CLAUDIA PINTO MARQUES SOUZA DE OLIVEIRA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Gastroenterologia, Faculdade de Medicina - Docente
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
178 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 178
- Ability of a Combined FIB4/miRNA181a Score to Predict Significant Liver Fibrosis in NAFLD Patients(2021) LIMA, Rodrigo Vieira Costa; STEFANO, Jose Tadeu; MALTA, Fernanda de Mello; PINHO, Joao Renato Rebello; CARRILHO, Flair Jose; ARRESE, Marco; OLIVEIRA, Claudia P.Liver biopsy is the gold standard for assessing fibrosis, but there is a need to seek non-invasive biomarkers for this purpose. The aim of this study was to evaluate the correlation between the serum levels of the microRNAs miR-21, miR-29a, miR-122, miR-155 and miR-181a and the phenotypic expression of NAFLD. A cross-sectional study was carried out on 108 NAFLD patients diagnosed by liver biopsy. FIB-4 and NAFLD fibrosis scores were calculated. The comparison between the distributions of microRNA values according to the presence or absence of histological fibrosis (F2-F4) was performed. A multivariate logistic regression analysis was performed to build a score for predicting fibrosis using FIB-4 and Ln (miR-181a) as independent variables. Only miR-181a showed a statistical difference between patients with significant liver fibrosis (>F2) and those without (F0-F1) (p = 0.017). FIB-4 revealed an AUC on the ROC curve of 0.667 to predict clinically significant fibrosis (F2-F4). When assessed using the score in association with Ln (miR-181a), there was an improvement in the ROC curve, with an AUC of 0.71. miR-181a can be used as a non-invasive method of predicting fibrosis in NAFLD, and an association with FIB-4 has the potential to increase the accuracy of each method alone.
- Synbiotic Supplementation Modulates Gut Microbiota, Regulates beta-Catenin Expression and Prevents Weight Gain in ob/ob Mice: Preliminary Findings(2022) DUARTE, Sebastiao Mauro B.; STEFANO, Jose Tadeu; FRANCO, Lucas A. M.; MARTINS, Roberta C.; MORAES, Bruna D. G. C.; BARBEIRO, Denise Frediani; OLIVEIRA, Nathalia; NERI, Junia Marielle Teixeira Rodrigues; COGLIATI, Bruno; VANNI, Denise Siqueira; SABINO, Ester C.; CARRILHO, Flair J.; OLIVEIRA, Claudia P.Background: Obesity is one of the main health problems in the world today, and dysbiosis seems to be one of the factors involved. The aim of this study was to examine the impact of synbiotic supplementation on obesity and the microbiota in ob/ob mice. Twenty animals were divided into four groups: obese treated (OT), obese control (OC), lean treated (LT) and lean control (LC). All animals received a standard diet for 8 weeks. The treated groups received a synbiotic (Simbioflora-Invictus Farmanutricao Ltd., Sao Paulo, Brazil) in water, while the nontreated groups received only water. After 8 weeks, all animals were sacrificed, and gut tissue and stool samples were collected for mRNA isolation and microbiota analysis, respectively. beta-Catenin, occludin, cadherin and zonulin in the gut tissue were analyzed via RT-qPCR. Microbiome DNA was extracted from stool samples and sequenced using an Ion PGM Torrent platform. Results: Synbiotic supplementation reduced body weight gain in the OT group compared with the OC group (p = 0.0398) and was associated with an increase in Enterobacteriaceae (p = 0.005) and a decrease in Cyanobacteria (p = 0.047), Clostridiaceae (p = 0.026), Turicibacterales (p = 0.005) and Coprococcus (p = 0.047). On the other hand, a significant reduction in Sutterella (p = 0.009) and Turicibacter (p = 0.005) bacteria was observed in the LT group compared to the LC group. Alpha and beta diversities were different among all treated groups. beta-Catenin gene expression was significantly decreased in the gut tissue of the OT group (p <= 0.0001) compared to the other groups. No changes were observed in occludin, cadherin or zonulin gene expression in the gut tissue. Conclusions: Synbiotic supplementation prevents excessive weight gain, modulates the gut microbiota, and reduces beta-catenin expression in ob/ob mice.
