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Dissertations |
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JÉSSICA TELES SOUZA
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Study of rutin effect on neural cells in a glutamatergic excitotoxicity model.
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Advisor : VICTOR DIOGENES AMARAL DA SILVA
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COMMITTEE MEMBERS :
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CLARISSA DE SAMPAIO SCHITINE
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FLAVIA CARLA MEOTTI
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VICTOR DIOGENES AMARAL DA SILVA
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Data: Feb 17, 2020
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Show Abstract
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Rutin is one of the most common used polyphenolic compounds described in the literature, with great scientific prominence due to its interesting pharmacological activities for of human health, including its neuroprotective potential. In the context of neurodegenerative diseases, glutamatergic excitotoxicity has been identified as an important mechanism of neuronal death associated with progression of these diseases. Therefore, this study aimed to investigate the rutin neuroprotective activity for neural cells under cytotoxic glutamate action. For this, cells of the PC12 strain were subjected to different treatments: direct treatment with rutin (0.5 - 1 μM) and /or glutamate (10 - 60 mM); indirect treatment using conditioned medium obtained from brain organotypic culture of Wistar rat (p7-p9) treated with rutin (0.5 μM) and glutamate (60 mM). In addition, we also treated primary culture of mesencephalic neurons/glial cells with 0.5 μM rutin. After 24 hours of direct or indirect treatment of PC12 cells, we performed cell viability analyzes from the Trypan Blue and Propidium Iodide exclusion test. In addition, we performed morphological analyzes after Rosenfeld staining for PC12 cells and for primary culture of mesencephalic neurons/glial cells. The results obtained with the cell viability test demonstrated that rutin was not toxic to PC12 cells. Glutamate, in turn, induced a toxic effect in PC12 cells in a concentration-dependent manner, and the concentration at 60 mM was able to cause almost 100% of death to the cells in culture. Regarding the direct neuroprotection assays, it was shown that, compared to the control group that presented 2% death, rutin was not able to protect PC12 cells against glutamate toxicity at high concentrations (30 and 60 mM) inducing about 20% and 100% death respectively. On the other hand, conditioned media from brain organotypic culture treated with rutin- (0.5 μM) + glutamate (60 mM) induced low toxicity in PC12 cultures, more specifically only 8% of cells died with treatment, whereas direct treatment presented 100% dead cells. Regarding morphological changes, indirect treatment with rutin induced a characteristic change in neuronal differentiation for approximately 26% of cells in culture, unlike direct treatment which induced 2.5%. These morphological changes related to the increase of branch points and the increase of neurite length were observed in PC12 cells and in primary culture of mesencephalic neurons/glial cells. These results indicate that the neuroprotective and morphogenic effects of rutin may be associated with modulation of glutamate metabolism by astrocytes and/ or release of soluble neuroprotective and inductors of neural differentiation factors.
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2
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THIAGO MENDONÇA DOS SANTOS
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PROGRESSION BIOMARKER POTENTIAL FOR DISEASE MANIFESTATION IN HTLV-1 INFECTED INDIVIDUALS.
