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Disertaciones |
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1
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BRUNA RAMOS TOSTA
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IMPACT OF VARIANTS IN THE MTOR GENE ON THE SEVERITY OF COVID-19 IN A BRAZILIAN POPULATION
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Líder : RYAN DOS SANTOS COSTA
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MIEMBROS DE LA BANCA :
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BARBARA DE CASTRO PIMENTEL FIGUEIREDO
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CINTHIA VILA NOVA SANTANA
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RYAN DOS SANTOS COSTA
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Data: 03-feb-2023
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Resumen Espectáculo
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SARS-CoV-2’s pandemic has caused thousands of deaths worldwide. The disease’s severity is associated with age, sex, ongoing comorbidities along with exacerbated and uncontrolled systemic inflammatory response resulting from cytokine storm. Cytokine storms are characterized by a large dysregulated release of cytokines that can be triggered by viral infections and modulated by various signaling pathways. The target protein of rapamycin in mammals (mTOR) is a serine threonine kinase capable of shaping cellular activation and inflammatory innate response of cells, which is the first line of defense against viruses. The mTORC1 pathway has been shown to be affected by SARS-CoV-2 and hyperactivated in COVID-19’s severe patients which suggest that dysregulation of this pathway might play an important role in poor prognosis of disease. In addition, the genetic background of patients could possibly contribute to this outcome. Objectives: To investigate the involvement of variants in the MTOR gene with the severity of COVID-19 in the Brazilian population. Methods: Individuals with severe and mild COVID-19 were recruited and peripheral blood samples and sociodemographic data were collected. The SNPs rs1057079 and rs2536 of the MTOR gene were genotyped by RT-qPCR. We performed logistic regression analysis and Kaplan-Meier survival curves. We applied a genetic risk score to estimate the cumulative contribution of risk alleles. Plasma levels of the cytokines TNF and IL-6 were measured by ELISA and analyzed. Results and Conclusions: The T allele of rs1057079 was associated with risk of severity and critical COVID-19, as well as increased plasma levels of TNF. Meanwhile, the T allele of rs2536 was associated with death from COVID-19. The variant risk alleles showed a cumulative risk when inherited together and may be useful in predicting a more severe outcome of COVID-19.
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2
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Thais Maia Miranda de Barreto
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CLINICAL AND GENETIC CHARACTERISTICS OF PATIENTS PEDIATRICS WITH MULTISYSTEMIC INFLAMMATORY SYNDROME ASSOCIATED WITH SARS-COV-2 INFECTION
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Líder : PABLO RAFAEL SILVEIRA OLIVEIRA
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MIEMBROS DE LA BANCA :
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SIMONE HASHIMOTO
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PABLO RAFAEL SILVEIRA OLIVEIRA
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RYAN DOS SANTOS COSTA
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Data: 09-feb-2023
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Resumen Espectáculo
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Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a potentially fatal complication of SARS-CoV-2 infection. It is a post-infectious condition, whose symptoms and laboratory findings demonstrate systemic hyperinflammation. There are still many doubts about risk factors, ideal management and different clinical courses, but studies have been developed to unravel the genetics of the syndrome's susceptibility. Ain: To identify genetic variants that are determinant for MIS-C. Methods: This is a case series study of patients with no prior health conditions, diagnosed with MIS-C in Brazil. Clinical and laboratory data were collected from medical records, as well as patient cells to perform exome sequencing. The prioritization of variants was carried out focusing on 126 human genes that encode proteins involved in the mechanisms by which SARS-CoV-2 modulates the immune response, from a list available in the Reactome database. For ancestry analysis, it was used the 1000 Genomes Project and genetic data from BR-MIS-C as a reference, using autosomal variants with MAF > 0.1 common to both. We have considered Europeans, Africans and Native Americans as forming groups of the Brazilian population. For functional analysis, the amino acid sequences, structure and functional domains of IL- 17RC, IFNA10 and NLRP12 were obtained and the evolutionary conservation of amino acid positions was evaluated. Results: A total of 21 patients with MIS-C was enrolled in this study; of these, 62% (n=13) were male and 67% (n=14) were declared as mixed race. The median age was 8 years (IQR, 5-12). In addition to fever, observed in 100% of patients, the most prevalent symptoms were abdominal pain (74%, n=15), followed by skin rash (57%, n=12) and dyspnea (57%, n=12). The main outcome observed was shock (48%). By analyzing the prioritization of coding variants in genes that participate of the SARS-CoV-2 infection process, we identified rare deleterious variants potentially involved in the development of MIS-C in 38% (n=8) of the individuals studied. Five out of twenty one (24%) patients had functional mutations in the NLRP12 gene, located at 19q13.42, which encodes a cytoplasmic protein involved in the suppression of inflammatory responses in activated monocytes. We also identified three mutations in the IL17RC gene, located on chromosome 3p25.3, which encodes one of the IL-17 receptor chains, and also a nonsense variant in the IFNA10 gene, located in the gene cluster at locus 9p21.3, which encodes the IFN-α10 factor and has great deleterious potential. Ancestry analysis revealed an admixed pattern of Brazilian children with MIS-C, ranging from 0.77 European ancestry (P7) to 0.78 African ancestry (P1). Variants in IL17RC, IFNA10 and NLPR12 were more frequently inherited from Europeans. Evaluation of evolutionary conservation of amino acids revealed intermediate to high degree of conservation for amino acid positions in IL-17RC, IFNA10 and NLRP12. Conclusion: Rare and deleterious mutations in coding regions of the NLRP12, IL17RC and IFNA10 genes may contribute to the occurrence of MIS-C.
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3
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Rildo Batista Freire
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ASSOCIATION OF POLYMORPHISMS IN THE IL1B, IL6 AND IL10 GENES WITH PERIODONTITIS
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Líder : CAMILA ALEXANDRINA VIANA DE FIGUEIREDO FONTANA
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MIEMBROS DE LA BANCA :
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CAMILA ALEXANDRINA VIANA DE FIGUEIREDO FONTANA
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DEISE SOUZA VILAS BOAS
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RAIMON RIOS DA SILVA
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Data: 13-feb-2023
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Resumen Espectáculo
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Introduction: Periodontitis involves bone loss of support tissue and consequent loss of dental units, which significantly impacts the quality of life of individuals from all social strata. The presence of dysbiotic microbial communities and an exacerbated immune response may result in the destruction of the microarchitecture of the supporting periodontium. Environmental and genetic factors are associated with the development of the disease, and it is necessary to elucidate the role of genetics in its development and progression. Objective:To investigate the association of polymorphisms of the IL1 B, IL6 and IL10 genes with periodontitis; and to determine the allelic frequencies of IL1 B, IL,6 and IL10 polymorphisms in African, American and European populations. Materials and methods: Cross-sectional study, conducted with 506 adult individuals, classified with presence (n=117) or absence (n=389) of periodontitis, participants in the cohort of the Bahia Asthma Control Program (ProAR) in Salvador/Bahia – Brazil. Genomic DNA was extracted and genotyped using the Illumina Multi-Ethnic Global Array (MEGA, Illumina) platform. The platforms NCBI, RegulomeDB, ENCODE (Encyclopedia of DNA Elements), Haploview 4.2 and rSNPBase were consulted. Statistical analysis was performed using the PLINK 1.9 software and logistic regression was adjusted for age, obesity, mouth breathing habit, flossing, asthma and ancestry. For quality control, Hardy-Weinberg equilibrium <0.05, genotyping rate <0.98 and frequency of the lowest allele (MAF) <1% were used. Results: Two polymorphisms were associated with periodontitis in the IL1 B gene. The rs3136557 A allele showed a negative association with periodontitis in both the additive and dominant models , respectively (OR = 0.48; CI 95% = 0.24-0.94) and (OR = 0.48; CI 95 % = 0.24-0.97; p<=0.05). The rs1143630 T allele showed a positive association (OR = 1.49; CI 95% = 1.02-2.18) in the additive model, while in the dominant model (OR = 1.61; CI 95% = 1.02-2.53, p<=0.05). In the IL6 gene, the rs2069841allele A polymorphism was positively associated with periodontitis in the additive model (OR = 2.61; CI 95% = 1.05-6.50) and in the dominant model (OR = 2.61; CI 95% = 1.05- 6.50). In the analysis of IL10 polymorphisms, no significant associations with periodontitis were found in the population studied. The frequency of the lowest A allele of the rs3136557 variant is present in 8% of the studied population of Salvador, similar to the American population that has approximately the same frequency, while the African population has 5%. The rs1143630 variant (T allele) has a frequency of 20% in the population studied, while the African population presents 28%, the American and European population presents 6%. The MAF of the rs2069841 variant (A allele) was 2% in the studied group, similar to the African population that presented 3%. Conclusion: Polymorphisms in the genes of interleukins IL- 1B and IL-6 were positively and negatively associated with periodontitis. No associations of IL10 gene polymorphisms with periodontitis were found in this population of the city of Salvador. The allelic frequency of polymorphisms is similar to those found in other populations, such as African and European.
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4
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LUANA ARAUJO DAS MERCÊS
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EFFECTS OF IMMUNOSTIMULATION BY Echinacea purpurea (L.) MOENCH ON THE HISTOARCHITECTURE OF THE COLON WALL OF RATS INFECTED BY Toxoplasma gondii
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Líder : MARCELO BIONDARO GOIS
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MIEMBROS DE LA BANCA :
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LUCAS PEDREIRA DE CARVALHO
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MARCELO BIONDARO GOIS
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WENDELL MARCELO DE SOUZA PERINOTTO
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Data: 15-feb-2023
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Resumen Espectáculo
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The objective of the present study is to evaluate changes in cells and tissues that make up the colonic wall of rats inoculated with oocysts of T. gondii (strain RH, genotype I) and immunostimulated with 100 mg/kg of E. purpurea (L.) Moench. Twenty-four male Rattus norvegicus were randomly divided into four groups (n=6), namely: control group (CG); group infected with 500 T. gondii oocysts and not immunostimulated (GI); control group immunostimulated with 100 mg/kg of E. purpurea (GC+EP); and group infected and immunostimulated with 100 mg/kg of E. purpurea (GI+EP). The experimental protocol (nº 7633021018) was approved by the Ethics Committee for the use of experimental animals. Twenty-eight days after inoculation, at 93 days of age, the rats were euthanized. The colon of each was collected, fixed and analyzed using histochemical and immunohistochemical techniques. Toxoplasmic infection, as well as immunostimulation with 100 mg/kg of E. purpurea, caused histomorphometric alterations, increase in the distribution of total mast cells and mast cells and enterochromaffin cells that express 5-HT and in theproportion of intraepithelial lymphocytes in the colon of rats. We demonstrated that there was an increase in all goblet cell phenotypes evaluated in the colonic mucosal epithelium. In addition, we demonstrated that the infection caused histopathological hanges to the colon wall which were attenuated by immunostimulation with 100 mg/kg of E. purpurea. Taken together, our results suggest that part of the changes in cells and tissues that make up the colonic wall were attenuated by immunostimulation with 100 mg/kg of E. purpurea (L.) Moench, suggesting that it can be used in the future as an adjunct to conventional treatment; however, for that, new studies are necessary.
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5
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CÍNTIA SENA CARVALHO
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DEVELOPMENT OF A MULTI-EPITOPE PROTEIN WITH IMMUNOGENIC POTENTIAL AND PROSPECTION OF NEW DRUGS AGAINST INFECTIONS CAUSED BY Corynebacterium pseudotuberculosis.
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Líder : THIAGO LUIZ DE PAULA CASTRO
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MIEMBROS DE LA BANCA :
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RICARDO WAGNER DIAS PORTELA
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SANDEEP TIWARI
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THIAGO LUIZ DE PAULA CASTRO
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Data: 28-feb-2023
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Resumen Espectáculo
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Corynebacterium pseudotuberculosis is a Gram-positive and intracellular facultative pathogen known to cause diseases of veterinary importance. Among these diseases is Caseous Lymphadenitis (CLA), a disease that affects goats and sheep, generating abscesses in the lymph nodes and internal organs, causing economic losses for the breeders of these animals. Prophylaxis is the most cost-effective alternative for controlling infectious diseases, however there is still no effective vaccine against CLA. Several in silico methodologies have contributed to the selection of molecular targets that can be explored in the development of therapeutic strategies, diagnostic methods and recombinant immunogens. Therefore, the present work aimed to select vaccine and therapeutic targets, as well as to construct a potentially immunogenic chimeric protein and to screen out compounds that could be used in the treatment of CLA. Based on data from the literature, the reactive proteins RpfB, SlpA, Nlpc/P60 and the virulence factors CP40 and PLD were selected and evaluated for their intraspecific conservation and homology with proteins from goat and sheep hosts. Subsequently, epitopes of MHC-I, MHC-II and B cells present in these proteins were predicted and evaluated. In addition, proteins shared by all C. pseudotuberculosis strains, both cytoplasmic and essential, were selected for virtual screening and molecular docking analysis with natural compounds. A chimeric protein was constructed from the epitopes of RpfB, SlpA, Nlpc/P60, CP40 and PLD proteins. This immunogenic potential proved to be stable, soluble, antigenic and non-allergenic in in silico analyses. In the therapeutic approach, The proteins WP_013241317.1, WP_013241598.1, WP_014522829.1, WP_013242887.1, WP_013241937.1 and WP_013241997.1 were selected and natural compounds ZINC04258889, ZINC04235924, ZINC04236001, ZINC04235972, ZINC08300419 and ZINC67902338 were the best binders for them, respectively. These results will contribute to the prophylaxis and treatment of CLA as well as other diseases caused by C. pseudotuberculosis.
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6
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Gabriel Barroso de Almeida
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ANCESTRALITY INFORMATIVE MARKERS AND IMMUNOLOGICAL RESPONSE IN INDIVIDUALS WITH COVID-19.
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Líder : SILVANA BEUTINGER MARCHIORO
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MIEMBROS DE LA BANCA :
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POLYANNA CAROZO DE OLIVEIRA
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SILVANA BEUTINGER MARCHIORO
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THAIS FERREIRA BOMFIM PALMA
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Data: 09-mar-2023
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Resumen Espectáculo
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COVID-19 is characterized by a wide spectrum of clinical manifestations and immune responses can determine unfavorable outcomes during the course of SARS-CoV-2 infection. Some minority ethnic groups seem to be more vulnerable to infection or to present severe clinical conditions, whether due to biological or sociodemographic factors. There are few data related to genomic ancestry and clinical outcomes of the disease, for this reason, this study aimed to estimate the ancestral profile by means of Ancestry Informative Markers (AIMs) and to evaluate the hematological and lymphocyte profile of individuals with COVID-19 from from the cities of Salvador-Ba and Feira de Santana-Ba. 58 individuals with COVID-19 classified into mild and severe clinical conditions were analyzed. Genotyping was performed using PCR and the lymphocyte profile was identified using immunophenotyping. Regarding the ancestral profile, the severe group presented 40.2%, 30.4% and 29.4% of European, African and Amerindian ancestry profiles, respectively. While the light group had 44.8%, 30.9% and 24.3% of European, Amerindian and African profile, respectively. The severe group presented: increase in total leukocytes and neutrophils; reduction in the parameters of erythrocytes, hemoglobin, hematocrit and lymphocytes in comparison with the mild group, as well as a decrease in the cell profiles of TCD4+, TCD8+ and B lymphocytes. with data describing that the individual's immune response may play a crucial role in the pathogenesis of the disease.