conferenceObject Integrative Molecular Profiling of Non-Alcoholic Steatohepatitis-Related Hepatocellular Carcinoma(2018) TORRECILLA, Sara; PINYOL, Roser; WEI-QIANG, Leow; WANG, Huan; MOEINI, Agrin; MONTIRONI, Carla; BASSAGANYAS, Laia; ANDREU-OLLER, Carmen; OLIVEIRA, Claudia P. M. S.; ALVES, Venancio A. F.; LACHENMAYER, Anja; ROESSLER, Stephanie; MINGUEZ, Beatriz; SCHIRMACHER, Peter; BOFFETTA, Paolo; DUFOUR, Jean-Francois; THUNG, Swan N.; UZILOV, Andrew; CARRILHO, Flair Jose; CHANG, Charissa Y.; SIA, Daniela; LLOVET, Josep M.- NLRP3 inflammasome as a target of berberine in experimental murine liver injury: interference with P2X(7) signalling(2016) VIVOLI, Elisa; CAPPON, Andrea; MILANI, Stefano; PIOMBANTI, Benedetta; PROVENZANO, Angela; NOVO, Erica; MASI, Alessio; NAVARI, Nadia; NARDUCCI, Roberto; MANNAIONI, Guido; MONETI, Gloriano; OLIVEIRA, Claudia P.; PAROLA, Maurizio; MARRA, FabioBerberine (BRB) is commonly used in herbal medicine, but its mechanisms of action are poorly understood. In the present study, we tested BRB in steatohepatitis induced by a methionine-and choline-deficient (MCD) diet, in acute acetaminophen intoxication and in cultured murine macrophages. BRB markedly improved parameters of liver injury and necroinflammation induced by the MCD diet, although increased mortality was observed by mechanisms independent of bacterial infections or plasma levels of BRB. The MCD diet induced up-regulation of all components of the NLRP3 (NACHT, LRR and PYD domain-containing protein 3) inflammasome, and increased hepatic levels of mature IL-1 beta (interleukin 1 beta). All of these parameters were significantly reduced in mice treated with BRB. In mice administered an acetaminophen overdose, a model dependent on inflammasome activation, BRB reduced mortality and ALT (alanine aminotransferase) elevation, and limited the expression of inflammasome components. In vitro, LPS (lipopolysaccharide)-induced activation of NLRP3 inflammasome in RAW264.7 murine macrophages was markedly decreased by pre-incubation with BRB. BRB significantly limited the activation of the purinergic receptor P2X(7), involved in the late phases of inflammasome activation. Upon P2X(7) knockdown, the ability of BRB to block LPS-induced secretion of IL-1 beta was lost. These data indicate that administration of BRB ameliorates inflammation and injury in two unrelated murine models of liver damage. We demonstrate for the first time that BRB interferes with activation of the NLRP3 inflammasome pathway in vivo and in vitro, through a mechanism based on interference with activation of P2X(7), a purinergic receptor involved in inflammasome activation.
- Metabolic signatures across the full spectrum of non-alcoholic fatty liver disease(2022) MCGLINCHEY, Aidan J.; GOVAERE, Olivier; GENG, Dawei; RATZIU, Vlad; ALLISON, Michael; BOUSIER, Jerome; PETTA, Salvatore; OLIVIERA, Claudia de; BUGIANESI, Elisabetta; SCHATTENBERG, Jorn M.; DALY, Ann K.; HYOTYLAINEN, Tuulia; ANSTEE, Quentin M.; ORESIC, MatejBackground & Aims: Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disease with potentially severe complications including cirrhosis and hepatocellular carcinoma. Previously, we have identified circulating lipid signatures associating with liver fat content and non-alcoholic steatohepatitis (NASH). Here, we develop a metabolomic map across the NAFLD spectrum, defining interconnected metabolic signatures of steatosis (non-alcoholic fatty liver, NASH, and fibrosis). Methods: We performed mass spectrometry analysis of molecular lipids and polar metabolites in serum samples from the European NAFLD Registry patients (n = 627), representing the full spectrum of NAFLD. Using various univariate, multivariate, and machine learning statistical approaches, we interrogated metabolites across 3 clinical perspectives: steatosis, NASH, and fibrosis. Results: Following generation of the NAFLD metabolic network, we identify 15 metabolites unique to steatosis, 18 to NASH, and 15 to fibrosis, with 27 common to all. We identified that progression from F2 to F3 fibrosis coincides with a key pathophysiological transition point in disease natural history, with n = 73 metabolites altered. Conclusions: Analysis of circulating metabolites provides important insights into the metabolic changes during NAFLD progression, revealing metabolic signatures across the NAFLD spectrum and features that are specific to NAFL, NASH, and fibrosis. The F2-F3 transition marks a critical metabolic transition point in NAFLD pathogenesis, with the data pointing to the pathophysiological importance of metabolic stress and specifically oxidative stress. Clinical Trials registration: The study is registered at Clinicaltrials.gov (NCT04442334). Lay summary: Non-alcoholic fatty liver disease is characterised by the build-up of fat in the liver, which progresses to liver dysfunction, scarring, and irreversible liver failure, and is markedly increasing in its prevalence worldwide. Here, we measured lipids and other small molecules (metabolites) in the blood with the aim of providing a comprehensive molecular overview of fat build-up, liver fibrosis, and diagnosed severity. We identify a key metabolic 'watershed' in the progression of liver damage, separating severe disease from mild, and show that specific lipid and metabolite profiles can help distinguish and/or define these cases. (c) 2022 The Author(s).
