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Peroxisome proliferator-activated receptors as targets to treat metabolic diseases:Focus on the adipose tissue,liver,and pancreas

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World Journal of Gastroenterology 2023年第26期29卷 4136-4155页

作者： Henrique Souza-Tavares Carolline Santos Miranda Isabela Macedo Lopes Vasques-Monteiro Cristian Sandoval Daiana Araujo Santana-Oliveira flavia Maria silva-Veiga Aline Fernandes-da-silva Vanessa Souza-Mello Department of Anatomy Rio de Janeiro State UniversityRio de Janeiro 20551030Brazil Escuela de Tecnología Médica Facultad de SaludUniversidad Santo TomásOsorno 5310431Chile Departamento de Ciencias Preclínicas Universidad de la FronteraTemuco 4780000Chile

The world is experiencing reflections of the intersection of two pandemics:Obesity and coronavirus disease *** prevalence of obesity has tripled since 1975 worldwide,representing substantial public health costs due to its *** adipose tissue is the initial site of obesity *** excessive energy intake,it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other *** pancreas is one of the organs most affected by *** lipotoxicity becomes chronic,there is an increase in insulin secretion by pancreatic beta cells,a surrogate for type 2 diabetes mellitus(T2DM).These alterations threaten the survival of the pancreatic islets,which tend to become dysfunctional,reaching exhaustion in the long *** for the liver,lipotoxicity favors lipogenesis and impairs beta-oxidation,resulting in hepatic *** silent disease affects around 30%of the worldwide population and can evolve into end-stage liver *** therapy for hepatic steatosis remains to be defined,peroxisome proliferator-activated receptors(PPARs)activation copes with T2DM *** PPARs are transcription factors found at the intersection of several metabolic pathways,leading to insulin resistance relief,improved thermogenesis,and expressive hepatic steatosis mitigation by increasing mitochondrial *** review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases,focusing on adipose tissue plasticity and hepatic and pancreatic remodeling.

关键词： Obesity Insulin resistance Peroxisome proliferator-activated receptors Pancreas Hepatic steatosis Adipose tissue

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Peroxisome proliferator-activated receptor-alpha activation and dipeptidyl peptidase-4 inhibition target dysbiosis to treat fatty liver in obese mice

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World Journal of Gastroenterology 2022年第17期28卷 1814-1829页

作者： flavia Maria silva-Veiga Carolline Santos Miranda Isabela Macedo Lopes Vasques-Monteiro Henrique Souza-Tavares Fabiane Ferreira Martins Julio Beltrame Daleprane Vanessa Souza-Mello Department of Anatomy Institute of BiologyState University of Rio de JaneiroLaboratory of MorphometryMetabolism and Cardiovascular DiseasesRio de Janeiro 20551-030Brazil Department of Clinical and Toxicology Analysis State University of Rio de JaneiroNutrition InstituteState University of Rio de JaneiroNutrition InstituteUniversity of Sao PauloRio de Janeiro 20551-030Brazil

BACKGROUND Obesity and comorbidities onset encompass gut dysbiosis,altered intestinal permeability,and *** that target gut dysbiosis can cope with obesity and nonalcoholic fatty liver disease(NAFLD)*** proliferator-activated receptor(PPAR)-alpha activation and dipeptidyl-peptidase-4(DPP-4)inhibition alleviate NAFLD,but the mechanism may involve gut microbiota modulation and merits further *** To address the effects of PPAR-alpha activation and DPP-4 inhibition(isolated or combined)upon the gut-liver axis,emphasizing inflammatory pathways in NAFLD management in high-fat-fed C57BL/6J *** Male C57BL/6J mice were fed a control diet(C,10%of energy as lipids)or a highfat diet(HFD,50%of energy as lipids)for 12 wk,when treatments started,forming the groups:C,HF,HFA(HFD+PPAR-alpha agonist WY14643,2.5 mg/kg body mass),HFL(HFD+DPP-4 inhibitor linagliptin,15 mg/kg body mass),and HFC(HFD+the combination of WY14643 and linagliptin).RESULTS The HFD was obesogenic compared to the C *** treatments elicited significant body mass loss,and the HFC group showed similar body mass to the C *** treatments tackled oral glucose intolerance and raised plasma glucagon-like peptide-1 *** metabolic benefits restored Bacteroidetes/Firmicutes ratio,resulting in increased goblet cells per area of the large intestine and reduced lipopolysaccharides concentrations in treated *** the gene level,treated groups showed higher intestinal Mucin 2,Occludin,and Zo-1 expression than the HFD *** reduced endotoxemia suppressed inflammasome and macrophage gene expression in the liver of treated *** observations complied with the mitigation of liver steatosis and reduced hepatic triacylglycerol,reassuring the role of the proposed treatments on NAFLD *** PPAR alpha activation and DPP-4 inhibition(isolated or combined)tackled NAFLD in dietinduced obese mice by restoration of gut-liver axis

