RESUMO Contexto: Helicobacter pylori (H. pylori) é uma bactéria gram-negativa associada à etiologia de várias patologias do trato gastrointestinal, e cepas positivas para cagA (cagA+) são encontradas em populações com úlceras gástricas e lesões pré-cancerígenas, induzindo respostas pró-inflamatórias. O desenvolvimento de neoplasias está relacionado à desregulação do microRNA (miRNA), indicando miRNA-629 altamente expresso. O artigo tem como objetivo correlacionar o nível de expressão do miRNA-629 com a presença de H. pylori e o marcador de patogenicidade cagA. Métodos: Foram avaliadas 203 amostras de biópsia gástrica de indivíduos com tecido gástrico normal (n=60), gastrite (n=96) e câncer gástrico (n=47) de ambos os sexos e com mais de 18 anos. As amostras foram subdivididas de acordo com a presença ou ausência de H. pylori, detectado por reação em cadeia da polimerase (PCR). O RNA foi extraído usando um kit comercial e quantificado. O DNA complementar (cDNA) foi sintetizado usando kits comerciais, e a expressão relativa foi calculada usando o método 2-ΔΔCt. Resultados: Indivíduos infectados com H. pylori têm nove vezes mais chances de desenvolver câncer gástrico. Pacientes com câncer parecem ter diminuição da expressão do miRNA-629; no entanto, a presença da bactéria não influenciaria essa redução. Indivíduos no grupo do câncer apresentaram menor expressão do miRNA-629 quando cagA+; no entanto, no grupo controle, a expressão foi maior quando cagA+. Conclusão: H. pylori é um fator envolvido na etiologia e progressão das doenças gástricas. A redução na expressão do miRNA-629 em pacientes com câncer ocorre independentemente da presença da bactéria, mas quando o marcador de patogenicidade cagA está presente, induz mudanças na expressão gênica do respectivo miRNA. Contexto H (H gramnegativa gram negativa gastrointestinal cagA+ (cagA+ précancerígenas, précancerígenas pré cancerígenas, cancerígenas pré-cancerígenas próinflamatórias. próinflamatórias pró inflamatórias. inflamatórias pró-inflamatórias miRNA, miRNA , (miRNA) miRNA629 629 miRNA-62 expresso Métodos 20 n=60, n60 n n=60 60 (n=60) n=96 n96 96 (n=96 n=47 n47 47 (n=47 1 anos PCR. PCR . (PCR) quantificado cDNA (cDNA comerciais 2ΔΔCt. 2ΔΔCt ΔΔCt 2 ΔΔCt. 2-ΔΔCt Resultados entanto controle Conclusão presente (cagA (miRNA miRNA62 62 miRNA-6 n6 n=6 6 (n=60 n=9 n9 9 (n=9 n=4 n4 4 (n=4 (PCR miRNA6 miRNA- n= (n=6 (n= (n

ABSTRACT Background: Helicobacter pylori (H. pylori) is a gram-negative bacterium associated with the etiology of several gastrointestinal tract pathologies, and cagA-positive (cagA+) strains are found in populations with gastric ulcers and precancerous lesions, inducing pro-inflammatory responses. The development of neoplasms is related to microRNA (miRNA) dysregulation, indicating highly expressed miRNA-629. The article aims to correlate the expression level of miRNA-629 with the presence of H. pylori and the pathogenicity marker cagA. Methods: 203 gastric biopsy samples were evaluated from individuals with normal gastric tissue (n=60), gastritis (n=96), and gastric cancer (n=47) of both genders and over 18 years old. The samples were subdivided according to the presence or absence of H. pylori, detected by polymerase chain reaction (PCR). RNA was extracted using a commercial kit and quantified. Complementary DNA (cDNA) was synthesized using commercial kits, and the relative expression was calculated using the 2-ΔΔCt method. Results: Individuals infected with H. pylori are nine times more likely to develop gastric cancer. Cancer patients appeared to have decreased expression of miRNA-629; however, the presence of the bacterium would not influence this reduction. Individuals in the cancer group showed lower miRNA-629 expression when cagA+; however, in the control group, the expression was higher when cagA+. Conclusion: H. pylori is a factor involved in the etiology and progression of gastric diseases. Reduction in miRNA-629 expression in cancer patients occurs independent of the presence of the bacterium, but when the cagA pathogenicity marker is present, it induces changes in the gene expression of the respective miRNA. Background H (H gramnegative gram negative pathologies cagApositive positive cagA+ (cagA+ lesions proinflammatory pro inflammatory responses miRNA (miRNA dysregulation miRNA629. miRNA629 629. 629 miRNA-62 Methods 20 n=60, n60 n n=60 , 60 (n=60) n=96, n96 n=96 96 (n=96) n=47 n47 47 (n=47 1 old PCR. PCR . (PCR) quantified cDNA (cDNA kits 2ΔΔCt ΔΔCt 2 method Results however reduction Conclusion diseases present (cagA miRNA62 62 miRNA-6 n6 n=6 6 (n=60 n9 n=9 9 (n=96 n=4 n4 4 (n=4 (PCR miRNA6 miRNA- n= (n=6 (n=9 (n= (n

RESUMO Contexto: Helicobacter pylori é um agente etiológico de doenças gastroduodenais. O microrganismo, considerado cancerígeno tipo I, afeta cerca de 50% da população mundial. Os fatores de virulência do H. pylori são determinantes para o desfecho clínico da infecção. O gene da proteína inflamatória externa A (oipA) codifica uma adesina da membrana externa e está relacionado a gastropatias severas, como o câncer gástrico. Objetivo: O objetivo deste estudo foi avaliar a associação do gene oipA com a gravidade das doenças gastroduodenais em pacientes dispépticos na região Brasil Central. Métodos: A reação em cadeia da polimerase (PCR) foi utilizada para determinar a presença de H. pylori. Amostras positivas foram utilizadas para triagem molecular do gene oipA. As gastropatias foram categorizadas como doenças não severas e severas. Resultados: Aproximadamente 68% dos pacientes apresentaram H. pylori e 36% estavam infectados com cepas H. pylori oipA+. A infecção foi significativamente associada em pacientes com idade superior a 44 anos (P=0,004). No entanto, não houve associação entre oipA e a idade dos pacientes (P=0,89). Aproximadamente 46% dos pacientes infectados com cepas oipA+ tiveram alguma doença severa. O adenocarcinoma gástrico foi a gastropatia severa mais frequente. O genótipo oipA de H. pylori foi inversamente associado à gravidade das doenças gastroduodenais (OR=0,247, IC95%: 0,0804-0,7149 P=0,007). Conclusão: A caracterização de possíveis marcadores moleculares contribuirá para a medicina personalizada, impactando no prognóstico dos pacientes. Contexto microrganismo I 50 mundial H (oipA Objetivo Central Métodos PCR (PCR Resultados 68 36 4 P=0,004. P0004 P P=0,004 . 0 004 (P=0,004) entanto P=0,89. P089 P=0,89 89 (P=0,89) 46 frequente OR=0,247, OR0247 OR 247 (OR=0,247 IC95% IC95 IC 0,08040,7149 0080407149 0,0804 0,7149 0804 7149 0,0804-0,714 P=0,007. P0007 P=0,007 007 P=0,007) Conclusão personalizada 5 6 3 P000 P=0,00 00 (P=0,004 P08 P=0,8 8 (P=0,89 OR=0,247 OR024 24 (OR=0,24 IC9 08040 0,08040,714 008040714 00804 0,080 07149 0,714 080 714 0,0804-0,71 P00 P=0,0 (P=0,00 P0 P=0, (P=0,8 OR=0,24 OR02 2 (OR=0,2 0,08040,71 00804071 0080 0,08 0714 0,71 08 71 0,0804-0,7 (P=0,0 P=0 (P=0, OR=0,2 OR0 (OR=0, 0,08040,7 0080407 008 0,0 071 0,7 7 0,0804-0, P= (P=0 OR=0, (OR=0 0,08040, 008040 0, 07 0,0804-0 (P= OR=0 (OR= 0,08040 0,0804- (P OR= (OR

ABSTRACT Background: Helicobacter pylori is an etiologic agent of gastroduodenal diseases. The microorganism, considered a type I carcinogen, affects about 50% of the global population. H. pylori virulence factors are determinant for the clinical outcome of the infection. The outer inflammatory protein A (oipA) gene encodes an outer membrane adhesin and is related to severe gastropathies, such as gastric cancer. Objective: The aim of this study was to evaluate the association of the oipA gene with the severity of gastroduodenal diseases in dyspeptic patients in region Central Brazil. Methods: The polymerase chain reaction (PCR) was used to determine the presence of H. pylori. Samples positives were used for molecular screening of the oipA gene. Gastropathies were categorized as non-severe and severe diseases. Results: Approximately 68% of patients had H. pylori and 36% were infected with H. pylori oipA+ strains. Infection was significantly associated in patients aged over 44 years (P=0.004). However, there was no association between oipA and patients’ age (P=0.89). Approximately 46% of patients infected with oipA+ strains had some severe illness. Gastric adenocarcinoma was the most frequent severe gastropathy. The H. pylori oipA genotype was inversely associated with the severity of gastroduodenal diseases (OR=0.247, 95%CI: 0.0804-0.7149 and P=0.007). Conclusion: The characterization of possible molecular markers will contribute to personalized medicine, impacting the prognosis of patients. Background microorganism carcinogen 50 population H infection (oipA gastropathies cancer Objective Brazil Methods PCR (PCR nonsevere non Results 68 36 4 P=0.004. P0004 P P=0.004 . 0 004 (P=0.004) However P=0.89. P089 P=0.89 89 (P=0.89) 46 illness gastropathy OR=0.247, OR0247 OR 247 (OR=0.247 95%CI 95CI CI 95 0.08040.7149 0080407149 0.0804 0.7149 0804 7149 0.0804-0.714 P=0.007. P0007 P=0.007 007 P=0.007) Conclusion medicine 5 6 3 P000 P=0.00 00 (P=0.004 P08 P=0.8 8 (P=0.89 OR=0.247 OR024 24 (OR=0.24 9 08040 0.08040.714 008040714 00804 0.080 07149 0.714 080 714 0.0804-0.71 P00 P=0.0 (P=0.00 P0 P=0. (P=0.8 OR=0.24 OR02 2 (OR=0.2 0.08040.71 00804071 0080 0.08 0714 0.71 08 71 0.0804-0.7 (P=0.0 P=0 (P=0. OR=0.2 OR0 (OR=0. 0.08040.7 0080407 008 0.0 071 0.7 7 0.0804-0. P= (P=0 OR=0. (OR=0 0.08040. 008040 0. 07 0.0804-0 (P= OR=0 (OR= 0.08040 0.0804- (P OR= (OR

Abstract Background Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the human stomach and causes a variety of gastric diseases. This study evaluated the correlations between the -251 (T>A) (rs4073) polymorphism of interleukin-8 (IL-8), the etiology of gastric disease, and H. pylori infection in pediatric and adolescent patients. Methods DNA samples were obtained from 285 gastric biopsies from pediatric patients. H. pylori was detected by PCR, whereas PCR-RFLP was used to characterize the -251 (T>A) polymorphism of IL-8. Results The histological analysis revealed the presence of gastritis in 158 patients (55.44%). H. pylori was found in 71 samples (24.9%). The -251 (T>A) polymorphism revealed that 58 (29.47%) samples were TT, 143 (50.18%) samples were TA, and 84 (20.35%) samples were AA. Conclusions Our findings suggest that IL8-251 A allele may be an important risk factor for the development of gastric disease when associated with H. pylori infection.

Abstract Background Tumor necrosis factor plays a critical role in the pathogenesis of gastric diseases such as gastric cancer, and an abnormal inflammatory response has frequently been observed in dyspeptic patients. Helicobacter pylori infection can induce a gastric mucosal inflammatory response that may be influenced by -308 (G > A) polymorphisms and gene expression of theTNF-α gene. Methods One hundred and thirty-four gastric biopsy samples were collected from patients of both genders (61♂ and 73♀, mean age 40.3 ± 24.2 years) with gastric symptoms. The -308 (G > A) polymorphism of TNF-α was characterized using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The expression level was measured using real-time PCR, and relative quantification (RQ) was calculated using the comparative CT method (2-ΔΔCT). Results The analysis revealed an increase in TNF-α gene expression in patients with gastritis; on the other hand, no statistical differences were observed in patients with gastric cancer. In addition, no association was found among -308 polymorphism genotypes, virulence markers, or TNF-α gene expression. Conclusions Helicobacter pylori induces a large increase in TNF-α expression in patients with gastritis, regardless of tissue inflammation, but after the tissue becomes neoplastic, the presence of bacteria did not influence expression. These results suggest that the TNF-α pathway may play an important role in the progression from gastritis to gastric cancer

Background:Only a few Helicobacter pylori-infected individuals develop severe gastric diseases and virulence factors of H. pyloriappear to be involved in such clinical outcomes. Duodenal ulcer promoting gene A (dupA) is a novel virulence factor ofHelicobacter pylori that is associated with duodenal ulcer development and reduced risk for gastric carcinoma in some populations. The aims of the present study were to determine the presence ofdupA gene and evaluate the association amongdupA and other virulence factors includingcagA and vacA in Brazilian patients. Gastric biopsies were obtained from 205 dyspeptic patients (100 children and 105 adults). DNA was extracted and analyzed for the presence of H. pylori and its virulence factors using the polymerase chain reaction method.Results:Patients with gastritis tested positive for H. pylori more frequently. The dupA gene was detected in 41.5% of them (85/205); cagA gene was found in 98 isolates (47.8%) andvacA genotype s1/m1 in 50.2%, s1/m2 in 8.3%, s2/m2 in 36.6%, s2/m1 in 0.5% and s1/s2/m1/m2 in 4.4%. We also verified a significant association between cagA and dupA genes [p = 0.0003, relative risk (RR) 1.73 and confidence interval [CI] = 1.3-2.3]. The genotypes s1/m1 were also associated with dupA gene (p = 0.0001, RR: 1.72 and CI: 1.3-2.2). The same associations were found when analyzing pediatric and adult groups of patients individually.Conclusion:Ours results suggest that dupA is highly frequent in Brazilian patients and is associated with cagA gene andvacA s1/m1 genotype, and it may be considered an important virulence factor in the development of gastric diseases in adults or children.

An inflammatory process has been involved in numerous neurodegenerative disorders such as Parkinson's disease, stroke and Alzheimer's disease (AD). In AD, the inflammatory response is mainly located in the vicinity of amyloid plaques. Cytokines, such as interleukin-8 (IL-8) and interleukin-1α (IL-1α), have been clearly involved in this inflammatory process. Polymorphisms of several interleukin genes have been correlated to the risk of developing AD. The present study investigated the association of AD with polymorphisms IL-8 -251T > A (rs4073) and IL-1α-889C > T (rs1800587) and the interactive effect of both, adjusted by the Apolipoprotein E genotype. 199 blood samples from patients with AD, 146 healthy elderly controls and 95 healthy young controls were obtained. DNA samples were isolated from blood cells, and the PCR-RFLP method was used for genotyping. The genotype distributions of polymorphisms IL-8, IL-1α and APOE were as expected under Hardy-Weinberg equilibrium. The allele frequencies did not differ significantly among the three groups tested. As expected, the APOE4 allele was strongly associated with AD (p < 0.001). No association of AD with either the IL-1α or the IL-8 polymorphism was observed, nor was any interactive effect between both polymorphisms. These results confirm previous studies in other populations, in which polymorphisms IL-8 -251T > A and IL-1α-889C > T were not found to be risk factors for AD.

Helicobacter pylori is an important human pathogen that causes chronic gastritis and is associated with the development of peptic ulcer disease and gastric malignancies. The oral cavity has been implicated as a potential H. pylori reservoir and may therefore be involved in the reinfection of the stomach, which can sometimes occur following treatment of an H. pylori infection. The objectives of this paper were (i) to determine the presence of H. pylori in the oral cavity and (ii) to examine the relationship between oral H. pylori and subsequent gastritis. Gastric biopsies, saliva samples and dental plaques were obtained from 78 dyspeptic adults. DNA was extracted and evaluated for the presence of H. pylori using polymerase chain reaction and Southern blotting methods. Persons with gastritis were frequently positive for H. pylori in their stomachs (p < 0.0001) and there was a statistically significant correlation between the presence of H. pylori in gastric biopsies and the oral cavity (p < 0.0001). Our results suggest a relationship between gastric infection and the presence of this bacterium in the oral cavity. Despite this, H. pylori were present in the oral cavity with variable distribution between saliva and dental plaques, suggesting the existence of a reservoir for the species and a potential association with gastric reinfection.