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7
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Vitor Cordeiro Pereira
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COMPARISON OF THE HUMORAL AND CELLULAR IMMUNE RESPONSE OF SHEEP IMMUNIZED WITH A RECOMBINANT VACCINE AND A MULTIPLE INACTIVATED VACCINE FOR CORYNEBACTERIUM PSEUDOTUBERCULOSIS
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Líder : SILVANA BEUTINGER MARCHIORO
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MIEMBROS DE LA BANCA :
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SIBELE BORUSK
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MARCOS BORGES RIBEIRO
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SILVANA BEUTINGER MARCHIORO
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Data: 13-mar-2023
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Resumen Espectáculo
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Corynebacteriumpseudotuberculosis (C.pseudotuberculosis) is a gram-positive,facultativeanaerobic,facultativeintracelularbacterium.Thisetiologicalagentcausescaseouslymphadenitis,a chronicinfectiousdiseasethatmainlyeffectssmallruminants. Infectedanimals presente as aclinicalsign,granulomainsuperficialandinternallymphnodes,whichcanaffectvitalorgans. Economic lossses causes byC. pseudotuberculosisinfectionassociatedwith late diagnosisandthelackofanefficientimmunizationprotocol serve as an incentive for thedevelopmentofstudiesrelatedtocaseouslymphadenitis. Thus, theobjectiveofthisworkistoevaluatethe humoral andcellularimmunomodulationofsheepimmunizedwith a recombinantsubunitvaccineconstitutedbytherNanh, rSodCandrPknGantigensofC. pseudotuberculosis, comparing it with a commercialmultipleinactivatedvaccineavailable in theBrazilianmarket. As a methodology, a heterologussytem for expressionofrNanH, rPknGandrSodCproteinsfromC.pseudotuberculosis. Twelvesheepswererandomlydivididintothreegroups : G1, a controlgroupthatreceived 0,9% saline solution, G2 a groupwasimmunizedwiththeinactivadedmultiplevaccineand G3 a groupthatwasimmunizedwith a vaccinecomposedofrNanh, rSodCandrPknGproteins. Allanimalswerechallengedwiththe CAP 76 strainofC.pseudotuberculosis.Immunoenzymaticassay (ELISA) wasusedtoverifytheinductionofthe humoral imune response. The verificationofcellularimmune response wasperformedfromthequantification, byqPCR, ofthecytokinesIFN-y, IL-10 and IL-12. In additiontothequantificationof interferon-gammaby ELISA. The C.pseudotuberculosisantigenssecreted in the BHI mediumshowedthatreceivedtheinactivatedmultiplevaccine (G2) had a increase in specific IgG levelswhencomparedtoyheanimalsthatreceivedtherecombinantvaccine (G3). When therecombinantproteinswereused as antigen in the ELISA, it waspossibleto observe thatthe G3 presentedanincrease in antibodylevelsaftertheapplicationoftwo doses ofthevaccinewhencomparedwithto G2, a group in which it wasnotpossibleto observe anincrease in antibodylevels. In theinductionofcerllularimmune response, it wasnotpossibletoverfythesignificantdifferencein animalsfrom G3 whencomparedto G2.Therefore,itwaspossibletoinferthatthe use ofrNanh, rSodCandrPknGproteinsfromC. pseudotuberculosisin a vaccineformulationwasabbletoinduce a humoral immune response in sheep, providingespecificantibodyagainstvaccineantigens
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8
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Fabiane da Silva Reis Góes
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EVALUATION OF THE EXPRESSION OF THE GENES SELPLG, ITGA4, ARG1, NOS2 IN TOTAL LEUKOCYTES AND PLASMA LEVELS OF P-SELECTIN AND PSGL-1 PROTEINS IN PATIENTS WITH COVID-19 AND THEIR CORRELATION WITH SEVERITY
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Líder : VITOR ANTONIO FORTUNA
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MIEMBROS DE LA BANCA :
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CYNARA GOMES BARBOSA
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PABLO RAFAEL SILVEIRA OLIVEIRA
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VITOR ANTONIO FORTUNA
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Data: 19-may-2023
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Resumen Espectáculo
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INTRODUCTION: COVID-19, a disease caused by the SARS-COV-2 virus, can progress to
severe cases and promote Acute Respiratory Distress Syndrome (ARDS). The pathophysiology of severe COVID is not well understood, but it appears to be related to endothelial dysfunction combined with a dysregulated immune response and cytokine storm. COVID-19 evolves quickly into severe cases, so it is of great importance to evaluate laboratory tests and biomarkers that are indicators of the host's immune response that are effective in predicting the evolution of severe cases, with the aim of optimizing clinical and therapeutic management to avoid adverse outcomes. unfavorable events, such as death. OBJECTIVE: To evaluate the expression of the ARG1, NOS2, ITGA4 and SELPLG genes in total leukocytes and to measure the levels of P-selectin and PSGL-1 proteins in the plasma of patients with COVID-19, associating it with the severity of the clinical picture and the prognosis of the disease . METHODOLOGY: In the present controlled observational study approved by CONEP (Opinion No.: 4,014,165) we recruited 117 patients with a confirmed diagnosis of COVID-19 (severe = 58 and mild = 59). Demographic, clinical, and laboratory parameters were collected at study admission. We used the RT-qPCR assay to measure the relative expression of genes. We evaluated plasmatic levels of P-selectin and PSGL-1 with ELISA assay. RESULTS: we found that men, elderly people with pre-existing comorbidities (p<0.0001) were more likely to have a severe outcome. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) (p<0.0001) were altered in the severe group. Patients with severe symptoms exhibit increased expression of the ARG1 (p=0.032) and SELPLG (p<0.0001) genes, as well as higher plasma concentrations of P-selectin (p=0.031) and PSGL-1 (p<0.002) proteins. CONCLUSION: Our data suggest that laboratory tests such as RNL, RPL, elevated expression of SELPLG / ARG1 genes in leukocytes and increased levels of P-selectin and PSGL-1 in plasma, may be potential useful diagnostic and prognostic biomarkers for severe disease, guiding strategic treatment for COVID-19.
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9
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Catarina de Jesus Nunes
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Investigation of the neuroprotective and anti-inflammatory potential of extracts from marine sponge species
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Líder : SILVIA LIMA COSTA
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MIEMBROS DE LA BANCA :
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CLAUDENER SOUZA TEIXEIRA
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RYAN DOS SANTOS COSTA
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SILVIA LIMA COSTA
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Data: 13-jun-2023
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Resumen Espectáculo
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INTRODUCTION: Neurodegenerative diseases are characterized by progressive loss of neurons, resulting in disability and death. The search for new therapies from natural compounds aims to investigate substances with anti-inflammatory potential in the CNS. Sponges are among the most prolific marine organisms for new substances, and in vitro studies have shown anti- cancer and anti-inflammatory activity of extracts or purified compounds from some species. OBJECTIVES: To evaluate in vitro the toxicity of extracts from marine sponge species; the neuroprotective potential against inflammatory damage in neurons and the association with the modulation of the microglial response. METHODS: Cultures of PC12 neuronal cells were treated with 20 different extracts (0.1 to 200 µg/mL) obtained with dichloromethane (DCM), ethyl acetate (EtOAc) and methanol (MeOH) solvents from marine sponge species of the genus Aplysina , Cladocroce, Chondrilla, Callyspongia and Haliclona. Cell viability was determined after 72 h of treatment by the MTT test. PC12 cells were subjected to inflammatory damage with LPS at 5 µg/mL for 12 h and then treated for 24 h with A. fulva extract (0.1 and 1 µg/mL), or with its purified compound AF-H1 (1 and 10 µM) and cell viability evaluated by exclusion of Trypan Blue and Propidium Iodide. Microglia, obtained from the cerebral cortex of newborn Wistar rats, were treated for 24 h with conditioned medium derived from PC12 cells under these conditions and the phenotype of these and PC12 cells under different conditions was evaluated by phase contrast microscopy and Rosenfeld panchromic staining. RESULTS: Most extracts showed toxicity at concentrations of 100 and 200 µg/mL, except for Ac- EtO extracts which were from 10 µg/mL. The MeOH extract of A. fulva (AF-MeOH) and its compound AF-H1 were not toxic in any of the tested concentrations. PC12 cells subjected to damage with LPS showed contracted cell bodies, an effect that was not observed in cultures treated with AF-MeOH and AF-H1 extracts at the adopted concentrations. Conditioned medium-treated microglia from PC12 cultures subjected to LPS showed amoeboid-like shape; in contrast, microglia subjected to conditioned medium from PC12 cells treated with LPS and AF-MeOH or LPS and AF-H1 showed a more branched phenotype, similar to that of microglia under control conditions. CONCLUSIONS: A. fulva MeOhH extract (AF-MeOH) and its AF-H1 component are able to protect these cells against inflammatory damage with LPS and modulate the inflammatory response of microglials towards a neuroprotective phenotype.
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10
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MONICA DE SOUSA PITA
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Influence Of Trypanosoma Cruzi Coinfection On The Immune Response And Clinical Outcome Of Patients With Cutaneous Leishmaniasis
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Líder : LUCAS PEDREIRA DE CARVALHO
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MIEMBROS DE LA BANCA :
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LUCAS PEDREIRA DE CARVALHO
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LUCIANA SANTOS CARDOSO
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AUGUSTO MARCELINO PEDREIRA DE CARVALHO
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Data: 14-jun-2023
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Resumen Espectáculo
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In several areas of Latin America, the geographic distribution of cutaneous leishmaniasis (CL) overlaps with areas of Chagas disease transmission ranging from 12 to 70% of patients with clinical symptoms of leishmaniasis. Studies show a difference in the expression of T cells in CL and in patients coinfected with Trypanosoma cruzi in relation to patients with isolated Leishmania. The aim of this study is to investigate whether the immune response of patients with CL caused by L. braziliensis and coinfected with T. cruzi is associated with the clinical course of leishmaniasis. A case-control study was carried out with one hundred and eighty sera from patients with CL caused by L. braziliensis, where chimeric proteins specific to Trypanosoma cruzi were used to detect coinfection with Chagas disease. We identified 20 patients with CL who were coinfected with T.cruzi, all of whom had higher anti-Leishmania antibody titers than patients infected with Leishmania alone. As for the production of cytokines, IL-6 was the one with the highest levels in the group of co-infected patients compared to the group with leishmaniasis alone. There was no statistical difference in the production of IFN-γ, TNF, IL-1β between patients coinfected with Leishmania braziliensis and T.cruzi. With regard to clinical outcome, fourteen (70%) of the co-infected patients failed antimonial therapy, and of patients with Leishmania infection alone, a total of sixty-two (42%) failed. These results indicate that co-infection can interfere with the immune response and influence the response to treatment of patients with CL caused by L. braziliensis.
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11
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Nívia Nonato Silva
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"Evaluation of Interferon Type 1 Expression and Receptors (IFNAR1 and IFNAR2), Interleukin 17A, Human Endogenous Retroviruses (HERVK-10 and HERVW-1) in peripheral blood and association with severity in patients with COVID-19."
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Líder : VITOR ANTONIO FORTUNA
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MIEMBROS DE LA BANCA :
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ELISANGELA VITORIA ADORNO
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RYAN DOS SANTOS COSTA
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VITOR ANTONIO FORTUNA
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Data: 28-jun-2023
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Resumen Espectáculo
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COVID-19 is characterized by hyperactivation of the immune system and uncontrolled release of cytokines. Recent studies indicate that impaired signaling of IFNA1 and its receptors, IL17A, HERVs and IFNG may be associated with the severity of COVID-19. Objective: To analyze the expression of IFNA1 genes and IFNAR1/IFNAR2 receptors, IL17A and HERVs (HERVK-10 and HERVW-1) in total leukocytes and baseline levels of IFNG in the plasma of patients with COVID-19. Methods: Prospective, observational and croos-sectional study with 117 recruited patients (severe=58 and mild=59). Demographic and clinical data were collected. Peripheral blood leukocytes were isolated and RT-qPCR assay was performed for gene expression analysis. Plasma levels of IFNG were measured by the ELISA method. Results: Among the evaluated sample, there was a prevalence of males (p<0.05), elderly (p<0.0001), blacks (p<0.0001) and pre-existing comorbidities (p<0.0001). Patients with severe COVID-19 had leukocytosis, neutrophilia, and elevated platelet counts with reduced lymphocytes compared with mild patients (p<0.0001). The SII, AISI and SII/Hb indexes were significantly higher in critically ill patients (p<0.0001). IFNA1, HERVW-1 and IL17A gene expression levels were significantly higher in critically ill patients (p<0.05, p<0.05, p<0.001, respectively). However, plasma levels of IFNG were not significant. ROC analysis showed that SII and SII/Hb indexes are good prognostic markers for the outcome of COVID-19, with AUC (0.98, 0.99, p<0.0001, respectively). Conclusion: Our results indicate that the segment most affected by COVID-19 comprises men, the elderly, black people and those with comorbidities, with higher gene expression of IFNA1, HERVW-1 and IL17A. Indices such as SII and SII/Hb can be promising predictors of severity for COVID-19.
