RÉSUMÉ
BACKGROUND: Helicobacter pylori infection is one of the most common chronic bacterial infections, especially in developing countries. MicroRNA-148a is involved in the regulation of various genes, including Rock1, which is altered in gastric cancer. Decreased expression of mir-148a leads to tumor metastasis and increased Rock1 gene expression in gastric cancer. This study aimed to investigate the expression of these genes in biopsies collected from patients with H. pylori induced gastritis. METHODS: Informed consent forms were gotten from the studied patients with gastritis who needed endoscopy. Gastric biopsies were taken by a gastroenterologist from patients with inflammation. Rapid urease test, stool antigen detection, and histopathological staining were used to determine the H. pylori infected patients. Real time PCR was used to evaluate the miRNA and Rock1 expression levels. RESULTS: The Rock1 expression level in biopsies that were positive for H. pylori was significantly increased compared to our control gastritis group that were H. pylori-negative, but the results were not statistically significant. Moreover, the mir-148a expression level in H. pylori-positive patients with gastritis was increased compared to our control group. However, the results were not statistically significant. We did not find a significant relation between the expression levels of Rock1 and mir-148a in samples with gastritis infected or uninfected by H. pylori. This result may be due to the small sample size. CONCLUSION: We suggest that this test should be carried out with more samples, and the comparison should be done between biopsies with inflammation and no inflammation in a patient.
Sujet(s)
Gastrite , Infections à Helicobacter , Helicobacter pylori , microARN , rho-Associated Kinases , Humains , Gastrite/microbiologie , Gastrite/anatomopathologie , Gastrite/métabolisme , microARN/métabolisme , microARN/génétique , Infections à Helicobacter/anatomopathologie , rho-Associated Kinases/métabolisme , rho-Associated Kinases/génétique , Helicobacter pylori/isolement et purification , Biopsie , Mâle , Femelle , Adulte d'âge moyen , Adulte , Muqueuse gastrique/anatomopathologie , Muqueuse gastrique/microbiologie , Sujet âgéRÉSUMÉ
The relationship between Helicobacter pylori infection and gallbladder diseases, particularly cholecystitis and gallbladder polyps, remains unclear. This study aimed to investigate the presence of H. pylori in gallbladder tissues and its potential role in gallbladder pathologies, as well as to examine the expression of chemokines CXCL2 and CXCL5 in these conditions. MATERIAL AND METHODS: A total of 137 laparoscopically excised gallbladders were analysed through histological examination, PCR for H. pylori-specific DNA, and quantitative real-time PCR for CXCL2 and CXCL5 gene expression. The study cohort included patients with acute calculous cholecystitis, chronic calculous cholecystitis, and gallbladder polyps. RESULTS: H. pylori was detected in 30.7% of cases by histological methods and 42.3% by PCR. Elevated expression of CXCL2 and CXCL5 was observed in 62% and 57.7% of cases, respectively, with a higher prevalence in acute cholecystitis compared to chronic conditions. However, no statistically significant association was found between H. pylori presence and the forms of cholecystitis, as well as between H. pylori presence and chemokine expression in gallbladder. CONCLUSIONS: The study did not establish a direct link between the presence of H. pylori infection and forms of gallbladder pathologies. The findings suggest that other factors other than H. pylori may contribute to the upregulation of CXCL2 and CXCL5 in gallbladder diseases. Further research is needed to elucidate the complex interactions between H. pylori, chemokines, and gallbladder pathologies.
Sujet(s)
Chimiokine CXCL2 , Chimiokine CXCL5 , Vésicule biliaire , Infections à Helicobacter , Helicobacter pylori , Humains , Helicobacter pylori/isolement et purification , Helicobacter pylori/pathogénicité , Infections à Helicobacter/microbiologie , Infections à Helicobacter/anatomopathologie , Infections à Helicobacter/complications , Infections à Helicobacter/génétique , Mâle , Vésicule biliaire/microbiologie , Vésicule biliaire/anatomopathologie , Vésicule biliaire/chirurgie , Femelle , Adulte d'âge moyen , Chimiokine CXCL5/génétique , Chimiokine CXCL5/métabolisme , Chimiokine CXCL2/génétique , Chimiokine CXCL2/métabolisme , Adulte , Cholécystite/microbiologie , Cholécystite/anatomopathologie , Cholécystite/chirurgie , Polypes/microbiologie , Polypes/anatomopathologie , Maladies de la vésicule biliaire/microbiologie , Maladies de la vésicule biliaire/anatomopathologie , Maladies de la vésicule biliaire/chirurgie , Sujet âgéRÉSUMÉ
The potential role of the transient receptor potential Vanilloid 1 (TRPV1) non-selective cation channel in gastric carcinogenesis remains unclear. The main objective of this study was to evaluate TRPV1 expression in gastric cancer (GC) and precursor lesions compared with controls. Patient inclusion was based on a retrospective review of pathology records. Patients were subdivided into five groups: Helicobacter pylori (H. pylori)-associated gastritis with gastric intestinal metaplasia (GIM) (n = 12), chronic atrophic gastritis (CAG) with GIM (n = 13), H. pylori-associated gastritis without GIM (n = 19), GC (n = 6) and controls (n = 5). TRPV1 expression was determined with immunohistochemistry and was significantly higher in patients with H. pylori-associated gastritis compared with controls (p = 0.002). TRPV1 expression was even higher in the presence of GIM compared with patients without GIM and controls (p < 0.001). There was a complete loss of TRPV1 expression in patients with GC. TRPV1 expression seems to contribute to gastric-mucosal inflammation and precursors of GC, which significantly increases in cancer precursor lesions but is completely lost in GC. These findings suggest TRPV1 expression to be a potential marker for precancerous conditions and a target for individualized treatment. Longitudinal studies are necessary to further address the role of TRPV1 in gastric carcinogenesis.
