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Decreased prevalence of celiac disease among Brazilian elderly

World Journal of Gastroenterology 2013年第12期19卷 1930-1935页

作者： Lucas Malta Almeida luiz claudio castro Rosa Harumi Uenishi Fernanda Coutinho de Almeida Patricia Maria Fritsch Lenora Gandolfi Riccardo Pratesi Yanna Karla de Medeiros Nóbrega Graduate Program in Medical Sciences University of Brasilia School of Medicin Doctoral fellow of Coordenao de Aperfeioamento de Pessoal de Nível Superior Graduate Program in Health Sciences University of Brasilia School of Health Sciences Research Center for Celiac disease University of Brasilia School of Medicine Department of Pharmaceutical Sciences University of Brasilia School of Health Sciences Research Center for Celiac Disease University of Brasilia School of Medicine

AIM: To evaluate the prevalence of celiac disease in a group of Brazilian individuals over 60 years of age and compare it with the previously known prevalence in a pediatric group living in the same geographical ***: The research protocol was approved by the Ethics Committee of the University of Brasilia School of Medicine, Brasilia, Brazil. Blood samples from 946 individuals (295 male and 651 female) aged 60 years or older were collected between May 2010 and July 2011. The study subjects' mean and median ages were 68.1 and 67 years, respectively, ranging from 60 to 92 years. That age distribution closely corresponded to the age distribution of the Brazilian population according to the Brazilian 2010 census. The participants were consecutive and unselected outpatients undergoing blood tests at the University of Brasilia Hospital's Clinical Pathology Laboratory. All sera were tested for immunoglobulin A anti-transglutaminase antibodies (IgA-tTG) by enzymelinked immunosorbent assay, and those that were positive were further tested for immunoglobulin A antiendomysium antibodies (IgA-EMA). Human leukocyte antigen (HLA) genotyping was performed for all individuals who exhibited positive serologic results for IgA-tTG and/or ***: Out of the 946 studied patients, only one previously diagnosed case of biopsy-proven celiac disease was detected. For the remaining subjects, nine serum samples tested positive for IgA-tTG antibodies; however, none of them tested positive for IgA-EMA antibodies. The HLA genotyping of those nine subjects revealed that one was carrying DQA1*0501 and two were carrying DQB1*0201 alleles. These data showed that, among those 946 elderly individuals, the prevalence of celiac disease (CD) was 0.1% (95%CI: 0.00-0.59). The prevalence of CD for the elderly group was compared with that observed for the group of 2034 children younger than 15 years (age range, 1-14 years; mean age, 8 years) who took part in our previous CD prevalence screen

关键词： Celiac disease Gluten-sensitive enteropathy Epidemiology Elderly Mortality

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G2/M inhibitors as pharmacotherapeutic opportunities for glioblastoma:the old,the new,and the future

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Cancer Biology & Medicine 2018年第4期15卷 354-374页

作者： Angel Mauricio castro-Gamero Julia Alejandra Pezuk Maria Sol Brassesco luiz Gonzaga Tone Human Genetics Laboratory Institute of Natural SciencesFederal University of Alfenas(UNIFAL-MG)Alfenas 37130-001Brazil Biotechnology and Innovation in Health Program and Pharmacy Program Anhanguera University Sao Paulo(UNIANSP)Sao Paulo 05145-200Brazil Department of Biology Faculty of PhilosophySciences and Letters at Ribeirao PretoUniversity of Sao PauloRibeirao Preto 14040-901Brazil Department of Pediatrics Department of Genetics Ribeirao Preto School of MedicineUniversity of Sao PauloRibeirao Preto 14049-900Brazil

Glioblastoma(GBM) is one of the deadliest tumors and has a median survival of 3 months if left untreated. Despite advances in rationally targeted pharmacological approaches, the clinical care of GBM remains palliative in intent. Since the majority of altered signaling cascades involved in cancer establishment and progression eventually affect cell cycle progression, an alternative approach for cancer therapy is to develop innovative compounds that block the activity of crucial molecules needed by tumor cells to complete cell division. In this context, we review promising ongoing and future strategies for GBM therapeutics aimed towards G2/M inhibition such as anti-microtubule agents and targeted therapy against G2/M regulators like cyclin-dependent kinases,Aurora inhibitors, PLK1, BUB, 1, and BUBR1, and survivin. Moreover, we also include investigational agents in the preclinical and early clinical settings. Although several drugs were shown to be gliotoxic, most of them have not yet entered therapeutic trials. The use of either single exposure or a combination with novel compounds may lead to treatment alternatives for GBM patients in the near future.