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12
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Leticia Reis de Oliveira
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IDENTIFICATION OF DIFFERENTIALLY EXPRESSED microRNA IN PATIENTS WITH HEART DYSFUNCTION DUE TO SEPSIS AND CORRELATION WITH INTRACELLULAR SIGNALING PATHWAYS: IN SILICO ANALYSIS OF POTENTIAL PROGNOSTIC BIOMARKERS
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Líder : SIMONE GARCIA MACAMBIRA
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MIEMBROS DE LA BANCA :
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BARBARA DE CASTRO PIMENTEL FIGUEIREDO
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NATALIA MACHADO TAVARES
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SIMONE GARCIA MACAMBIRA
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Data: 13-jul-2023
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Resumen Espectáculo
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Introdução: A sepse é uma condição clínica com elevado risco de morte, definida como uma disfunção orgânica decorrente de uma resposta desregulada do hospedeiro à infecção, sendo a disfunção cardíaca uma das principais complicações dos pacientes com sepse e está intimamente associada à elevada mortalidade induzida por esta condição clínica. Atualmente, a incidência e a mortalidade da sepse ainda são elevadas, apontando a importância do uso de biomarcadores no diagnóstico precoce e no seu prognóstico. Nesse cenário, os microRNA surgem como candidatos potenciais com alta especificidade e sensibilidade para a sepse. Diante desse contexto, o presente estudo visou investigar o perfil de expressão dos miRNA e sua correlação com as vias intracelulares envolvidas no remodelamento do miocárdio decorrente da sepse. Métodos & Resultados : O levantamento dos transcriptomas publicamente disponíveis em NCBI, GEO e ENA, resultou na obtenção do conjunto de dados GSE171546. Este conjunto dispõe de 20 amostras : 5 compondo o grupo controle e 15 amostras constituindo o grupo com cardiomiopatia séptica, separadas nos intervalos de tempo: 24h, 48h e 72h. A importação e análise desse conjunto de dados foram feitas a partir da plataforma online do Galaxy. Foi então avaliado o valor de p <0,05 e Fold change para encontrar os Genes Diferencialmente Expressos (GDE) e microRNA Diferencialmente Expressos (MDE). A partir desta análise, 768 GDE foram encontrados no período de 24h, 312 no grupo 48h e 255 GDE no intervalo de 72h, além de dois MDE (miR-8110 e miR-574-5p). As análises de enriquecimento de vias e de ontologia genética foram feitas pelo Webgestalt. A verificação dos mRNA alvos dos MDE foi realizado através do Mirwalk e posterior construção de rede de interação entre GDE e MDE, no Cytoscape. Conclusão : Os dois miRNA identificados estão relacionados a diversas vias intracelulares envolvidas no remodelamento do miocárdio associado à disfunção cardíaca decorrente da sepse e estão diferencialmente modulados no transcriptoma analisado neste estudo, sugerindo um papel relevante como potenciais biomarcadores de prognóstico da cardiomiopatia decorrente da sepse.
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13
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Lara Sousa Cruz de Oliveira
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Identification Of Differentially Expressed Genes In Patients With Sepsis And The Correlation With The Inflammatory Profile: In Silico Analysis Of Potential Biomarkers.
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Líder : SIMONE GARCIA MACAMBIRA
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MIEMBROS DE LA BANCA :
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ALINE CRISTINA ANDRADE MOTA MIRANDA MASCARENHAS
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PABLO RAFAEL SILVEIRA OLIVEIRA
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SIMONE GARCIA MACAMBIRA
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Data: 13-jul-2023
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Resumen Espectáculo
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Sepsis is a global public health problem and represents the leading cause of morbidity and mortality worldwide in non-cardiac intensive care units. Despite all the dedication to a more thorough investigation for early and accurate diagnosis and prognosis in the last decades, this approach remains a considerable and growing challenge to healthcare. In this context of developing rapid, accessible, and appropriate diagnostic tools to improve sepsis identification, prevention, andtreatment, the use of differentially expressed genes (DEGs) as potential biomarkers in sepsis diagnosis and prognosis stands out. Therefore, the objective of this research was to study the gene expression profile and its correlation with intracelular pathways modulated by cytokines and growth factors associated with sepsis progression and severity. For this purpose, a search was conducted in the NCBI and GEO databases, and subsequently, three sequencing datasets, namely GSE12624, GSE131761, and GSE69063, were selected. DEGs with a p-value <0.05 and expression fold change (FC) less than -1.1 or greater than +1.1 were chosen. The genes were analyzed using the Enrichr pathway enrichment program to verify if the gene expression of individuals is consistent with the studied disease. An interaction network between the genes was constructed using the String program. Based on this, we obtained preliminary results, and the ontology analysis of genes in the main intracellular pathways showed significantly increased expression. Through the Venn diagram, five genes present in all three studies were identified, and these five genes were further analyzed using the String program to construct an interaction network. The genes evaluated for sensitivity and specificity were analyzed based on the signal intensity of each sample through the statistical tool SPSS 20.0 and the genes ARG1, HPGD, DAAM2 and PCOLCE2 showed good specificity and sensitivity to identify sepsis. These results contribute to the understanding of the role of the 4 genes in sepsis and will help in the construction of a signature profile for the early diagnosis of the disease.
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14
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Taiane de Macêdo Gondim
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EXPRESSION OF IFN, IL-17, IL-2, CCL2, CCL3 AND HERVs ASSOCIATED WITH COVID-19 SEVERITY
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Líder : SORAYA CASTRO TRINDADE
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MIEMBROS DE LA BANCA :
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MARCOS DA COSTA SILVA
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SORAYA CASTRO TRINDADE
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VERA LUCIA COSTA VALE
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Data: 25-jul-2023
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Resumen Espectáculo
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COVID-19 is an acute respiratory illness caused by the new coronavirus (SARS-CoV-2). Although most cases are asymptomatic or have mild symptoms, about 20% of those affected by the disease develop its severe form. The progression of COVID-19 has been associated with hypoxia, systemic physiological dysregulation and coagulopathies, but the risk factors for its evolution to the severe form are not yet fully understood. The poor prognosis of the disease seems to be associated with factors involved in the virus-host interaction, such as impaired IFN type I signaling –the main innate line of defense for mounting an effective antiviral immune response –associated with dysregulated expression of the pro-inflammation cytokine. Furthermore, human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, appear to be reactivated in response to infectious agents such as SARS-CoV-2, modulating the innate immune response and leading to various deleterious systemic effects, but with a role the worsening of COVID-19 are still incipient.This study analyzed gene expression and plasma levels of some molecules identified as markers of COVID-19 severity, comparing mild and severe disease. We evaluated 71 individuals (46 mild and 25 severe cases) for gene expression analysis, and 139 for plasma cytokine dosage (58 mild and 81 severe cases). Expressions of IFN genes and their receptors (INFAR1 and INFAR2), IL-17 and HERVs were analyzed in both groups, as well as IL-2, CCL2 and CCL3 cytokines. The INFAR2 gene and the IL-2 cytokine were higher in the mild group, while CCL3 chemokine levels were more significant inthe severe group. These findings add to the evidence of how the dynamics of the host's immune response can impact the clinical outcome of SARS-CoV-2 infection.
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15
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EDSON HENRIQUE BISPO AMARAL
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DENTIFICATION OF GENETIC AND IMMUNOLOGICAL MECHANISMS ASSOCIATED WITH THE HARMFUL USE OF ALCOHOL IN A MIXED LATIN AMERICAN POPULATION
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Líder : PABLO RAFAEL SILVEIRA OLIVEIRA
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MIEMBROS DE LA BANCA :
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CAROLINE ALVES FEITOSA
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PABLO RAFAEL SILVEIRA OLIVEIRA
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THIAGO MAGALHÃES DA SILVA
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Data: 03-ago-2023
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Resumen Espectáculo
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Introduction: Harmful use of alcohol (HUA) is a public health problem that imposes considerable costs on healthcare systems worldwide. Ethanol consumption affects the quality of life of users, leading to a range of mental and physical health issues. Alcohol-related disorders are complex conditions influenced by various factors, such as alterations in neurotransmission systems, immune/inflammatory mediators, and genetic variants. These disorders have an estimated heritability of 50% to 60%. Genome-wide association studies have revealed numerous genetic variants associated with alcohol-related phenotypes, particularly in drug metabolism-related genes. However, most of these studies have focused on populations of European or Asian ancestries, limiting potential extrapolations to other ethnic groups. Objective: To investigate genetic/immunogenetic mechanisms associated with HUA in admixed Latin American individuals. Methods: The Alcohol Use Disorder Identification Test (AUDIT) was used to assess the risk of HUA in 2,840 individuals from the city of Pelotas (Brazil). The participants were genotyped for 2.3 million Single Nucleotide Variants (SNVs) using the Illumina HumanOmni 2.5-8v1 BeadChip platform, followed by genotype imputation. Ancestry patterns were investigated through Principal Component Analysis and ADMIXTURE method. Genetic association analyses were conducted using multivariate logistic regression. The potential functional implications of variants associated with HUA were evaluated through in silico analyses. Additionally, pathway enrichment and interaction analyses were performed to identify mechanisms potentially involved in HUA. Results: Ancestry analyses revealed the admixed pattern of the Pelotas population. Individuals with high risk of HUA exhibited significantly higher median European ancestry compared to low/moderate-risk participants (0.84 and 0.82, respectively; p = 2.13x10-2). Notably, a significant association of the HUA phenotype was identified with an intronic variant in the Cytochrome P450 Family 4 Subfamily B Member 1 (CYP4B1) gene (rs1097611; [p = 4.88x10-8, odds ratio (OR) = 1.8, confidence interval (CI) = 1.46-2.23]. Several variants in linkage disequilibrium with rs1097611 may have functional implications at the locus and are associated with differential CYPB1 gene expression in multiple human tissues. A suggestive association (5x10-8 < p < 10-5) was also observed with an SNV located in the Vav Guanine Nucleotide Exchange Factor 1 (VAV1) gene (p = 6.33x10-6, OR = 3.16, CI = 1.92-5.20), which encodes a product with immune function. Finally, multiple pathways related to nervous and immune systems are involved in HUA. Conclusion: Taken together, these findings support the multifactorial nature of HUA, suggesting the involvement of the immune system and neurotransmission pathways on drug consumption behaviors. Studies like this, with individuals from underrepresented ethnic groups, are essential to identify new variants associated with HUA.
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16
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Itamara Raquel dos Anjos
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THE INFLUENCE OF TEMPERATURE ON ASTROCYTE REACTIVITY IN PRIMARY CULTURES OF NEONATED RATS
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Líder : CLARISSA DE SAMPAIO SCHITINE
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MIEMBROS DE LA BANCA :
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CLARISSA DE SAMPAIO SCHITINE
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QUIARA LOVATTI ALVES
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REJANE CONCEICAO SANTANA
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Data: 10-ago-2023
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Resumen Espectáculo
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Astrocytes are heterogeneous glial cells, essential for the functioning of the CNS. They provide nutrients, reuptake excess neurotransmitters, contribute to neuronal plasticity, remove reactive oxygen species, contribute to the integrity and permeability of the BBB, have neurogenic and synaptogenic functions, and axonal growth and neuronal survival. Astrocytes are also involved in modulating inflammatory responses by releasing pro-inflammatory, regulatory, and anti-inflammatory cytokines. Within this context, astrocytes respond to tissue injury or harmful stimuli through morphological changes such as hypertrophy, exacerbated proliferation, changes in processes, and increased expression of markers such as GFAP, in a process known as astrogliosis reactive. This astrocytic response is present in several pathological scenarios including neurodegenerative diseases and infections. A prevalent feature in many infections is the change in temperature. Furthermore, heat shock may be associated with the induction or severity of neurodegenerative diseases. Therefore, the main objective of this work is to evaluate the influence of temperature on astroglial reactivity, analyzing the effects of thermal stress on the expression of the main astrocytic marker, the GFAP protein, the viability and the impact of this thermal insult on the modulation of the astrocytic response. To investigate a possible effect of temperature, primary cultures of astrocytes were prepared from two-day postnatal mice and subjected to a temperature of 42 degrees Celsius for 30 minutes. After this period, the cultures were recovered at 37°C in C02 for another 24 hours. In order to verify cell viability in enriched cultures of astrocytes subjected to heat shock, we performed the MTT test. We did not observe a significant difference in the number of viable cells in cultures subjected to heat shock compared to control cultures. Then, we analyzed the morphology of enriched astrocyte cultures through Rosenfeld staining, and ICQ assay, where we obtained a response associated with astrogliosis with the presence of extensive extensions, formation of cell clusters, cells with expanded ramifications, and the presence of binucleated cells. In addition, the ICQ assays showed an increase in the number of GFAP-positive cells, which contrasted with the results obtained with the Western blot technique, which showed that GFAP expression in cultures exposed to high temperature does not differ significantly from the culture control. To evaluate the inflammatory modulation induced by high temperature, we measured the concentration of NO and there was no change in NO levels between the experimental groups. In addition, we analyzed the inflammatory profile of enriched cultures of astrocytes measuring IL-10, IL-1B, and GFAP protein through gene expression by qRT-PCR. The results indicate that the high temperature, 42 degrees Celsius, for 30 minutes, induces remodeling of GFAP expression in astrocytes by approximately 40%, without increasing the amount of expressed protein or gene transcription according to the data obtained. There was also no change in the profile of cytokines expressed in cultures exposed to heat shock, suggesting the presence of an initial astroglial reactivity induced by heat shock. Thus, new experiments must be carried out to complement and deepen the dynamics and progression of astrocytic reactivity in thermal shock models.
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17
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Natália da Rocha Lopes
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Expression evaluation of resuscitation-promoting factor of Corynebacterium pseudotuberculosis
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Líder : SILVANA BEUTINGER MARCHIORO
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MIEMBROS DE LA BANCA :
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MARCOS BORGES RIBEIRO
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NUBIA SEYFFERT
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SILVANA BEUTINGER MARCHIORO
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Data: 10-ago-2023
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Resumen Espectáculo
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Goat and sheep breeding are prevalent activities in the Brazilian Northeast. However, these animals suffer from infectious and contagious diseases such as caseous lymphadenitis (CL) caused by Corynebacterium pseudotuberculosis bacteria, which presents challenges in treatment. Understanding the behavior of resuscitation-promoting factors (Rpf) may aid to solve this issue, as there is an indication of a correlation between the ability to produce biofilm and the expression of rpf. To observe the expression of rpfB in the bacteria as a potential therapeutic target, we aimed to evaluate the expression of this gene in the CAP3W and CAPJ4 strains of C. pseudotuberculosis, non-biofilm producer and biofilm producer strains, respectively. To analyze, these strains were cultured in nutritive BHI broth and subjected to oxidative and acid stresses. The stresses were applied at the early and middle of exponential phases, and aliquots were collected at predetermined times. The aliquots were stored at -70°C in TRI Reagent®, and RNA extraction was performed, followed by conversion to cDNA and used this to evaluate rpfB expression by RT-qPCR. There was expression of rpfB in both strains under all conditions analyzed. In the nutritive culture, significant expression of rpfB was observed in the early hours in CAPJ4 strain. Acid and oxidative stresses induced significant gene expression in CAPJ4 strain during resuscitation, except for oxidative stress at early exponential phase. Therefore, we can conclude that the studied strains of C. pseudotuberculosis presented rpfB expression under all evaluated conditions. The CAPJ4 strain, known for its biofilm-forming capacity, showed higher rpfB production.