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Advisor : ALINE CRISTINA ANDRADE MOTA MIRANDA MASCARENHAS
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COMMITTEE MEMBERS :
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ALINE CRISTINA ANDRADE MOTA MIRANDA MASCARENHAS
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ANTONIO RICARDO KHOURI CUNHA
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GLÓRIA REGINA FRANCO
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Data: Feb 27, 2020
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Show Abstract
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Adult T-cell Lymphotropic Virus 1 (HTLV-1) is a sexually transmitted human retrovirus that exhibits preferential CD4+ T-cell tropism. Although most individuals infected with this virus remain asymptomatic (ASS), the main clinical manifestations such as HTLV-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) and Adult T-Cell Leukemia/Lymphoma (ATLL) are troublesome conditions. HAM/TSP is an inflammatory manifestation of the central nervous system that may culminate in partial loss of lower limbs movements. ATLL is a type of non-Hodgkin's lymphoma that usually leads to death. This work aims to propose differential transcriptional profile, suggestive of the HTLV-1-associated pathologies, and to investigate the implications of deregulation on gene expression. A meta-analysis of ten publicly available microarray datasets was performed to identify differentially expressed genes (DEGs). Enriched KEGG pathways analysis was performed. Protein-protein interaction (PPI) networks, module extraction and gene hubs selection were implemented with STRING, MCODE and CytoHubba. A total of 907, 368 and 150 DEGs were identified for ATLL, HAM/TSP, and ASS respectively. The KEGG analysis identified "Cancer Pathways" and "Endocytosis" as ATLL-enriched pathways in the set of upregulated and downregulated DEGs respectively. No enriched pathways were identified for the full set of HAM/TSP and ASS DEGs. From the PPI networks generated by STRING, three modules were extracted for each clinical manifestation. Combining the results from MCODE and CytoHubba, five hub genes selected for each condition. Only ATLL presented differentially expressed micro-RNAs: hsa-mir-21, directly involved in the development of the disease and hsa-mir-6840, which is still poorly known. This study generated a database of candidate genetic markers and enriched pathways for the clinical status associated with HTLV-1 infection, facilitating the definition and understanding of prognostic therapeutic biomarkers.
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3
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FERNANDA VIDAL CARVALHO
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METABOLITE PROFILING, ANTIOXIDANT, CYTOXOTIC AND ANTIMICROBIAL ACTIVITIES OF Lepidium meyenii EXTRACTS
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Advisor : PAULO ROBERTO RIBEIRO DE JESUS
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COMMITTEE MEMBERS :
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ANDERSON DE SOUZA SANTANA
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PAULO ROBERTO RIBEIRO DE JESUS
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SILVIA LIMA COSTA
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Data: Jun 4, 2020
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Show Abstract
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INTRODUCTION: Lepidium meyenii is a plant that has several medicinal properties, however, the correlation between the metabolites and the biological activities tested in the plant is limited. OBJECTIVE: To characterize the metabolomic profile as well as to evaluate the antioxidant, antimicrobial and cytotoxic activities of extracts obtained from the dehydrated plant and its commercial products and to correlate the metabolomic profile with biological activities. MATERIALS AND METHODS: The extracts were obtained from the root of the plant and its commercial products by maceration in different organic solvents. The metabolomic profile was evaluated by mass performance coupled high chromatography (HPLC-MS) and gas chromatography coupled to mass spectrometry (GC-MS). The antioxidant activity was determined by the free radical sequestration method 2,2-diphenyl-1-picrylhydrazyl (DPPH) and total phenols will be quantified by the Folin-Ciocalteu method. Antimicrobial activity was evaluated against bacteria and yeast by broth microdilution method, cytotoxicity was evaluated against C6 cell line and astrocytes. RESULTS AND DISCUSSION: The antioxidant activity (IC50) ranged from 64.97 μg∙mL-1 for the ethyl acetate extract from the root of the dehydrated plant to 935.61 μg∙mL-1 for the hexane extract of the plant commercial product. The total phenol values ranged from 6.83 mg∙GAE∙g-1 for the ethanol extract at 49.83 mg∙GAE∙g-1 for the ethyl acetate extract, both extracts are form the commercial products. The ethanol extracts and ethyl acetate were the most active and had the highest antioxidant potential, in addition they also showed antimicrobial activity against M. luteus and B. cereus and antitumor activity against C6 cells, with no cytotoxicity to astrocytes. Seventy-six metabolites were identified in the extracts and among these, terpenes were the main metabolites responsible for antioxidant and cytotoxic activities and fatty acids for antibacterial activity. CONCLUSION: The metabolomic approach through the several analytical techniques allowed to correlate the obtained results being possible to identify the main bioactive compounds of L. meyenii related to the antioxidant, antimicrobial and antitumor activities of the plant.