关键词： Chemotherapy PLK1 AURK survivin BUB BUR1

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Intestinal anti-inflammatory activity of Ground Cherry(Physalis angulata L.)standardized CO2 phytopharmaceutical preparation

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World Journal of Gastroenterology 2017年第24期23卷 4369-4380页

作者： luiz domingues almeida junior ana elisa valencise quaglio celso acácio rodrigues de almeida costa luiz claudio Di Stasi laboratory of phytomedicines pharmacology and biotechnology(phytopharmatech)department of pharmacologyinstitute of biosciencesuniversidade estadual paulista unespbotucatusao paulocep 18618-970

AIM To investigate the effects of Ground Cherry(Physalis angulata L.)standardized supercritical CO_2 extract in trinitrobenzenesulphonic acid(TNBS)model of rat intestinal *** The animals were divided into groups that received vehicle or *** extract(PACO_2)orally at the doses 25,50 and 100 mg/kg daily by 5 d before TNBS *** effects of PACO_2 were assessed by macroscopic analysis,biochemical determinations of the levels of myeloperoxidase(MPO),alkaline phosphatase(ALP),glutathione and cytokines(such as INF-γ,IL-1β,IL-6,IL-10 and TNF-α),gene expression evaluation(including Hsp70,heparanase,NF-κB,mitogenactivated protein kinases(Mapk)1,3,6 and 9,and the mucins genes Muc 1,2,3 and 4)and histopathological studies using optical,and electronic(transmission and scanning)*** PACO2 extract promoted a significant reduction in MPO and ALP activities,reducing oxidative stress and neutrophil *** effects were accompanied by significant reduction of colonic levels of IFN-γand IL-6 and down-regulation of heparanase,Hsp70,Mapk3,Mapk9,Muc1 and Muc2 genes expression when compared with TNBS-control *** addition,protective effects were also evidenced by reduced neutrophil infiltration,recovery of cell architecture and replacement of mucin by histopathological and ultrastructural *** Physalis angulata supercritical CO2 extract is an intestinal anti-inflammatory product that modulates oxidative stress,immune response and expression of inflammatory mediators,with potentially utility for treating inflammatory bowel disease.

关键词： Intestinal disease Inflammatory bowel disease Physalis angulata L.trinitrobenzenesulphonic acid

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Damage-associated molecular patterns in inflammatory bowel disease:From biomarkers to therapeutic targets

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World Journal of Gastroenterology 2018年第41期24卷 4622-4634页

作者： Hayandra Ferreira Nanini claudio Bernardazzi Fernando castro Heitor Siffert Pereira de Souza Servico de Gastroenterologia e Laboratorio Multidisciplinar de Pesquisa Departamento de Clinica MedicaHospital Universitario Clementino Fraga FilhoUniversidade Federal do Rio de JaneiroRio de JaneiroRJ 21941-913Brazil D’Or Institute for Research and Education(IDOR) Rua Diniz Cordeiro 30BotafogoRio de JaneiroRJ 22281-100Brazil

The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. These components include environmental elements and gut microbiota a dysbiosis. For decades, immune abnormalities have been investigated as critically important in IBD pathogenesis, and attempts to develop effective therapies have predominantly targeted the immune system. Nevertheless, immune events represent only one of the constituents contributing to IBD pathogenesis within the context of the complex cellular and molecular network underlying chronic intestinal inflammation. These factors need to be appreciated within the milieu of nonimmune components. Damage-associated molecular patterns (DAMPs), which are essentially endogenous stress proteins expressed or released as a result of cell or tissue damage, have been shown to act as direct proinflammatory mediators. Excessive or persistent signalling mediated by such molecules can underlie several chronic inflammatory disorders, including IBD. The release of endogenous DAMPs amplifies the inflammatory response driven by immune and non-immune cells and promotes epigenetic reprogramming in *** effects determine pathologic changes,which may sustain chronic intestinal inflammation and also underlie specific disease *** addition to highlighting the potential use of DAMPs such as calprotectin as biomarkers,research on DAMPs may reveal novel mechanistic associations in IBD pathogenesis and is expected to uncover putative therapeutic targets.

