAL MARKERS FOR DIAGNOSIS OF HUMAN STRONGYLOIDIASIS USING HETEROLOGOUS ANTIGENS(2017) GRYSCHEK, Ronaldo; CORRAL, Marcelo; PAULA, Fabiana; MEISEL, Dirce; CASTILHO, Vera; GONCALVES, Elenice; LEVY, Debora; BYDLOWSKI, Sergio; CHIEFFI, Pedro Paulo; CASTRO-BORGES, William- Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata(2017) SOUSA, Carolina Bruno de; GANGADHAR, Katkam N.; MORAIS, Thiago R.; CONSERVA, Geanne A. A.; VIZETTO-DUARTE, Catarina; PEREIRA, Hugo; LAURENTI, Marcia D.; CAMPINO, Lenea; LEVY, Debora; UEMI, Miriam; BARREIRA, Luisa; CUSTODIO, Luisa; PASSERO, Luiz Felipe D.; LAGO, Joao Henrique G.; VARELA, JoaoThe development of novel drugs for the treatment of leishmaniases continues to be crucial to overcome the severe impacts of these diseases on human and animal health. Several bioactivities have been described in extracts from macroalgae belonging to the Cystoseira genus. However, none of the studies has reported the chemical compounds responsible for the antileishmanial activity observed upon incubation of the parasite with the aforementioned extracts. Thus, this work aimed to isolate and characterize the molecules present in a hexane extract of Cystoseira baccata that was found to be bioactive against Leishmania infantum in a previous screening effort. A bioactivity-guided fractionation of the C. baccata extract was carried out and the inhibitory potential of the isolated compounds was evaluated via the MIT assay against promastigotes and murine macrophages as well as direct counting against intracellular amastigotes. Moreover, the promastigote ultrastructure, DNA fragmentation and changes in the mitochondrial potential were assessed to unravel their mechanism of action. In this process, two antileishmanial meroditerpenoids, (3R)- and (3S)-tetraprenyltoluquinol (1a/1b) and (3R)- and (3S)-tetraprenyltoluquinone (2a/2b), were isolated. Compounds 1 and 2 inhibited the growth of the L. infantum promastigotes (IC50 = 44.9 +/- 4.3 and 94.4 +/- 10.1 mu M, respectively), inducing cytoplasmic vacuolization and the presence of coiled multilamellar structures in mitochondria as well as an intense disruption of the mitochondrial membrane potential. Compound 1 decreased the intracellular infection index (IC50 = 25.0 +/- 4.1 mu M), while compound 2 eliminated 50% of the intracellular amastigotes at a concentration > 88.0 mu M. This work identified compound 2 as a novel metabolite and compound 1 as a biochemical isolated from Cystoseira algae displaying antileishmanial activity. Compound 1 can thus be an interesting scaffold for the development of novel chemotherapeutic molecules for canine and human visceral leishmaniases studies. This work reinforces the evidence of the marine environment as source of novel molecules.
- Presence of t(14;18) translocation in healthy individuals varies according to ethnic background in the Brazilian population(2017) LEVY, D.; BERTOLDI, E. R. M.; RUIZ, J. L. M.; PEREIRA, J.; BYDLOWSKI, S. P.Several groups have demonstrated that healthy individuals can present the t(14;18) translocation. In this report, the presence of the translocation was examined in healthy blood donors in Brazil, a country considered an ethnic melting pot. The translocation was detected by nested PCR in 227 peripheral blood samples from individuals with different ethnic backgrounds. The t(14;18) translocation was found in 45 of 85 White individuals (52.94%); in 57 of 72 Black individuals (79.17%); and in 68 of 70 individuals (97.14%) of Japanese-descent. In conclusion, the frequency of the t(14;18) translocation in the Brazilian population varies according to the ethnic background.
