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2.
Eur J Clin Microbiol Infect Dis ; 39(10): 1821-1830, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32557327

RESUMO

Helicobacter pylori (H. pylori) infection is associated with some gastric diseases, such as gastritis, peptic ulcer, and gastric cancer. CagA and VacA are known virulence factors of H. pylori, which play a vital role in severe clinical outcomes. Additionally, the expression of outer membrane proteins (OMPs) helps H. pylori attach to gastric epithelial cells at the primary stage and increases the virulence of H. pylori. In this review, we have summarized the paralogs of H. pylori OMPs, their genomic loci, and the different receptors of OMPs identified so far. We focused on five OMPs, BabA (HopS), SabA (HopP), OipA (HopH), HopQ, and HopZ, and one family of OMPs: Hom. We highlight the coexpression of OMPs with other virulence factors and their relationship with clinical outcomes. In conclusion, OMPs are closely related to the pathogenic processes of adhesion, colonization, persistent infection, and severe clinical consequences. They are potential targets for the prevention and treatment of H. pylori-related diseases.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , Fatores de Virulência/metabolismo , Células Epiteliais/microbiologia , Expressão Gênica , Humanos , Fatores de Virulência/genética
3.
Medicine (Baltimore) ; 99(21): e20361, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481329

RESUMO

INTRODUCTION: Gastric adenocarcinoma of the fundic gland type (GA-FG) is a newly described entity that is characterized by well-differentiated neoplasm with unclear etiopathogenesis. PATIENT CONCERNS: A 60-year-old Chinese man was referred to our hospital for abdominal distension. DIAGNOSIS: Esophagogastroduodenoscopy (EGD) showed a depressed lesion found using in the greater curvature of the stomach. The pathological diagnosis of the biopsy specimens indicated that the tumor was GA-FG (chief cell predominant type, GA-FG-CCP). INTERVENTIONS: Endoscopic submucosal dissection (ESD) was performed. The histopathological examination of the ESD specimen revealed gastric hyperplasia of the fundic gland type around the adenocarcinoma cells. OUTCOMES: The surgical outcomes were good. The EGD showed a scar with no recurrence, and no symptoms were observed 1 year postoperatively during the follow-up. CONCLUSION: We present a rare case of a depressed lesion with a pathogenic expression suggesting gastric hyperplasia of the fundic gland type around the adenocarcinoma cells. Considering the origin of oxyntic mucosa, we consider that it may develop into GA-FG. To understand this issue better, similar cases should be monitored in the future.


Assuntos
Adenocarcinoma/diagnóstico , Mucosa Gástrica/anormalidades , Adenocarcinoma/diagnóstico por imagem , China , Ressecção Endoscópica de Mucosa/métodos , Endoscopia do Sistema Digestório/métodos , Feminino , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/fisiopatologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/patogenicidade , Humanos , Pessoa de Meia-Idade , Mucina-6/análise , Pepsinogênio A/análise
4.
Virchows Arch ; 477(4): 489-496, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32356024

RESUMO

Pyloric metaplasia (PM) and pseudopyloric metaplasia (PPM) are metaplastic changes resulting in pyloric-type glands in the gastric oxyntic mucosa that mainly occur in chronic gastritis caused by Helicobacter pylori (H. pylori) infection. Focusing on PM and PPM, we classified the histological changes in gastric mucosa according to the Updated Sydney System, using 314 biopsy specimens of gastric greater curvature of the middle body before H. pylori eradication (HPE). Next, the numbers of PM and PPM glands were counted in 47 specimens, and subjects were followed up over 10 years after HPE. PPM was recognized jointly with inflammation, activity, atrophy, and intestinal metaplasia, but PM was recognized more frequently than PPM as atrophy and intestinal metaplasia progressed. Both PM and PPM regressed significantly within 6 years after HPE. Additionally, we demonstrated that PM and PPM are not always coincident with spasmolytic polypeptide-expressing metaplasia (SPEM). In conclusion, PM and PPM are considered different modulations of the same line of differentiation, which are both reversible, with PM potentially emerging from PPM upon progression.