关键词： Nonalcoholic fatty liver disease High-fat diet Peroxisome proliferator-activated receptor-alpha Dipeptidyl-peptidase-4-inhibitor Dysbiosis Inflammation

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Brazilian Sugar in Domestic Retail: The Quality of Sugar Consumed in the State of Sao Paulo

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Natural Science 2016年第3期8卷 160-169页

作者： Anna flavia de Souza silva Sandra Helena da Cruz Escola Superior de Agricultura Luiz de Queiroz Universidade de Sao Paulo Piracicaba Brazil

Brazil is the largest producer of sugarcane and its derivatives in the world, and one of the largest consumers of sugarcane derivatives. Sugar places a position of great prominence in Brazilian feed, either by direct consumption or as a component of industrialized products, from increasing consumption in the country. Sugar samples taken from local market were analyzed as the quality of table sugar consumed in the state of Sao Paulo (Brazil). The analysis of the parameters and basic attributes of characterization of sugar was according to the methodology developed by ICUMSA (2005;2011) and ICUMSA modified by Copersucar (2002). Samples of sugar from this region showed that medium-low quality. It can be observed in fundamental aspects such as purity and insoluble residues, which were below the standard. In addition, it should be noted the difficulty of obtaining information about the limit values for each attribute, by virtue of Legislation not be assertive to the product and, also, the scientific studies have not been unified to present the specifics for each type of sugar.

关键词： Table Sugar Quality Parameters Demerara Sugar Brazilian Legislation

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Prevalence of congenital cytomegalovirus infection in preterm,small for gestational age and low birth weight newborns:characteristics and cytokines profile

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World Journal of Pediatrics 2022年第7期18卷 498-504页

作者： Janaina Fortes Lino Llian Martins Oliveira Diniz Debora Marques de Miranda Daniela Valadao Freitas Rosa Nathalia Gualberto Souza e silva Eduardo de Souza Nicolau Larissa Goncalves Rezende Lais silva Carvalho Marianna Fischer de Paula Lopes Luisa Petri Correa Gabriela Mafra de Oliveira flavia Miranda da silva Alves Lorena Batista Pascoal Erika Lima Dolabella Teixeira da Costal Leni Marcia Anchieta Roberta Maia de Castro Romaneli Odete Valadares Maternity Hospital Belo HorizonteBrazil Pediatrics Department.Faculy of Medice of Federal University of Minas Gerais Belo Horizonte.Brazil Molecular Laboratory of the INCT-MM.Faculy of Medicine.Federal University of Minas Gerais-UFMG.Belo Horizonte Brazil Faculty of Medicine.Federal University of Minas Gerais-UFMG Belo Horizonte.Brazil Risoleta Tolentino.Neves University Hospital's Maternity Belo HorizonteBrazil Sofia Feldman Maternity Hospital Belo HorizonteBrazil Hospital das Clinicas Maternity-Federal University of Minas Gerais.Belo Horizonte Brazil Pediatrics Department of Federal University of Minas Gerais School Medicine.Minas Gerais.Av Professor Alfredo Balena 190.Belo Horizonte 30130-100Brazil

Cytomegalovirus is the most frequent agent of congenital viral infections,affecting approximately 0.2%-2.4%of live births in different countries[1-7].Universal screening for congenital cytomegalovirus infection in newborns is not a standard practice considering cost-benefit issues and viabil-ity of diagnostic ***,most newborns are asympto-matic and there is no effective treatment for this population[2-5].

关键词： weight birth characteristics

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Time-dependent impact of a high-fat diet on the intestinal barrier of male mice

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World Journal of Methodology 2024年第1期14卷 114-123页

作者： Carolline Santos Miranda Daiana Araujo Santana-Oliveira Isabela Lopes Vasques-Monteiro Nathan Soares Dantas-Miranda Jade Sancha de Oliveira Glauser flavia Maria silva-Veiga Vanessa Souza-Mello Department of Anatomy Rio de Janeiro State UniversityRio de Janeiro 20551030Brazil

BACKGROUND Excessive saturated fat intake compromises the integrity of the intestinal mucosa,leading to low-grade inflammation,impaired mucosal integrity,and increased intestinal permeability,resulting in the migration of lipopolysaccharide(LPS)to other *** To evaluate the chronic effects(at 10 and 16 wk)of a high-fat diet(HFD)(with 50%energy as fat)on the phylogenetic gut microbiota distribution and intestinal barrier structure and protection in C57BL/6 *** Forty adult male mice were divided into four nutritional groups,where the letters refer to the type of diet(control and HFD or HF)and the numbers refer to the period(in weeks)of diet administration:Control diet for 10 wk,HFD for 10 wk,control diet for 16 wk,and HFD for 16 *** sacrifice,biochemical,molecular,and stereological analyses were *** The HF groups were overweight,had gut dysbiosis,had a progressive decrease in occludin immunostaining,and had increased LPS *** progression reduced the number of goblet cells per large intestine area and Mucin2 expression in the HF16 group,consistent with a completely disarranged intestinal ultrastructure after 16 wk of HFD *** Chronic HFD intake causes overweight,gut dysbiosis,and morphological and functional alterations of the intestinal barrier after 10 or 16 ***-dependent reductions in goblet cell numerical density and mucus production have emerged as targets for countering obesity-driven intestinal damage.

关键词： High-fat diet Intestine Ultrastructure Goblet cells Gut microbiota

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Therapeutic and prophylactic thalidomide in TNBS-induced colitis: Synergistic effects on TNF-α, IL-12 and VEGF production

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World Journal of Gastroenterology 2007年第15期13卷 2166-2173页

作者： Ana Teresa Carvalho Heitor Souza Antonio Jose Carneiro Morgana Castelo-Branco Kalil Madi Alberto Schanaider flavia silva Fernando Antonio Pereira Júnior Márcia G Pereira Cláudio Tortori Ilana Dines Jane Carvalho Eduardo Rocha Celeste Elia Departamento de Clínica Médica Hospital Universitário Clementino Fraga Filho Brazil Departamento de Histologia e Embriologia Laboratório de Imunologia Celular Instituto de Ci(e|^)ncias BiomédicasUniversidade Federal do Rio de Janeiro21941-590Brazil Laboratório Multidisciplinar de Pesquisa Anatomia Patológica Hospital Universitário Clementino Fraga FilhoBrazil e Cirurgia Experimental Hospital Universitário Clementino Fraga Filho Brazil

AIM： To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid （TNBS）-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor α （TNF-α）, IL-12, and vascular endothelial growth factor （VEGF）, hallmarks of intestinal inflammation in Crohn＇s disease （CD）. METHODS： Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4＋ T cells, macrophages, and VEGF＋ cells were detected by immunohistochemistry. TNF-α and IL-12 were quantified in the supernatant of organ cultures by ELISA. RESULTS： Significant reduction in the inflammatory score and in the percentage of VEGF＋ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-α and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide. TNF-α levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-α and IL-12 were significantly correlated with the inflammatory score and the number of VEGF＋ cells. CONCLUSION： Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-α, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD.

关键词： Thalidomide Experimental colitis Inflammatory bowel disease Tumor necrosis factor α IL-12 Vascular endothelial growth factor

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Up-regulation of tumor necrosis factor-a pathway survival genes and of the receptor TNFR2 in gastric cancer

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World Journal of Gastrointestinal Oncology 2019年第4期11卷 281-294页

作者： Ana flavia Teixeira Rossi Julia Cocenzo Contiero Fernanda da silva Manoel-Caetano Fabio Eduardo Severino Ana Elizabete silva Department of Biology Sao Paulo State University–UNESP Department of Surgery and Orthopedics Faculty of Medicine Sao Paulo State University–UNESP

BACKGROUND Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori(H. pylori) infection. Tumor necrosis factor(TNF)-α and its receptors(TNFR1 and TNFR2) regulate important cellular processes, such as apoptosis and cell survival, and the disruption of which can lead to cancer. This signaling pathway is also modulated by microRNAs(miRNAs), altering gene *** To evaluate the mRNA and miRNAs expression involved in the TNF-α signaling pathway in gastric cancer(GC) tissues and its *** Quantitative polymerase chain reaction(qPCR) by TaqMan? assay was used to quantify the RNA transcript levels of TNF-α signaling pathway(TNF, TNFR1,TNFR2, TRADD, TRAF2, CFLIP, NFKB1, NFKB2, CASP8, CASP3) and miRNAs that targets genes from this pathway(miR-19 a, miR-34 a, miR-103 a, miR-130 a,miR-181 c) in 30 GC fresh tissue samples. Molecular diagnosis of H. pylori was performed by nested PCR for gene HSP60. A miRNA:mRNA interaction network was construct using Cytoscape v3.1.1 from the in silico analysis performed using public *** Up-regulation of cellular survival genes as TNF, TNFR2, TRADD, TRAF2, CFLIP,and NFKB2, besides CASP8 and miR-34 a was observed in GC tissues, whereas mediators of apoptosis such as TNFR1 and CASP3 were down-regulated. When the samples were stratified by histological type, the expression of miR-103 a and miR-130 a was significantly increased in the diffuse-type of GC compared to the intestinal-type. However, no influence of H. pylori infection was observed on the expression levels of mRNA and miRNAs analyzed. Moreover, the miRNA:mRNA interaction network showed several interrelations between the miRNAs and their target genes, highlighting miR-19 a and miR-103 a, which has as predicted or validated target a large number of genes in the TNF-α pathway,including TNF, TNFR1, TNFR2, CFLIP, TRADD, CASP3 and *** Our findings show that cell survival genes mediated by TNF/TNFR2 binding