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4
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TÁYLA DA CRUZ SANTOS PEREIRA
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METABOLOMIC ANALYSIS OF THE PLASMA OF INDIVIDUALS WITH OSTEONECROSIS SECONDARY TO SICKLE CELL DISEASE
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Advisor : PAULO ROBERTO RIBEIRO DE JESUS
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COMMITTEE MEMBERS :
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ANTONIO GILBERTO FERREIRA
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ELISANGELA VITORIA ADORNO
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PAULO ROBERTO RIBEIRO DE JESUS
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Data: Jul 29, 2020
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Show Abstract
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Sickle cell disease is the most common hemoglobinopathy in Brazil and constitutes a worldwide public health problem, with a great impact on the morbidity and mortality of the affected population. In patients with this pathology, the predominant joint clinical manifestation is osteonecrosis, which commonly progresses to terminal disease. Analyzes related to metabolites and unregulated metabolic pathways in complex systems have become a powerful tool for investigating metabolic processes, identifying potential biomarkers and unraveling metabolic reprogramming in various diseases. In this context, this work had as main objective to use a metabolic approach by nuclear magnetic resonance to identify biomarkers related to sickle cell disease, as well as to osteonecrosis secondary to sickle cell disease. Blood plasma from control subjects and patients with sickle cell disease with and without osteonecrosis was used. Based on the clinical stage of osteonecrosis, graduated using the modified Ficat and Arlet method, the samples were classified as early, intermediate and advanced stages of osteonecrosis. To obtain the uni and bidimensional spectra, a nuclear magnetic resonance equipment - Bruker Avance III of 14.1 Tesla - (600 MHz) was used. The optimization of the sample preparation and spectrum acquisition protocol involved the use of different pulse sequences; Zg, Zgpr, Lcipnf2, Noesypr 1D as well as, some protocols for protein precipitation with methanol. The identification of the metabolites was performed with the aid of the Chenomx NMR Suite 8.4 software. Processing and quantification were performed using the NMRProcflow software. Statistical analyzes were performed using MetaboAnalyst 3.0 software. Twenty-nine metabolites were identified by 1H NMR, including 12 amino acids, 9 organic acids, 4 lipids, 3 organic compounds, 1 carbohydrate. The metabolic profile of the blood plasma of the control group was significantly different from the sickle cell groups without osteonecrosis and the sickle cell group with osteonecrosis. Twenty metabolites with VIP score > 0.5 were responsible for the differences between samples in these groups. Sn-glycerol-3-phosphocholine and phenylalanine were the metabolites with the most promising results for future investigations of the sickle cell disease marker. 3-hydroxybutyrate and VLDL + HDL were the metabolites with the most promising results for future studies of osteonecrosis biomarker secondary to DF. The discriminant analysis also revealed that the plasma of patients with osteonecrosis secondary to DF at different stages of osteonecrosis has different metabolic profiles. In the peripheral blood plasma, fourteen metabolites with VIP score > 0.5 were responsible for this difference. Histidine and lactate were the metabolites with the most promising results for future investigations of osteonecrosis staging biomarkers secondary to sickle cell disease, especially for the early diagnosis of this pathology in peripheral blood plasma. Histidine, VLDL + HDL and citrate were the metabolites with the most promising results for future investigations of biomarker of advanced stages of osteonecrosis secondary to sickle cell disease in peripheral blood plasma. Fifteen metabolites with VIP score > 0.5 were classified as the set of metabolites responsible for the differences between the bone marrow plasma of individuals in different stages of osteonecrosis secondary to sickle cell disease. Citrate was the metabolite with the most promising result for future investigations of osteonecrosis staging biomarkers secondary to sickle cell disease, especially for the early diagnosis of this pathology in bone marrow