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18
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Ingrid Marins de Almeida
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AKT1 variants are associated with worse outcome of COVID-19
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Líder : RYAN DOS SANTOS COSTA
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MIEMBROS DE LA BANCA :
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ALEX JOSE LEITE TORRES
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CINTHIA VILA NOVA SANTANA
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RYAN DOS SANTOS COSTA
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Data: 10-ago-2023
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Resumen Espectáculo
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The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is a global crisis. Brazil is the second country with the highest number of deaths due to COVID-19 in the world, 701,494 deaths. Many factors can determine the severity of COVID-19, including viral load, genetic factors, presence of comorbidities, age, gender, and uncontrolled inflammation. It is estimated that approximately 5% of cases develop severe acute respiratory distress syndrome due to cytokine storm. A cell signaling pathway that may be involved in this process is PI3K/AKT/MTOR. Studies demonstrate that AKT inhibition can potentially suppress pathologic inflammation, cytokine storm, fibroproliferation, and platelet activation associated with COVID-19. Objectives: To investigate the association between AKT1 gene variants and the severity of COVID-19. Methods: Peripheral blood samples and sociodemographic data were collected from 508 individuals with COVID-19, 216 mild cases and 292 severe cases, from April 2020 to April 2021. Plasma cytokine concentrations were measured by ELISA. Genotyping of the SNPs, rs1130214 and rs2494746, and AKT1 gene expression were performed using Thermo Fisher kits and analyzed by qRT-PCR in the QuantStudio 12K (Applied Biosystems). Results and Conclusions: The rs2494746-C allele was associated with severity, ICU admission, and death from COVID-19. Meanwhile, the C allele of rs1130214 was associated with elevated TNF-α and D-dimer levels. In addition, variants demonstrated a cumulative risk associated with severity, criticality, and death from COVID-19. In the predictive analysis, the rs2494746 obtained an accuracy of 71%, suggesting a high probability of the test determining the severity of the disease. Therefore, the present study contributes to understanding the influence of the AKT1 gene and its variants on immune damage in individuals infected with SARS-CoV-2, which may be useful in the future to help predict a worse outcome of COVID-19.
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19
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Irlã Santos Lima
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Characterization of antitumor and immunomodulatory mechanisms of the flavonoid rutin in glioma cells interacting with microglia and its relationship with miRNA expression.
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Líder : SILVIA LIMA COSTA
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MIEMBROS DE LA BANCA :
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FABIOLA CARDILLO
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GISELLE PINTO DE FARIA LOPES
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SILVIA LIMA COSTA
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Data: 24-ago-2023
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Resumen Espectáculo
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Glioblastoma (GBM) is the most aggressive and treatment-resistant brain tumor. In the GBM microenvironment, interaction with microglia is associated with dysregulation of cytokines, chemokines, and miRNAs, which contribute to angiogenesis, proliferation, anti-apoptosis, and chemoresistance. The flavonoid rutin has been shown to induce inhibition of rat glioma cell growth associated with microglial activation and production of pro-inflammatory mediators by mechanisms that are still poorly understood. The present study aimed to characterize the antitumor and immunomodulatory mechanisms of the flavonoid rutin in human glioma cells in indirect interaction with microglia and the relationship with miRNA expression. For this, human GL15 GBM cells and human C20 microglia were used. Cell viability was analyzed by MTT test in both cell types treated or not with rutin (1-50 μM) for 24 h. The migration capacity of GL-15 cells after treatment with rutin (30 μM) was analyzed by interference microscopy in a monolayer lesion assay. The expression of miR-125b in GL15 cells treated or not with rutin (30 μM) and in their secretome was evaluated 24 h after treatment by RT-qPCR. The expression of mRNA for cytokines IL-1β, IL-6, IL-10, TNF and for the signaling protein STAT3 in C20 microglia controls, treated with conditioned medium of GL-15 under control conditions (GCCM) or treated with conditioned medium of GL-15 treated with rutin (MCGR) was evaluated 24 h after treatment by RT-qPCR. Additionally, the expression of STAT3 protein in GL15 and C20 cell in the different conditions was evaluated by Western blot, and the morphology of the cells was analyzed by interference microscopy. It was observed that rutin (30-50 μM) significantly reduced the viability of GL15 cells (about 50%) after 24 h, and abolished migration after 48 h, however, it did not affect the viability of microglia. In addition, the treatment of GL15 cells with rutin significantly reduced the expression of miR-125b and the STAT3 protein. On the other hand, microglia submitted to MCGR showed morphological changes suggestive of reactivity and showed a reduction in the expression of mRNA for IL-6, TNF and STAT3 and in STAT3 protein. The results of this study reiterate the antiglioma potential of the flavonoid rutin and reveal its property in modulating the expression of onco miRNA-125b which, by studies of indirect interaction with microglia, should be implyed in the modulation of the inflammatory profile of these cells for a more responsive antitumor phenotype.
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20
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CLARA MACÊDO MIMOSO
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TISSUE INJURY AND REPAIR INDUCED BY Bothrops leucurus VENOM IN SKELETAL MUSCLE AND THE THERAPEUTIC POTENTIAL OF G-CSF ADMINISTRATION
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Líder : LUCIANA LYRA CASAIS E SILVA
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MIEMBROS DE LA BANCA :
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LUCIANA LYRA CASAIS E SILVA
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MARCIO CAJAZEIRA AGUIAR
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VICTOR DIOGENES AMARAL DA SILVA
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Data: 29-sep-2023
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Resumen Espectáculo
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Ophidian accidents are a major public health problem in tropical regions of the world, due to the large number of people affected and the risk of morbidity and mortality after envenoming. In Bahia approximately 70% of the accidents are caused by the species Bothrops leucurus. Snake venoms are a complex mixture of organic and inorganic substances that change between species and according to factors such as evolutionary development, geographical, dietary and biological variations, which reinforces the need to investigate the mechanisms involved in the actions of each venom. Local manifestations triggered by envenoming, such as persistent inflammation, tissue damage and myonecrosis, are inefficiently neutralized and irreversible tissue damage may result. Coadjuvant therapies are proposed to reduce the local damage of bothropic envenoming, however there is still no alternative therapy applied in the clinic. G-CSF treatments have been used in the functional and structural recovery of injured muscles. The aim of this study was to characterize the temporal profile of injury and repair induced by B. leucurus venom envenomation, as well as the degree of structural impairment of skeletal muscle, the profile of inflammatory cells and cytokines released after venom inoculation, and to evaluate the effect of treatment with G-CSF on envenoming skeletal muscle in an experimental model. For this, Swiss mice were inoculated with 50 μg/mL of B. leucurus venom and euthanized in the experimental periods of 3 h, 6h and 24 h, 7 d, 14 d and 28 d. Animals inoculated with B. leucurus venom were treated with G-CSF for two consecutive days after completing 7 d and 28 d of envenomation. Serum and muscle samples were collected, processed and used to assess the myotoxic activity of the venom, through plasma CK dosage, histopathological analysis of muscle lesions and quantification of inflammatory cells and cytokine gene expression by RT-qPCR. CK results demonstrated peak release after 6 h. Histological sections stained with HE showed inflammatory infiltrate in all analyzed periods, with predominance of the concentration in 7 d and 14 d; presence of ‘delta lesion’, oedema, hemorrhage, myonecrosis and myofibrillar hypercontraction. The evaluation of cytokine gene expression showed an increase in TNF-α, IL-1β, INFy, IL-6, IL-10, ARG and VEGF at the different times analyzed. In general, the treatment with G-CSF had an immunomodulatory action on the inflammatory process, altering the expression of cytokines, but not in the histological evaluation, indicating the possibility of a positive development in the treatment with G-CSF for skeletal muscle injuries caused by envenoming by B. leucurus, using a different treatment protocol.
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21
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ALLAN SOUZA DOS SANTOS
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CHARACTERIZATION OF LYMPHOCYTE SUBSETS AND PROGNOSTIC MARKERS IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA UNDERGOING FIRST-LINE THERAPY WITH CYCLOPHOSPHAMIDE, THALIDOMIDE, DEXAMETHASONE AND DARATUMUMAB
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Líder : ALEX JOSE LEITE TORRES
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MIEMBROS DE LA BANCA :
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ALEX JOSE LEITE TORRES
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SIMONE GARCIA MACAMBIRA
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MARINHO MARQUES DA SILVA NETO
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Data: 27-oct-2023
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Resumen Espectáculo
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Multiple Myeloma (MM) is the second most common hematological malignancy, resulting from the proliferation of monoclonal protein-producing plasma cells, predominantly affecting the elderly population. In the last decade, therapeutic advances have led to an increase in the overall survival of patients, however the disease remains incurable. Therapeutic protocols combining alkylating agents, immunomodulators, immunosuppressants, and immunotherapy induce an immunological shift that is still not fully understood. The aim of this study was to characterize lymphocyte subsets in patients with Multiple Myeloma eligible for Autologous Stem Cell Transplant (ASCT) using first-line therapy with cyclophosphamide, thalidomide, dexamethasone combined with daratumumab (CTd-Dara), an anti-CD38 monoclonal antibody. Between 2018 and 2022, 23 newly-diagnosed MM patients had their lymphocyte profiles analyzed at five distinct time points, and the therapeutic response was monitored by Next Generation Flow (NGF), through the detection of measurable residual disease (MRD). It was observed that the treatment induced significant changes in the lymphocyte profile, with emphasis on the decrease in B cells and NK cells. The composition of the B cell subsets changed significantly throughout the treatment. When evaluating prognostic variables, the expression of the CD38 molecule on the surface of plasma cells emerged as a promising marker, correlating with lower MRD levels for this therapy and the R-ISS system. Although the lymphocyte subpopulations and Circulating Tumor Cells (CTCs) did not achieve statistical significance in prognostic terms, they indicate a pattern warranting further investigation. These findings enhance our understanding of the immunomodulatory effects of therapies in MM and signal ways to optimize treatments and patient monitoring.
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22
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UENDERSON CONCEIÇÃO ROCHA
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Seroprevalence of SARS-CoV-2 Infection in Blood Donors in the Interior of Bahia
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Líder : PABLO RAFAEL SILVEIRA OLIVEIRA
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MIEMBROS DE LA BANCA :
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RODRIGO FELICIANO DO CARMO
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PABLO RAFAEL SILVEIRA OLIVEIRA
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SARA NUNES DE OLIVEIRA ARAUJO
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Data: 22-nov-2023
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Resumen Espectáculo
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Introduction: COVID-19 has brought complications to various countries. In Brazil, the spread of the infection generally moved from state capitals to interior cities. This pattern was also identified in Bahia, making it important to trace the level of viral circulation and the impact of the infection in the regions of the state. Objective: To investigate the relationship between the seroprevalence of SARS-CoV-2 infection in blood donor samples and the notification of virus infection cases in the Interior of Bahia in 2020. Materials and Methods: The population sample originally consisted of 6,877 blood donors in 13 cities, located in four regions of the state of Bahia (north, south, east, and west). Subsequently, serum samples were tested for the detection of anti-SARS-CoV-2 antibodies using the TR COVID-19 IGM/IGG Kit – Bio-Manguinhos. Statistical analyses were conducted to estimate the crude seroprevalence of the infection and a Bayesian correction method was used to determine the seroprevalence adjusted by region of the state. The data on notification/incidence are sourced from the public database of the Secretary of Health of the State of Bahia (SESAB) and DATASUS. Only records marked as "POSITIVE" and "SRAG for COVID-19" in the year 2020, between April and November, were preserved. Results: The blood donors had a median age of 34 years (IQR: 25-42). Most of the tested donors were from the western region of Bahia. The seroprevalence among blood donors and the cumulative incidence of infection/hospitalization between April and November 2020 were 12.2% and 5.0%, respectively. Differences were identified between the seroprevalence of blood donors and the accumulated incidence of cases, mainly in the west and east regions of Bahia, in November 2020. Conclusion: This study reveals a discrepancy between the seroprevalence of SARS-CoV-2 in blood donors and the reported cases of infection in Bahia in 2020, particularly in the western and eastern regions of the state. The prevalence of 12.2% among blood donors, compared to the cumulative incidence of 5.0% of infections/hospitalizations, suggests substantial underreporting of COVID-19 cases. The research contributes to a better understanding of the dynamics of SARS-CoV-2 infection in the interior of Bahia, providing valuable data for planning more targeted and efficient public health strategies to contain the virus's spread, especially in less accessible areas and among vulnerable populations.
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23
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Raquel Bispo de São Pedro
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Genetic screening of autoinflammatory genes in Latin American Individuals with Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 infection
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Líder : PABLO RAFAEL SILVEIRA OLIVEIRA
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MIEMBROS DE LA BANCA :
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PABLO RAFAEL SILVEIRA OLIVEIRA
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THIAGO LUIZ DE PAULA CASTRO
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VIVIAN BOTELHO LORENZO
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Data: 13-dic-2023
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Resumen Espectáculo
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Introduction: Multisystem inflammatory syndrome in children (MIS-C) is an inflammatory condition associated with SARS-CoV-2 infection. It is characterized by fever, prominent gastrointestinal symptoms, mucocutaneous manifestations, respiratory symptoms, and shock. The occurrence of P-MIS may be linked to innate immunological errors that selectively affect the host's immune response against SARS-CoV-2. Ain: Identify variants in genes involved in primary autoinflammatory conditions that may be implicated in MIS-C. Methods: Cells and clinical/laboratory information were collected from 21 pediatric patients with MIS-C recruited from three public hospitals in the Northeast region of Brazil. The MIS-C cases were categorized as severe or moderate based on the need for Positive Pressure Ventilation (PPV) and/or vasopressor medication, respectively. Subsequently, whole exome sequencing (WES) was performed on the individuals, and a strategy for prioritizing Single Nucleotide Variants (SNVs) with potential deleterious effects was applied. The focus was on 56 genes previously implicated in autoinflammatory diseases (according to the International Union of Immunological Societies Immunodeficiency Committee, 2022). Results: Nine individuals presented with the moderate form of MIS-C, while the remaining 12 were included in the severe MIS-C group. In the variant prioritization approach, six Single Nucleotide Variants (SNVs) were identified in five different genes (ADAM17, CARD14, IKBKG, PSTPIP1, and SH3BP12). All these variants were found in children/adolescents with the severe form of MIS-C. Notably, two variants (rs1200631089 and rs144458353) in the ADAM17 gene were selected. This gene encodes a protease implicated in the processing of tumor necrosis factor-alpha (TNF-α) and plays a crucial role in SARS-CoV-2 infection by cleaving Angiotensin-Converting Enzyme 2 (ACE2), the primary human receptor for SARS-CoV-2. Conclusion: Our data suggest that rare deleterious variants in genes previously implicated in autoinflammatory conditions, including ADAM17, IKBKG, PSTPIP1, SH3BP2, and CARD14, may account for the occurrence of P-MIS in previously healthy Brazilian children and adolescents.