关键词： Gastric cancer Tumor necrosis factor-a signaling TNFR1 TNFR2 Cellular survival MicroRNAs

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Bartter's syndrome:clinical findings,genetic causes and therapeutic approach

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World Journal of Pediatrics 2021年第1期17卷 31-39页

作者： flavia Cristina Carvalho Mrad Sílvia Bouissou Morais Soares Luiz Alberto Wanderley de Menezes silva Pedro Versiani dos Anjos Menezes Ana Cristina Simoes-e-silva Interdisciplinary Laboratory of Medical Investigation Faculty of MedicineFederal University of Minas Gerais(UFMG)Av.Alfredo Balena190Room#281Belo HorizonteMG 30130-100Brazil Pediatric Nephrology Unit Faculty of MedicineUFMGBelo HorizonteBrazil

Backgound Bartter's syndrome(BS)is a rare group of salt losing tubulopathies due to the impairment of transport mecha-nisms at the thick ascending limb of the Henle's *** sources Literature reviews and original research articles were collected from database,including PubMed and *** According to the time of onset and symptoms,BS can be classified into antenatal and classic *** studies have identified different subtypes of *** types Ⅰ,Ⅱ and Ⅲ are caused by mutations on genes encoding the luminal Na^(+)-K^(+)-2Cl^(-) co-transporter,the luminal K+ channel ROMK,and the basolateral chloride channel ClC-Kb(CLCNKB),***-of-function mutations of Barttin CLCNK type accessory beta subunit cause BS type Ⅳ*** mutations of CLCNKB and CLCNKA cause BS type Ⅳ*** type Ⅴ consists in a novel transient form characterized by antenatal presentation due to mutations in the MAGE family member *** gain-of-function mutations of the extracellular calcium sensing receptor gene can result in an autosomal dominant condition of *** clinical and biochemical alterations in BS include polyuria,dehydration,hypokalemia,hypochloremic metabolic alka-losis,hyperreninemia,high levels of prostaglandins,normal or low blood pressure,hypercalciuria and failure to *** focuses mainly at correcting dehydration and electrolyte disturbances and in measures to reduce polyuria,including the use of nonsteroidal anti-inflammatory medications to control excessive renal prostaglandin E2 *** Early diagnosis and treatment of BS may prevent long-term consequences such as growth failure,nephrocal-cinosis and end-stage renal disease.

关键词： Bartter's syndrome Hypercalciuria Hypokalemia Metabolic alkalosis Nephrocalcinosis

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Evaluation of the Antibacterial and Antifungal Capacity of Nanoemulsions Loaded with Synthetic Chalcone Derivatives Di-Benzyl Cinnamaldehyde and Benzyl 4-Aminochalcone

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Journal of Renewable Materials 2024年第2期12卷 285-304页

作者： flavia Oliveira Monteiro da silva Abreu Taysse Holanda Joice Farias do Nascimento Henety Nascimento Pinheiro Rachel Menezes Castelo Hélcio silva dos Santos Thais Benincá Patrícia da silva Malheiros Júlio César Sousa Prado Raquel de Oliveira Fontenelle Maria Madalena de Camargo Forte Natural Polymers Laboratory PPGCNState University of CearáFortaleza60.714.903Brazil Polymeric Materials Laboratory PPGE3MFederal University of Rio Grande do SulPorto Alegre91501-970Brazil Natural Product Chemistry Laboratory PPGCNState University of CearáFortaleza60.714.903Brazil Food Hygiene and Microbiology Laboratory PPGCTAFederal University of Rio Grande do SulPorto Alegre91501-970Brazil Microbiology Laboratory Medicine SchoolFederal University of CearáSobral62010-560Brazil

With the increase in antimicrobial resistance,it has become necessary to explore alternative approaches for combating and preventing ***-cinnamaldehyde(CNM)and Benzyl4-amino(B4AM)are bioactive compounds derived from chalcones but with restricted solubility in aqueous *** can enhance the solubility of compounds and can be a promising alternative in the development of novel antimicrobials,with reduced side effects and prolonged *** objective of this study was to evaluate the stability of oil-in-water nanoemulsions loaded with two distinct types of chalcones at two different dosages,to propose a stable formulation with antimicrobial *** showed that nanoemulsions presented high encapsulation efficiency,low polydispersity index(PDI)and particle size below 200 nm,indicating that emulsification was a suitable method for nanoemulsion *** with higher dosages exhibited significant antimicrobial effects when compared to free chalcones and positive ***,B4AM nanoemulsions at higher dosages showed expressive activity against Salmonella minnesota,with a 420%greater inhibitory response compared to the free form and showing equivalence to the positive *** nanoemulsions showed excellent inhibitory activity at the highest dosage,equivalent to the positive control against *** and Staphylococcus *** greater number of conjugated bonds in CNM increased the antimicrobial activity in comparison with B4AM,and the formation of nanometric domains enhanced the bioavailability,being a promising alternative for antimicrobial applications.

关键词： Polysaccharide nanoemulsions S.aureus S.minnesota chalcones alginate

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Toll-like receptor 9 polymorphisms and Helicobacter pylori influence gene expression and risk of gastric carcinogenesis in the Brazilian population

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World Journal of Gastrointestinal Oncology 2019年第11期11卷 998-1010页

作者： Manoela Dias Susi de Matos Lourenco Caroline Lucas Trevizani Rasmussen Spencer Luis Marques Payao Ana flavia Teixeira Rossi Ana Elizabete silva Juliana Garcia de Oliveira-Cucolo Department of Graduate-Level Research USCSacred Heart UniversityBauru 17011-970SPBrazil Department of Genetics and Molecular Biology FAMEMA-Marilia Medical SchoolMarília 17519-030SPBrazil Department of Biology Sao Paulo State University-UNESPSao Jose do Rio Preto 15054-000SPBrazil Department of Molecular Biological and Genetics and Molecular Biology Research Unit-UPGEMFaculty of Medicine of Sao Jose do Rio Preto-FAMERPSao Jose do Rio Preto 15090-000SPBrazil

BACKGROUND Toll-like receptors(TLRs)are the first line of host defense,and are involved in Helicobacter pylori(***)recognition and activation of both inflammatory and carcinogenic *** presence of single nucleotide polymorphisms(SNPs)in genes that activate the immune response may modulate the risk of precancerous lesions and gastric cancer(GC).Among them,Toll-like receptor 9(TLR9)polymorphisms have emerged with a risk factor of infectious diseases and cancer,however the studies are still *** To evaluate whether TLR9 rs5743836 and rs187084 SNPs contribute to the risk of gastric carcinogenesis,and its influence on mRNA *** A case-control study was conducted to evaluate two TLR9 SNPs(TLR9-1237 TCrs5743836 and TLR9-1486 CT-rs187084)in chronic gastritis(CG)and GC patients.A total of 609 DNA samples of peripheral blood[248 CG,161 GC,and 200 samples from healthy individuals(C)]were genotyped by polymerase chain reaction-restriction fragment length *** samples were tested for the *** infection using Hpx1 and Hpx2 *** polymerase chain reaction by TaqMan?assay was used to quantify TLR9 mRNA from fresh gastric tissues(48 GC,26 CG,and 14 C).RESULTS For TLR9-1237,the TC+CC or CC genotypes were associated with a higher risk of GC than C[recessive model odds ratio(OR)=5.01,95%confidence interval(CI):2.52-9.94,P<0.0001],and the CG(recessive model OR=4.63;95%CI:2.44-8.79,P<0.0001)*** TLR9-1486,an association between the CT+TT genotypes and increased risk of both GC(dominant model OR=2.72,95%CI:1.57-4.72,P<0.0001)and CG(dominant model OR=1.79,95%CI:1.15-2.79,P=0.0094)was observed when compared to the C ***,the presence of TLR9-1237 TC/CC+TLR9-1486 CC genotypes potentiate the risk for this neoplasm(OR=18.57;95%CI:5.06-68.15,P<0.0001).The TLR9 mRNA level was significantly higher in the GC group(RQ=9.24,P<0.0001)in relation to the CG group(RQ=1.55,P=0.0010)and normal mucosa(RQ=1.0).When the sa

关键词： Toll-like receptor 9 Helicobacter pylori Gastric cancer Chronic gastritis Polymorphisms Gene expression

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