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Association between the CYBA and NOX4 genes of NADPH oxidase and its relationship with metabolic syndrome in non-alcoholic fatty liver disease in Brazilian population

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Hepatobiliary & Pancreatic Diseases International 2018年第4期17卷 330-335页

作者： Fabiola Rabelo jose tadeu stefano Ana Mercedes Cavaleiro Rodrigo Vieira Costa Lima Daniel Ferraz de Campos Mazo Flair jose Carrilho Maria Lúcia Correa-Giannellac Claudia P.Oliveiraa Departamento de Gastroenterologia Faculdade de Medicina FMUSPUniversidade de Sao PauloSao PauloSPBrazil Hospital das Clinicas HCFMUSP Departamento de GastroenterologiaLIM07Faculdade de MedicinaUniversidade de Sao PauloSao PauloSPBrazil Laboratório de Carboidratos e Radioimunensaio LIM18Hospital das Clinicas HCFMUSP(LIM07)Faculdade de MedicinaUniversidade de Sao PauloSao PauloBrazil Programa de Pos-Graduacao em Medicina Universidade Nove de Julho(UNINOVE)Sao PauloBrazil

Background: Oxidative stress has been implicated in the progression of severe forms of non-alcoholic fatty liver disease(NAFLD). NADPH oxidase produces reactive oxygen species. In the present study, we investigated for the first time two single nucleotide polymorphisms(SNPs) in the regulatory region of genes encoding NADPH oxidase 4(NOX4) and p22 phox(CYBA) in ***: A total of 207 biopsy-proven NAFLD patients [simple steatosis(n = 27); nonalcoholic steatohepatitis(NASH)(n = 180)] were evaluated. Genomic DNA was extracted from peripheral blood cells, and polymorphisms in CYBA(unregistered) and NOX4(rs3017887) were determined by direct sequencing of ***: Associations of CYBA-675 T/A with high-density lipoprotein(HDL)(TT vs TA vs AA; P < 0.01) and triglycerides(TGL)(TT vs XA; P < 0.01) were observed only in NASH patients. For polymorphisms in the NOX4 gene, NOX4(rs3017887) CA + AA genotypes was significant associated with alanine aminotransferase(ALT)(CA + AA vs CC; P = 0.02). However, there was no association of SNPs in the CYBA and NOX4 genes encoding the NADPH oxidase system proteins and the presence of NASH. Regarding the clinical results, it was observed that the most advanced degrees of fibrosis occurred in patients diagnosed with type 2 diabetes mellitus(66.9% vs 37.5%, P < 0.01) and those who were more obese(32.2 vs 29.0 kg/m2,P < 0.01). In addition, serum glucose and insulin levels increased significantly in the presence of ***: There were associations between the presence of the allele A in the NOX4 SNP and a higher concentration of ALT in the NAFLD population; between the presence of the AA genotype in the polymorphism of the CYBA-675 T/A CYBA gene and a higher level of TGL and lower HDL in NASH patients. The presence of metabolic syndrome was associated with advanced degrees of fibrosis in NAFLD patients.

关键词： Non-alcoholic fatty liver disease Nonalcoholic steatohepatitis Genetic polymorphism Metabolic syndrome

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The transcontinental variability of nonalcoholic fatty liver disease

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Hepatoma Research 2020年第10期6卷 75-87页

作者： Claudia P.Oliveira Angelo Paredes Mohammed Siddiqui Lawrence Serfaty Abhijit Chowdhury jose tadeu stefano Denise Siqueira Vanni Sherry Boyett Arun J.Sanyal Department of Gastroenterology Faculdade de Medicina da Universidade de São PauloSão PauloSP 01000-000Brazil Laboratório de Gastroenterologia Clínica e Experimental(LIM-07)do Departamento de Gastroenterologia e Hepatologia do Hospital das Clínicas HCFMUSP da Faculdade de Medicina da Universidade de São Paulo São PauloSP 01000-000Brazil Internal Medicine Gastroenterology and Hepatology ServicesBrooke Army Medical CenterSan AntonioTX 78234USA Div.of Gastroenterology Hepatology and NutritionDept.of Internal MedicineVirginia Commonwealth University School of MedicineRichmondVA 23298-0341USA Viral and Metabolic Liver Unit Department of HepatologySaint-Antoine Hospital75012 ParisParis Department of Hepatology School of Digestive and Liver DiseaseInstitute of Post Graduate Medical Education&ResearchKolkata 700020India Disease Biology John C Martin Centre for Liver Research and Innovations SonarpurKolkata 7000150India

