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1.
Emerg Microbes Infect ; 9(1): 548-557, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160805

RESUMO

Helicobacter pylori (H. pylori) recurrence remains a significant public health concern. The study aimed to assess H. pylori reinfection rate and identify its risk factors in China. This prospective open cohort, observational study was performed at 18 hospitals across 15 provinces in China. Consecutive patients who received the successful initial eradication during 1 January 2012 and 31 December 2018 were eligible for enrolment. H. pylori recurrence was defined as reinfection that occurred at more than the 12-month interval after successful initial eradication. Surveyed risk factors that might be associated with reinfection were preliminarily estimated by log-rank test and further determined by Cox regression model to calculate the hazard ratio (HR) and 95% confidence interval (CI). A total of 5193 subjects enrolled in the study. The follow-up intervals varied from 6 to 84 months with a general follow-up rate of 67.9%. Annual reinfection rate was 1.5% (95% CI: 1.2-1.8) per person-year. H. pylori reinfection was independently associated with the following five risk factors: minority groups (HR = 4.7, 95% CI: 1.6-13.9), the education at lower levels (HR = 1.7, 95% CI: 1.1-2.6), a family history of gastric cancer (HR = 9.9, 95% CI: 6.6-14.7), and the residence located in Western China (HR = 5.5, 95% CI: 2.6-11.5) following by in Central China (HR = 4.9, 95% CI: 3-8.1) (all P < 0.05). Reinfection rate of H. pylori in China is relatively low. Patients with specific properties of ethnic groups, education level, family history, or residence location appear to be at higher risk for reinfection.


Assuntos
Infecções por Helicobacter/virologia , Helicobacter pylori/fisiologia , Adulto , Erradicação de Doenças , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Fatores de Risco , Fatores de Tempo
2.
New Microbiol ; 42(4): 210-220, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31524946

RESUMO

Helicobacter pylori (H. pylori) is involved in the etiology of gastric cancer (GC). miRNAs are short RNAs that regulate gene expression by marking mRNAs for degradation. miRNAs are involved in tumorigenesis, metastasis, and cell proliferation. We aimed to investigate the miRNA expression profiles of tissues from H. pylori (+) and (-) GC patients. Forty GC patients, 20 H. pylori (+) and 20 H. pylori (-), and a healthy control group were included. The miRNA expression levels were investigated by microarrays and quantitative RT-PCR. We detected 9 upregulated and 4 downregulated miRNAs by microarray. We selected 5 upregulated and 5 downregulated miRNAs for the quantitative RT-PCR assay. The relative fold changes of miRNAs in the cancerous tissue and non-tumor mucosa specimens of H. pylori (+) GC patients for hsa-miR-194 were 4.24- and 3.83-fold higher, respectively, whereas the hsa-miR-145 expression levels were downregulated 0.33-fold and 0.43-fold, respectively, in the same group. The presence of H. pylori significantly upregulated hsa-miR-194 and downregulated hsa-miR-145 expression levels in H. pylori (+) GC cases, compared to H. pylori (-) GC cases. Regional differences in the virulence of H. pylori strains may also be involved in the up- or downregulation of miRNA expression levels.


Assuntos
Regulação Neoplásica da Expressão Gênica , Infecções por Helicobacter , Helicobacter pylori , MicroRNAs , Neoplasias Gástricas , Infecções por Helicobacter/complicações , Helicobacter pylori/fisiologia , Humanos , MicroRNAs/metabolismo , Estudos Prospectivos , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Turquia
3.
World J Gastroenterol ; 25(32): 4629-4660, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31528091

RESUMO

Helicobacter pylori (H. pylori) infection is highly prevalent in the human population and may lead to severe gastrointestinal pathology including gastric and duodenal ulcers, mucosa associated tissue lymphoma and gastric adenocarcinoma. In recent years, an alarming increase in antimicrobial resistance and subsequently failing empiric H. pylori eradication therapies have been noted worldwide, also in many European countries. Therefore, rapid and accurate determination of H. pylori's antibiotic susceptibility prior to the administration of eradication regimens becomes ever more important. Traditionally, detection of H.pylori and its antimicrobial resistance is done by culture and phenotypic drug susceptibility testing that are cumbersome with a long turn-around-time. Recent advances in diagnostics provide new tools, like real-time polymerase chain reaction (PCR) and line probe assays, to diagnose H. pylori infection and antimicrobial resistance to certain antibiotics, directly from clinical specimens. Moreover, high-throughput whole genome sequencing technologies allow the rapid analysis of the pathogen's genome, thereby allowing identification of resistance mutations and associated antibiotic resistance. In the first part of this review, we will give an overview on currently available diagnostic methods for detection of H. pylori and its drug resistance and their implementation in H. pylori management. The second part of the review focusses on the use of next generation sequencing technology in H. pylori research. To this end, we conducted a literature search for original research articles in English using the terms "Helicobacter", "transcriptomic", "transcriptome", "next generation sequencing" and "whole genome sequencing". This review is aimed to bridge the gap between current diagnostic practice (histology, rapid urease test, H. pylori culture, PCR and line probe assays) and new sequencing technologies and their potential implementation in diagnostic laboratory settings in order to complement the currently recommended H. pylori management guidelines and subsequently improve public health.