plasma. Lactate was the metabolite with the most promising result for future investigations of biomarker of advanced stages of osteonecrosis secondary to sickle cell disease in bone marrow plasma. The topological analysis of metabolic pathways revealed a potential relationship between sickle cell disease and osteonecrosis secondary to DF and some metabolic pathways, namely; metabolism of nitrogen, pyruvate, thiamine, arginine and proline, phenylalanine; biosynthesis of aminoacyl t-RNA, phenylalanine, tyrosine and tryptophan, valine, leucine and isoleucine; glycolysis or gluconeogenesis; degradation of valine, leucine and isoleucine; synthesis and degradation of ketone bodies. These results provide strong evidence of a metabolic signature for individuals with sickle cell disease and osteonecrosis secondary to DF, defined mainly by a set of twenty metabolites with altered blood plasma levels including, proline, lactate, creatine + creatinine, 2-hydroxy -3-methylbutyric, phenylalanine, glycine, acetone, format, citrate, glucose, trimethylamione-n-oxide, histidine, tyrosine, azelate, 3-hydroxybutyrate, leucine + isoleucine, sn-glycerol-3-phosphocoline and acetate. It is hoped that these findings will help to guide future research in the area and may further elucidate the biochemical changes in sickle cell disease and osteonecrosis secondary to DF.
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5
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VICTOR DE BARROS SERRANO NEVES
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microRNA AS BIOMARKERS FOR THE IDENTIFICATION OF INDIVIDUALS WITH PRE-DIABETES AND EARLY DIAGNOSIS OF DIABETES.
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Advisor : SIMONE GARCIA MACAMBIRA
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COMMITTEE MEMBERS :
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CAROLINA KYMIE VASQUES NONAKA
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GLÓRIA REGINA FRANCO
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SIMONE GARCIA MACAMBIRA
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Data: Aug 4, 2020
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Show Abstract
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Introduction: Diabetes Mellitus (DM) is a chronic disease developed by defects in insulin signaling, secretion or production. Prediabetes is a asymptomatic state in which subjects fasting glucose is between 100-120mg/dl and glycated hemoglobin is at the range of 5,7-6,5%. Defined before as a latent state it is now known that is a risk factor for nephro and neuropathy development and also increase in β-cell destruction. In this context, becomes necessary the identification of biological markers that presents a disrupted expression due to the pathological state thus contributing to an early diagnostic. miRNAs are non-coding RNA considered important in the pos-translation regulation of genes. They are pointed out as potential biomarkers, since their expression level becomes altered due to the development or aggravation of many diseases such as diabetes, cancer and schizophrenia. The present study aimed to identify an expression microRNA (miRNA) profile capable of confer early prediabetes diagnostic. Publicly available transcriptome was analyzed through bioinformatic tools. Results: After screening conducted at NCBI GEO datasets, one transcriptome matched our inclusion criteria. From which thirty-three miRNA were significatively upregulated in prediabetic subjects versus control (FC>1,5 p-valor≤ 0,05) and two were upregulated in the diabetix cersus control group (FC>1,5 p-valor≤ 0,05) A miRNA-mRNA network was created using the upregulated miRNA and its regulated targets in the validation transcriptome using the Cytoscaped software. Five miRNAs presented a greater centrality score from the miRNA-mRNA network. In which two (miR-93 and Let-7a) had better values for sensibility and specificity (AUC =0,829 e 0,824 respectively). Conclusion: The five miRNA identified are involved in several intracellular pathways related to insulin resistance and destruction of β-pancreatic cells and are differentially modulated in the transcriptome analyzed in this study, which can be identified as promising exploratory biomarkers for the early diagnosis of DM2.
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NATAN RODRIGUES SANTANA DA HORA
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Metabolite profiling, antioxidant, cytotoxic and antimicrobial activities of extracts of the stigma of Zea mays L.