关键词： Damage-associated molecular patterns Environmental factors Epigenetics Inflammatory bowel disease Therapeutic targets

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Liver involvement in pediatric celiac disease

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World Journal of Gastroenterology 2015年第19期21卷 5813-5822页

作者： Caterina Anania Ester De Luca Giovanna De castro claudio Chiesa Lucia Pacifico Caterina Anania Ester De Luca Giovanna De Castro Lucia Pacifico Department of Pediatrics and Child Neuropsychiatry Sapienza University of Rome Rome Viale Regina Elena 324 00161 Rome Italy.

Celiac disease （CD） is an intestinal inflammatory diseasethat manifests in genetically susceptible individualswhen exposed to dietary gluten. It is a common chronicdisorder, with a prevalence of 1% in Europe and NorthAmerica. Although the disease primarily affects the gut,the clinical spectrum of CD is remarkably varied, andthe disease can affect many extraintestinal organs andsystems, including the liver. The hepatic dysfunctionpresenting in CD ranges from asymptomatic liverenzyme elevations or nonspecific reactive hepatitis（cryptogenic liver disorders）, to chronic liver *** this article, we review the clinical presentationsand possible mechanisms of CD-related liver injury toidentify strategies for the diagnosis and treatment ofthese disorders in childhood.

关键词： Celiac disease Cryptogenic hypertransaminasemia Autoimmune liver disease End-stage liverdisease Fatty liver

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A new technique for separation of partial discharge sources and electromagnetic noise in radiofrequency measurements using energy ratios of different antennas

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High Voltage 2021年第3期6卷 525-530页

作者： Jorge A.Ardila‐Rey Matias Cerda‐Luna Rodrigo Rozas‐Valderrama Bruno Albuquerque de castro Andréluiz Andreoli Benjamin Cevallos Departamento de Ingeniería Eléctrica Universidad Técnica Federico Santa MaríaSantiago de ChileChile Department of Electrical Engineering São Paulo State University(UNESP)School of Engineering BauruBauru‐SPBrazil

One of the main tools for monitoring the condition of high voltage equipment is the measurement of partial discharges(PD).The electromagnetic(EM)radiation originated from this degradation phenomenon can be captured by various types of ultra‐high fre-quency(UHF)antennas carefully designed and optimised for specific frequency ***,the presence of environmental noise may limit the use of this *** types of monopole antennas normally used in UHF PD measurement have been evaluated in order to validate the performance of a novel separation technique of EM ***,a new separation technique based on the energy ratio of the captured signals was developed,considering noise *** results revealed that the new technique allows an adequate separation,even when three sources act simultaneously.

关键词： antennas separation noise

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MicroRNAs expression influence in ulcerative colitis and Crohn's disease:A pilot study for the identification of diagnostic biomarkers

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World Journal of Gastroenterology 2021年第45期27卷 7801-7812页

作者： Ana Elisa Valencise Quaglio Felipe Jose Santaella Maria Aparecida Marchesan Rodrigues Ligia Yukie Sassaki luiz claudio Di Stasi Laboratory of Phytomedicines Pharmacology and Biotechnology(PhytoPharmaTec)Department of Biophysics and PharmacologySão Paulo State University(Unesp)Institute of BiosciencesBotucatu 18618-689São PauloBrazil Department of Pathology Botucatu Medical SchoolSao Paulo State University(Unesp)Botucatu 18618-687São PauloBrazil Department of Internal Medicine Botucatu Medical SchoolSão Paulo State University(Unesp)Botucatu 18618-687São PauloBrazil