Assuntos
Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Genoma Bacteriano/genética , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/fisiologia , Humanos , Testes de Sensibilidade Microbiana , Tipagem Molecular/métodos , Reação em Cadeia da Polimerase em Tempo Real , Sequenciamento Completo do Genoma
4.
Int J Mol Sci ; 20(18)2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31500233

RESUMO

Helicobacter pylori colonises the human stomach and has tropism for the gastric mucin, MUC5AC. The majority of organisms live in the adherent mucus layer within their preferred location, close to the epithelial surface where the pH is near neutral. Trefoil factor 1 (TFF1) is a small trefoil protein co-expressed with the gastric mucin MUC5AC in surface foveolar cells and co-secreted with MUC5AC into gastric mucus. Helicobacter pylori binds with greater avidity to TFF1 dimer, which is present in gastric mucus, than to TFF1 monomer. Binding of H. pylori to TFF1 is mediated by the core oligosaccharide subunit of H. pylori lipopolysaccharide at pH 5.0-6.0. Treatment of H. pylori lipopolysaccharide with mannosidase or glucosidase inhibits its interaction with TFF1. Both TFF1 and H. pylori have a propensity for binding to mucins with terminal non-reducing α- or ß-linked N-acetyl-d-glucosamine or α-(2,3) linked sialic acid or Gal-3-SO42-. These findings are strong evidence that TFF1 has carbohydrate-binding properties that may involve a conserved patch of aromatic hydrophobic residues on the surface of its trefoil domain. The pH-dependent lectin properties of TFF1 may serve to locate H. pylori deep in the gastric mucus layer close to the epithelium rather than at the epithelial surface. This restricted localisation could limit the interaction of H. pylori with epithelial cells and the subsequent host signalling events that promote inflammation.


Assuntos
Helicobacter pylori/fisiologia , Lipopolissacarídeos/metabolismo , Estômago/microbiologia , Fator Trefoil-1/metabolismo , Mucinas Gástricas/metabolismo , Glucosidases/farmacologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Lipopolissacarídeos/química , Manosidases/farmacologia , Mucina-5AC/metabolismo , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/metabolismo , Ligação Proteica/efeitos dos fármacos , Multimerização Proteica , Fator Trefoil-1/química , Tropismo
5.
Artif Cells Nanomed Biotechnol ; 47(1): 3862-3872, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31556767

RESUMO

Zinc finger and BTB domain containing 20 (ZBTB20), a sequence-specific transcriptional repressor, has been found to be involved in tumorigenesis. However, its role(s) in gastric cancer and the molecular mechanisms involved are poorly investigated. Here, our data demonstrated that ZBTB20 expression was markedly upregulated in gastric cancer cell lines infected with Helicobacter pylori (H. pylori) and in gastric cancer tumor samples. Loss- and gain-of-function studies showed that ZBTB20 promoted cell proliferation, invasion and migration of gastric cancer cell lines. Mechanistically, the phosphorylation of NF-κBp65 and expression and activity of MMP-2 and MMP-9 were increased, while IκBα expression was decreased by ZBTB20 in gastric cancer cells. We further revealed that IκBα overexpression significantly inhibited NF-κB signaling as well as cell migration, invasion and proliferation in gastric cancer cell lines induced by ZBTB20 overexpression. Therefore, our findings emphasize an important role for ZBTB20 in controlling gastric cancer development, which is helpful to identify potential therapeutic targets for its treatment.


Assuntos
Movimento Celular , Inibidor de NF-kappaB alfa/antagonistas & inibidores , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neoplasias Gástricas/patologia , Fatores de Transcrição/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Helicobacter pylori/fisiologia , Humanos , Invasividade Neoplásica , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/microbiologia , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética
6.
Infect Immun ; 87(11)2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31383743