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Advisor : PAULO ROBERTO RIBEIRO DE JESUS
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COMMITTEE MEMBERS :
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DÉBORAH YARA ALVES CURSINO DOS SANTOS
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LOURDES CARDOSO DE SOUZA NETA
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PAULO ROBERTO RIBEIRO DE JESUS
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Data: Nov 16, 2020
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Show Abstract
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INTRODUCTION: The stigma of corn is the female flower of Zea mays L., well known for traditional Chinese medicine. The scientific literature reports its pharmacological activities, but there are few scientific studies that perform a global chemical mapping, and correlate metabolites with the investigated biological activities, by means of a metabolomic. OBJECTIVE: To characterize the metabolomic profile and the antioxidant, antimicrobial and cytotoxic activities of extracts of the stigma of Zea mays L. in natura and its commercial product. MATERIALS AND METHODS: The extracts were obtained from the stigma of corn, by maceration in different solvents, such as hexane, ethyl acetate and ethanol. The antioxidant activity was provided by the 2,2-diphenyl-1-picryl-hydrazyl free radical sequestration method (DPPH) and the total phenols were quantified by the Folin-Ciocalteu method. The antimicrobial activity was evaluated by the microdilution method in broth against Gram-positive and Gram-negative bacteria, besides non filamentous fungi. The cytotoxicity was evaluated against a tumoral line of mouse glioma (C6), through the analysis of the cellular viability evaluated by the method of 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium (MTT) bromide reduction. The metabolic profile was evaluated by high efficiency liquid chromatography coupled to mass spectrometry (CLAE-EM) and gas chromatography coupled to mass spectrometry (CG-EM). In the univariate analysis, analysis of variance (ANOVA), volcano plotting and correlation analysis were used. In multivariate analysis the methods were PLS-DA, VIP and heat map. In general, the ethanolic extracts present better antioxidant activity and higher values of total phenols. RESULTS AND DISCUSSION: The antioxidant activity (IC50) varied from 77.44 μg.mL-1 for the ethanolic extract of reproductive stage 1 (E1R1) to 950, 31 μg.mL-1 for the hexanic extract of commercial product (CH). Total phenol values ranged from 12, 95 mg.EAG.g-1 for ethanolic extract of commercial product to 46, 14 mg.EAG.g-1 for ethanolic extract of reproductive stage 1. The extract with ethyl acetate reproductive stage 1 (EAR1) showed better antibacterial activity against Bacillus subtilis and Pseudomonas aeruginosa (500 μg.mL-1). The EAR1 extract presented higher cytotoxic activity, because it was able to reduce the viability of the C6 tumor lineage (100 μg.mL-1 ) by 40.74%. Thirty metabolites were identified. The organic acids, carbohydrates and a saponin have greater correlation with the antioxidant activity; cytotoxic and antimicrobial. CONCLUSION: Although some studies present the biological activities of Zea Mays L. extracts, this was the pioneer in presenting an overall metabolic evaluation of extracts with different polarities and correlating the results of antioxidant, cytotoxic and antitumicrobial activities with the metabolites located in the extracts. In addition, the influence of solvents, phenological stages and natural and commercial nature on the variation of the metabolome were identified and suggesting the main metabolites responsible for influencing greater biological activities.
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Thesis |
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PÂMELA SANTANA DALTRO
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"Evaluation of the therapeutic potential of mesenchymal cells and the conditioned medium in the treatment of cardiac dysfunctions resulting from obesity and type 2 diabetes mellitus."