conferenceObject IMPACT OF BASELINE STEATOSIS AND SEVERITY OF ISCHAEMIA-REPERFUSION INJURY IN PREDICTING HCV RECURRENCE POST TRANSPLANTATION(2013) JOSHI, D.; QUAGLIA, A.; HEATON, N.; OLIVEIRA, C.; ALVARES-DA-SILVA, M.; SANCHEZ-FUEYO, A.; AGARWAL, K.; HENEGHAN, M. A.Introduction: Recurrent HCV (rHCV) infection is universal post-transplantation and is associated with significant morbidity and mortality. HCV recurrence is influenced by a combination of donor, recipient, viral and immunosuppressive factors. Methods: We hypothesised that baseline steatosis and the severity of ischaemia–reperfusion (IR) injury can predict slow and rapid fibrosis progression at 12 months. IR injury and steatosis was graded as none (0) – severe (3). Predictive ability was assessed using area under the curve generated by receiver operator characteristic analysis (AUROC). Results: During January 2000 and January 2011, 303 patients (> 18 years) with chronic HCV underwent primary liver transplantation at King’s College Hospital, London. Of these 303 patients, 141 had an IR liver biopsy performed. Median age at transplant was 53 years (19–67), median donor age was 46 years (15–85). Median IR grade was 1 (0–3) and median grade of steatosis was 0 (0–3). Median peak AST was 1218 IU/ml (236–5045). Patients were followed up for 46 months (4–143). Patients were then divided into groups according to the result of their 12 month biopsy result (slow fibrosis progression rate – F < 2 Ishak; fast fibrosis progression rate – F≥2). Patients with slow fibrosis progression at 12 months were male, had younger donors, and a longer time to F≥4 post-LT (p < 0.04). Moderate/severe IR injury was a poor predictor of fast fibrosis progression (AUROC 0.54, 95%CI 0.36–0.71, p=0.67), although the presence of steatosis along with moderate/severe IR injury was a sensitive predictor of F≥2 at 12 month (0.79, 0.66–0.89, p < 0.0001). Patients with the combination of steatosis and moderate/severe IR injury were more likely to develop F≥2 at 12 months (86% vs. 30%, p < 0.0001). Conclusion: The combination of steatosis and moderate/severe degree of IR injury appears to correctly identify patients with rapid fibrosis of rHCV in the post-transplant setting.- MTP-493G/T gene polymorphism is associated with steatosis in hepatitis C-infected patients(2012) SIQUEIRA, E. R. F.; OLIVEIRA, C. P. M. S.; CORREA-GIANNELLA, M. L.; STEFANO, J. T.; CAVALEIRO, A. M.; FORTES, M. A. H. Z.; MUNIZ, M. T. C.; SILVA, F. S.; PEREIRA, L. M. M. B.; CARRILHO, F. J.The reduction of hepatic microsomal transfer protein (MTP) activity results in fatty liver, worsening hepatic steatosis and fibrosis in chronic hepatitis C (CHC). The G allele of the MTP gene promoter, -493G/T, has been associated with lower transcriptional activity than the T allele. We investigated this association with metabolic and histological variables in patients with CHC. A total of 174 untreated patients with CHC were genotyped for MTP -493G/T by direct sequencing using PCR. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and had current and past daily alcohol intake lower than 100 g/week. The sample distribution was in Hardy-Weinberg equilibrium. Among subjects with genotype 1, 56.8% of the patients with fibrosis grade 3+4 presented at least one G allele versus 34.3% of the patients with fibrosis grade 1+2 (OR = 1.8; 95%CI = 1.3-2.3). Logistic regression analysis with steatosis as the dependent variable identified genotypes GG+GT as independent protective factors against steatosis (OR = 0.4, 95%CI = 0.2-0.8; P = 0.01). The results suggest that the presence of the G allele of MTP -493G/T associated with lower hepatic MTP expression protects against steatosis in our CHC patients.