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24
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VERÔNICA MOREIRA DE SOUSA
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“CHARACTERIZATION OF MODULATION OF GLIAL RESPONSE BY THE FLAVONOID AGATISFLAVONE IN AN IN VITRO MODEL OF SKULL BRAIN TRAUMA”
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Líder : SILVIA LIMA COSTA
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MIEMBROS DE LA BANCA :
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ANIBAL DE FREITAS SANTOS JUNIOR
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DENIS DE MELO SOARES
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SILVIA LIMA COSTA
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Data: 14-dic-2023
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Resumen Espectáculo
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Introduction: Traumatic Brain Injury (TBI) is a complex and multifactorial pathology, being a major cause of death and disability for humans. Immediately after TBI, astrocytes and microglia react with complex morphological and functional changes known as reactive gliosis and forms, in the area immediately adjacent to the lesion, the glial scar, the major barrier to neuronal regeneration in the central nervous system. The flavonoid agathisflavone (bis-apigenin), present in Poincianella pyramidalis leaves, has been shown to have neurogenic, neuroprotective, and anti-inflammatory effects, demonstrated in in vitro models of glutamate-induced toxicity, neuroinflammation, and demyelination. The present study investigated, the effect of agathisflavone in neuronal integrity and in the modulation of gliosis in ex vivo models of TBI. Methodology: Microdissections from the encephalon of Wistar rats (P6-8), were prepared and subjected to mechanical injury (MI) and treated or not daily with agathisflavone (5 μM) for 3 days. Astrocyte reactivity was investigated by measuring mRNA and expression of GFAP protein in the lesioned area by immunofluorecence and westernblot; proportion of microglia was determined by immunofluorescence for Iba-1; mRNA expression for inflammasome NRPL3 and interleukin -1 beta (IL-1β) was determined by RT-qPCR. Results: It was observed that lesion of the cortical tissue induced astrocytes over expressing GFAP in the typical glial scar formed, and agathisflavone modulated GFAP expression at transcriptional and pos-transcriptional level associated with reduction of glial scar. MI induced increase in the proportion of microglia (Iba-1+) that was not observed in agathisflavone treated cultures. Moreover, the flavonoid modulated negatively both NRLP3 and IL-1β mRNA expression that was increases in the lesioned area of the tissue. Conclusion: All of these findings reiterate the regulatory property of the inflammatory response of glial cells by the flavonoid agathisflavone, which can impact in neuroprotection and should be considered for future pre-clinical and clinical studies for CNS pathologies, including TBI.
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25
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ADLAS MICHEL DE JESUS RIBEIRO
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EVALUATION OF THE CLINICAL-DEMOGRAPHIC PROFILE OF PEDIATRIC AND ADOLESCENT PATIENTS WITH COVID-19 TREATED AT A HOSPITAL IN SALVADOR/BA
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Líder : LUCIANA SOUZA DE ARAGAO FRANCA
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MIEMBROS DE LA BANCA :
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LUCIANA SOUZA DE ARAGAO FRANCA
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LUCIANE AMORIM SANTOS
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PABLO RAFAEL SILVEIRA OLIVEIRA
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Data: 19-dic-2023
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Resumen Espectáculo
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Introduction: The global COVID-19 pandemic has resulted in thousands of cases and deaths worldwide. The widespread and continuous spread of the SARS-CoV-2 virus has created conditions for the emergence of new variants. Children and adolescents play a significant role in the transmission of the virus. In Brazil, the Gamma, Delta, and Omicron variants were widely present; however, there is a scarcity of data on the impact of these variants in this demographic group. Therefore, understanding the implications of these variants in the evolution of COVID-19 in children and adolescents becomes crucial. Objective: The objective of this retrospective study is to describe the clinical and epidemiological characteristics of patients under 18 years old with COVID-19 treated at a private hospital in the city of Salvador during the period of highest prevalence of the Gamma, Delta, and Omicron variants. Methods: This is a retrospective study that included 619 participants aged 0 to 17 years treated in the pediatric emergency department of the hospital. Clinical and laboratory data, as well as information on hospitalization and death, were collected through electronic medical record reviews. Results: A similar distribution of confirmed COVID-19 cases was observed during the prevalence periods of the Gamma and Omicron variants, with a reduction in cases during the Delta variant prevalence period. The same pattern was observed for ICU hospitalizations. The median time of symptom onset varied between 3 to 4 days. The main reported symptoms were fever, cough, runny nose, and headache, with cough being more prevalent during the Delta and Omicron variant periods. Few comorbidities were observed, no mortality was recorded, and only one case of multisystem inflammatory syndrome in children (MIS-C) was identified during the study period. Regarding inflammatory markers, a significant increase in C-reactive protein associated with the Omicron variant was observed, indicating a higher inflammatory or infectious process. In the hematological assessment, monocyte levels showed differences between the periods, suggesting a more active immune response during the Omicron variant prevalence period. Conclusion: This study provides a detailed understanding of the clinical, epidemiological, and laboratory characteristics of SARS-CoV-2 variants in pediatric patients. It underscores the ongoing need for surveillance and research to address the evolutions of COVID-19, particularly in contexts where new variants are in circulation. The data analysis contributes to a deeper understanding of the impact of these variants on children and adolescents, providing valuable insights for prevention and control strategies in this demographic group.
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Tesis |
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1
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ALINE CLARA DA SILVA
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DEVELOPMENT OF A TEST FOR QUANTITATIVE DETECTION OF HTLV INFECTED CELLS BY IMMUNOPHENOTYPING
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Líder : ALEX JOSE LEITE TORRES
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MIEMBROS DE LA BANCA :
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EVERTON DA SILVA BATISTA
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ALEX JOSE LEITE TORRES
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MARCOS BORGES RIBEIRO
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MARCOS DA COSTA SILVA
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RYAN DOS SANTOS COSTA
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Data: 10-feb-2023
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Resumen Espectáculo
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HTLV infection establishes a low proviral load since the spread of the virus occurs by virological synapse and by mitotic multiplication of infected cells. The clonal expansion of infected cells, in addition to being important for latency of infection, seems to lead to dysfunctions in the host's immune system, generating autoimmunity (HAM/TSP, uveitis and cardiovascular diseases) and malignancy (ATL). The impairment of the immune system caused by HTLV-1/2 infection makes the infected individual susceptible to other infectious diseases such as tuberculosis and Acquired Immunodeficiency Syndrome (AIDS). HIV and HTLV have similar genomic organization and tropism for cells of the immune system (CD4+ T cells). However, the influence of HTLV-1/2 on the progression of the pathology developed by HIV has been widely discussed. This work intends, through flow cytometry, to identify the intracytoplasmic infection of cells infected by HTLV and in coinfected patients, demonstrating the participation of the immune system in both patients. 14 individuals monoinfected by HTLV-1 and 15 individuals coinfected by HTLV-1/HIV-1 participated in the research. Detection of intracellular HTLV-1 infection was performed by labeling anti-CD4 monoclonal antibodies and a mix of probes complementary to an HTLV-1 LTR domain to target proteins in cells. Infected cells were identified by flow cytometry and statistically analyzed. At the end of the study, it was found that the anti-HTLV probe mix was able to identify infected cells in different cell types, in mono or co-infection. A smaller number of CD4+ monocytes was observed in co-infected individuals, as well as in patients using ART. When evaluating the phenotypic profile of cellular activation, a trend towards a decrease in the expression of HLA-DR and an increase in the expression of CTLA-4 was observed in monoinfected individuals with clinical manifestations associated with HTLV-1. It is suggested that the presented methodology be used as a tool in the definition of infected cell populations in patients with HTLV-1, which would open new possibilities for monitoring and therapeutic definition in these individuals.
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2
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TALITA DOS SANTOS DE JESUS
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EVALUATION OF IMMUNOGENETIC FACTORS ASSOCIATED WITH SEVERE ASTHMA EXACERBATIONS AND THEIR PHENOTYPES
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Líder : CAMILA ALEXANDRINA VIANA DE FIGUEIREDO FONTANA
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MIEMBROS DE LA BANCA :
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CAMILA ALEXANDRINA VIANA DE FIGUEIREDO FONTANA
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GUSTAVO NUNES DE OLIVEIRA COSTA
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JAMILLE SOUZA FERNANDES
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PABLO RAFAEL SILVEIRA OLIVEIRA
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VALDIRENE LEAO CARNEIRO
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Data: 24-feb-2023
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Resumen Espectáculo
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Severe asthma exacerbations lead to loss in quality of life and high costs for the National Brazilian health system, SUS. There are patients who even under appropriate treatment do not reach asthma control, which can be caused by genetic variations. Pharmacogenetic studies seek to identify variants interfering in treatment response. In this context, studies aimed at identifying genetic markers associated with asthma treatment in literature are frequent, especially, involving genes that are therapeutic target, such as bronchodilators β2-adrenergic and glucocorticoids. Objective: To evaluate the impact of variants on candidate genes associated with severe exacerbations of asthma and clinical and functional phenotypes of the disease. Methods: At first, a systematic review and meta-analysis in candidates genes (ADRB2, GLCCI1, CRHR1, NR3C1) for exacerbations and treatment response was done. Papers published until February 2022 in Pubmed and Cochrane Library with phenotypes and variants of interest were included. Meta-analysis was performed for the ADRB2 (rs1042713) variant using RStudio 4.1.2 software. A study to evaluate candidate genes was also conducted in 172 adults participating in a severe asthma exacerbation cohort where clinical evaluations, biological material collection and evaluation of pulmonary function were performed. The participants were followed-up with a specialized team in ProAr for one year. The genotyping of variants in ADRB2 (rs1042713, rs1042714), ADCY9 (rs2601814, rs2601796) and NR3C1 (rs41423247, rs10052957) was conducted and logistic regressions for exacerbations and other functional phenotypes were done. Statistical analyzes were performed on PLINK v.1.9, RStudio, SPSS v.20, GraphPa D Prism 20, in addition to other online platforms. Results: In the metanalysis results we observed that the most replicated gene is ADRB2 (rs1042713) and that the A allele (Arg) of this variation is positively associated with exacerbation in children when stratified by treatment. This same variant was also positively associated to asthma exacerbation in our exacerbation cohort (OR 4.10 IC: 1.47-11.4, 7.19 IC: 2.05-25.1, additive and dominant model, respectively), rs1042714 was also positively associated with severe exacerbation, but before from follow-up in the study (OR 1.79, IC 1.07-3.01), the rs2601814 (ADCY9) was negatively associated with the use of oral corticosteroids and non-controlled asthma, and GG genotype was associated with a lower neutrophils level in the blood. The rs10052957 (NR3C1) was negatively associated with the use of oral corticosteroids and with severe exacerbations before follow-up. Two other variants were not significantly associated with any of the phenotypes analyzed (rs41423247 and rs2601796). CONCLUSION: The rs1042713 variant has been increasingly established a risk factor for severe asthma exacerbation, and should be better studied in order to elucidate the mechanisms by which it operates and start to be used as a predictive variant.
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3
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Geraldo Pedral Sampaio
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ANALYSIS OF CD105 EXPRESSION (ENDOGLIN) IN NORMAL AND LYMPHOID PRECURSORS IN BLASTS NEOPLASTIC OF PEDIATRIC PATIENTS WITH CELL ACUTE LYMPHOBLASTIC LEUKEMIA PRECURSOR B IN THE STATE OF BAHIA
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Líder : ROBERTO JOSE MEYER NASCIMENTO
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MIEMBROS DE LA BANCA :
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BRUNO DIAZ PAREDES
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EUGÊNIA TERRA GRANADO PINA
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LUCIANA SANTOS CARDOSO
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LUCIANA SOUZA DE ARAGAO FRANCA
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MARCO AURELIO SALVINO DE ARAUJO
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ROBERTO JOSE MEYER NASCIMENTO
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Data: 06-mar-2023
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Resumen Espectáculo
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Acute lymphocytic leukemia (ALL) has a bimodal incidence, characterized by loss of normal ability to differentiate and proliferate, with an accumulation of lymphoid progenitor cells and clonal expansion in bone marrow, peripheral blood, and other tissues. It is the most common in childhood and adolescence, with several factors associated with its etiology. The use of flow cytometry, in conjunction with morphological analysis, is essential for the diagnosis and followup of such diseases. In this context, the analysis of the expression of molecules in the maturation curve of normal and neoplastic lymphoid precursors is a tool that contributes to elucidating the behavior of the medullary environment in the analysis of Measurable Residual Disease (MRD). The endoglin molecule (ENG, CD105) is a co-receptor of the TGF-β family that plays a crucial role in the regulation of angiogenesis. Although best known for its expression in endothelial cells, endoglin is also expressed in hematopoietic stem cells (HSC) and has recently been suggested as a marker of poor prognosis for pediatric patients with B Cell Precursor ALL (BCP-ALL). In this context, the present work evaluated the expression of CD105 in normal precursors of B cells, also called hematogonia, and in leukemic blasts from pediatric patients with BCP-ALL. The study was carried out on onco-pediatric patients samples from Hospital Aristides Maltez, Martagão Gesteira, and Santa Casa de Itabuna, using pre-defined panels for the analysis of CD105 expression. Events were acquired using a BD FACSCalibur flow cytometer and analyzes were performed using the Infinicyt™ 9 1.8 software. Patient samples, evaluated at diagnosis or during MRD, were individually analyzed for the presence or absence of antigenic expression of each marker used in flow cytometry. CD105, at diagnosis, was expressed in 73.33% of VIII patients with BCP-ALL, with the highest expression in leukemic blasts. When compared with MRD, the highest expression was in hematogonia in negative MRD (67.28%), with a mean MFI of 87.26. When analyzed individually (patient 1), the blasts had a higher expression and MFI, 21.56 and 26.14, respectively. CD105 can be considered a potential prognostic marker for the detection of response to induction therapy in childhood BCP-ALL, and may serve to optimize treatment decisions.
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4
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Maria Borges Rabêlo de Santana
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Development of a genetic panel to predict severe asthma exacerbation through genome-wide study and Machine Learning algorithms.
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Líder : RYAN DOS SANTOS COSTA
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MIEMBROS DE LA BANCA :
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ALEX JOSE LEITE TORRES
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LAURA MARIA DE LIMA BELIZARIO FACURY LASMAR
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LEA CRISTINA DE CARVALHO CASTELLUCCI
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PABLO DE MOURA SANTOS
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RYAN DOS SANTOS COSTA
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Data: 31-mar-2023
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Resumen Espectáculo
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Severe asthma exacerbations are determined to worsen respiratory symptoms and can cause death. However, predictive biomarkers for this outcome are still lacking. Our aim was to perform genome-wide association studies (GWAS) for severe asthma exacerbations in patients with mild, moderate, and severe asthma, and to evaluate its functional role. Additionally, integrate ten Machine Learning algorithms using a list of top Single Nucleotide Variants (SNVs) from previous GWAS in subjects with asthma or severe asthma with the aim of creating predictive genetic panels of severe exacerbations. The GWAS for severe asthma exacerbations was performed in 727 Brazilians with asthma, including 12 million genetic variants. Exacerbation was defined as systemic corticosteroid use ≥ 3 days and/or emergency room visit and/or hospitalization in the last year. GWAS replication for severe exacerbations was evaluated in U-BIOPRED, GALA II and SAGE. The epigenetic effects of the variants were evaluated in silico. Variants with p-value <0.05 in the GWAS were filtered out and integrative prediction models were built using ten Machine Learning algorithms. A GWAS was also performed for treatment failure in 364 Brazilians with severe asthma, followed by integrative prediction. The intergenic variants G-rs55670125, G-rs10854420, C-rs68160941, A-rs11910414 and A-rs35834033 were in complete linkage and are related to severe asthma exacerbations (Odds ratio (OR): 2.5; P value: 3.47e-8). These variants are located close to the CXADR gene (coxsackievirus and adenovirus receptor) on chromosome 21. Our findings have not been validated in the U-BIOPRED, GALA II and SAGE populations. Four of the SNVs were identified associated with histone modification of H3K4me1, which was previously associated with the pathogenesis of asthma. The best predictive algorithm was XGBoost, in which 68 genetic variants were considered more important to effectively predict severe asthma exacerbations in individuals with asthma, with 80% accuracy. For individuals regularly treated with inhaled corticosteroids and long-acting beta-agonists, the best predictive algorithm was C5.0, which considered 14 predictive variants with an accuracy of 81%. These panels can help in clinical practice in the Brazilian population. It is necessary to validate this method in other tolerated ones.