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Advisor : SIMONE GARCIA MACAMBIRA
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COMMITTEE MEMBERS :
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ELISALVA TEIXEIRA GUIMARÃES
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GYSELLE CHRYSTINA BACCAN
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LUCIANA SOUZA DE ARAGAO FRANCA
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NATALIA MACHADO TAVARES
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SIMONE GARCIA MACAMBIRA
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Data: Feb 14, 2020
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Show Abstract
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Eating habits with high fat levels and sedentary lifestyle are triggers factors for obesity, type 2 diabetes (DM2), and heart failure. Mesenchymal stem cells (MSC) arise as a therapeutic tool capable of improving cardiovascular disease, but also of other degenerative conditions, due to its regenerative effect induced by its paracrine action. Based on this, the factors secreted in the conditioned medium (CM) of this cells are also investigated in tissue regeneration. Therefore, this study aimed to evaluate the therapeutic potential of MSC and its CM in the treatment of cardiac complications in an experimental model of obesity and diabetes induced by high fat diet (HFD). Cardiac, murinometric and biochemistry evaluations were done at different periods such as pre-indcution, pos-induction and pos-treatment. After 36 weeks of HFD administration this diet were replaced by the standard diet and then mice were treated with MSC, MC and DMEM (vehicle). Cardiac function was assessed by electrocardiography, echocardiography, and treadmill test. Metabolic dysfunction was assessed through measurements of body weight and biochemical parameters. Molecular mechanisms of action of the treatment were investigated using qRT-PCR in cardiac tissue. The presence of cardiac fibrosis were evaluated by histopathological analysis. The characterization of MC by protein array showed the presence of 19 proteins including cytokines and growth factors. Mice fed HFD developed cardiac arrhythmias, expression alterations of cardiac genes and myocardial fibrosis, reflecting in the reduction of physical activity due to obesity and DM2. Administration of MSC or CM improved the severity arrhythmias and recovery exercise capacity. The first part of this study the improvement of cardiac function was in agreement with the expression normalization of GATA4, conexin 43 e COL1A1 genes in HFD mice treated with MSC ou MC. By other side the gene expression of troponin I, adiponectin, TGFβ, PPARγ, IGF-1, SOCS3, MMP9 and TIMP1 were normalized only after MSC treatment, but not with CM. Moreover, MSC or CM administration reduced the intensity of cardiac fibrosis. In order to elucidate the significant improvement achieved by MSC, in the second stage of this study, the investigation on the molecular mechanisms involved in this therapeutic effect. The expression of genes related to tissue remodeling (SPARC and CTGF), apoptosis (SMAD7 and PDCD4), inflammation (CCl2 and CHI3I3), as well as cell survival and proliferation (PTEN and STAT3) by qRT-PCR were investigated. High levels of gene expression of SMAD7, PDCD4, SPARC, CTGF, CCL2, STAT3 and PTEN were detected only in the MSC-treated group, whereas in CHI3I3 and NPPA gene expression was reduced in both MSC-treated and DMEM-treated mice. The results suggest that MSC and MC have a therapeutic effect on cardiac alterations due to obesity and T2DM, being the factors related to the development of fibrosis, apoptosis and cell survival modulated, demonstrating the relevance of the factors secreted by MSC reinforcing their action paracrine.
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2
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JÉSSICA LAIS ALMEIDA DOS SANTOS
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HTLV-1 INFECTION AND HAM/TSP PROGRESSION: CONTRIBUTION OF HUMAN AND VIRAL MOLECULAR MARKERS
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Advisor : ALINE CRISTINA ANDRADE MOTA MIRANDA MASCARENHAS
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COMMITTEE MEMBERS :
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ALINE CRISTINA ANDRADE MOTA MIRANDA MASCARENHAS
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JOANA PAIXAO MONTEIRO CUNHA
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GISELLE CALASANS DE SOUZA COSTA
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MARIA FERNANDA DE CASTRO AMARANTE
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MARIA LUIZA SARAIVA PEREIRA
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Data: Dec 16, 2020
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Show Abstract
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Human T-cell lymphotropic virus type 1 (HTLV-1) is a sexually transmitted human retrovirus. Its main clinical manifestations are HTLV-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) and T-Cell Leukemia / Lymphoma of the Adult (ATLL). HAM/TSP is an inflammatory disorder of the central nervous system that can result in partial loss of lower limb movements. Although many events aspects that lead to the disease development are unclear, the host's immune response, especially the cellular response triggered by specific CD8+ T cells, is recognized as a crucial event. The objective of this work is to investigate molecular markers in the virus and in the host that may be related to the manifestation of the disease, mainly HAM/TSP. In Chapter I we have search for viral markers, with regard to the differential epitope presentation, for the different clinical profiles. We carried out a survey (Genbank) of 46 HTLV-1 complete genomes, and separated the coding regions of Tax, HBZ, p12, gp21 and gp46 proteins. Such gene regions were translated and evaluated for the presence of SNPs (Single Nucleotide Polymorphism). These SNPs were represented in AA sequences that were submitted to the IEDB (Immune Epitope Database Analysis Resource) to predict linear epitopes linking HLA-I molecules. It was possible to identify 7 “protein alleles” for the gp21 protein, 23 for gp46, 20 for HBZ, 13 for the Tax protein, and 15 for the p12 protein, all distributed among individuals ASS, fHAM/TSP (Familiar), sHAM/TSP (Sporadic) and ATLL. In prediction results, more than 15,741 epitopes were identified for p12, the lowest amount of predicted epitopes and more than 50,000 for Tax, with the highest amount of predicted epitopes. The p12 protein had the highest proportion of specific epitopes, also followed by the Tax protein. The HBZ protein had the lowest percentages in all specificity ranges. The results found for structural proteins gp46 and gp21 were similar. There was no specificity/exclusivity of HLA alleles among proteins, "protein alleles" and/or host clinical profiles. Each protein presented an HLA allele as being the most frequent among the “protein alleles”, with no similarity in this occurrence. Finally, the HLA * A 32:01 allele was cited as the most frequent in all proteins, and the gp21 and HBZ proteins showed similar profiles with regard to the occurrence of the most frequent HLA alleles. The HAM/TSP clinical profile showed the highest number of molecular variations among the studied proteins: there were 42 “protein alleles” against 19 of individuals with ATLL and 16 of ASS individuals (Non-HAM/TSP). The affinity findings revealed that 9 epitopes showed differences in affinity to HLA molecules, 6 of them were associated with ATLL individuals, 4 with sHAM/TSP individuals and 2 with ASS individuals. We conclude that there is no epitope presentation profile that is associated with the host clinical status, since there was great similarity in the HLA alleles and in the predicted epitopes positions among the “protein alleles”. However, we have identified important molecular variations in the epitopes prediction, especially in the genomes of individuals with ATLL and HAM/TSP. In Chapter II, we looked for markers in the host, in a group of infected individuals (HAM/TSP and asymptomatic) (N = 44). For this, we have performed the determination of Exoma through the Illumina Platform and using a chip for 551,004 SNPs. The overall genotyping rate of samples was 0.997001, with a loss of 35,163 SNPs (~ 6%), identified 515,841 variants. The ancestral determination revealed a proportionality of genetic contribution more marked for the African origin in the studied population. We observed a predominance of women in the case group, as has already been documented in the literature. The average age of infected individuals was 59 years (27-89 years), with an average proviral load of 55,253.41/106 cells. Among the SNPs identified, four of them stood out regarding the allele frequencies in the case and control groups, and they are: rs2857596_C, rs7917905_A, rs1265564_C and rs376863_A. After multivariate regression analysis, adjusted for ancestry, only the SNPs “rs1265564” (p = 7.2 * 10-4) and “rs376863” (p = 1.25 * 10-3) are associated with the outcome. The SNP rs1265564, was identified in the gene that codes for the CUX-2 protein that is associated with the repair of oxidized DNA by the action of reactive oxygen species produced in neurons. The initial four SNPs show to be in linkage disequilibrium with other SNPs, but none of those already described in the literature and cited in this work. We suggest a thorough search for the SNPs indicated in this work, as well as the association of host molecular markers with viral markers, as a way of understanding the process of infection and disease manifestation as a result of a complex and successful integration.
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