LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental

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O Laboratório de Gastroenterologia e Clínica Experimental é ligado ao Departamento de Gastroenterologia da Faculdade de Medicina da Universidade de São Paulo (FMUSP).

Linhas de pesquisa: doenças inflamatórias, autoimunes e funcionais do intestino: genética, etiopatogenia, imunologia e epidemiologia, doença celíaca: imunologia e epidemiologia; quantificação do glúten em alimentos; nano partículas e micropartículas em processo inflamatório intestinal; modelos experimentais de colite; hepatites virais, cirroses e suas complicações e hepatopatias; doença hepática gordurosa; obesidade; estresse oxidativo e síndrome metabólica.

Site oficial: http://limhc.fm.usp.br/portal/lim07-laboratorio-de-gastroenterologia-clinica-e-experimental/

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article 2 Citação(ões) na Scopus
Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Immunohistochemical Assessment of Markers of Cancer Cell Metabolism
(2022) GRANJA, S. C.; LONGATTO-FILHO, A.; CAMPOS, P. B. De; OLIVEIRA, C. P.; STEFANO, J. T.; MARTINS-FILHO, S. N.; CHAGAS, A. L.; HERMAN, P.; D'ALBUQUERQUE, L. C.; ALVARES-DA-SILVA, M. Reis; CARRILHO, F. J.; BALTAZAR, F.; ALVES, V. A. F.
Introduction: Hepatocellular carcinoma (HCC) has been associated to non-alcoholic fatty liver disease (NAFLD). We sought to investigate the immunoexpression of several glycolytic metabolism-associated markers in patients with HCC associated to NAFLD and associate these factors to their clinical-pathological characteristics. Methods: We evaluated 35 HCC specimens from 21 patients diagnosed with non-alcoholic steatohepatitis (NASH) undergoing liver resection (12 patients), liver transplantation (8 patients), or both (1 patient). Histological features, clinical aspects, demographic and biochemical data, as well as the immunohistochemical reactivity for monocarboxylate transporters 1, 2, and 4; their chaperone CD147; carbonic anhydrase IX; and glucose transporter-1 (GLUT1) were assessed. Results: Metabolic-associated cirrhosis was present in 12 of the 21 patients (8 child A and 4 child B scores). From 9 patients without cirrhosis, 3 presented NASH F3 and 6 NASH F2. Sixteen (76%) had diabetes mellitus, 17 (81%) arterial hypertension, and 19 (90%) body mass index above 25 kg/m2; 8 (38%) had dyslipidemia. From 35 nodules, steatosis was found in 26, ballooning in 31 nodules, 25 of them diagnosed as steatohepatitic subtype of HCC. MCT4 immunoexpression was associated with extensive intratumoral fibrosis, advanced clinical stages, and shorter overall survival. GLUT1 was noticeable in nodules with extensive intratumoral steatosis, higher intratumoral fibrosis, and advanced clinical stages. Immunohistochemical expression of the metabolic biomarkers MCT4 and GLUT1 was higher in patients with Barcelona-clinic liver cancer B or C. GLUT1 correlated with higher degree of steatosis, marked ballooning, intratumoral fibrosis, and higher parenchymal necroinflammatory activity. Conclusion: Our data indicate that the expression of the glycolytic phenotype of metabolic markers, especially GLUT1 and MCT4, correlates with a more severe course of HCC occurring in NASH patients.
article 0 Citação(ões) na Scopus
Potential Beneficial Effect of Rifaximin in the Prevention of Hepatocellular Carcinoma through the Modulation of the Microbiota in an Experimental Model of Non-alcoholic Fatty Liver Disease
(2023) FERRARI, J. Tonin; GUERREIRO, G. Tayguara Silveira; LONGO, L.; SILVEIRA, T. R. D.; CERSKI, C. T. Schmidt; TOZAWA, E.; OLIVEIRA, C. P.; ÁLVARES-DA-SILVA, M. R.; URIBE-CRUZ, C.