- Nutrition and Physical Activity in Nonalcoholic Fatty Liver Disease(2016) OLIVEIRA, Claudia P.; SANCHES, Priscila de Lima; ABREU-SILVA, Erlon Oliveira de; MARCADENTI, AlineNonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and it is associated with other medical conditions such as diabetes mellitus, metabolic syndrome, and obesity. The mechanisms of the underlying disease development and progression are not completely established and there is no consensus concerning the pharmacological treatment. In the gold standard treatment for NAFLD weight loss, dietary therapy, and physical activity are included. However, little scientific evidence is available on diet and/or physical activity and NAFLD specifically. Many dietary approaches such asMediterranean and DASH diet are used for treatment of other cardiometabolic risk factors such as insulin resistance and type-2 diabetes mellitus (T2DM), but on the basis of its components their role in NAFLD has been discussed. In this review, the implications of current dietary and exercise approaches, including Brazilian and other guidelines, are discussed, with a focus on determining the optimal nonpharmacological treatment to prescribe for NAFLD.
conferenceObject Polymorphisms in the cyclooxygenase-2 (COX-2) gene, vascular endothelial growth factor (VEGF) and methylenetetrahydrofolate reductase (MTHFR) gene in patients with hepatocellular carcinoma and hepatitis C virus infection(2017) CARVALHO, S. C. R. D.; VASCONCELOS, L. R. S.; CARMO, R. F.; AROUCHA, D. C. B. L.; TOMITAO, M. T.; RIBEIRO JR., U.; PEREIRA, L. M. M. B.; OLIVEIRA, C. P.; CARRILHO, F. J.- Aerobic Physical Exercise Improves Exercise Tolerance and Fasting Glycemia Independent of Body Weight Change in Obese Females(2021) BOSCHETTI, Daniela; MULLER, Cynthia R.; AMERICO, Anna Laura V.; VECCHIATTO, Bruno; MARTUCCI, Luiz Felipe; PEREIRA, Renata O.; OLIVEIRA, Claudia P.; FIORINO, Patricia; EVANGELISTA, Fabiana S.; AZEVEDO-MARTINS, Anna KareninaObesity is associated with increased risk of several chronic diseases and the loss of disease-free years, which has increased the focus of much research for the discovery of therapy to combat it. Under healthy conditions, women tend to store more fat in subcutaneous deposits. However, this sexual dimorphism tends to be lost in the presence of comorbidities, such as type 2 diabetes mellitus (T2DM). Aerobic physical exercise (APE) has been applied in the management of obesity, however, is still necessary to better understand the effects of APE in obese female. Thus, we investigated the effect of APE on body weight, adiposity, exercise tolerance and glucose metabolism in female ob/ob mice. Eight-weeks-old female wild-type C57BL/6J and leptin-deficient ob/ob mice (Lep(ob)) were distributed into three groups: wild-type sedentary group (Wt; n = 6), leptin-deficient sedentary group (Lep(ob)S; n = 5) and leptin-deficient trained group (Lep(ob)T; n = 8). The Lep(ob)T mice were subjected to 8 weeks of aerobic physical exercise (APE) at 60% of the maximum velocity achieved in the running capacity test. The APE had no effect in attenuating body weight gain, and did not reduce subcutaneous and retroperitoneal white adipose tissue (SC-WAT and RP-WAT, respectively) and interscapular brown adipose tissue (iBAT) weights. The APE neither improved glucose intolerance nor insulin resistance in the Lep(ob)T group. Also, the APE did not reduce the diameter or the area of RP-WAT adipocytes, but the APE reduced the diameter and the area of SC-WAT adipocytes, which was associated with lower fasting glycemia and islet/pancreas area ratio in the Lep(ob)T group. In addition, the APE increased exercise tolerance and this response was also associated with lower fasting glycemia in the Lep(ob)T group. In conclusion, starting APE at a later age with a more severe degree of obesity did not attenuate the excessive body weight gain, however the APE promoted benefits that can improve the female health, and for this reason it should be recommended as a non-pharmacological therapy for obesity.