Sujet(s)
Infections à Helicobacter , Tumeurs de l'estomac , Canaux cationiques TRPV , Humains , Canaux cationiques TRPV/métabolisme , Canaux cationiques TRPV/génétique , Tumeurs de l'estomac/métabolisme , Tumeurs de l'estomac/anatomopathologie , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Infections à Helicobacter/métabolisme , Infections à Helicobacter/complications , Infections à Helicobacter/anatomopathologie , Carcinogenèse/métabolisme , Carcinogenèse/anatomopathologie , Études rétrospectives , États précancéreux/métabolisme , États précancéreux/anatomopathologie , Helicobacter pylori/pathogénicité , Métaplasie/métabolisme , Métaplasie/anatomopathologie , Gastrite/métabolisme , Gastrite/anatomopathologie , Gastrite/microbiologie , Adulte , Immunohistochimie , Muqueuse gastrique/métabolisme , Muqueuse gastrique/anatomopathologie , Gastrite atrophique/métabolisme , Gastrite atrophique/anatomopathologieRÉSUMÉ
BACKGROUND: Helicobacter pylori (H. pylori) infection is critical in the development and occurrence of gastric cancer. H. pylori secretes gamma-glutamyl transferase (GGT), which affects energy metabolism and histone methylation in mesenchymal stem cells. However, its effect on human gastric epithelial cells remains unclear. This study aimed to investigate the effects of GGT on energy metabolism and histone methylation in gastric epithelial cells and determine its role in the development and progression of H. pylori-induced gastric cancer. METHODS: A GGT knockout H. pylori strain and mouse gastric cancer model were constructed, and alpha-ketoglutarate (α-KG) was added. The underlying mechanism was investigated using proteomics, immunohistochemistry, Western blotting, and other experimental assays. RESULTS: H. pylori can colonize the host's stomach and destroy the gastric epithelium. GGT secreted by H. pylori decreased the concentration of glutamine in the stomach and increased H3K9me3 and H3K27me3 expression, which promoted the proliferation and migration of gastric epithelial cells. Additionally, α-KG reversed this effect. GGT increased the tumorigenic ability of nude mice. GGT, secreted by H. pylori, promoted the expression of ribosomal protein L15 (RPL15), while GGT knockout and supplementation with α-KG and trimethylation inhibitors reduced RPL15 expression and Wnt signaling pathway expression. CONCLUSIONS: H. pylori secreted GGT decreased the expression of glutamine and α-KG in gastric epithelial cells, increased the expression of histones H3K9me3 and H3K27me3, and activated the Wnt signaling pathway through RPL15 expression, ultimately changing the biological characteristics of the gastric epithelium and promoting the occurrence of gastric cancer. Altered energy metabolism and histone hypermethylation are important factors involved in this process.