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5
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Maiara Nelma Bonfim Costa
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THE USE OF ADJUVANT THERAPIES AND THEIR ANTI-TUMOR EFFECTS IN EXPERIMENTAL MELANOMA IN C57BL/6 MICE
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Líder : FABIOLA CARDILLO
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MIEMBROS DE LA BANCA :
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DANIEL PEREIRA BEZERRA
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FABIOLA CARDILLO
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KARINE ARAUJO DAMASCENO
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PABLO RAFAEL SILVEIRA OLIVEIRA
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SILVIA LIMA COSTA
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Data: 16-jun-2023
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Resumen Espectáculo
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Imiquimod (IMIQ) is a TLR7 agonist that potentiates the antitumor response quickly and persistently, and BCG is an attenuated vaccine (strain) of Mycobacterium bovis, which induces a increase in the activation of the immune system, which can be an essential aid in the antitumor response.
This research aimed to test the effects of IMIQ on experimental melanoma to determine if it is essential to restrict tumor growth and to prolong animal survival after treatment in C57Bl/6 wild-type (WT) and C57Bl/6 CD1-knockout mice (CD1-/-). This study also aimed to test the BCG vaccine as an adjuvant anti- melanoma therapy in wild C57Bl/6 animals. Mice were treated with IMIQ or BCG after injection of tumor cells subcutaneously (s.c) into the pinna of the ear. Parameters for both treatments were evaluated, such as tumor size, survival, and splenic cell phenotypes were analyzed. Furthermore, intracellular cytokines were evaluated after stimulation with anti-CD3. Treatment with IMIQ effectively restricted initial tumor growth and increased survival only in WT animals. Antigen-presenting cell (APC) frequencies were higher in WT animals than in CD1-/- animals, regardless of IMIQ treatment. There was an increase in the number of splenic perforin+ NK+ cells in WT mice and an increase in splenic IFN-γ-producing CD4+ T cells stimulated with anti-CD3 when compared to WT mice with CD1-/- treated with IMIQ. In addition, there was also an increase in splenic CD8+ T cells producing TNF+ in unstimulated splenic cells from WT animals compared to CD1-/- animals. In animals treated with BCG injection in situ, there was reduced tumor growth and increased survival compared to animals that only received tumor cells. There was an increase in dendritic cells and a decrease in splenic Treg cells at the splenic level. Cytokine production revealed a decrease in IL-10, an increase in INF-γ by splenic CD4+ and CD8+ T cells, an increase in INF-γ and perforin and granzyme B factors by NK cells, and an increase in INF-γ by NKT cells. Also, at the tumor level, the histopathological analysis indicated that the animals treated with BCG had a greater cellular infiltrate and a lower percentage of necrosis and muscle tumor invasion. In conclusion, animals treated with IMIQ: WT mice were protected by IMIQ from early mortality, with a decrease in melanoma development. Besides, BCG treatment limited tumor development and significantly increased survival in C57Bl/6 mice, which parallels with strong activation of the immune system, characterized by innate and adaptative responses, and had a more significant infiltration of inflammatory cells and less necrosis, and muscular tumor infiltration.
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6
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JORDANA BATISTA SANTANA
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REGULATORY T LYMPHOCYTES IN SCHISTOSOMA MANSONI INFECTION
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Líder : LUCIANA SANTOS CARDOSO
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MIEMBROS DE LA BANCA :
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LUCIANA SANTOS CARDOSO
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LUCAS PEDREIRA DE CARVALHO
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BARBARA DE CASTRO PIMENTEL FIGUEIREDO
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THIAGO MARCONI DE SOUZA CARDOSO
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SILVANE MARIA BRAGA SANTOS
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Data: 03-jul-2023
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Resumen Espectáculo
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Introduction: Schistosomiasis is a neglected tropical disease with a great impact on public health; Chronic infection by Schistosoma mansoni is associated with polarization of the type 2 immune response, however this helminth explores immunoregulatory pathways as a survival mechanism. The aim of this study was to analyze the regulatory signature mediated by regulatory T lymphocytes (Treg) of individuals infected with S. mansoni. Materials and Methods: The individuals recruited live in an endemic area for schistosomiasis in Bahia, unicipality of Conde, approximately 150 km from the capital, Salvador. After parasitological evaluation, a prevalence of 24.21% of S. mansoni infection was observed. For immunological evaluation, 19 individuals were recruited, 12 (63.1%) infected by S. mansoni and 7 (36.8%) not infected at the time of recruitment. Regulatory lymphocytes were obtained from PBMC and stimulated with soluble S. mansoni egg antigen (SEA) for phenotypic and intracellular cytokine evaluation by flow cytometry. Then, the depleted Treg cells using magnetic beads by positive selection, for use in depleted cultures of Treg lymphocytes. In these cultures, the levels of IL-10, IL-13 IL-17 and IFN- were valuated by ELISA. Results: We observed higher frequencies of Treg lymphocytes (TCD4 + CD25 + FoxP3 + ), as well as higher expression of IL-10 and TGF-β by these cells, in the group of infected individuals. In this same group, there were higher frequencies of TCD4 + CD25 + FoxP3 + PD-1 + lymphocytes, while there was no difference in CTLA-4 expression by these cells. Increased expression of PD-1 and TGF-β were also observed in populations of non-regulatory T lymphocytes (CD4 + CD25 Low FOXP3 neg ) suggesting that some regulatory pathways may not be exclusive to Treg populations. Individuals infected with S. mansoni have higher PBMC supernatant levels of IL-10 and IL- 13 and lower levels of IFN- compared to non-infected individuals. Treg cell depletion reduced IL-10 and IL-13 levels, while it did not alter IFN-γ levels in the group of infected individuals. Conclusion: Regulation mediated by S. mansoni seems to involve IL-10, TGF-β, PD-1 pathways, and Treg cells seem to play a key role in controlling IL-10 and IL-13 production. These results expand our knowledge about the pathways explored by these parasites to survive in the host.
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7
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Fabíola Ramos Jesus
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STUDY OF AGING IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE: IMMUNE AND ENDOCRINE ASPECTS
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Líder : GYSELLE CHRYSTINA BACCAN
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MIEMBROS DE LA BANCA :
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CAROLINA ARRUDA DE FARIA
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ERCY MARA CIPULO RAMOS
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AQUILES ASSUNCAO CAMELIER
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GYSELLE CHRYSTINA BACCAN
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RYAN DOS SANTOS COSTA
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Data: 13-jul-2023
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Resumen Espectáculo
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Considered a disease associated with aging, Chronic Obstructive Pulmonary Disease (COPD) presents airflow limitation associated with chronic lung inflammation involving changes in the respiratory and systemic systems. Risk factors such as smoking, inhalation of harmful gases, and genetic mutations can influence the development of the disease. COPD results from the complex interaction between genetic and environmental factors over time. Both COPD and the aging process share similar mechanisms of immunosenescence. These changes are thought to result in an "accelerated aging" process in COPD patients. The immunosenescence found in COPD is related to the clinical course of the disease, associated with worsening gas exchange, pulmonary hyperinflation, and increased risk of mortality. Pulmonary function testing is a valuable tool in identifying patients at risk of developing COPD. A specific subtype of this disease is known as spirometry with impaired preserved relationship (PRISm). The interference of endocrine aging was identified in individuals with COPD by analyzing DHEA-S (dehydroepiandrosterone sulfate) levels and GH (growth hormone). Accelerated lung, immune, and endocrine aging in the disease are often discussed individually in the literature. Studies that assess how relaxing these systems are require renewed attention, given that COPD is not limited to repercussions only at the local level. The objective of this study was to evaluate the clinical, endocrine, and immunological profile in individuals diagnosed with COPD, as well as in individuals with risk factors for the development of the disease, in addition to reviewing the aspect of immunosenescence in COPD. This study presents a systematic review addressing immunosenescence changes in COPD and discussing their clinical repercussions. In addition, an original article presents the immunoendocrine profile of individuals with COPD and PRISm, as well as the influence of these hormones on lung function and immunological markers.
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8
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Balbino Lino dos Santos
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"EFFECT OF THE FLAVONOID AGATHISFLAVONE ON THE MODULATION OF NRLP3-INFLAMOSOME, MICRO-RNAS AND PRO-INFLAMMATORY CYTOKINES ASSOCIATED WITH THE MICROGLIAL RESPONSE TO INFLAMMATORY STIMULUS AND Aβ-AMYLOID PEPTIDES"
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Líder : SILVIA LIMA COSTA
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MIEMBROS DE LA BANCA :
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EDUARDO RIGON ZIMMER
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GYSELLE CHRYSTINA BACCAN
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JOSÉ CLÁUDIO FONSECA MOREIRA
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SILVIA LIMA COSTA
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SIMONE GARCIA MACAMBIRA
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Data: 28-jul-2023
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Resumen Espectáculo
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Microglial activation plays a crucial role in the pathogenesis of neurodegenerative diseases (NDD), and the control of this activation has been the subject of investigations as a strategy for the development of new therapeutic approaches for NDD. Agatisflavone, purified from Cenostigma pyramidale (Tul.), has been shown to be neuroprotective in in vitro models of glutamate-induced excitotoxicity and inflammatory damage. However, the potential role of microglial regulation by agathisflavone in these neuroprotective effects remains unclear. In this work, we investigated in microglial cells from the cortex of rats and in microglial cells of human lineage induced to inflammatory damage, the effects of agatisflavone in modulating the inflammatory response in order to elucidate mechanisms of neuroprotection. For this purpose, cultures of human microglia of the C20 lineage and microglia isolated from the cortex of newborn Wistar rats were exposed to β-amyloid peptide oligomers (500nM) for 4h or Escherichia coli lipopolysaccharide (LPS, 1µg/mL) for 24h and then treated or not with agathisflavone (1µM) for 24h. Cultures of PC12 neuronal cells were exposed to rat microglia conditioned medium (MCM) treated or not with agathisflavone. In a first study, we observed that LPS induced microglia to assume an activated inflammatory state (increased CD68, with a more rounded/amoeboid phenotype). However, most microglia exposed to LPS and agathisflavone showed an anti-inflammatory profile (increased CD206 and branched phenotype), associated with reduced expression of NO, GSH, NRLP3 inflammasome, IL1-β, IL-6, IL-18, TNF, CCL5 and CCL2. Molecular docking also showed that agathisflavone bound to the NLRP3 NACTH inhibitory domain. Furthermore, in cultures of PC12 cells exposed to MCM previously treated with the flavonoid, most cells preserved their neurites and increased expression of β-tubulin III. In the second study, we observed that β-amyloid and LPS induced microglia cultures to assume an activated inflammatory state, with increased expression of miR-146a and miR-155 and inflammatory mediators IL1-β, IL-6 and NOS2. However, in cells exposed to inflammatory damage and treated with agathisflavone, we observed a significant reduction in the concentration of miR146a and miR-155, as well as the inflammatory cytokines evaluated. We also observed in cells stimulated only with β-amyloid, an increase in the ratio of p-STAT3/STAT3 signaling proteins, and in cells stimulated with β-amyloid and treated with flavonoid, a reduction in this ratio. Thus, these data reinforce the anti-inflammatory activity and the neuroprotective effect of agathisflavone, associated with the control of the NLRP3 inflammasome and inflammatory mediators, also highlighting its potential in the regulation of miRNAs associated with neuroinflammation. These results strengthen the potential of this flavonoid as a promising molecule for the treatment or prevention of neurodegenerative diseases.
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9
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JESSICA VIEIRA CERQUEIRA
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"ASSOCIATION STUDY OF BDNF GENE VARIANTS WITH ASTHMA PHENOTYPES IN A BRAZILIAN POPULATION"
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Líder : CAMILA ALEXANDRINA VIANA DE FIGUEIREDO FONTANA
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MIEMBROS DE LA BANCA :
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CAMILA ALEXANDRINA VIANA DE FIGUEIREDO FONTANA
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CINTIA RODRIGUES MARQUES
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LAURA MARIA DE LIMA BELIZARIO FACURY LASMAR
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PABLO RAFAEL SILVEIRA OLIVEIRA
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RAFAEL VALENTE VEIGA
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Data: 07-ago-2023
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Resumen Espectáculo
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"Asthma is one of the most common noncommunicable diseases in the world, affecting from 1 to 29% of the population in different countries. The inflammatory process of asthma is associated with immune system activation, airway hyperresponsiveness, epithelial cell activation, mucus overproduction, and airway remodeling. It is well recognized that Th2 cells are the main drivers of eosinophilic allergic airway inflammation, generating abundant amounts of IL-4, IL-5, IL-9 and IL-13. However, asthma in adults is more often non-allergic than allergic. Although inflammation appears as a key feature of the exacerbated response in asthma, anti-inflammatory therapy only reduces this exaggerated response but is not able to suppress it, leading to the hypothesis that other factors besides the inflammatory process contribute to the symptoms. observed in asthma. Barrier tissues, such as the lungs, are innervated by the peripheral nervous system, which detects stimuli, including harmful ones, and responds to them by regulating autonomic reactions. The nervous system in the tract plays an important role in regulating mucus intensity, vascular permeability, airway smooth muscle tone, and blood flow. BDNF is an NT present in the lower airways and may contribute to changes in airway structure and function. In this context, this research aimed to evaluate the impact of variants in the BDNF gene on asthma phenotypes. The association study of the variants was carried out with the population of asthmatic adults from the ProAR. The results showed that the G allele of rs962369 was negatively associated with mild asthma (OR 0.74, 95% CI 0.564-0.985, p= 0.038). The A, G, G, G, T and A alleles of rs6265, rs11030104, rs7103411, rs988748, rs10767664, rs2030323, respectively, were positively associated with a lack of reversibility. The G allele of SNVs rs7124442 was significantly associated with lower chances for atopy (OR 0.75, 95% CI 0.575-0.989, p= 0.041). While the G and A alleles of the SNVs rs2030324 and rs7934165, respectively, were associated with a higher chance of atopy (OR 1.26, 95% CI 1.048-1.516, p= 0.014) and (OR 1.25, 95% CI 1.041-1.506, p= 0.016). G allele of the rs7124442 and A allele of the rs11030119, were associated with an increased chance of exacerbation (OR = 1.575, Pperm =0.037 and OR = 1.823, Pperm = 0.029). Furthermore, the G allele of the SNVs rs7124442 reduced IL-5 and IgE levels and increased blood neutrophil counts. These data show that BDNF gene variants have an impact on asthma in our population.