Assuntos
Mucosa Gástrica/patologia , Gastrite/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Biópsia , Diferenciação Celular , Doença Crônica , Mucosa Gástrica/química , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Gastrite/tratamento farmacológico , Gastrite/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Metaplasia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
5.
PLoS One ; 15(4): e0230064, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271765

RESUMO

Serum pepsinogens have been widely acknowledged as gastric mucosal biomarkers; however, a multicountry report on the benefits of pepsinogens as biomarkers has not yet been published. We analyzed 1,206 sera and gastric mucosal samples collected from Bangladesh, Bhutan, Indonesia, Myanmar, Nepal and Thailand then assessed the association between gastric mucosal changes and Helicobacter pylori infection. The new cutoff values for serum pepsinogen values were evaluated using a receiver operating characteristic analysis. The participants with H. pylori infection had significantly lower pepsinogen I and higher pepsinogen II values, but a lower pepsinogen I/II ratio than participants without the infection (all P < .001). The pepsinogen I and pepsinogen I/II values were significantly higher and lower, respectively, in individuals with atrophic gastritis than in those without (both P < .001). Among uninfected individuals, only the pepsinogen I/II ratio was significantly lower in atrophic individuals. Pepsinogen I/II ratio also were significantly different between disease among H. pylori-positive and H. pylori-negative individuals, suggesting the pepsinogen I/II ratio is a robust biomarker for determining both chronic and atrophic gastritis. The cutoffs for detecting chronic and atrophic gastritis for the pepsinogen I/II ratio were 4.65 and 4.95, respectively. In conclusion, pepsinogen levels are useful biomarker for both chronic gastritis and atrophic gastritis, but they should be used with caution. Population-based validation is necessary to determine the best cutoff values. Among all pepsinogen values, the pepsinogen I/II ratio was the most reliable gastric mucosal-change biomarker.


Assuntos
Gastrite/sangue , Pepsinogênio A/sangue , Pepsinogênio C/sangue , Neoplasias Gástricas/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia , Biomarcadores/sangue , Doença Crônica , Feminino , Gastrite Atrófica/sangue , Helicobacter pylori/patogenicidade , Helicobacter pylori/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco , Fatores de Virulência/metabolismo , Adulto Jovem
6.
Adv Exp Med Biol ; 1238: 11-22, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32323177

RESUMO

The gastrointestinal (GI) tract is inhabited by a diverse array of microbes, which play crucial roles in health and disease. Dysbiosis of microbiota has been tightly linked to gastrointestinal inflammatory and malignant diseases. Here we highlight the role of Helicobacter pylori alongside gastric microbiota associated with gastric inflammation and cancer. We summarize the taxonomic and functional aspects of intestinal microbiota linked to inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), and colorectal cancer in clinical investigations. We also discuss microbiome-related animal models. Nevertheless, there are tremendous opportunities to reveal the causality of microbiota in health and disease and detailed microbe-host interaction mechanisms by which how dysbiosis is causally linked to inflammatory disease and cancer, in turn, potentializing clinical interventions with a personalized high efficacy.


Assuntos
Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Disbiose/microbiologia , Disbiose/patologia , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Animais , Helicobacter pylori/patogenicidade , Humanos , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/patologia
7.
Medicine (Baltimore) ; 99(17): e19890, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332662

RESUMO

RATIONALE: Dabigatran is an anticoagulant medication that has been widely used to prevent strokes caused by atrial fibrillation, deep vein thrombosis, and pulmonary embolism. However, the potential adverse effect of dabigatran of gastrointestinal mucosal injury is often neglected, and even induces esophagitis. PATIENT CONCERNS: A 77-year-old woman was admitted to the hospital with symptoms of progressive retrosternal pain, upper abdominal discomfort, and dysphagia. DIAGNOSIS: Esophagogastroduodenoscopy showed longitudinal sloughing mucosal casts in the distal esophagus. Histological examination showed squamous epithelium with neutrophil infiltration, partial epithelial degeneration, and Helicobacter pylori. Based on a literature review, medical history, and imaging examination, the patient was diagnosed with dabigatran-induced esophagitis. INTERVENTIONS: The patient recovered with standard H. pylori eradication therapy and proton pump inhibitor without discontinuing dabigatran. OUTCOMES: After 2 weeks, the retrosternal pain and dysphagia were relieved and upper abdominal discomfort was attenuated. LESSONS: Our case highlights the importance of physicians' awareness of the clinical and endoscopic characteristics of dabigatran-induced esophagitis and the importance of H. pylori-associated tests and eradication if necessary for patients with long-term dabigatran treatment.