BACKGROUND Inflammatory bowel disease(IBD)comprises two distinct diseases,Crohn’s disease(CD)and ulcerative colitis(UC),both of which are chronic,relapsing inflammatory disorders of the gastrointestinal tract with a mostly unknown *** incidence and prevalence of IBD are continually increasing,indicating the need for further studies to investigate the genetic determinants of these *** microRNAs(miRNAs)regulate protein translation via complementary binding to mRNA,discovering differentially expressed miRNAs(DE)in UC or CD patients could be important for diagnostic biomarker identification,assisting in the appropriate disease differentiation progressing the understanding of IBD *** To determine the miRNA expression profile in UC and CD patients and the potential pathophysiological contributions of differentially expressed *** A total of 20 formalin-fixed paraffin-embedded colonic samples were collected from the Pathology Department of Botucatu Medical School at São Paulo State University(Unesp).The diagnosis of UC or CD was based on clinical,endoscopic,radiologic,and histological criteria and confirmed by histopathological analysis at the time of *** TaqMan™Array Human MicroRNA A+B Cards Set v3.0(Applied Biosystems™)platform was used to analyze 754 *** of DE-miRNAs were predicted using miRNA Data Integration Portal(mirDIP)and the miRNA Target Interaction database(MiRTarBase).All statistical analyses were conducted using GraphPad Prism *** and nonparametric data were analyzed using t-tests and Mann-Whitney U tests,*** The results showed that of the 754 miRNAs that were initially evaluated,643 miRNAs were found to be expressed in at least five of the patients who were diagnosed with either CD or UC;the remaining 111 miRNAs were not considered to be expressed in these *** expression levels of 28 miRNAs were significantly different between the CD and UC patients(P≤0.05

关键词： Crohn’s disease Ulcerative colitis Inflammatory bowel disease miRNA Differential diagnosis Biomarker

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Gut microbiota,inflammatory bowel disease and colorectal cancer

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World Journal of Gastroenterology 2022年第30期28卷 4053-4060页

作者： Ana Elisa Valencise Quaglio Thais Gagno Grillo Ellen Cristina Souza De Oliveira luiz claudio Di Stasi Ligia Yukie Sassaki Departament of Biophysics and Pharmacology Sao Paulo State University(Unesp)Institute of BiosciencesBotucatu 18618-689Sao Paulo StateBrazil Department of Internal Medicine Sao Paulo State University(Unesp)Medical SchoolBotucatu 18618-686Sao Paulo StateBrazil

The gut microbiota is a complex community of microorganisms that inhabit the digestive tracts of humans,living in symbiosis with the ***,characterized by an imbalance between the beneficial and opportunistic gut microbiota,is associated with several gastrointestinal disorders,such as irritable bowel syndrome(IBS);inflammatory bowel disease(IBD),represented by ulcerative colitis and Crohn’s disease;and colorectal cancer(CRC).Dysbiosis can disrupt the mucosal barrier,resulting in perpetuation of inflammation and *** increase in some specific groups of harmful bacteria,such as Escherichia coli(***)and enterotoxigenic Bacteroides fragilis(ETBF),has been associated with chronic tissue inflammation and the release of pro-inflammatory and carcinogenic mediators,increasing the chance of developing CRC,following the inflammationdysplasia-cancer sequence in IBD ***,the aim of the present review was to analyze the correlation between changes in the gut microbiota and the development and maintenance of IBD,CRC,and IBD-associated *** with IBD and CRC have shown reduced bacterial diversity and abundance compared to healthy individuals,with enrichment of Firmicute sand *** bacteria are also associated with the onset and progression of CRC,such as Fusobacterium nucleatum,***,Enterococcus faecalis,Streptococcus gallolyticus,and *** research can evaluate the advantages of modulating the gut microbiota as preventive measures in CRC high-risk patients,directly affecting the prognosis of the disease and the quality of life of patients.

关键词： Gut microbiota Dysbiosis Ulcerative colitis Crohn’s disease Inflammatory bowel disease Colorectal cancer

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Antioxidant properties of glutamine and its role in VEGF-Akt pathways in portal hypertension gastropathy

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World Journal of Gastroenterology 2013年第28期19卷 4464-4474页

作者： Camila Marques Francielli Licks Ingrid Zattoni Beatriz Borges luiz Eduardo Rizzo de Souza claudio Augusto Marroni Norma Possa Marroni Universidade Federal do Rio Grande do Sul-PPG Fisiologia Porto Alegre 90000100 Brazil Universidade Federal do Paraná Curitiba 81531900 Brazil Departamento de Medicina Interna-Gastroenterologia-Universidade Federal de Ciências da Saúde de Porto Alegre Porto Alegre 90000100 Brazil Universidade Federal do Rio Grande do Sul-PPG Fisiologia Universidade Luterana do Brasil Porto Alegre 90000100 Brazil

AIM: To investigate the effects of glutamine on oxidative/nitrosative stress and the vascular endothelial growth factor (VEGF)-Akt-endothelial nitric oxide synthase (eNOS) signaling pathway in an experimental model of portal hypertension induced by partial portal vein ligation (PPVL). METHODS: Portal hypertension was induced by PPVL. The PPVL model consists of a partial obstruction of the portal vein, performed using a 20 G blunt needle as a guide, which is gently removed after the procedure. PPVL model was performed for 14 d beginning treatment with glutamine on the seventh day. On the fifteenth day, the mesenteric vein pressure was checked and the stomach was removed to test immunoreactivity and oxidative stress markers. We evaluated the expression and the immunoreactivity of proteins involved in the VEGF-Akt-eNOS pathway by Western blotting and immunohistochemical analysis. Oxidative stress was measured by quantification of the cytosolic concentration of thiobarbituric acid reactive substances (TBARS) as well as the levels of total glutathione (GSH), superoxide dismutase (SOD) activity, nitric oxide (NO) production and nitrotyrosine immunoreactivity. RESULTS: All data are presented as the mean ± SE. The production of TBARS and NO was significantly increased in PPVL animals. A reduction of SOD activity was detected in PPVL + G group. In the immunohistochemical analyses of nitrotyrosine, Akt and eNOS, the PPVL group exhibited significant increases, whereas decreases were observed in the PPVL + G group, but no difference in VEGF was detected between these groups. Western blotting analysis detected increased expression of phosphatidylinositol-3-kinase (PI3K), P-Akt and eNOS in the PPVL group compared with the PPVL + G group, which was not observed for the expression of VEGF when comparing these groups. Glutamine administration markedly alleviated oxidative/nitrosative stress, normalized SOD activity, increased levels of total GSH and blocked NO overproduction as well

关键词： Partial portal vein ligation Oxidative stress Glutamine Portal hypertension Rats

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MicroRNAs in inflammatory bowel disease:What do we know and what can we expect?

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World Journal of Gastroenterology 2024年第16期30卷 2184-2190页

作者： Ellen Cristina Souza de Oliveira Ana Elisa Valencise Quaglio Thais Gagno Grillo luiz claudio Di Stasi Ligia Yukie Sassaki Department of Internal Medicine Medical SchoolSão Paulo State University(Unesp)Botucatu 18618-686São PauloBrazil Verum Ingredients Botucatu Technology ParkBotucatu 18605-525São PauloBrazil Department of Biophysics and Pharmacology Institute of BiosciencesSão Paulo State University(Unesp)Botucatu 18618-689São PauloBrazil

MicroRNAs(miRNAs),small non-coding RNAs composed of 18–24 nucleotides,are potent regulators of gene expression,contributing to the regulation of more than 30%of protein-coding *** that miRNAs are regulators of inflammatory pathways and the differentiation of intestinal epithelial cells,there is an interest in exploring their importance in inflammatory bowel disease(IBD).IBD is a chronic and multifactorial disease of the gastrointestinal tract;the main forms are Crohn's disease and ulcerative *** studies have investigated the dysregulated expression of miRNAs in IBD,demonstrating their important roles as regulators and potential biomarkers of this *** editorial presents what is known and what is expected regarding miRNAs in *** the important regulatory roles of miRNAs in IBD are clearly established,biomarkers for IBD that can be applied in clinical practice are lacking,emphasizing the importance of further *** regarding the influence of miRNAs on the inflammatory process and the exploration of their role in gene regulation are expected to provide a basis for the use of miRNAs not only as potent biomarkers in IBD but also as therapeutic targets for the control of inflammatory processes in personalized medicine.

关键词： MicroRNAs Inflammatory bowel disease Crohn’s disease Ulcerative colitis Biomarker Therapy

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