Aim:To compare the phenotype of lean versus overweight(OW)and obese(OB)subjects with non-alcoholic fatty liver disease(NAFLD)across multiple ***:A retrospective study of histologically defined subjects from a single center each in France(Fr),Brazil(Br),India(In)and United States(US)was ***:A total of 70 lean[body mass index(BMI)25 kg/m2,BMI29 kg/m2)(n=81:11:22:103).Lean French subjects had the lowest incidence of type 2 diabetes while those from Brazil(P<0.01)had the *** subjects had similar low-density lipoprotein-cholesterol,but higher high-density lipoprotein-cholesterol compared to obese subjects in all *** both lean and obese subjects,there were both insulin-sensitive and insulin-resistant *** French subjects were most insulin-sensitive while those from Brazil were mostly *** each weight category,subjects from India were more insulin-sensitive than those from other *** activity increased from lean to overweight to obese in France but was similar across weight categories in other ***:The phenotype of NAFLD in lean subjects varies by *** obese subjects with NAFLD are *** hypothesize that genetics and region-specific disease modifiers account for these differences.

关键词： Non-alcoholic fatty liver disease phenotype epidemiology demographics

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Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal

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World Journal of Hepatology 2015年第10期7卷 1433-1438页

作者： Lourianne Nascimento Cavalcante jose tadeu stefano Mariana V Machado Daniel F Mazo Fabiola Rabelo Kiyoko Abe Sandes Flair jose Carrilho Helena Cortez-Pinto Andre Castro Lyra Claudia P de Oliveira Gastro-Hepatology Department Hospital Sao Rafael Division of Gastroenterology and Hepatology Department of GastroenterologyUniversity of Sao Paulo School of Medicine Department of Gastroenterology Laboratory of NutritionUniversity Hospital of Santa Maria University Life Sciences Department University of Bahia State Faculty of Medicine Federal University of Bahia

AIM:To study the association between genetic ancestry,non-alcoholic fatty liver disease(NAFLD) metabolic characteristics in two cohorts of patients,from Brazil and Portugal. METHODS:We included 131 subjects from Brazil [(n = 45 with simple steatosis(S. Steatosis) and n = 86 with nonalcoholic steatohepatitis(NASH)] and 90 patients from Portugal(n = 66,S. Steatosis; n = 24,NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis:simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers(AT3-I/D,LPL,Sb19.3,APO,FYNull,PV92,and CKMM) with the greatest ethnicgeographical differential frequencies(≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP onlineand the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant(P 2.5 [NASH 5.3(70.8%) vs S. Steatosis 4.6(29.2%) P = 0.04]. In the Portuguese study population,dyslipidemia was present in all patients with NASH(P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group(P = 0.003,respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort(Brazilian cohort:P = 0.75; Po

关键词： Ancestry Nonalcoholic fatty liver disease Simple steatosis Nonalcoholic steatohepatitis Admixed population

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Hypolactasia is associated with insulin resistance in nonalcoholic steatohepatitis

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World Journal of Hepatology 2016年第24期8卷 1019-1027页

作者： Daniel Ferraz de Campos Mazo Rejane Mattar jose tadeu stefano Joyce Matie Kinoshita da Silva-Etto Marcio Augusto Diniz Sebastiao Mauro Bezerra Duarte Fabíola Rabelo Rodrigo Vieira Costa Lima Priscila Brizolla de Campos Flair jose Carrilho Claudia P Oliveira Division of Gastroenterology and Hepatology Department of Gastroenterology(LIM 07)University of Sao Paulo School of Medicine

AIM To assess lactase gene(LCT)-13910C>T polymorphisms in Brazilian non-alcoholic fatty liver disease(NAFLD) and nonalcoholic steatohepatitis(NASH) patients in comparison with healthy *** This was a transverse observational clinical study with NAFLD patients who were followed at the Hepatology Outpatient Unit of the Hospital das Clínicas, S?o Paulo, Brazil. The polymorphism of lactase non-persistence/lactase persistence(LCT-13910C>T) was examined by PCR-restriction fragment length polymorphism technique in 102 liver biopsy-proven NAFLD patients(steatosis in 9 and NASH in 93) and compared to those of 501 unrelated healthy volunteers. Anthropometric, clinical, biochemical and liver histology data were analyzed. Continuous variables were compared using the t or Mann-Whitney tests, and categorical data were compared with the Fisher's exact test. Univariate logistic regression and multivariate logistic regression adjusted for gender and age were *** No differences in the LCT-13910 genotype frequencies were noted between the NAFLD patients(66.67% of the patients with steatosis were CC, 33.33% were CT, and none were TT; 55.91% of the patients with NASH were CC, 39.78% were CT, and 4.3% were TT; P = 0.941) and the healthy controls(59.12% were CC, 35.67% were CT, and 5.21% were TT) or between the steatosis and NASH patients. That is, the distribution of the lactase non-persistence/lactase persistence polymorphism(LCT-13910C>T) in the patients with NAFLD was equal to that in the general population. In the NASH patients, the univariate analysis revealed that the lactase nonpersistence(low lactase activity or hypolactasia) phenotype was associated with higher insulin levels(23.47 ± 15.94 μU/m L vs 15.8 ± 8.33 μU/m L, P = 0.027) and a higher frequency of insulin resistance(91.84% vs 72.22%, P = 0.02) compared with the lactase persistence phenotype. There were no associations between the LCT genotypes and diabetes(P = 0.651), dyslipidaemia(P = 0.328), h

关键词： Lactose intolerance Genetic polymorphism Insulin resistance Non-alcoholic fatty liver disease Nonalcoholic steatohepatitis

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Epidemiology and Clinical Features of Mycobacterium avium Complex Pulmonary Disease in a Brazilian Amazon Cohort

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Advances in Microbiology 2024年第6期14卷 287-302页

作者： jose tadeu Colares Monteiro Adriana Rodrigues Barretto Ruan Seguin Azevedo Quaresma Bianca Miranda Gouveia Ismari Perini Furlaneto Victória Menezes da Costa Yan Corrêa Rodrigues Layana Rufino Ribeiro Ricardo J. de Paula Souza e Guimarães Alex Brito Souza Ana Roberta Fusco da Costa Karla Valéria Batista Lima Joao de Barros Barreto University Hospital Federal University of Par Belm Brazil Center for Biological and Health Sciences Ph.D. Program in Parasitic Biology in the Amazon Region (PPGBPA) State University of Par (UEPA) Belm Brazil Department of Medicine Centro Universitrio do Par CESUPA Belm Brazil Bacteriology and Mycology Section Evandro Chagas Institute (SABMI/IEC) Ministry of Health Ananindeua Brazil Geoprocessing Laboratory Evandro Chagas Institute/SVSA/MS Ananineua Brazil

The incidence of Mycobacterium avium complex pulmonary disease (MACPD) has been globally increasing. The present study aims to provide a comprehensive analysis of clinical characteristics and treatment response among patients in the Amazon region of Brazil and conduct a retrospective cohort study at a prominent referral hospital in the State of Par, Brazil, from 2012 to 2020. The M. avium group represented 58.9% of cases, followed by M. intracellulare (35.7%), M. colombiense (3.6%), and M. chimaera (1.8%). The majority of patients (73.2%) were female and with an average age of 63 years. Primary clinical manifestations included persistent cough and sputum production. The Charlson comorbidity index (CCI) averaged 2.47, with 36.3% of patients having a CCI score equal to higher than 3. Notably, over 70% of patients had received treatment for pulmonary tuberculosis before initiating treatment for MAC infection. The fibrocavitary radiologic form was the most prevalent (55.4%), frequently exhibiting a bilateral distribution (53.6%). Antimicrobial susceptibility revealed a significant prevalence of MAC resistance to drugs in the therapeutic regimen. Despite this, most of the patients experienced clinical improvement (50%). In conclusion, this study highlights a higher prevalence of MAC infections among middle-aged women, with a history of pulmonary tuberculosis treatment and presenting the fibrocavitary radiological form was predominant.

关键词： MACDP Nontuberculous Mycobacteria Mycobacterium avium Lung Disease

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Life cycle and nymphal feeding of Besdolus ravizzarum （Plecoptera： Perlodidae）, a threatened stonefly

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Insect Science 2010年第2期17卷 149-153页

作者： stefano Fenoglio Tiziano Bo Manuel Jesus Lepez-Rodriguez jose Manuel Tierno de Figueroa Dipartimento di Scienze dell'Ambiente e della Vita Universita del Piemonte Orientale Alessandria Italy Departamento de Biologia Animal Facultad de Ciencias Universidad de Granada Granada Spain

We have studied some aspects of Besdolus ravizzarum biology in the Apen- nines. This stonefly has a very localized distribution in southeastern France and northern Italy. This species is considered threatened. For this reason it is especially relevant to improve knowledge about its natural history, previously unknown. Despite the large size of nymphs, this species shows a univoltine life cycle. The growth is slow but uniform from October to April or May when the short flight period occurs. The analysis of the gut con- tents indicates this species is a predator, feeding mainly on Baetidae and Chironomidae. It is notable that the development of this carnivorous species through cold periods coincides with the season with higher richness and density of potential prey in Apennine streams. Further studies are needed to improve knowledge of the distribution of the species and to start planning effective conservation efforts.

关键词： conservation life history northern Italy stonefly threatened species trophic role

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Increased hepatic expression of insulin-like growth factor-Ⅰreceptor in chronic hepatitis C

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World Journal of Gastroenterology 2006年第24期12卷 3821-3828页

作者： José tadeu stefano Maria Lúcia Corr(e|^)a-Giannella Cristiane Maria Freitas Ribeiro Ven(a|^)ncio Avancini Ferreira Alves Paulo Celso Bosco Massarollo Marcel Cerqueira Cesar Machado Daniel Giannella-Neto Laboratory for Cellular and Molecular Endocrinology University of Sao Paulo Medical School Brazil Laboratory for Cellular and Molecular Endocrinology University of Sao Paulo Medical School Diabetes UnitDivision of EndocrinologyBrazil Department of Pathology Santa Casa de Misericórdia de Sao Paulo Brazil Department of Pathology University of Sao Paulo Medical School Brazil Laboratory for Experimental Surgery University of Sao Paulo Medical School Brazil

AIM： Although increased insulin-like growth factor-I receptor （IGF-IR） gene expression has been reported in hepatocellular carcinoma, studies assessing IGF-IR in chronic hepatitis C （CHC） and cirrhosis are scarce. We therefore aimed to evaluate IGF-IR and IGF-I rnRNA expression in liver from patient with CHC. METHODS： IGF-IR and IGF-I rnRNA content were determined by semi-quantitative RT-PCR and IGF-IR protein expression was determined by immunohistochemistry in hepatic tissue obtained from patients with CHC before （34 patients） and after （10 patients） therapy with interferon-α and ribavirin. RESULTS： An increase of IGF-IR rnRNA content was observed in hepatic tissue obtained from all CHC patients as well as from 6 cadaveric liver donors following orthopic transplantation （an attempt to evaluate normal livers） in comparison to normal liver, while no relevant modifications were detected in IGF-I mRNA content. The irnrnunohistochemical results showed that the raise in IGF-IR rnRNA content was related both to ductular reaction and to increased IGF-IR expression in hepatocytes. A decrease in IGF-IR rnRNA content was observed in patients who achieved sustained virological response after therapy, suggesting an improvement in hepatic damage. CONCLUSION： The up-regulation of IGF-IR expression in hepatocytes of patients with CHC could constitute an attempt to stimulate hepatocyte regeneration. Considering that liver is the organ with the highest levels of IGF-I, our finding of increased IGF-IR expression after both acute and chronic hepatic damage highlights the need for additional studies to elucidate the role of IGF-I in liver regeneration.

关键词： Chronic hepatitis C Insulin-like growth factorI Insulin-like growth factor I receptor Ductular reaction Hepatocyte regeneration Ischemia-reperfusion

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The macrophage soluble receptor AIM/Api6/CD5L displays a broad pathogen recognition spectrum and is involved in early response to microbial aggression

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Cellular & Molecular Immunology 2014年第4期11卷 343-354页

作者： Vanesa G. Martinez Cristina Escoda-Ferran Ines tadeu Simees Satoko Arai Marc Orta Mascaro Esther Carreras Mario Martinez-Florensa jose Yelamos Toru Miyazaki Francisco Lozano Grup d'Immunoreceptors del Sistema Innat i Adaptatiu Institut d'Investigacions Biomediques August Pii Sunyer (IDIBAPS) Barcelona Spain Center for Disease Biology and Integrative Medicine Faculty of Medicine University of Tokyo Tokyo Cancer Research Program Hospital del Mar Medical Research Institute and Department of Immunology Hospital del Mar Barcelona Spain Servei d'Immunologia Centre de DiagnOstic Biomedic Hospital Clinic Barcelona Barcelona Spain Departament de Biologia Cellular Immunologia i Neurociencies Facultat de Medicina Universitat de Barcelona Barcelona Spain