Sujet(s)
Métabolisme énergétique , Cellules épithéliales , Helicobacter pylori , Histone , Tumeurs de l'estomac , gamma-Glutamyltransferase , Tumeurs de l'estomac/microbiologie , Tumeurs de l'estomac/anatomopathologie , Tumeurs de l'estomac/métabolisme , Tumeurs de l'estomac/génétique , Animaux , Histone/métabolisme , Méthylation , Cellules épithéliales/métabolisme , Cellules épithéliales/microbiologie , Cellules épithéliales/anatomopathologie , gamma-Glutamyltransferase/métabolisme , gamma-Glutamyltransferase/génétique , Souris , Humains , Souris nude , Muqueuse gastrique/métabolisme , Muqueuse gastrique/microbiologie , Muqueuse gastrique/anatomopathologie , Prolifération cellulaire , Infections à Helicobacter/métabolisme , Infections à Helicobacter/microbiologie , Infections à Helicobacter/anatomopathologie , Infections à Helicobacter/complications , Acides cétoglutariques/métabolismeRÉSUMÉ
Impaired E-cadherin (Cdh1) functions are closely associated with cellular dedifferentiation, infiltrative tumor growth and metastasis, particularly in gastric cancer. The class-I carcinogen Helicobacter pylori (H. pylori) colonizes gastric epithelial cells and induces Cdh1 shedding, which is primarily mediated by the secreted bacterial protease high temperature requirement A (HtrA). In this study, we used human primary epithelial cell lines derived from gastroids and mucosoids from different healthy donors to investigate HtrA-mediated Cdh1 cleavage and the subsequent impact on bacterial pathogenesis in a non-neoplastic context. We found a severe impairment of Cdh1 functions by HtrA-induced ectodomain cleavage in 2D primary cells and mucosoids. Since mucosoids exhibit an intact apico-basal polarity, we investigated bacterial transmigration across the monolayer, which was partially depolarized by HtrA, as indicated by microscopy, the analyses of the transepithelial electrical resistance (TEER) and colony forming unit (cfu) assays. Finally, we investigated CagA injection and observed efficient CagA translocation and tyrosine phosphorylation in 2D primary cells and, to a lesser extent, similar effects in mucosoids. In summary, HtrA is a crucially important factor promoting the multistep pathogenesis of H. pylori in non-transformed primary gastric epithelial cells and organoid-based epithelial models.
Sujet(s)
Protéines bactériennes , Cadhérines , Cellules épithéliales , Muqueuse gastrique , Helicobacter pylori , Organoïdes , Humains , Cadhérines/métabolisme , Organoïdes/métabolisme , Cellules épithéliales/métabolisme , Cellules épithéliales/microbiologie , Muqueuse gastrique/métabolisme , Muqueuse gastrique/microbiologie , Muqueuse gastrique/anatomopathologie , Protéines bactériennes/métabolisme , Protéines bactériennes/génétique , Antigènes bactériens/métabolisme , Infections à Helicobacter/métabolisme , Infections à Helicobacter/microbiologie , Infections à Helicobacter/anatomopathologie , Antigènes CD/métabolisme , Estomac/microbiologie , Estomac/anatomopathologie , Lignée cellulaire , Tumeurs de l'estomac/métabolisme , Tumeurs de l'estomac/anatomopathologie , Tumeurs de l'estomac/microbiologie , Protéases à sérineRÉSUMÉ
Helicobacter pylori is a highly prevalent human gastric pathogen that causes gastritis, ulcer disease, and gastric cancer. It is not yet fully understood how H. pylori injures the gastric epithelium. The Na,K-ATPase, an essential transporter found in virtually all mammalian cells, has been shown to be important for maintaining the barrier function of lung and kidney epithelia. H. pylori decreases levels of Na,K-ATPase in the plasma membrane of gastric epithelial cells, and the aim of this study was to demonstrate that this reduction led to gastric injury by impairing the epithelial barrier. Similar to H. pylori infection, the inhibition of Na,K-ATPase with ouabain decreased transepithelial electrical resistance and increased paracellular permeability in cell monolayers of human gastric cultured cells, 2D human gastric organoids, and gastric epithelium isolated from gerbils. Similar effects were caused by a partial shRNA silencing of Na,K-ATPase in human gastric organoids. Both H. pylori infection and ouabain exposure disrupted organization of adherens junctions in human gastric epithelia as demonstrated by E-cadherin immunofluorescence. Functional and structural impairment of epithelial integrity with a decrease in Na,K-ATPase amount or activity provides evidence that the H. pylori-induced downregulation of Na,K-ATPase plays a role in the complex mechanism of gastric disease induced by the bacteria.
Sujet(s)
Muqueuse gastrique , Infections à Helicobacter , Helicobacter pylori , Ouabaïne , Sodium-Potassium-Exchanging ATPase , Sodium-Potassium-Exchanging ATPase/métabolisme , Sodium-Potassium-Exchanging ATPase/génétique , Humains , Animaux , Ouabaïne/pharmacologie , Infections à Helicobacter/métabolisme , Infections à Helicobacter/microbiologie , Infections à Helicobacter/anatomopathologie , Muqueuse gastrique/métabolisme , Muqueuse gastrique/microbiologie , Muqueuse gastrique/anatomopathologie , Muqueuse gastrique/effets des médicaments et des substances chimiques , Gerbillinae , Membrane cellulaire/métabolisme , Membrane cellulaire/effets des médicaments et des substances chimiques , Cellules épithéliales/métabolisme , Cellules épithéliales/microbiologie , