FRANCIELLE TRAMONTINI GOMES DE SOUSA
Projetos de Pesquisa
Unidades Organizacionais
LIM/46 - Laboratório de Parasitologia Médica, Hospital das Clínicas, Faculdade de Medicina
7 resultados
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conferenceObject COCULTURE OF ENDOTHELIAL CELLS AND MONOCYTES AS A POTENTIAL MODEL TO STUDY DENGUE PATHOGENESIS AND SCREEN COMPOUNDS WITH THERAPEUTIC POTENTIAL(2017) CARDOZO, Francielle T.; ROMANO, Camila M.; SABINO, Ester C.- Intradermal Delivery of Dendritic Cell-Targeting Chimeric mAbs Genetically Fused to Type 2 Dengue Virus Nonstructural Protein 1(2020) PEREIRA, Lennon Ramos; VICENTIN, Elaine Cristina Matos; PEREIRA, Sara Araujo; MAEDA, Denicar Lina Nascimento Fabris; ALVES, Rubens Prince dos Santos; ANDREATA-SANTOS, Robert; SOUSA, Francielle Tramontini Gomes de; YAMAMOTO, Marcio Massao; CASTRO-AMARANTE, Maria Fernanda; FAVARO, Marianna Teixeira de Pinho; ROMANO, Camila Malta; SABINO, Ester Cerdeira; BOSCARDIN, Silvia Beatriz; FERREIRA, Luis Carlos de SouzaTargeting dendritic cells (DCs) by means of monoclonal antibodies (mAbs) capable of binding their surface receptors (DEC205 and DCIR2) has previously been shown to enhance the immunogenicity of genetically fused antigens. This approach has been repeatedly demonstrated to enhance the induced immune responses to passenger antigens and thus represents a promising therapeutic and/or prophylactic strategy against different infectious diseases. Additionally, under experimental conditions, chimeric alpha DEC205 or alpha DCIR2 mAbs are usually administered via an intraperitoneal (i.p.) route, which is not reproducible in clinical settings. In this study, we characterized the delivery of chimeric alpha DEC205 or alpha DCIR2 mAbs via an intradermal (i.d.) route, compared the elicited humoral immune responses, and evaluated the safety of this potential immunization strategy under preclinical conditions. As a model antigen, we used type 2 dengue virus (DENV2) nonstructural protein 1 (NS1). The results show that the administration of chimeric DC-targeting mAbs via the i.d. route induced humoral immune responses to the passenger antigen equivalent or superior to those elicited by i.p. immunization with no toxic effects to the animals. Collectively, these results clearly indicate that i.d. administration of DC-targeting chimeric mAbs presents promising approaches for the development of subunit vaccines, particularly against DENV and other flaviviruses.
- In vitro and in vivo genotoxic evaluation of Bothrops moojeni snake venom(2015) ZOBIOLE, Nathalia Novak; CAON, Thiago; BERTOL, Jessica Wildgrube; PEREIRA, Cintia Alves de Souza; OKUBO, Brunna Mary; MORENO, Susana Elisa; CARDOZO, Francielle Tramontini Gomes de SousaContext: Bothrops moojeni Hoge (Viperidae) venom is a complex mixture of compounds with therapeutic potential that has been included in the research and development of new drugs. Along with the biological activity, the pharmaceutical applicability of this venom depends on its toxicological profile. Objective: This study evaluates the cytotoxicity and genotoxicity of the Bothrops moojeni venom (BMV). Material and methods: The in vitro cytotoxicity and genotoxicity of a pooled sample of BMV was assessed by the MTT and Comet assay, respectively. Genotoxicity was also evaluated in vivo through the micronucleus assay. Results: BMV displayed a 50% cytotoxic concentration (CC50) on Vero cells of 4.09 mu g/mL. Vero cells treated with 4 mu g/mL for 90 min and 6 h presented significant (p<0.05, ANOVA/Newman-Keuls test) higher DNA damage than the negative control in the Comet assay. The lower DNA damage found after 6 h compared with the 90 min treatment suggests a DNA repair effect. Mice intraperitoneally treated with BMV at 10, 30, or 80 mu g/animal presented significant genotoxicity (p<0.05, ANOVA/Newman-Keuls test) in relation to the negative control after 24 h of treatment. Contrary to the in vitro results, no DNA repair seemed to occur in vivo up to 96 h post-venom inoculation at a dose of 30 mu g/animal. Discussion and conclusion: The results show that BMV presents cyto- and genotoxicity depending on the concentration/dose used. These findings emphasize the importance of toxicological studies, including assessment of genotoxicity, in the biological activity research of BMV and/or in the development of BMV-derived products.