RESUMO

Interleukin-21 (IL-21), a cytokine produced by many subsets of activated immune cells, is critical for driving inflammation in several models. Using Helicobacter pylori infection as a model for chronic mucosal infection, we previously published that IL-21 is required for the development of gastritis in response to infection. Concomitant with protection from chronic inflammation, H. pylori-infected IL-21-/- mice exhibited limited Th1 and Th17 responses in their gastric mucosa. Here we report that H. pylori-infected IL-21-/- mice express significantly higher levels of IL-17A than H. pylori-infected wild-type (WT) mice in the Peyer's patches and mesenteric lymph nodes. This led us to hypothesize that IL-21 may indirectly regulate H. pylori-specific T cell responses by controlling dendritic cell (DC) functions in mucosa-associated lymphoid tissue. It was found that IL-21 treatment reduced the ability of dendritic cells to produce proinflammatory cytokines in response to H. pylori While H. pylori increased the expression of costimulatory proteins on DCs, IL-21 reduced the expression of CD40 in the presence of H. pylori Also, Th17 recall responses were intact when DCs were used as antigen-presenting cells in the presence of IL-21, but IL-21 did impact the ability of DCs to induce antigen-specific proliferation. These data suggest that IL-21, while proinflammatory in most settings, downregulates the proinflammatory cytokine microenvironment through modulating the cytokine expression of DCs, indirectly modifying IL-17A expression. Understanding how these proinflammatory cytokines are regulated will advance our understanding of how and why H. pylori infection may be tolerated in some individuals while it causes gastritis, ulcers, or cancer in others.


Assuntos
Citocinas/metabolismo , Células Dendríticas/fisiologia , Helicobacter pylori/fisiologia , Interleucina-17/metabolismo , Interleucinas/metabolismo , Linfócitos T/metabolismo , Animais , Citocinas/genética , Células Dendríticas/microbiologia , Feminino , Regulação da Expressão Gênica/fisiologia , Infecções por Helicobacter , Interleucina-17/genética , Interleucinas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nódulos Linfáticos Agregados/metabolismo
7.
Clin Lab ; 65(12)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414587

RESUMO

BACKGROUND: Screening and timely treatment of precancerous gastric cancer diseases or of gastric cancer in the early stages has important significance in reducing the incidence and mortality of gastric cancer. Gastroscopy and histopathological biopsy are still the gold standards for the diagnosis of gastric diseases. But the application of astroscopy for the screening and diagnosis of gastric diseases is limited. In recent years, serum pepsinogen (PG), gastrin, and Helicobacter pylori (H. pylori) IgG antibodies have become indicators for "serological biopsy" of the gastric mucosa. METHODS: From January 2016 to January 2018, a total of 2,394 patients with digestive tract symptoms underwent gastroscopy. According to the endoscopic examination and pathological diagnosis, there were four case groups: 1,376 cases of chronic non-atrophic gastritis, 708 cases of chronic atrophic gastritis, 265 cases of gastric ulcer, and 45 cases of gastric cancer. Serological gastric biopsies were performed and analyzed. RESULTS: The serum levels of PGI in the chronic atrophic gastritis group was significantly lower than that in the chronic non-atrophic gastritis group, gastric ulcer group, and gastric cancer group (p < 0.05). The serum levels of PGII and G-17 in the gastric cancer group were significantly higher than those in the chronic non-atrophic Gastritis group, chronic atrophic gastritis group, and gastric ulcer group (p < 0.05). The PGR in the gastric cancer group was significantly lower than that in the chronic non-atrophic gastritis group, chronic atrophic Gastritis group, and gastric ulcer group (p < 0.05). The H. pylori positive rates in the chronic atrophic gastritis group and gastric cancer group were higher than those in the chronic non-atrophic gastritis group and gastric ulcer Group (p < 0.05). CONCLUSIONS: Serological gastric biopsy is closely correlated to gastric mucosal disease and can be used as a Screening tool in gastric disease.


Assuntos
Anticorpos Antibacterianos/sangue , Biomarcadores/sangue , Mucosa Gástrica/metabolismo , Gastrinas/sangue , Pepsinogênio A/sangue , Neoplasias Gástricas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/imunologia , Biópsia , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Helicobacter pylori/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias Gástricas/patologia , Adulto Jovem
8.
J Med Life ; 12(2): 133-139, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31406514

RESUMO

Colon cancer is the most commonly diagnosed gastrointestinal cancers in developed countries with varied incidence and the onset age of disease worldwide. Overall, 161 participants who were under patronage of a local relief foundation and referred to the endoscopy ward of Razi Hospital affiliated to the Guilan University of Medical Sciences. These patients have been aged more than 50 or more than 40 years with history of colorectal cancer in their first-degree family were enrolled from March 2016-March 2017. Demographic information were collected. Colonoscopy was performed and histopathological evaluation of observed lesions and polyps was done. Most of participants were female (113 individuals, 70.2%) and aged 50-60 years (83 individuals, 51.6%). Seventy-four (46%) had certain lesions. Most of colonoscopy findings were observed in the ascending colon in which depressed polyps and diverticulum were most frequent. However, rectum showed the most histological findings. All polyps of descending and ascending colons were neoplastic, while most of rectal polyps were non-neoplastic. Male patients, who were aged more than 60 years and smokers had significant higher percentage of both lesions and polyps in their colon (p<0.05). Moreover, significant positive association was detected between exposure to harmful industries and having polyps (p=0.01). We found male gender, higher age, smoking, and exposure to harmful industries as important risk factors for having colorectal lesions, which must be confirmed in further studies.