Apoptosis inhibitor of macrophages （AIMs）, a homologue of human Spa, is a mouse soluble member of the scavenger receptor cysteine-rich superfamily （SRCR-SF）. This family integrates a group of proteins expressed by innate and adaptive immune cells for which no unifying function has yet been described. Pleiotropic functions have been ascribed to AIM, from viability support in lymphocytes during thymic selection to lipid metabolism and anti-inflammatory effects in autoimmune pathologies. In the present report, the pathogen binding properties of AIM have been explored. By using a recombinant form of AIM （rAIM） expressed in mammalian cells, it is shown that this protein is able to bind and aggregate Gram-positive and Gram-negative bacteria, as well as pathogenic and saprophytic fungal species. Importantly, endogenous AIM from mouse serum also binds to microorganisms and secretion of AIM was rapidly induced in mouse spleen macrophages following exposure to conserved microbial cell wall components. Cytokine release induced by well-known bacterial and fungal Toll-like receptor （TLR） ligands on mouse splenocytes was also inhibited in the presence of rAIM. Furthermore, mouse models of pathogen-associated molecular patterns （PAMPs）-induced septic shock of bacterial and fungal origin showed that serum AIM levels changed in a time-dependent manner. Altogether, these data suggest that AIM plays a general homeostatic role by supporting innate humoral defense during pathogen aggression.

关键词： innate immunity pattern recognition receptor scavenger receptor

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Prediction of Canola Seed Longevity in the Drying Process

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Journal of Agricultural Science and Technology(B) 2017年第5期7卷 326-331页

作者： Armando Kazuo Fujii jose tadeu Jorge Juliana Aparecida Fracarolli Department of Post-Harvest Technology School of Agricultural Engineering University of Campinas Campinas 13083-875 SPBrazil

The probit analysis has been an important tool to predict seed longevity during storage and has been applied for seed drying simulation. Sealed aluminum pouches containing approximately 50 g of canola seed at moisture range of 7% to 21% of water content web basis （%） were conditioned in water-bath at 50, 60 and 70℃ to obtain the model to evaluate the reduction of canola seed germination. This model was included in the drying simulation program and the estimated germination was compared to the experimental values of germination during drying to validate the model. Canola seeds at 21% of moisture content and germination of 93% were dried at 51℃ and 61 ℃, and the model represented significantly the drying experiments. The aim of this study was to propose a germination model to evaluate the quality of canola seeds during the drying process and to offer the seed producers an important tool to control the drying process. The experimental data validated the objectives of the proposed drying model, optimizing the process at given conditions, managing the energy consumption, according to the minimum germination or maximum moisture content limitation for seed storage. For 51℃, the drying time for canola seed would be about 6 h to maintain germination above 90% and for 61℃, 4 h of drying time maintained germination up to 89%.

关键词： Rapeseed seed drying simulation quality parameter estimation germination.

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Pro-atherosclerotic markers and cardiovascular risk factors one year after liver transplantation

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World Journal of Gastroenterology 2014年第26期20卷 8667-8673页

作者： Mario Reis Alvares-da-Silva Claudia Pinto Marques Souza de Oliveira José tadeu stefano Hermes V Barbeiro Denise Barbeiro Francisco G Soriano Alberto Queiroz Farias Flair José Carrilho Luiz Augusto Carneiro D’Albuquerque Division of Liver and Gastrointestinal Transplant (LIM-37) Department of GastroenterologyUniversity of S?o Paulo School of Medicine Division of Gastroenterology Hospital de Clínicas de Porto AlegreUniversidade Federal do Rio Grande do SulRua Ramiro Barcellos90035-903 Porto AlegreBrazil Division of Clinical (LIM-07) Department of GastroenterologyUniversity of S?o Paulo School of Medicine Division of Emergency Medicine (LIM-51) University of S?o Paulo School of Medicine

AIM: To investigate pro-atherosclerotic markers (endothelial dysfunction and inflammation) in patients one year after liver transplantation.

关键词： Cell adhesion molecules Endothelial biomarkers Cardiovascular disease Nonalcoholic steatohepatitis Metabolic syndrome

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