- Serum from dengue virus-infected patients with and without plasma leakage differentially affects endothelial cells barrier function in vitro(2017) CARDOZO, Francielle Tramontini Gomes de Sousa; BAIMUKANOVA, Gyulnar; LANTERI, Marion Christine; KEATING, Sheila Marie; FERREIRA, Frederico Moraes; HEITMAN, John; PANNUTI, Claudio Sergio; PATI, Shibani; ROMANO, Camila Malta; SABINO, Ester CerdeiraBackground Although most of cases of dengue infections are asymptomatic or mild symptomatic some individuals present warning signs progressing to severe dengue in which plasma leakage is a hallmark. Methodology/Principal findings The present study used Electric Cell-substrate Impedance Sensing (ECIS (R)) which allows for electrical monitoring of cellular barrier function measuring changes in Transendothelial Electric Resistance (TEER) to investigate the parameters associated with dengue induced leakage. Three groups of individuals were tested: dengue-positives with plasma leakage (leakage), dengue-positives without plasma leakage (no leakage), and dengue-negatives (control). Data show that TEER values of human umbilical vein endothelial cells (HUVECs) was significantly lower after incubation with serum from subjects of the leakage group in comparison to the no leakage or control groups. The serum levels of CXCL1, EGF, eotaxin, IFN-gamma, sCD40L, and platelets were significantly decreased in the leakage group, while IL-10, IL-6, and IP-10 levels were significantly increased. We also found a strong correlation between TEER values and augmented levels of IP-10, GM-CSF, IL-1 alpha, and IL-8, as well as decreased levels of CXCL1 and platelets. Conclusions/Significance The present work shows that the magnitude of the immune response contributes to the adverse plasma leakage outcomes in patients and that serum components are important mediators of changes in endothelial homeostasis during dengue infections. In particular, the increased levels of IP-10 and the decreased levels of CXCL1 and platelets seem to play a significant role in the disruption of vascular endothelium associated with leakage outcomes after DENV infection. These findings may have important implications for both diagnostic and therapeutic approaches to predict and mitigate vascular permeabilization in those experiencing the most severe clinical disease outcomes after dengue infection.
- Anti-Zika virus activity of several abietane-type ferruginol analogues(2020) SOUSA, Francielle T. G.; NUNES, Cristina; ROMANO, Camila Malta; SABINO, Ester Cerdeira; GONZALEZ-CARDENETE, Miguel AngelAbietane diterpenoids are naturally occurring plant metabolites with a broad spectrum of biological effects including antibacterial. antileishmanial, antitumor, antioxidant, as well as antiinfiammatory activities. Recently, we found that some analogues of natural ferruginol (2) actively inhibited dengue virus 2 (DENV-2) replication. Due to the similarity with DENY, we envisaged that abietane diteipenoids would also be active against Zika virus (ZIKV). Six selected semi-synthetic abietane derivatives of (+)-dehydroabietylatnine (3) were tested. Cytotoxicity was determined by Mn' assay in Vero cells. In vitro anti-ZIKV (clinical isolate. imT17) activity was evaluated by plaque assay. Interestingly, these molecules showed potential as anti-ZIKV agents, with EC50 values ranging from 0.67 to 18.57 mu M. and cytotoxicity (CC50 values) from 256 to 35.09 mu M. The 18-Oxoferruginol (8) (EC50 = 2.60 mu M, SI = 13.51) and 12-nitro-N-benzoyldehydroabietylamine (9) (ECG 0.67 mu M, SI = 3.82) were the most active compounds, followed by 12-hydroxy-N-tosyldehydroabietylamine (7) (EC50 = 3.58 mu M, SI = 3.20) and 12-hydroxy-N,N-phthaloyldehydroabietylamine (5) (EC50 = 7.76 mu M, SI = 1.23). To the best of our knowledge, this is the first report on anti-Zika virus properties of abietanes.