Assuntos
Neoplasias do Colo/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Colo/patologia , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/microbiologia , Neoplasias do Colo/patologia , Pólipos do Colo/patologia , Colonoscopia , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Humanos , Incidência , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico por imagem , Prevalência , Análise de Regressão , Fatores de Risco
9.
J Med Life ; 12(2): 168-172, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31406519

RESUMO

There is evidence that infection by H. pylori can have a critical proportion in the development of hepatocyte injury and both noncancerous and malignant liver conditions including non-alcoholic fatty liver disease (NAFLD). This is attributed to several mechanisms, the most important one being the toxic products of the bacterium H. pylori and oxidative injury for hepatocytes which promotes hepatic injury. The present research was aimed at determining the association between H. pylori infection and the prevalence of NAFLD in Birjand, Iran. Two groups were included in this cross-sectional study at the outpatient university clinic. One group had NAFLD (65 patients) and the other group was healthy controls without NAFLD (65 subjects). The diagnosis of NAFLD was performed using abdominal ultrasound examination and the absence of taking steatogenic medications or alcohol. Serum anti-H. pylori IgG and fecal H. pylori antigen were tested for diagnosing of H. pylori infection using ELISA method. H. pylori infection diagnosis was made if both tests were positive. None of the subjects in either group had symptoms related to the digestive system including dyspepsia, GERD (gastroesophageal reflux disease), or epigastric pain suspicious of peptic ulcer disease. There were 37 patients (28.5%) in both NAFLD (22 cases, 33.8%) and control (15 cases, 23.1%) groups whose H. pylori tests (both IgG and fecal antigen) were positive. Statistically, no significant difference was observed between the two studied groups regarding H. pylori infection frequency (p = 0.37). Asymptomatic H. pylori infection rate was not significantly different between NAFLD patients and control subjects in Birjand, Iran.


Assuntos
Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/fisiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Infecções por Helicobacter/sangue , Humanos , Irã (Geográfico)/epidemiologia , Lipídeos/sangue , Fígado/enzimologia , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Transaminases/metabolismo
10.
PLoS Biol ; 17(8): e3000395, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31465435

RESUMO

The gastric pathogen Helicobacter pylori requires a noncanonical cytosolic chemoreceptor transducer-like protein D (TlpD) for efficient colonization of the mammalian stomach. Here, we reconstituted a complete chemotransduction signaling complex in vitro with TlpD and the chemotaxis (Che) proteins CheW and CheA, enabling quantitative assays for potential chemotaxis ligands. We found that TlpD is selectively sensitive at micromolar concentrations to bleach (hypochlorous acid, HOCl), a potent antimicrobial produced by neutrophil myeloperoxidase during inflammation. HOCl acts as a chemoattractant by reversibly oxidizing a conserved cysteine within a 3His/1Cys Zn-binding motif in TlpD that inactivates the chemotransduction signaling complex. We found that H. pylori is resistant to killing by millimolar concentrations of HOCl and responds to HOCl in the micromolar range by increasing its smooth-swimming behavior, leading to chemoattraction to HOCl sources. We show related protein domains from Salmonella enterica and Escherichia coli possess similar reactivity toward HOCl. We propose that this family of proteins enables host-associated bacteria to sense sites of tissue inflammation, a strategy that H. pylori uses to aid in colonizing and persisting in inflamed gastric tissue.


Assuntos
Quimiotaxia/fisiologia , Helicobacter pylori/metabolismo , Receptores de Formil Peptídeo/metabolismo , Proteínas de Bactérias/metabolismo , Clareadores , Células Quimiorreceptoras/metabolismo , Fatores Quimiotáticos/metabolismo , Citosol/metabolismo , Citosol/fisiologia , Helicobacter pylori/fisiologia , Ácido Hipocloroso , Oxirredução , Receptores de Formil Peptídeo/fisiologia , Transdução de Sinais
11.
Oncogene ; 38(37): 6461-6477, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31332288

RESUMO

Helicobacter pylori (Hp) infection and overexpression of hepatoma-derived growth factor (HDGF) are involved in gastric carcinogenesis. However, the relationship between Hp-induced gastric diseases and HDGF upregulation is not yet completely clear. This study aimed to elucidate the role of HDGF in Hp-induced gastric inflammation and carcinogenesis. HDGF expression in gastric biopsy and serum from patients was analyzed by immunohistochemical and ELISA analysis, respectively. Hp and gastric cells coculture system was employed to delineate the mechanism underlying HDGF overexpression during Hp infection. The gastric pathologies of wild type and HDGF knockout mice after Hp infection were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. HDGF level was significantly elevated in patients with Hp infection or intestinal metaplasia (IM, a precancerous lesion), and HDGF overexpression was positively correlated with Hp load, IM, and neutrophil infiltration in gastric biopsy. Consistently, patients with Hp infection or IM had significantly higher serum HDGF level. By using coculture assay, Hp infection led to HDGF upregulation and secretion in gastric cells. In mice model, HDGF ablation significantly suppressed the Hp-induced neutrophil infiltration and inflammatory TNF-α/COX-2 signaling, thereby relieving the tissue damage in stomach. This was further supported by that recombinant HDGF (rHDGF) stimulated the differentiation/chemotaxis of cultured neutrophils and oncogenic behaviors of gastric cells. Time series studies showed that Hp infection elicited an inflammatory TNF-α/HDGF/COX-2 cascade in stomach. HDGF secretion by Hp infection promotes the neutrophils infiltration and relays Hp-induced inflammatory signaling. Thus, HDGF may constitute a novel diagnostic marker and therapeutic target for Hp-induced gastritis and carcinogenesis.