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10
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Brysa Mariana Dias Silveira
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REGENERATIVE AND IMMUNOMODULATORY ASPECTS OF MESENCHYMAL STROMAL CELLS FROM ADIPOSE TISSUE IN SICKLE CELL MODEL
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Líder : VITOR ANTONIO FORTUNA
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MIEMBROS DE LA BANCA :
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VITOR ANTONIO FORTUNA
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NATALIA MACHADO TAVARES
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ELISANGELA VITORIA ADORNO
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BRUNO SOLANO DE FREITAS SOUZA
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JAIME RIBEIRO FILHO
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Data: 08-ago-2023
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Resumen Espectáculo
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Chronic leg ulcers (CLU) are common microvascular complications in patients with sickle cell anemia. CLUs are recalcitrant and the absence of treatment can lead to lower limb amputation. Adipose tissue stromal cells (ASC) represent an alternative for the treatment of CLUs, due to their ability to secrete soluble mediators involved in tissue repair. Thus, we evaluated the effects of the ASC secretome in vitro model of umbilical cord endothelial cells (HUVECs) and in vivo model with transgenic C57BL/6 mice and sickle Towness mice. Our work found that the secret of ASC preconditioned in normoxia (condition with 20% oxygen) and hypoxia (condition with 5% oxygen) presented in its composition markers of tissue regeneration (eg: VEGF, MCP1, IL-8 and angiogenin). In vitro analysis demonstrated that both conditioned media (CMs) exerted anti- apoptotic and angiogenic action on HUVECs, with better performance of cells treated with CM in normoxia. Our in vivo model using C57BL/6 transgenic mice revealed radiation from the healing process of wounds treated with MCs. Considering that our therapeutic product performed better under conditions of normoxia, we analyzed the therapeutic potential of MC normoxia in wound healing model with sickle cell mice. In this work, we sought to evaluate the pro- angiogenic and immunomodulatory effect in skins treated with CM using immunohistochemistry, immunofluorescence and RT-PCR techniques. Our results revealed that CM administration was able to stimulate the healing process by reducing local inflammation, increasing the number of fibroblasts and increasing collagen production. Just as we identified reduced expression of inflammatory transcripts, evidencing the therapeutic effect of MC on immunomodulation.
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11
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Regina Santos Nascimento
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Functional evaluation of polymorphisms in the EBI3 and IL12A genes associated with the development of asthma in a cohort of children in the city of Salvador-BA.
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Líder : CAMILA ALEXANDRINA VIANA DE FIGUEIREDO FONTANA
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MIEMBROS DE LA BANCA :
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ALEX JOSE LEITE TORRES
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CAMILA ALEXANDRINA VIANA DE FIGUEIREDO FONTANA
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JAILTON DE AZEVEDO SILVA JUNIOR
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JAMILLE SOUZA FERNANDES
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TAMIRES CANA BRASIL CARNEIRO
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Data: 09-ago-2023
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Resumen Espectáculo
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Asthma is a chronic inflammatory disease of the airways, non-transmissible, influenced by environmental and genetic factors. Allergic asthma is the most common phenotype of the disease and is associated with an exacerbation of the Th2 immune response. Several cell types are involved in the regulation of the immune system in the lung, with emphasis on regulatory cells (Treg and Breg). Several inhibitory controls included by these cells have already been admitted, among which are the release of suppressive cytokines such as IL-10, TGF-β and IL-35. IL-35 is a heterodimeric cytokine, composed of the EBI3 and IL12p35 subunits, which are encoded by the EBI3 and IL12A genes, respectively. Changes in the levels of this cytokine have been associated with asthma and atopy. The consternation of the genetic component in the development of asthma is widely reported in the literature. In this context, given the importance of Treg cells and genetic susceptibility, this study set out to investigate the functional impact of polymorphisms in the regulatory genes EBI3 and IL12A in a population of Brazilian children. DNA from 1.218 children was genotyped using the Illumina 2.5 Human Chip Omni Bead. Logistic regression analyzes were performed using PLINK 1.9 software to verify the association between polymorphisms in EBI3 and IL12A, asthma and atopic markers, adjusted for sex, age, helminth survivors and ancestry markers. mRNA expression was performed using real-time qPCR. A total of 4 markers for IL12A and 5 for EBI3 were found. The surprising results that the C allele of rs2243131 in IL12A was positively associated with asthma (OR 1.35, CI 1.06–1.71), asthma severity (OR 1.36, CI 1.02–1.81), positive skin test for Blatella germanica (OR 1.59, CI 1.09–2.22), and also positively associated with the spontaneous production of IL-5 (OR: 1.71; CI: 1.11–2.62). The A allele of rs568408 in IL12A was also positively associated with a positive skin test for B. germanica (OR 1.65, CI 1.10-2, 37). rs582537 in IL12A was associated with a positive skin test for B. germanica (OR 0.64, CI 0.42-0.98) and Dermatophaoides pteronyssinus (OR 0.77, CI 0.60-0.98), in addition to being associated with the natural production of INF-y (OR : 0.52; CI: 0.52–0.99). With regard to EBI3, all the variants found were incorporated into atopy markers: the C allele of rs78749916 (OR 0.61, CI 0.40-0.93), the G allele of rs77145509 (OR 0.66, CI 0.46-0.94), and the A allele of rs76353132 (OR 0.68, CI 0.43-0.96), were associated with a positive skin test for Periplaneta americana. The rs76353132 variant was also associated with spontaneous INF-y production (OR: 0.72; CI: 0.52-0.99). The rs428253 C allele was associated with a positive skin test for at least one allergen (OR: 0.64; CI: 0.44–0.92), and the rs4905 G allele was associated with a positive IgE for at least one allergen (OR 0.62, CI 0 .40-0.95). IL12A mRNA expression levels were reduced in atopic asthmatic subjects when compared to controls. EBI3 expression levels were decreased in atopic asthmatic subjects compared to non-asthmatic and atopic subjects, and when compared to controls. In this study, we were able, for the first time, to describe new variants in the IL-35 regulatory pathway linked to asthma and atopy, highlighting the importance of immune regulation in the pathogenesis of asthma.
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12
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LUCIANO GAMA DA SILVA GOMES
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Predictive genetic panel analysis for the diagnosis of asthma and phenotypes using machine learning
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Líder : RYAN DOS SANTOS COSTA
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MIEMBROS DE LA BANCA :
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MÔNICA VERSIANI NUNES PINHEIRO DE QUEIROZ
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PAULO AUGUSTO MOREIRA CAMARGOS
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RAFAEL VALENTE VEIGA
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RYAN DOS SANTOS COSTA
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SORAYA CASTRO TRINDADE
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Data: 14-ago-2023
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Resumen Espectáculo
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Asthma is a multifactorial chronic inflammatory disease of the airways. Its heterogeneity and the variability of the response to treatment are the main barriers to the success of adequately managing certain types of asthmatic patients. The main objective of the study was to carry out computational modeling and prediction of genetic panels in the development of asthma and its endophenotypes, using machine learning techniques. The ProAR cohort included adults diagnosed with asthma. Latent class analysis was used to group individuals into different asthma endotypes based on variables. The study focused on 1,009,762 SNVs using the Boruta algorithm for variable selection. Ten different algorithms were employed to develop predictive models (KNN, NB, ANN, SVM, CART, C5.0, Bagging, AdaBoost, RF, and XGBoost) to accurately identify patients with asthma and their subtypes. The predictive genetic panel of overall asthma was completed with 155 single nucleotide variants with 91.18% accuracy, 92.75% sensitivity, and 89.55% specificity using the support vector machine algorithm. Furthermore, our study differentiated distinct subtypes of asthma, and from these, we defined genetic panels with high performance. In this way, machine learning can be a useful tool in researching complex outcomes, capable of helping to predict asthma and contributing to the personalization of clinical management.
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13
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Anaque de Oliveira Pires
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ASSOCIATION OF GENETIC VARIANTS IN GENES DAD1 AND OXA1L WITH ASTHMA AND ATOPIA IN A BRAZILIAN POPULATION
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Líder : CAMILA ALEXANDRINA VIANA DE FIGUEIREDO FONTANA
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MIEMBROS DE LA BANCA :
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CAMILA ALEXANDRINA VIANA DE FIGUEIREDO FONTANA
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CARINA DA SILVA PINHEIRO
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CINTHIA VILA NOVA SANTANA
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TATIANE DE OLIVEIRA TEIXEIRA MUNIZ CARLETTO
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VALDIRENE LEAO CARNEIRO
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Data: 31-ago-2023
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Resumen Espectáculo
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Asthma is a highly complex immune-mediated disease, characterized by a reversible and intermittent obstruction of the airways that, despite having a higher prevalence in childhood, has shown a high incidence and mortality in adults. In recent years, several genomic wide association studies (GWAS) have identified a significant number of genetic variants responsible for asthma susceptibility. These variants have been shown to play an important role in the regulation of gene expression and in the heritability of asthma, including variants in DAD1 e OXA1L genes. The DAD1 gene is known for its role in the regulation of programmed cell death, and OXA1L is described for its involvement in mitochondrial biogenesis and oxidative phosphorylation. The present study aimed to identify new variants in the DAD1 and OXA1L genes and to evaluate the association with asthma and atopy markers in adults. The study involved the participation of 1,084 adult individuals divided into mild to moderate asthma, severe asthma and healthy controls belonging to a case-control study cohort of the Programa para Controle da Asma na Bahia-ProAR. Analyzes of associations between variants in the studied genes and asthma or atopy were performed using a multivariate logistic regression model adjusted for sex, age, body mass index (BMI), smoking, forced expiratory volume in 1 second (FEV1) and ancestry (PC1) using PLINK 1.9 software. Additive, dominant and recessive genetic models were used for all analyzed variables. In this study, new variants in the DAD1 and OXA1L genes that had never been described before were identified. These genes have been associated with asthma and atopy markers such as skin prick test (SPT), specific IgE for aeroallergens, eosinophils and Th2-type cytokine production. In silico gene expression analyzes demonstrated that some of the polymorphisms in both genes are able to affect their respective levels of gene expression. Thus, our findings demonstrate that variants in the DAD1 and OXA1L genes may influence asthma and atopy in Brazilian adults.
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14
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FLAVIA MARTINS DA SILVA
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EVALUATION OF HSP EXPRESSION IN Corynebacterium pseudotuberculosis.
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Líder : ROBERTO JOSE MEYER NASCIMENTO
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MIEMBROS DE LA BANCA :
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BRUNO DE ALMEIDA LOPES
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LILIA FERREIRA DE MOURA COSTA
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MARCOS DA COSTA SILVA
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ROBERTO JOSE MEYER NASCIMENTO
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SUZANA TELLES DA CUNHA LIMA
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THIAGO LUIZ DE PAULA CASTRO
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Data: 15-sep-2023
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Resumen Espectáculo
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Corynebacterium pseudotuberculosis is an intracellular bacterium responsible for caseous lymphadenitis in sheep and goats, which brings great economic losses to agriculture. The resistance of C. pseudotuberculosis within macrophages, during infection, points to the activation of molecular mechanisms involved in adaptation to stress generated by the host. Heat shock proteins (HSPs) have demonstrated an important role for these molecules in increasing microbial resistance under stress conditions during infection, in addition to being immunologically important for being recognized by the host, they are therefore capable of inducing cellular and humoral immunity responses in mammals. This research aims to identify and evaluate the expression of possible HSP genes in C. pseudotuberculosis as a response to stress that may contribute to the understanding of resistance, virulence and pathogenicity mechanisms used by this pathogen, and compare them to the physiological condition. The study simulated in vitro five stress conditions (acid, thermal, nitric oxide, osmotic and oxidative) with two concentrations and three exposure times (15min, 30min, 45 min) to evaluate the resistance of C. pseudotuberculosis. Three different strains were used: T1(attenuated), ER1409 (virulent) and CapJ4 (76) (strong biofilm producer). The strains were cultivated in BHI with growth monitored and aliquots isolated in the initial exponential phase (OD600nm= 0.2) which were subjected to stress and then total RNA was extracted. The cDNAs generated by reverse transcription were submitted to RT- qPCR (quantitative PCR) assays to quantify the 5 HSPs genes (ClpB, DnaJ, Hspr, Hsp10, Hsp65). The results achieved suggest that the ER1409 and CapJ4 strains (76) had greater adaptability despite showing a slight loss of replicative potential that was observed through the survival rate. These had a higher number of transcripts (Hsp65, Hsp10, HspR. Cpl -B, DnaJ) during different stresses. These HSPs are involved in adaptive response, bacterial growth, and virulence, playing a promising role in activating the immune system. The discovery of the participation of these genes in the response to the host's stressful cellular conditions may help in the search for new treatments for caseous lymphadenitis, through the possible reduction in the expression of these resistance genes, as well as new mechanisms to combat the disease.
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15
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Pedro Augusto Silva dos Santos Rodrigues
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VARIANTS IN TNF PATHWAY GENES CONTRIBUTE TO WORSE RESPONSE TO ANTI-TNF TREATMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS
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Líder : RYAN DOS SANTOS COSTA
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MIEMBROS DE LA BANCA :
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ALEX JOSE LEITE TORRES
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CHARLESTON RIBEIRO PINTO
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GENARIO OLIVEIRA SANTOS JUNIOR
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RAFAEL VALENTE VEIGA
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RYAN DOS SANTOS COSTA
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Data: 28-nov-2023
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Resumen Espectáculo
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In recent decades, the use of biological medications (immunobiologicals) such as anti-TNF agents has gained prominence for the treatment of autoimmune diseases, especially rheumatological ones, such as Rheumatoid Arthritis (RA). The presence of tumor necrosis factor (TNF) as a crucial immune defense molecule in the pathogenesis of autoimmune diseases has made anti-TNF therapy a major step forward in the treatment of chronic inflammatory disorders, but a significant portion of patients do not respond or lose their response to these medications, requiring higher doses or therapy replacement, which have sometimes been associated with variations in genetic factors. There are still no studies that evaluate the response to these medications by correlating them with genetic polymorphisms in the Brazilian population. Therefore, this study aimed to evaluate the association of genetic variants in the TNF pathway with the diagnosis of RA and the response profile to anti-TNF immunobiologics in patients followed in public infusion centers in the state of Bahia, Brazil. In this ambispective cohort study, we used clinical, sociodemographic and genetic data to evaluate the associations of variants in the TNF, TNFRSF1A and TNFRSF1B genes with the diagnosis of RA, standardized scores, laboratory tests and response to treatment with TNFi. 360 healthy controls and 294 patients diagnosed with RA were included. In a subsample, measurements of serum levels of cytokines TNF and IL-6 were performed. Our main results suggest that rs767455-C may play a role in the response to anti-TNF treatment, being related to a better therapeutic response. Additionally, other SNPs such as rs1061622-G and rs1800629-A also seem to interfere with the anti-TNF response profile. Our binary logistic models were able to significantly predict the response to anti-TNFs from a few variables. The rs1800629-A allele and high Visual Analogue Scale scores were shown to be associated with a worse response. Phenotypes such as male sex, use of synthetic medications and seropositive RA seem to contribute to a better response to TNFi treatment. Our results highlight the importance of evaluating the effect of these polymorphisms within the individual's clinical and sociodemographic context with the aim of developing a useful panel in defining clinical approaches in the therapeutic management of RA.