- Antiherpetic Mechanism of a Sulfated Derivative of Agaricus brasiliensis Fruiting Bodies Polysaccharide(2014) CARDOZO, Francielle Tramontini Gomes de Sousa; CAMELINI, Carla Maisa; LEAL, Paulo Cesar; KRATZ, Jadel Mueller; NUNES, Ricardo Jose; MENDONCA, Margarida Matos de; SIMOES, Cluadia Maria OliveiraObjective: To study the anti-herpes simplex virus (HSV) activity of a (1 -> 6)-(1 -> 3)-beta-D-glucan isolated from Agaricus brasiliensis fruiting bodies (FR) as well as its chemically sulfated derivative (FR-S). Methods: The antiherpetic activity and mechanism of action was studied by viral plaque assay applying different methodological strategies. Results: Although FR presented no in vitro antiherpetic action at 1 mg/ml, FR-S displayed promising anti-HSV-1 and anti-HSV-2 activities in both simultaneous and postinfection treatments, resulting in selectivity indices (CC50/EC50) higher than 393. FR-S had no virucidal effect, but significantly suppressed HSV-1 (EC50 = 0.32 mu g/ml) and HSV-2 (EC50 = 0.10 mu g/ml) adsorption. FR-S was less effective on adsorption inhibition of mutant virus strains devoid of gC (HSV-1 gC-39 and HSV-2 gCneg1), indicating a possible interaction with this glycoprotein. The reduction of viral adsorption upon cell pretreatment with FR-S also suggests its interaction with cellular components. FR-S inhibited HSV-1 (EC50 = 8.39 mu g/ml) and HSV-2 (EC50 = 2.86 mu g/ml) penetration more efficiently than heparin. FR-S reduced HSV-1 and HSV-2 cell-to-cell spread. A synergic effect between FR-S and acyclovir was also detected. Conclusions: FR-S displays an interesting mechanism of antiviral action and represents a promising candidate for the treatment and/or prevention of herpetic infections, to be used as a single therapeutic agent or in combination with acyclovir. (C) 2014 S. Karger AG, Basel.
- Whole transcriptome analysis of multiple Sclerosis patients reveals active inflammatory profile in relapsing patients and downregulation of neurological repair pathways in secondary progressive cases(2020) NALI, Luiz H.; OLIVAL, Guilherme S.; SOUSA, Francielle T. G.; OLIVEIRA, Ana Carolina S. de; MONTENEGRO, Horacio; SILVA, Israel T. da; DIAS-NETO, Emamnuel; NAYA, Hugo; SPANGENBERG, Lucia; PENALVA-DE-OLIVEIRA, Augusto C.; ROMANO, Camila M.Background: Multiple sclerosis (MS) is an inflammatory autoimmune neurologic disease that causes progressive destruction of myelin sheath and axons. Affecting more than 2 million people worldwide, MS may presents distinct clinical courses. However, information regarding key gene expression and genic pathways related to each clinical form is still limited. Objective: To assess the whole transcriptome of blood leukocytes from patients with remittent-recurrent (RRMS) and secondary-progressive (SPMS) forms to explore the gene expression profile of each form. Methods: Total RNA was obtained and sequenced in Illumina HiSeq platform. Reads were aligned to human genome (GRCh38/hg38), BAM files were mapped and differential expression was obtained with DeSeq2. Up or downregulated pathways were obtained through Ingenuity IPA. Pro-inflammatory cytokines levels were also assessed. Results: The transcriptome was generated for nine patients (6 SPMS and 3 RRMS) and 5 healthy controls. A total of 731 and 435 differentially expressed genes were identified in SPMS and RRMS, respectively. RERE, IRS2, SIPA1L1, TANC2 and PLAGL1 were upregulated in both forms, whereas PAD2 and PAD4 were upregulated in RRMS and downregulated in SPMS. Inflammatory and neuronal repair pathways were upregulated in RRMS, which was also observed in cytokine analysis. Conversely, SPMS patients presented IL-8, IL-1, Neurothrophin and Neuregulin pathways down regulated. Conclusions: Overall, the transcriptome of RRMS and SPMS clearly indicated distinct inflammatory profiles, where RRMS presented marked pro-inflammatory profile but SPMS did not. SPMS individuals also presented a decrease on expression of neuronal repair pathways.