Assuntos
Gastrite , Infecções por Helicobacter/complicações , Helicobacter pylori/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Infiltração de Neutrófilos , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Animais , Carcinogênese/genética , Carcinogênese/imunologia , Carcinogênese/patologia , Células Cultivadas , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/genética , Gastrite/imunologia , Gastrite/microbiologia , Gastrite/patologia , Células HL-60 , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos/genética , Neutrófilos/imunologia , Neutrófilos/metabolismo , Estômago/imunologia , Estômago/microbiologia , Estômago/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia
12.
Clin Lab ; 65(6)2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31232019

RESUMO

BACKGROUND: While all modalities used for diagnosis of Helicobacter pylori (H. pylori) have demonstrated sufficient sensitivity and specificity, each test has advantages and limitations. The serum test for anti-H. pylori antibody with the latex method is noninvasive, easy, and inexpensive; it is thus a useful tool for mass-screening for H. pylori. In this study, we evaluated the utility of a newly developed latex kit, in comparison with other serum diagnostic kits based on enzyme-linked immunosorbent assay (ELISA). METHODS: In total, 187 subjects (77: H. pylori-positive, 75: H. pylori-negative, 35: previous infection with H. pylori) seen at Oita University Hospital during the period from January 1988 to September 2014 were enrolled in the study. All subjects were evaluated with 4 types of serum H. pylori antibody kits. One modality was based on the use of latex (Denka Kit, Denka Seiken Co., Ltd., Tokyo, Japan). Three kits were based on the use of ELISA. The E-Plate II Eiken (Eiken Chemical Co., Ltd., Tokyo, Japan) is henceforth referred to as Kit A. The Premier H. pylori kit (Meridian Bioscience, Inc., USA) is referred to as Kit B. The Platelia H. pylori IgG (Bio-Rad, Marnes-la-Coquette, France) is referred to as Kit C. RESULTS: Evaluation of 152 study participants, including some who were positive for H. pylori and some who were negative, sensitivity, specificity, and accuracy values were as follows: for the Denka kit, these values were, respec-tively, 92.2%, 93.3%, and 92.8%. For Kit A, these values were 88.3%, 100.0%, and 194.1%. For Kit B, these values were 98.7%, 76.0%, and 87.5%. For Kit C, these values were 98.7%, 80.0%, and 89.5%. The specificity of Kit A was > 90%. Sensitivity was > 90% for Kits B and C. For the Denka kit, both sensitivity and specificity were > 90%. Among the 35 subjects previously infected with H. pylori, the rate of positive diagnosis was 48.6% (17/35) with the Denka kit, 17.1% (6/35) with Kit A, 54.3% (19/35) with Kit B, and 54.3% (19/35) with Kit C. The rate of positive diagnosis was significantly higher with the Denka kit than with Kit A (p < 0.05). CONCLUSIONS: An assay based on use of the latex method, H. pylori-latex Seiken, demonstrated satisfactory sensitivity and specificity for detecting serum levels of H. pylori antibody. The performance of this kit was equivalent to that of ELISA kits currently used for the same purpose. This kit is therefore considered to be extremely suitable for diagnosis of H. pylori and mass-screening of patients at high risk for gastric cancer.


Assuntos
Anticorpos Antibacterianos/imunologia , Especificidade de Anticorpos/imunologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/imunologia , Imunoturbidimetria/métodos , Kit de Reagentes para Diagnóstico/normas , Anticorpos Antibacterianos/sangue , Ensaio de Imunoadsorção Enzimática/métodos , França , Infecções por Helicobacter/sangue , Infecções por Helicobacter/virologia , Helicobacter pylori/fisiologia , Humanos , Japão , Látex , Kit de Reagentes para Diagnóstico/classificação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estados Unidos
13.
Ann Hematol ; 98(8): 1981-1987, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177299