- Hepcidin: Homeostasis and Diseases Related to Iron Metabolism(2017) REICHERT, Cadiele Oliana; CUNHA, Joel da; LEVY, Debora; MASELLI, Luciana Morganti Ferreira; BYDLOWSKI, Sergio Paulo; SPADA, CelsoIron is an essential metal for cell survival that is regulated by the peptide hormone hepcidin. However, its influence on certain diseases is directly related to iron metabolism or secondary to underlying diseases. Genetic alterations influence the serum hepcidin concentration, which can lead to an iron overload in tissues, as observed in haemochromatosis, in which serum hepcidin or defective hepcidin synthesis is observed. Another genetic imbalance of iron is iron-refractory anaemia, in which serum concentrations of hepcidin are increased, precluding the flow and efflux of extra-and intracellular iron. During the pathogenesis of certain diseases, the resulting oxidative stress, as well as the increase in inflammatory cytokines, influences the transcription of the HAMP gene to generate a secondary anaemia due to the increase in the serum concentration of hepcidin. To date, there is no available drug to inhibit or enhance hepcidin transcription, mostly due to the cytotoxicity described in the in vitro models. The proposed therapeutic targets are still in the early stages of clinical trials. Some candidates are promising, such as heparin derivatives and minihepcidins. This review describes the main pathways of systemic and genetic regulation of hepcidin, as well as its influence on the disorders related to iron metabolism. (C) 2017 S. Karger AG, Basel
- Potential immunological markers for diagnosis of human strongyloidiasis using heterologous antigens(2017) CORRAL, M. A.; PAULA, F. M.; MEISEL, D. M. C. L.; CASTILHO, V. L. P.; GONCALVES, E. M. N.; LEVY, D.; BYDLOWSKI, S. P.; CHIEFFI, P. P.; CASTRO-BORGES, W.; GRYSCHEK, R. C. B.Strongyloides venezuelensis is a parasitic nematode of rodents that is frequently used to obtain heterologous antigens for immunological diagnosis of human strongyloidiasis. The aim of this study was to identify antigens from filariform larvae of S. venezuelensis for immunodiagnosis of human strongyloidiasis. Soluble and membrane fractions from filariform larvae of S. venezuelensis were obtained in phosphate saline (SS and SM) and in Tris-HCl buffer (TS and TM), and were analysed by Western blotting. Different antigenic components were recognized by IgG antibodies from the sera of strongyloidiasis patients. Highest recognition was observed for a 30-40 kDa mass range present in all antigenic fractions. The band encompassing this mass range was then excised and subjected to mass spectrometry for protein identification. Immunoreactive proteins identified in the soluble fractions corresponded to metabolic enzymes, whereas cytoskeletal proteins and galectins were more abundant in the membrane fractions. These results represent the first approach towards identification of S. venezuelensis antigens for use in immunodiagnostic assays for human strongyloidiasis.
- Oxysterols in adipose tissue-derived mesenchymal stem cell proliferation and death(2017) SILVA, Suelen Feitoza; LEVY, Debora; RUIZ, Jorge Luis Maria; MELO, Thatiana Correa de; ISAAC, Cesar; FIDELIS, Maira Luisa; RODRIGUES, Alessandro; BYDLOWSKI, Sergio PauloMesenchymal stem cells (MSCs) are multipotent cells characterized by self-renewal and cellular differentiation capabilities. Oxysterols comprise a very heterogeneous group derived from cholesterol through enzymatic and non-enzymatic oxidation. Potent effects in cell death processes, including cytoxicity and apoptosis induction, were described in several cell lines. Very little is known about the effects of oxysterols in MSCs. 7-ketocholesterol (7-KC), one of the most important oxysterols, was shown to be cytotoxic to human adipose tissue-derived MSCs. Here, we describe the short-term (24 h) cytotoxic effects of cholestan-3 alpha-5 beta-6 alpha-triol, 3,5 cholestan-7-one, (3 alpha-5 beta-6 alpha)- cholestane-3,6-diol, 7-oxocholest-5-en-3 beta-ylacetate, and 5 beta-6 beta epoxy-cholesterol, on MSCs derived from human adipose tissue. MSCs were isolated from adipose tissue obtained from three young, healthy women. Oxysterols, with the exception of 3,5 cholestan-7-one and 7-oxocholest-5-en-3 beta-yl acetate, led to a complex mode of cell death that include apoptosis, necrosis and autophagy, depending on the type of oxysterol and concentration, being cholestan-3 alpha-5 beta-6 alpha-triol the most effective. Inhibition of proliferation was also promoted by these oxysterols, but no changes in cell cycle were observed.
conferenceObject Clinical Outcome and Characteristics of Patients with Primary Central Nervous System Lymphomas (PCNSL) in a Brazilian Population(2017) REIS, Diego; ISHIDA, Tatiane; LAGE, Luis A. P. C.; CULLER, Hebert F.; COSTA, Renata O.; ZERBINI, Maria C.; LEVY, Debora; ROCHA, Vanderson; PEREIRA, JulianaconferenceObject Paraoxonases 1 and 2 (PON1 and 2) Polymorphisms in Diffuse Large B-Cell Lymphoma (DLBCL): Correlation with Clinical Outcomes(2017) LEVY, Debora; REIS, Diego; SILVA, Karolline Santana da; LAGE, Luis A. P. C.; SINI, Bruno; MASELI, Luciana M. F.; ROCHA, Vanderson; PEREIRA, Juliana; BYDLOWSKI, Sergio P.- Oxysterols and mesenchymal stem cell biology(2017) LEVY, Debora; MELO, Thatiana Correa de; RUIZ, Jorge L. M.; BYDLOWSKI, Sergio P.Oxysterols are oxidized products of cholesterol that play several roles in various pathophysiological processes, including the control of lipid metabolism, immunological processes, and cytotoxicity. Mesenchymal stem cells are multipotent cells with properties of self-renewal and the ability to differentiate into other cell types, including osteoblasts and adipocytes. Here,, we review the literature regarding the effects of oxysterols on mesenchymal stem cell differentiation and the main signaling pathways involved in this process.