Summary Aim. To evaluate the effects of rifaximin through microbiota modulation in a model of hepatocellular carcinoma secondary to non-alcoholic fatty liver disease. Methods. Three groups of 8 adult male Sprague-Dawley rats each were divided as follows: the HCC group: rats fed a high-fat and choline-deficient diet plus diethylnitrosamine as a carcinogen, the hepatocellular carcinoma treated group: rats fed a high-fat and choline-deficient diet plus diethylnitrosamine and treated with rifaximin and the control group: animals fed standard diet and water. The rats were euthanized after 16 weeks. We performed analyses of liver pathology for non-alcoholic fatty liver disease severity and cancer grading, gene expression in intestinal and hepatic tissues and fecal microbiota. Results. All animals in the hepatocellular carcinoma group had non-alcoholic fatty liver disease and developed hepatocellular carcinoma lesions. Rifaximin animals showed less intense non-alcoholic fatty liver disease (assessed by non-alcoholic fatty liver disease activity score [NAS]) compared to the hepatocellular carcinoma group. Both the hepatocellular carcinoma and hepatocellular carcinoma + rifaximin groups showed areas of fibrosis as assessed by picrosirius red. Three animals in the rifaximin group did not develop cancerous lesions. Gut microbiota analyses revealed differences in diversity and composition in the control group vs hepatocellular carcinoma and rifaximin groups. Twelve differentially abundant genera were identified between the hepatocellular carcinoma and rifaximin groups. In the rifaximin group, gene expression of intestinal tight junctions decreased. Conclusions. In a rodent model of non-alcoholic fatty liver disease-related hepatocellular carcinoma, rifaximin reduces the histological severity of non-alcoholic fatty liver disease and the occurrence of hepatocellular carcinoma, probably by modulating the gut microbiota independently of markers of intestinal permeability.
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Lung ECM composition, its influence factors and transcriptomics in the lungs of severe COVID-19.
(2023) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; NASCIMENTO, Ellen Toledo Do; BRITO, Jose Mara De; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; PINHO, Joao Renato Rebello; PEREIRA, Roberta Verciano; MONTEIRO, Renata Aparecida De Almeida; DUARTE NETO, Amaro Nunes; SALDIVA, Paulo Hilario Nascimento; SILVA, Luiz Fernando Ferraz Da; DOLHNIKOFF, Marisa; MAUAD, Thais
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YSTRATEGIES TO ELIMINATE HEPATITIS C VIRUS INFECTION IN THE AMERICAS
(2023) DIAZ, Luis Antonio; GARCIA, Sergio; AYARES, Gustavo; URIBE, Javier; IDALSOAGA, Francisco; FUENTEALBA, Jose Miguel; FUENTES-LOPEZ, Eduardo; MEDEL, Maria Paz; RAMIREZ-CADIZ, Carolina A.; KHAN, Rayan; LAZO, Mariana; FERRECCIO, Catterina; MENDIZABAL, Manuel; DIRCHWOLF, Melisa Melisa; SALAZAR, Patricia Guerra; OLIVEIRA, Claudia P. M. S.; PESSOA, Mario G.; ALVARES-DA-SILVA, Mario R.; SEBASTIANI, Giada; BRAHMANIA, Mayur; RAMJI, Alnoor; NIAZI, Mina; KO, Hin Hin; FELD, Jordan J.; RESTREPO, Juan Carlos; QUESADA, Wagner Enrique Ramirez; ALFARO, Omar; FERNANDEZ, Marlen Ivon Castellanos; ESTUPINAN, Enrique Carrera; AGUIRRE, Jose Roberto; MALDONADO, Katherine; SANCHEZ, Abel; SANCHEZ, Marco; SR., Teresa Andara; CASTRO-NARRO, Graciela Elia; CHAVEZ-TAPIA, Norberto Carlos; MENDEZ-SANCHEZ, Nahum; ADAMES-ALMENGOR, Enrique; LOMBARDO, Julissa; SR., Marcos Girala; MORAN, Elias; PADILLA-MACHACA, Martin; FERRER, Javier Diaz; TAGLE, Martin; MAINARDI, Vitoria; HERNANDEZ, Nelia; MARTINEZ, Edmundo; ALVARADO-TAPIAS, Edilmar; LEON, Roberto; TALAL, Andrew; THOMAS, Emmanuel; SPRINGER, Sandra; SICILIA, Mauricio Garcia Saenz de; ZHANG, Wei; BAJAJ, Jasmohan S.; TAPPER, Elliot B.; IZZY, Manhal; GISH, Robert G.; ATTAR, Bashar M.; COTTER, Thomas G.; LUCEY, Michael R.; KAMATH, Patrick S.; SINGAL, Ashwani K.; BATALLER, Ramon; MEZZANO, Gabriel; SOZA, Alejandro; LAZARUS, Jeffrey V.; ARRESE, Marco; ARAB, Juan Pablo
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SITOSTEROLEMIA AND PREMATURE CORONARY ATHEROSCLEROSIS IN A YOUNG WOMAN: A CASE REPORT.
(2023) CORSO, Mariana P. Xerfan; MARTINHAGO, Gustavo; BORGES, Kartagena; BECERE, Matheus AndraDe lazzari; CHACRA, Ana Paula Marte; MIZUTA, Marjorie Hayashida; MINAME, Marcio Hiroshi; SANTOS, Raul; ROCHA, Viviane Zorzanelli
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