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16
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PATRÍCIA MARES DE MIRANDA
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ASSOCIATION BETWEEN VARIANTS IN METALLOPROTEINASE GENES AND PERIODONTITIS
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Líder : SORAYA CASTRO TRINDADE
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MIEMBROS DE LA BANCA :
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ERICA DEL PELOSO RIBEIRO
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PAULO JOSE LIMA JUIZ
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RYAN DOS SANTOS COSTA
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SORAYA CASTRO TRINDADE
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VIVIANE ALMEIDA SARMENTO
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Data: 05-dic-2023
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Resumen Espectáculo
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Periodontitis is a chronic inflammatory disease characterized by the destruction of tooth-supporting tissues and triggered by the host's immune response to the presence of a dysbiotic subgingival biofilm. Among the various molecules produced in the pathogenic process of periodontitis, proteolytic enzymes, such as metalloproteinases (MMP) play a prominent role in tissue destruction. This cross-sectional study sought to evaluate the association of SNV of MMP 1, 2, 3, 7, 8, 9, 13, 14 and 16 genes with periodontitis in individuals over 18 years of age. SNV genotyping was performed using the Multi Ethnic Global Array. The association of genotypic frequencies of MMP SNPs with periodontitis was investigated using bivariate and multiple analysis, in additive, dominant and recessive models, considering SNV as exposure and periodontitis as outcome. Covariates related to socioeconomic-demographic characteristics, lifestyle behavior and general and oral health conditions were obtained through a questionnaire. Furthermore, quantitative trait locus (eQTL) expression and linkage disequilibrium (LD) were analyzed. There was no association of MMP 2, 3, 7, 8, 12,13 and 14 genes with periodontitis in the models tested. There was a positive association between MMP-1 SNV rs2071230 (G) and periodontitis in the additive model (OR=1.42 and CI [95% 1.002-2.03]). There was a negative association between periodontitis and the MMP-9 SNV rs13925 (A allele) in the dominant model (OR=0.56 and 95% CI [0.33-0.95]), and the MMP-16 SNV rs10097366 (G allele) in the recessive model (OR=0.01; 95% CI=0.01-0.98) and rs6994019 (A allele) in the additive (OR=0.71; 95% CI=0.52-0.97) and recessive (OR=0.53; CI) models 95%=0.29-0.95). A positive association was observed with the MMP-16 variants: rs13261974 (G allele) in the additive (OR=1.42; 95% CI= 1.03-2.00) and dominant (OR=1.67; 95% CI= 1.04-2.70) models, rs28986473 (G allele) in the additive (OR=2.472; 95% CI= 1.05-5.79) and dominant (OR=2.472; 95% CI= 1.05-5.79) models and rs9771895 (A allele) in the recessive model (OR= 1.75; CI 95%= 1.04-2.96). In the in silico comparison of quantitative expression in whole blood, the G allele showed greater expression in homozygosity than in heterozygosity (p<0.01) for rs13925 of MMP-9. In both the MMP-9 and MMP-16 genes, many SNV were in high linkage disequilibrium. Variants in MMP-9 and MMP-16 genes increase the chance of periodontitis occurring.
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17
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REJANE RODRIGUES SOUZA DOS SANTOS
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“ASPECTS OF THE ROLE OF SpaC PILIN IN CORYNEBACTERIUM AND IN SILICO EVALUATIONS IN CORYNEBACTERIUM PSEUDOTUBERCULOSIS.”
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Líder : ROBERTO JOSE MEYER NASCIMENTO
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MIEMBROS DE LA BANCA :
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RICARDO WAGNER DIAS PORTELA
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ROBERTO JOSE MEYER NASCIMENTO
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SANDEEP TIWARI
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SORAYA CASTRO TRINDADE
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VASCO ARISTON DE CARVALHO AZEVEDO
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Data: 11-dic-2023
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Resumen Espectáculo
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Caseous lymphadenitis, a worldwide disease that mainly affects goats and sheep in Brazil, has as its etiological agent Corynebacterium pseudotuberculosis, a gram-positive bacterium that has a cell wall with a structure called pili responsible for adhesion and made up of pilin proteins, with the SpaC subunit being great importance in cell adhesion, maintaining initial contact with the host, in addition to grouping epitopes capable of stimulating an immune response against C. pseudotuberculosis, data confirmed in the literature through in silico analyses, highlighting the importance of using this method. Bioinformatics tools that characterize in silico analysis were used in this study with the aim of identifying epitopes of the SpaC protein referring to strains PA01, NCTC 4681 and NCTC 4656 of C. pseudotuberculosis associated with MHCII, MHCII and B cells, for construction of a chimeric protein that provides an effective immunological response. Characteristics such as a low number of transmembrane helices, the presence of cytoplasmic domains called signal peptides, the identification of proteins such as transmembrane, extracytoplasmic, analysis of physicochemical parameters and the identification of amino acids in specific regions of these proteins contributed to the selection of the best epitopes in the construction of a chimeric peptide-based protein that can be used in the development of a synthetic vaccine. The final selection resulted in 12 epitopes associated with MHC I and MHCII used to construct the chimeric protein. According to the analyses, the protein was non-allergenic, with great antigenic potential, exhibiting physicochemical parameters that guarantee the stability of the model and interaction with Toll-like 2 receptors, confirming its immunoprotective potential.
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18
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RAÍSA SANTOS COÊLHO
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GENETIC VARIANTS ARE ASSOCIATED WITH OBESITY IN A POPULATION IN SALVADOR
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Líder : RYAN DOS SANTOS COSTA
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MIEMBROS DE LA BANCA :
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CINTIA RODRIGUES MARQUES
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GISELLE CALASANS DE SOUZA COSTA
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LEA CRISTINA DE CARVALHO CASTELLUCCI
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PABLO RAFAEL SILVEIRA OLIVEIRA
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RYAN DOS SANTOS COSTA
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Data: 14-dic-2023
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Resumen Espectáculo
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Obesity is considered a chronic disease, with multifactorial etiology, characterized by low-grade systemic inflammation, resulting from changes in the secretion of cytokines/adipokines, by adipose tissue, and commonly associated with insulin resistance. Polygenic obesity, investigated in GWAS and candidate gene studies, results from cumulative effects on large numbers of variants with modest individual consequences. Objectives: To investigate the contribution of genetic variants to obesity susceptibility in an admixed population, through a genome-wide association study (GWAS) and a candidate gene study (genes LEP, LEPR, INS and INSR genes). Methods: The studies were carried out with 1036 individuals (333 eutrophic and 703 overweight), from ProAR (Program for Asthma Control in Bahia), to identify variants associated with obesity. The MEGA chip (Illumina) was used for genotyping. Subsequently, in GWAS, we performed imputation with the CAAPA (Consortium on Asthma among Populations with African Ancestry) reference panel. Analyzes were performed using Plink software. We performed in silico analyzes in GTex, RegulomeDB, Ensembl, Haploreg and Var Elect Phenotyper. Furthermore, 11 cytokines (Eotaxin, IFNγ, IL-10, IL-6, IL-12, IL-13, IL-17A, IL-1β, IL-5, IL-8 and TNFα) were quantified in peripheral blood, in a subsample (n=657), and related to the genotypes of the variants associated with the GWAS study. Results: In GWAS, thirty-five variants were suggestively associated (5 x 10-8 < p-value < 1 x 10-5) with excess weight. Chromosome 4 brought together the main genes associated with the outcome (SPON2, RNF212, COL4A3, TMED11P and PCSK2), expressed in adipose tissue. In addition to these, a variant in the ZZEF1 gene, on chromosome 17. The variants rs10014526-T (OR 0.44; 95% CI: 0.32 - 0.60) and rs77703123-T (OR 0.44; 95% CI: 0.32 - 0.60), in TMED11P present elevated linkage disequilibrium (LD) with variants in SPON2, rs75448245-G (OR 0.43; 95% CI: 0.31 - 0.60), rs11538062-T (OR 0.44; 95% CI: 0.32 - 0.61) and rs75654334-T (OR 0.44; 95% CI 0.32 – 0.60) and in COL4A3, rs13419630-A (OR 0.42; 95% CI 0.30 – 0.59). The rs781851-G variant, in the ZZEF1 gene, unlike the previous ones, was positively associated with the outcome (OR 1.70; 95% CI 1.38 – 2.10). The polymorphic alleles were associated with the cytokines IL-6, IL-10 and IL-12. In the candidate gene study, the association was investigated between variants in the LEP, LEPR, INS and INSR genes. The rs10954174-A variant, in the LEP gene, was positively associated with excess weight (OR 1.74; 95% CI 1.06 – 2.87), as were 10 of the 11 variants observed in the leptin receptor (LEPR) gene, with the exception of rs113424381 -T (OR 0.53; 95% CI 0.30 – 0.93), negatively associated with the outcome. In the insulin gene (INS), only one variant passed the adopted quality control and was not associated with the outcome. While in the receptor gene (INSR), six variants were associated with excess weight, only two with risk: rs148418658-G (OR 3.33; 95% CI 1.12 – 9.87) and rs10427021-C (OR 1.32; 95% CI 1.02 – 1.70). Conclusions: Our research suggests that genes associated with excess weight, especially SPON2, in the GWAS, and the leptin (LEPR) and insulin (INSR) receptors, in the candidate gene study, were associated with the outcome of obesity, which indicates a possible relationship with metabolic dysfunctions that characterize it, to be investigated. Our study presents some novel associations and may contribute to precision medicine in the treatment of obesity.
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19
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Rebeca Pereira Bulhosa Santos
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EVALUATION OF GENE EXPRESSION OF OSTEOBLASTS PRODUCED IN BIOMATERIALS (ABS M30i, PC-ISO, PLA)
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Líder : SORAYA CASTRO TRINDADE
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MIEMBROS DE LA BANCA :
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LUCAS NOVAES TEIXEIRA
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Antonio Pedro Fróes de Farias
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SORAYA CASTRO TRINDADE
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VALDIRENE LEAO CARNEIRO
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VIVIANE ALMEIDA SARMENTO
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Data: 15-dic-2023
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Resumen Espectáculo
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Some orofacial injuries are related to the loss of bone continuity and, consequently, to structural and functional damage that impair quality of life. The production of biological tissues from cell cultures is suggested as an auxiliary strategy for orofacial reconstructive surgeries, but the effectiveness of the technique depends on a support structure that guides the formation of functional tissues according to the receptor bed. In this context, the gene expression signature of osteoblastic cells (SAOS-2) cultured on rigid matrices produced with a three-dimensional printer was investigated. To this end, osteoblasts cultured on polylactic acid polycarbonate (PLA), acrylonitrilebutadiene-styrene (ABS M30i) and Polycarbonate-ISO (PC-ISO) scaffolds were evaluated by Array Real time PCR system to determine the expression of genes related to osteoblastic differentiation, bone mineralization, ossification, growth factors, and transcription factors involved in inflammation and healing. The results obtained showed that the ABS-M30i scaffolds, with emphasis on the genes bmp5, bmp6, col9A2, col11A1, spp1, Ibsp, fgf2, vegfA, smad4, smad9, runx2 / bmpr1A, fgfr1 and Igfr1, the PC-ISO with emphasis on in the genes bmp5, bmp6, col19A1, col11A1, cfs2, Ibsp, fgf2, vegfa, smad1, runx2, bmPr1a and Fgfr and the PLA, highlighting the genes bmp5, bmp6, col19A1, col11A1, cfs2, spp1, minpp1, ibsp, fgf2 , tgfb2, smad1, smad5, smad4, bmpr1 and fgr1, allow the expression of a large number of genes responsible for bone formation in vitro, however, PLA seems to have allowed more exuberant expression in the genes that were highlighted, and PC-ISO allowed a more uniform overall response. Thus, the use of the three biomaterials in tissue engineering becomes promising.
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20
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CAIO LOPES BORGES ANDRADE
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Use of Machine Learning to identify plasma cells in bone marrow aspirate slides from Multiple Myeloma cases
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Líder : SONGELI MENEZES FREIRE
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MIEMBROS DE LA BANCA :
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EDVAN DE QUEIROZ CRUSOE
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JOÃO PAULO PEREIRA DE SÁ CANÁRIO
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MARINHO MARQUES DA SILVA NETO
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RYAN DOS SANTOS COSTA
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SONGELI MENEZES FREIRE
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Data: 20-dic-2023
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Resumen Espectáculo
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Multiple myeloma (MM) is a hematological neoplasm caused by dysregulated regulation of plasma cells in the bone marrow, which generally affects patients over 50 years of age. It is currently the 2nd most common oncohematology and responsible for 1% of cancer types in the world. To stage myeloma, responsible physicians must follow the criteria of the International Staging System (ISS), with the myelogram showing plasma cell infiltration (>10%) being an observer-dependent method that takes specific time for the hematologist. The present study aims to develop and train Artificial Intelligence to identify Plasmocytes and Non-Plasmocyte nucleated cells in Bone Marrow slides from patients diagnosed with Multiple Myeloma. The Immunophenotyping sector of the Laboratory of Immunology and Molecular Biology (LABIMUNO-UFBA) made available coded bone marrow slides from MM carriers. As of today, images were acquired using a cell phone adapted specifically for the production of digital image banks. The images were labeled with plasma cells and other cell groups. The labels were validated by doctors and hematology experts. The stock images went through a normalization process to obtain a standard that facilitated computer vision. Ultimately, the images fed deep machine learning for AI development. With this, it was possible to obtain a bank of digital images of bone marrow slides from individuals diagnosed with MM, containing images of plasma cells and other properly labeled nucleated cell groups, which allowed the advancement of the project, which includes the development of an AI with capacity identification of plasma cells and other nucleated cell groups in bone marrow slide images. An AI with this proposal could assist the medical team in the morphological and quantitative evaluation of cells for a more effective microscopic diagnosis.
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