RESUMO

Infection with Helicobacter pylori (H. pylori) is associated with an increased risk of gastric malignant lymphoma. The chronic inflammation of gastric mucosa by H. pylori infection induces lymphomagenesis. Although this chronic mucosal inflammation also results in atrophic gastritis, evidence supporting the possible significance of atrophic gastritis in gastric lymphomagenesis is scarce. Here, to evaluate the association between gastric mucosal atrophy and the risk of gastric lymphoma, we conducted a matched case-control study at Aichi Cancer Center focusing on the attribution of H. pylori infection status and pepsinogen (PG) serum levels. In total, 86 patients with gastric lymphoma (including 49 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and 24 cases of diffuse large B cell lymphoma (DLBCL)) and 1720 non-cancer controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results failed to show a statistically significant association between atrophic gastritis and the risk of gastric lymphoma. The adjusted ORs of positive atrophic gastritis relative to negative for overall gastric lymphoma, MALT lymphoma, DLBCL, and other lymphomas were 0.77 (95% CI 0.45-1.33), 0.65 (0.30-1.39), 1.03 (0.38-2.79), and 0.84 (0.22-3.29), respectively. In contrast, a positive association between overall gastric lymphoma and H. pylori infection was observed (OR = 2.14, 95% CI 1.30-3.54). A consistent association was observed for MALT lymphoma, DLBCL, and other lymphomas with ORs of 1.96 (1.00-3.86), 1.92 (0.74-4.95), and 5.80 (1.12-30.12), respectively. These findings suggest that H. pylori infection triggers gastric lymphoma but that epithelial changes due to atrophic gastritis do not inherently affect the development of gastric lymphoma.


Assuntos
Infecções por Helicobacter/diagnóstico , Helicobacter pylori/patogenicidade , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma não Hodgkin/diagnóstico , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Carcinogênese/patologia , Estudos de Casos e Controles , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite Atrófica/complicações , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/fisiologia , Humanos , Japão , Modelos Logísticos , Linfoma de Zona Marginal Tipo Células B/etiologia , Linfoma de Zona Marginal Tipo Células B/microbiologia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Difuso de Grandes Células B/etiologia , Linfoma Difuso de Grandes Células B/microbiologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/etiologia , Linfoma não Hodgkin/microbiologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pepsinogênio A/sangue , Fatores de Risco , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
14.
PLoS One ; 14(6): e0217645, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31163069

RESUMO

BACKGROUND: Eradication of Helicobacter pylori infection with standard triple therapy has been accepted to curb associated risks of chronic gastritis andpeptic ulcer disease. OBJECTIVE: To assess H. pylori eradication rate of standard triple therapy and patient related factors affecting eradication rate. METHODS: A facility based prospective follow up study was conducted in Bahir Dar City Administration, Ethiopia, on consented outpatients presented with gastritis and peptic ulcer disease and positive for H. pylori stool antigen test from May 2016 to April 2018. Eradication was confirmed with stool antigen test made after 4-6 weeks of standard triple therapy, comprising of proton pump inhibitor, clarithromycin and amoxicillin. Pre-developed questionnaire and data collection formats were used to collect variables before and after therapy. Bivariate and backward stepwise multivariate logistic regression was used to analyze data. P-value < 0.05 at 95%CI was considered as significant. RESULTS: The overall H. pylori eradication rate was 90.3% (379/421). Almost 80% of the patients were urban residents. Mean (±SD) age and body weight of patients were 30.63 (± 10.74) years and 56.79 (± 10.17) kg, respectively. Self-reported adverse drug effects and area of residence of patients were factors affecting eradication rate significantly. Patients with no self-reported adverse drug effect were 3.85 (AOR: 3.85; 95%CI (1.41-5.26)) times more likely to eradicate H. pylori infection compared to those reported adverse effects. Patients living in rural area were 2.7 (AOR: 2.7; 95%CI (1.19-20.0)) times more likely to achieve eradication compared to urban residents. CONCLUSION: H. pylori eradication rate is within the recommended level for clinical practice, indicating that modifications of the standard triple therapy observed in the different healthcare institutions are not evidence-based. Emphasis should be given to adverse drug effects of medications and tailored counseling based on area of residence could have a contribution in improving eradication rate.


Assuntos
Erradicação de Doenças , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Etiópia , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
15.
Biomolecules ; 9(6)2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216758

RESUMO

The gut microbiota is significantly involved in the preservation of the immune system of the host, protecting it against the pathogenic bacteria of the stomach. The correlation between gut microbiota and the host response supports human gastric homeostasis. Gut microbes may be shifted in Helicobacter pylori (Hp)-infected individuals to advance gastric inflammation and distinguished diseases. Particularly interesting is the establishment of cooperation between gut microbiota and antimicrobial peptides (AMPs) of the host in the gastrointestinal tract. AMPs have great importance in the innate immune reactions to Hp and participate in conservative co-evolution with an intricate microbiome. ß-Defensins, a class of short, cationic, arginine-rich proteins belonging to the AMP group, are produced by epithelial and immunological cells. Their expression is enhanced during Hp infection. In this review, we discuss the impact of the gut microbiome on the host response, with particular regard to ß-defensins in Hp-associated infections. In microbial infections, mostly in precancerous lesions induced by Hp infection, these modifications could lead to different outcomes.


Assuntos
Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Microbiota , beta-Defensinas/metabolismo , Microbioma Gastrointestinal , Humanos
16.
Clin Lab ; 65(5)2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31115218

RESUMO

BACKGROUND: Helicobacter pylori is a gram-negative bacterium infecting approximately 50% of the world's population. Antibiotic resistance in H. pylori has significantly increased due to the overuse and misuse of common antibiotics. Mutations in the 23S rRNA gene and other H. pylori genetic mutations have been identified as significant drivers in the emergence of resistance. Therefore, there is an urgent need for genetic analysis of H. pylori antibiotic resistance. METHODS: Published H. pylori resistance genes were collected from PubMed websites by bibliometrics. Pathway analysis and operon analysis were performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), the Database for Annotation, Visualization and Integrated Discovery (DAVID), and Database of prOkaryotic OpeRons (DOOR) databases to investigate pathways and biological functions of resistance genes and statistically discover novel resistance genes. RESULTS: A total of 148 genes were mined from the literature using bibliometrics, and 46 enriched pathways were identified using KEGG. Subsequently, 7 novel resistant genes of H. pylor, including HP0776, HP0192, HP0193, HP0475, HP1057, HP0632, and HP0633, were identified and predicted by functional enrichment analysis of pathways and operons. CONCLUSIONS: The discovery of these novel H. pylori resistance genes is of great significance to treat H. pylori-induced diseases and develop optimal treatment regimens. They also provide theoretical fundamentals for epidemiological prevention and strengthen our understanding of the molecular mechanism of H. pylori resistance to antibiotics.


Assuntos
Bibliometria , Farmacorresistência Bacteriana/genética , Helicobacter pylori/genética , Óperon , Transdução de Sinais/genética , Antibacterianos/farmacologia , DNA Bacteriano/genética , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/fisiologia , Humanos , Testes de Sensibilidade Microbiana , Mutação , RNA Ribossômico 23S/genética
17.
Clin Lab ; 65(5)2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31115224

RESUMO

BACKGROUND: A sensitive, non-invasive molecular test for identifying Helicobacter pylori (H. pylori) in stool samples is important in the context of a "test-and-treat strategy". The goal of this study was to elucidate the benefit of an initial reverse transcription (RT) step for the sensitivity of H. pylori 23S rDNA Real-time PCR in stool samples. METHODS: We compared a LightMix® Modular Helicobacter 23S rDNA PCR assay without (LightMix® PCR) and with an initial reverse transcription step (LightMix® RT-PCR) assay for rapid detection of Helicobacter pylori in fecal samples. For maximum sensitivity, all Lightmix® RT-PCR assays were performed in triplicate for each sample. Additionally, the LightMix® RT-PCR was compared to H. pylori AG ELISA. RESULTS: Direct detection of H. pylori in feces by Lightmix® PCR was less sensitive than LightMix® RT-PCR. Only 2 out of 44 stool samples (4.5%) from patients with diarrhea were positive for H. pylori in the LightMix® PCR assay. In contrast, a reverse transcription step prior Lightmix® PCR increased the assay sensitivity markedly (19 out of 44 positives, 43.2%). When re-testing 65 samples initially analyzed with H. pylori AG ELISA with LightMix® RT-PCR, the detection rate for H. pylori was similarly increased from 23.1% (15/65) with H. pylori AG ELISA to 43.1% (28/65) with H. pylori LightMix® RT-PCR. 21.5% of the 28 H. pylori positive samples were positive in 1/3, 32% in 2/3, and 46.5% in 3/3 triple RT-PCR approaches. When re-testing the 28 LightMix® RT-PCR positive samples by LightMix® PCR, only 17.9% (5/28) RT-PCR positive samples were positive in PCR. CONCLUSIONS: LightMix® RT-PCR is much more sensitive than Lightmix® PCR. In comparison to H. pylori AG ELISA, the LightMix® RT-PCR shows a markedly higher sensitivity. An initial reverse transcription step is crucial for reliable Helicobacter pylori 23S rDNA Real-time PCR diagnostics. The triple RT-PCR approach can additionally improve the detection of H. pylori in fecal samples. Thus, the method presented provides a highly sensitive, noninvasive assay to detect H. pylori in fecal samples with potential advantages compared to other H. pylori detection methods currently used in routine diagnostics.