Assuntos
Dabigatrana/efeitos adversos , Esofagite/etiologia , Dor Abdominal/tratamento farmacológico , Dor Abdominal/fisiopatologia , Idoso , Antitrombinas/efeitos adversos , Antitrombinas/uso terapêutico , Dabigatrana/uso terapêutico , Transtornos de Deglutição/tratamento farmacológico , Transtornos de Deglutição/fisiopatologia , Endoscopia do Sistema Digestório/métodos , Esofagite/fisiopatologia , Feminino , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/patogenicidade , Humanos
8.
Am J Physiol Gastrointest Liver Physiol ; 318(5): G931-G945, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32174134

RESUMO

Helicobacter pylori infection always induces gastritis, which may progress to ulcer disease or cancer. The mechanisms underlying mucosal injury by the bacteria are incompletely understood. Here, we identify a novel pathway for H. pylori-induced gastric injury, the impairment of maturation of the essential transport enzyme and cell adhesion molecule, Na-K-ATPase. Na-K-ATPase comprises α- and ß-subunits that assemble in the endoplasmic reticulum (ER) before trafficking to the plasma membrane. Attachment of H. pylori to gastric epithelial cells increased Na-K-ATPase ubiquitylation, decreased its surface and total levels, and impaired ion balance. H. pylori did not alter degradation of plasmalemma-resident Na-K-ATPase subunits or their mRNA levels. Infection decreased association of α- and ß-subunits with ER chaperone BiP and impaired assembly of α/ß-heterodimers, as was revealed by quantitative mass spectrometry and immunoblotting of immunoprecipitated complexes. The total level of BiP was not altered, and the decrease in interaction with BiP was not observed for other BiP client proteins. The H. pylori-induced decrease in Na-K-ATPase was prevented by BiP overexpression, stopping protein synthesis, or inhibiting proteasomal, but not lysosomal, protein degradation. The results indicate that H. pylori impairs chaperone-assisted maturation of newly made Na-K-ATPase subunits in the ER independently of a generalized ER stress and induces their ubiquitylation and proteasomal degradation. The decrease in Na-K-ATPase levels is also seen in vivo in the stomachs of gerbils and chronically infected children. Further understanding of H. pylori-induced Na-K-ATPase degradation will provide insights for protection against advanced disease.NEW & NOTEWORTHY This work provides evidence that Helicobacter pylori decreases levels of Na-K-ATPase, a vital transport enzyme, in gastric epithelia, both in acutely infected cultured cells and in chronically infected patients and animals. The bacteria interfere with BiP-assisted folding of newly-made Na-K-ATPase subunits in the endoplasmic reticulum, accelerating their ubiquitylation and proteasomal degradation and decreasing efficiency of the assembly of native enzyme. Decreased Na-K-ATPase expression contributes to H. pylori-induced gastric injury.


Assuntos
Retículo Endoplasmático/enzimologia , Células Epiteliais/enzimologia , Mucosa Gástrica/enzimologia , Gastrite/enzimologia , Proteínas de Choque Térmico/metabolismo , Infecções por Helicobacter/enzimologia , Helicobacter pylori/patogenicidade , ATPase Trocadora de Sódio-Potássio/metabolismo , Células Cultivadas , Retículo Endoplasmático/microbiologia , Estabilidade Enzimática , Células Epiteliais/microbiologia , Mucosa Gástrica/microbiologia , Gastrite/genética , Gastrite/microbiologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Interações Hospedeiro-Patógeno , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo , Dobramento de Proteína , Proteólise , ATPase Trocadora de Sódio-Potássio/genética , Ubiquitinação
9.
Curr Med Sci ; 40(1): 95-103, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32166670

RESUMO

Helicobacter pylori (H. pylori) was reported to be associated with gastric carcinogenesis. Resistin-like molecule beta (RELMß), a recently described goblet cell-specific protein, was demonstrated to aberrantly express in gastric cancer and correlated with its clinicopathological features. This study aimed to examine the association between H. pylori and RELMß expression in gastric carcinoma and precursor lesions. H. pylori infection and RELMß expression were immunohistochemically evaluated in gastric biopsies from 230 patients. The biopsies consisted of normal gastric mucosa (n=20), mucosa with chronic gastritis (n=41), intestinal metaplasia (n=42), dysplasia (n=31), intestinal-type adenocarcinoma (n=56), and diffuse-type adenocarcinoma (n=40). RELMß expression was measured in gastric biopsies after H. pylori eradication therapy in a subgroup of 32 patients. Cultured gastric cancer cell line SGC-7901 was infected with H. pylori strains, and RELMß expression was detected by reverse transcription PCR, real-time PCR and Western blotting. Higher RELMß immunoreactivity was observed in H. pylori-positive intestinal metaplasia (P=0.003), dysplasia (P=0.032), intestinal-type (P=0.037) and diffuse-type adenocarcinomas (P=0.001) than in H. pylori-negative specimens. Expression rates of RELMß in dysplasia (P=0.005), intestinal-type adenocarcinoma (P<0.001), and diffuse-type adenocarcinoma (P=0.001) were significantly correlated with the grade of H. pylori density. In addition, H. pylori eradication reduced the RELMß intensity in intestinal metaplasia (P=0.001). Infection of gastric cancer SGC-7901 cells with cag pathogenicity island (PAI)-positive H. pylori TN2, but not with its PAI totally deleted mutant (TN2-ΔPAI) for 4-8 h, resulted in enhanced protein and transcript levels of RELMß (P<0.05). In summary, our study suggested that H. pylori infection facilitated the expression of RELMß in gastric garcinoma and precursor lesions.


Assuntos
Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/patogenicidade , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Gástricas/metabolismo , Regulação para Cima , Adenocarcinoma/metabolismo , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Adulto , Idoso , Amoxicilina/farmacologia , Amoxicilina/uso terapêutico , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Infecções por Helicobacter/complicações , Infecções por Helicobacter/metabolismo , Helicobacter pylori/efeitos dos fármacos , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Metaplasia , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Neoplasias Gástricas/microbiologia
10.
Georgian Med News ; (298): 109-112, 2020 Jan.
Artigo em Russo | MEDLINE | ID: mdl-32141861

RESUMO

Rosacea is a chronic, recurrent skin disease. It may be aggravated by various factors. An increased incidence of rosacea has been reported in those who carry the stomach bacterium Helicobacter pylori. The purpose of this study was determination of the relationship of this infection with rosacea and to investigate effectiveness of eradication therapy of H. pylori. As our results showed, 80.9% of study patients were infected with H. pillory. There was correlation between infection rates and rosacea severity. In most cases the positive test results for H. Pylori was found in patients with moderate to severe form of disease. The results of the treatment of different forms of rosacea confirmed the effectiveness of the eradication therapy of H. Pylori, regarding as one of the pathogenic cause of rosacea and the way in the choice of treatment. More wide studies of pathophysiological aspects of causes of rosacea will be promising and help in treating rosacea. These data indicate the important role of H.Pylori in the development of rosacea and recommend taking into account in the therapy of this dermatosis.


Assuntos
Infecções por Helicobacter/diagnóstico , Helicobacter pylori/patogenicidade , Rosácea/microbiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Humanos , Rosácea/epidemiologia
11.
Cancer Causes Control ; 31(6): 601-606, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32222845

RESUMO

PURPOSE: Helicobacter pylori (H. pylori) is the leading cause of gastric cancer. High antibody levels to H. pylori virulence factors Vacuolating cytotoxin A (VacA) and Cytotoxin-associated gene A (CagA) have been suggested as gastric cancer risk markers. In the USA, H. pylori sero-prevalence is twofold higher in African Americans compared to whites. We sought to assess whether African Americans also exhibit higher antibody levels to VacA and CagA. METHODS: Antibody responses to H. pylori proteins were measured by multiplex serology in 686 African Americans and whites of the Southern Community Cohort Study. Among VacA- and CagA-seropositives, we analyzed the association of race with antibody level using logistic regression models to produce odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Sero-positive African Americans had significantly higher mean antibody levels to both VacA and CagA, which resulted in increased odds for the highest quartile of antibody levels compared to sero-positive whites (VacA, OR: 6.08; 95% CI 3.41, 10.86; CagA, OR: 3.77; 95% CI 1.61, 8.84). CONCLUSION: Our findings support future studies to assess the association of differential antibody responses by race with risk of gastric cancer in the USA, which could then aid in developing targeted H. pylori eradication strategies.


Assuntos
Afro-Americanos/estatística & dados numéricos , Anticorpos Antibacterianos , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Helicobacter pylori , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Humanos , Estudos Soroepidemiológicos , Sudeste dos Estados Unidos , Fatores de Virulência/imunologia
12.
Cell Mol Life Sci ; 77(14): 2751-2769, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32002588

RESUMO

Atherosclerotic vascular disease (ASVD) is a chronic process, with a progressive course over many years, but it can cause acute clinical events, including acute coronary syndromes (ACS), myocardial infarction (MI) and stroke. In addition to a series of typical risk factors for atherosclerosis, like hyperlipidemia, hypertension, smoking and obesity, emerging evidence suggests that atherosclerosis is a chronic inflammatory disease, suggesting that chronic infection plays an important role in the development of atherosclerosis. Toll-like receptors (TLRs) are the most characteristic members of pattern recognition receptors (PRRs), which play an important role in innate immune mechanism. TLRs play different roles in different stages of infection of atherosclerosis-related pathogens such as Chlamydia pneumoniae (C. pneumoniae), periodontal pathogens including Porphyromonas gingivalis (P. gingivalis), Helicobacter pylori (H. pylori) and human immunodeficiency virus (HIV). Overall, activation of TLR2 and 4 seems to have a profound impact on infection-related atherosclerosis. This article reviews the role of TLRs in the process of atherosclerosis after C. pneumoniae and other infections and the current status of treatment, with a view to providing a new direction and potential therapeutic targets for the study of ASVD.


Assuntos
Aterosclerose/genética , Infecções Bacterianas/genética , Infecções por HIV/genética , Receptores Toll-Like/genética , Aterosclerose/complicações , Aterosclerose/microbiologia , Aterosclerose/virologia , Infecções Bacterianas/complicações , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , Chlamydophila pneumoniae/patogenicidade , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Helicobacter pylori/patogenicidade , Humanos , Porphyromonas gingivalis/patogenicidade
13.
Gastroenterology ; 158(6): 1650-1666.e15, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32032583

RESUMO

BACKGROUND & AIMS: Gastric chief cells, a mature cell type that secretes digestive enzymes, have been proposed to be the origin of metaplasia and cancer through dedifferentiation or transdifferentiation. However, studies supporting this claim have had technical limitations, including issues with the specificity of chief cell markers and the toxicity of drugs used. We therefore sought to identify genes expressed specifically in chief cells and establish a model to trace these cells. METHODS: We performed transcriptome analysis of Mist1-CreERT-traced cells, with or without chief cell depletion. Gpr30-rtTA mice were generated and crossed to TetO-Cre mice, and lineage tracing was performed after crosses to R26-TdTomato mice. Additional lineage tracing experiments were performed using Mist1-CreERT, Kitl-CreERT, Tff1-Cre, and Tff2-Cre mice crossed to reporter mice. Mice were given high-dose tamoxifen or DMP-777 or were infected with Helicobacter pylori to induce gastric metaplasia. We studied mice that expressed mutant forms of Ras in gastric cells, using TetO-KrasG12D, LSL-KrasG12D, and LSL-HrasG12V mice. We analyzed stomach tissues from GPR30-knockout mice. Mice were given dichloroacetate to inhibit pyruvate dehydrogenase kinase (PDK)-dependent cell competition. RESULTS: We identified GPR30, the G-protein-coupled form of the estrogen receptor, as a cell-specific marker of chief cells in gastric epithelium of mice. Gpr30-rtTA mice crossed to TetO-Cre;R26-TdTomato mice had specific expression of GPR30 in chief cells, with no expression noted in isthmus stem cells or lineage tracing of glands. Expression of mutant Kras in GPR30+ chief cells did not lead to the development of metaplasia or dysplasia but, instead, led to a reduction in labeled numbers of chief cells and a compensatory expansion of neck lineage, which was derived from upper Kitl+ clones. Administration of high-dose tamoxifen, DMP-777, or H pylori decreased the number of labeled chief cells. Chief cells were eliminated from epithelia via GPR30- and PDK-dependent cell competition after metaplastic stimuli, whereas loss of GRP30 or inhibition of PDK activity preserved chief cell numbers and attenuated neck lineage cell expansion. CONCLUSIONS: In tracing studies of mice, we found that most chief cells are lost during metaplasia and therefore are unlikely to contribute to gastric carcinogenesis. Expansion of cells that coexpress neck and chief lineage markers, known as spasmolytic polypeptide-expressing metaplasia, does not occur via dedifferentiation from chief cells but, rather, through a compensatory response from neck progenitors to replace the eliminated chief cells.


Assuntos
Celulas Principais Gástricas/fisiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Receptores Estrogênicos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Animais , Azetidinas/toxicidade , Comunicação Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula/efeitos dos fármacos , Linhagem da Célula/fisiologia , Ácido Dicloroacético/administração & dosagem , Modelos Animais de Doenças , Mucosa Gástrica/citologia , Mucosa Gástrica/efeitos dos fármacos , Infecções por Helicobacter/microbiologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Metaplasia/induzido quimicamente , Metaplasia/microbiologia , Metaplasia/patologia , Camundongos , Camundongos Knockout , Piperazinas/toxicidade , Quinase Piruvato Desidrogenase (Transferência de Acetil)/antagonistas & inibidores , Receptores Estrogênicos/genética , Receptores Acoplados a Proteínas-G/genética , Células-Tronco/fisiologia , Tamoxifeno/toxicidade
14.
Rev Med Suisse ; 16(680): 268-271, 2020 Feb 05.
Artigo em Francês | MEDLINE | ID: mdl-32022492

RESUMO

Peptic ulcer induced upper gastrointestinal hemorrhage is a frequent digestive emergency and is one of the most common cause of hospitalization. There are several intrinsic risk factors for peptic ulcer bleed such as advanced age, previous gastro-intestinal hemorrhage, male sex and the presence of Helicobacter pylori. In high risk patients for peptic ulcer disease, gastric protection measures should be considered, most often by treatment with proton pump inhibitors. The eradication of Helicobacter pylori should also be discussed for long-term treatments.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/prevenção & controle , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/patogenicidade , Humanos , Úlcera Péptica/complicações , Inibidores da Bomba de Prótons/uso terapêutico
15.
Life Sci ; 248: 117456, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097666

RESUMO

AIMS: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated. MATERIALS AND METHODS: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured. KEY FINDINGS: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Fatores Reguladores de Interferon/genética , Interferon gama/genética , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL1/antagonistas & inibidores , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Quimiocina CXCL9/antagonistas & inibidores , Quimiocina CXCL9/genética , Quimiocina CXCL9/imunologia , Doença Crônica , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Gastrite Atrófica/genética , Gastrite Atrófica/imunologia , Gastrite Atrófica/microbiologia , Regulação da Expressão Gênica , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/patogenicidade , Humanos , Fatores Reguladores de Interferon/antagonistas & inibidores , Fatores Reguladores de Interferon/imunologia , Interferon gama/antagonistas & inibidores , Interferon gama/imunologia , Interleucina-17/agonistas , Interleucina-17/genética , Interleucina-17/imunologia , Masculino , Proteínas NLR/antagonistas & inibidores , Proteínas NLR/genética , Proteínas NLR/imunologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Uridina Fosforilase/antagonistas & inibidores , Uridina Fosforilase/genética , Uridina Fosforilase/imunologia
16.
J Med Microbiol ; 69(4): 617-624, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32100708

RESUMO

Introduction. Growing concern about the increasing frequency of resistance of Helicobacter pylori to the available antimicrobial agents worldwide has encouraged the search for new strategies in treating and eradicating H. pylori infections. Endoscopic blue-light therapy has been used in patients with H. pylori gastritis with limited success due to subsequent repopulation with H. pylori. Clinical trials using Curcumin could not eradicate infection either.Aim. We studied the effect of blue light emitting diodes (LEDs) in conjunction with Curcumin on H. pylori, since this has not been previously reported.Methodology. We examined the effect of Curcumin with and without irradiation with blue LEDs on the viability of H. pylori and four key factors important for colonization and establishment of H. pylori infection, namely urease production, motility, adhesion and biofilm formation.Results. We found that a combination of Curcumin and blue LEDs caused significant reductions in viability, urease production, motility, haemagglutination activity, as well as increased disruption of mature preformed biofilms of H. pylori, in comparison to Curcumin alone (P<0.0001), at sublethal concentrations of Curcumin.Conclusion. Targeting the virulence factors of H. pylori with blue LED photoactivated Curcumin would theoretically cripple this pathogen from colonizing and causing tissue damage and perhaps overcome the problem of repopulation with H. pylori that often occurs following endoscopic blue-light therapy.


Assuntos
Antibacterianos/farmacologia , Curcumina/farmacologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/efeitos da radiação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Feminino , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/patogenicidade , Humanos , Luz , Viabilidade Microbiana/efeitos dos fármacos , Viabilidade Microbiana/efeitos da radiação , Virulência/efeitos dos fármacos , Virulência/efeitos da radiação , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
17.
Helicobacter ; 25(2): e12681, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32088936

RESUMO

BACKGROUND: Helicobacter pylori occupy a unique niche, located within the mucus layer lining the stomach, and attached to the apical surface of the gastric epithelium. As such, antibodies would be expected to play a major role in regulating infection and/or pathogenesis. However, experiments using antibody-deficient mice to study gastric helicobacter infection have yielded inconsistent results, although some pointed toward antibodies increasing colonization levels and decreasing gastritis severity. The variability in these studies is possibly due to their use of nonmatched wild-type controls. This current study presents the first evaluation of the role of antibodies in H pylori infection by comparing antibody-deficient mice with matched wild-type siblings. METHODS: Matched wild-type and antibody-deficient µMT mice were generated by heterozygous crossings. In two separate experiments, appropriately genotyped sibling littermates were infected with H pylori for 4 months and then sera and stomachs were collected. RESULTS: There was no difference in H pylori colonization levels between infected µMT mice and sibling wild-type controls. Similarly, there was no significant difference in the severity of gastritis between these groups of mice, although there was a trend toward less severe gastritis in µMT mice which was supported by a significantly lower IFNγ (Th1) gastric cytokine response. CONCLUSIONS: Comparing matched antibody-deficient and antibody-competent mice indicates that an antibody response does not influence H pylori colonization levels. Contrary to previous studies, these results suggest antibodies might have a minor pro-inflammatory effect by promoting gastric Th1 cytokines, although this did not translate to a significant effect on gastritis severity.


Assuntos
Anticorpos/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori , Animais , Citocinas/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/patogenicidade , Imunidade nas Mucosas , Camundongos , Camundongos Endogâmicos C57BL , Estômago/microbiologia , Estômago/patologia
18.
J Med Microbiol ; 69(3): 457-464, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32100714

RESUMO

Introduction. Helicobacter pylori is associated with gastrointestinal disease, most notably gastric cancer. Cytotoxin-associated antigen A (CagA), an important virulence factor for H. pylori pathogenicity, induces host cells to release inflammatory factors, especially interleukin-8 (IL-8). The mechanism by which C-terminal CagA induces IL-8 production has been studied extensively, but little is known about the role of the N-terminus.Aim. To investigate the effect of CagA303-456aa (a peptide in the N-terminal CagA) on IL-8 production by gastric epithelial cells.Methodology. CagA303-456aa was produced by a prokaryotic expression system and purified by Strep-tag affinity chromatography. An integrin ß1 (ITGB1)-deficient AGS cell line was constructed using the CRISPR/Cas9 technique, and NCTC 11637 cagA and/or cagL knockout mutants were constructed via homologous recombination. The levels of IL-8 production were determined by enzyme-linked immunosorbent assay (ELISA), and p38 and ERK1/2 phosphorylation were examined by Western blot.Results. CagA303-456aa induced IL-8 expression by AGS cells. IL-8 induction by CagA303-456aawas specifically inhibited by ITGB1 deficiency. Notably, CagA303-456aa activated the phosphorylation of both p38 and ERK1/2, and blocking p38 and ERK1/2 activity significantly reduced IL-8 induction by CagA303-456aa. ITGB1 deficiency also inhibited the activation of p38 phosphorylation by CagA303-456aa. Finally, experiments in CagA and/or CagL knockout bacterial lines demonstrated that extracellular CagA might induce IL-8 production by AGS cells.Conclusion. Residues 303-456 of the N-terminal region of CagA induce IL-8 production via a CagA303-456-ITGB1-p38-IL-8 pathway, and ERK1/2 is also involved in the release of IL-8. Extracellular CagA might induce IL-8 production before translocation into AGS cells.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Integrina beta1/metabolismo , Interleucina-8/metabolismo , Peptídeos/metabolismo , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Linhagem Celular Tumoral , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Feminino , Helicobacter pylori/patogenicidade , Humanos , Sistema de Sinalização das MAP Quinases , Peptídeos/genética , Fosforilação , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
20.
Virchows Arch ; 476(4): 551-559, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31897816

RESUMO

Lymphocytic gastritis (LG) is an uncommon reaction pattern of gastric injury characterized by intraepithelial lymphocytosis of the surface foveolar epithelium and chronic inflammation in the lamina propria. It most commonly occurs in association with gluten-sensitive enteropathy, Helicobacter pylori gastritis, non-steroidal anti-inflammatory drugs, and microscopic colitis. While the topography of LG has been described in gluten-sensitive enteropathy and H. pylori infection, no definite morphologic features have been used to further subcategorize LG based on possible etiologies. Furthermore, new immunotherapy agents have been associated with lymphocytic infiltrate in the gastrointestinal tract, but their association with LG has not been reported. Cases of LG were collected from our institution in the period between August 2011 and September 2017. The topography of LG and morphologic features such as glandular microabscesses, intestinal metaplasia, lymphoid aggregates, surface vs pit distribution of lymphocytes, and number of intraepithelial lymphocytes per 100 epithelial cells were assessed for each case using the updated Sydney System where applicable. Twenty-seven cases of LG were identified in the recent 6-year period at our institution. Gluten-sensitive enteropathy is the main reported cause of LG followed by NSAID injury. Cases of LG associated with gluten-sensitive enteropathy are antral predominant, those associated with H. pylori are body predominant, and those occurring in the setting of NSAID injury show pangastritis. Glandular microabscesses are observed in all cases of LG associated with H. pylori, and not in the setting of GSE or NSAID injury. In addition, a case of LG associated with melanoma immunotherapy has been identified. Topography and morphology of lymphocytic gastritis may point to the cause of injury, allowing for proper treatment of the underlying disease.


Assuntos
Gastrite/etiologia , Gastrite/patologia , Infecções por Helicobacter/patologia , Linfocitose/patologia , Biópsia/métodos , Doença Celíaca/patologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/diagnóstico , Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , Humanos , Metaplasia/patologia
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