Assuntos
DNA Ribossômico/genética , Fezes/microbiologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/genética , RNA Ribossômico 23S/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Transcrição Reversa , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Humanos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
18.
Helicobacter ; 24(4): e12594, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31119830

RESUMO

BACKGROUND: Bismuth-containing quadruple therapy (BQT) is a recommended alternative first-line therapy for Helicobacter pylori (H. pylori) infection. We aim to evaluate the efficacy and safety of a new BQT with amoxicillin and doxycycline as a first-line treatment for H. pylori infection in clinical practice. METHODS: An open, prospective pilot clinical study including H. pylori-positive outpatients who had never received eradication treatment was carried out. An RADB regimen (10 mg rabeprazole, 1000 mg amoxicillin, 100 mg doxycycline, and 220 mg colloidal bismuth tartrate, all given bid for 14 days) was prescribed by gastroenterologists. H. pylori eradication was confirmed by a 13 C-urea breath test performed at least 6 weeks after the end of treatment. Regimen efficacy was evaluated by per-protocol (PP) and intention-to-treat (ITT) analyses. RESULTS: One hundred eighteen patients were included in the study. The eradication rate of RADB was 93.8% (105/112; 95% CI 89.2%-98.3%) in PP analysis and 89.8% (106/118; 95% CI 84.3%-95.4%) in ITT analysis. The patient compliance rate was 97.5% (115/118). The adverse event rate was 6.8% (8/118). Adverse events included asthenia, loss of appetite, dry mouth, heartburn, diarrhea, and abdominal pain. All adverse events disappeared after completion of therapy. CONCLUSION: Our results suggest that 14-day BQT with amoxicillin and doxycycline can be an effective and safe eradication regimen for first-line therapy against H. pylori infection in clinical practice.


Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Doxiciclina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Rabeprazol/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Adulto Jovem
19.
Curr Top Microbiol Immunol ; 421: 303-318, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123894

RESUMO

Microbes within the gastrointestinal tract communicate with each other and with the host, which has profound effects on health and disease development. Only now, it is becoming apparent that how and when we acquire our own unique collection of "gut microbes" and also how we choose to maintain them is fundamental to our health. Helicobacter pylori is the most common bacterial infection worldwide, colonizing around half of the world's population, and is the major risk factor for gastric adenocarcinoma. More recently, it has also been shown to have some beneficial effects in terms of protecting against the development of other diseases. Here, we review the current knowledge on how H. pylori has shaped gastrointestinal microbiota colonization and the host immune system with specific focus on the impact of H. pylori on the various microbiome niches of the gastrointestinal tract. We discuss how the presence of H. pylori influences the physiology of three major regions within the gastrointestinal tract-specifically the oesophagus, stomach and colon. We pay particular attention to the role of H. pylori under chronic inflammatory conditions including the development of cancer. With increased incidence of diseases such as eosinophilic oesophagitis, oesophageal adenocarcinoma and squamous cell carcinoma being attributed to the decline in H. pylori, their disease pathogenesis in light of changing H. pylori colonization is also discussed.


Assuntos
Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Sistema Imunitário/imunologia , Sistema Imunitário/microbiologia , Colo/imunologia , Colo/microbiologia , Esôfago/imunologia , Esôfago/microbiologia , Helicobacter pylori/fisiologia , Humanos , Estômago/imunologia , Estômago/microbiologia
20.
Helicobacter ; 24(4): e12590, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31124220

RESUMO

BACKGROUND: The eradication of Helicobacter pylori (H pylori) has been suggested to reduce the risk of gastric cancer, but its impact on the gut microbiota has attracted public attention. This study aimed to investigate the short-term and long-term effects of bismuth quadruple therapy on both gastric and fecal microbiota. METHODS: Ten asymptomatic young adults with H pylori-related gastritis were treated with bismuth quadruple therapy for 14 days, and 7 age-matched adults without H pylori infection were enrolled as healthy controls. Both fecal and gastric mucosa samples were collected from H pylori-positive patients at weeks 0, 6, and 26, while fecal samples were collected from healthy controls. The gastric and gut microbiota were analyzed by 16S rRNA gene sequencing. RESULTS: The structure of the gastric microbiota was significantly changed after the eradication of H pylori with increased alpha diversity over time. The relative abundance of H pylori sharply decreased from more than 70% to nearly 0% after treatment, while some beneficial bacteria, such as Lactobacillus and Bifidobacterium, were increased. The microbial diversity of gut microbiota was higher in H pylori-infected patients than in healthy controls, which tended to decrease after eradication. The potentially beneficial gut bacteria Blautia and Lachnoclostridium were enriched at week 26 compared to week 0, while the pathogenic Alistipes were depleted to a level close to that of the healthy controls. CONCLUSIONS: Bismuth quadruple therapy for H pylori eradication can restore the diversity of gastric microbiota with enrichment of beneficial bacteria. The composition of gut microbiota after H pylori eradication trends toward healthy status instead of becoming dysbiotic.


Assuntos
Antibacterianos/uso terapêutico , Doenças Assintomáticas/terapia , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Adulto , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Bismuto/uso terapêutico , Feminino , Gastrite/tratamento farmacológico , Gastrite/microbiologia , Infecções por Helicobacter/patologia , Humanos , Masculino , Adulto Jovem
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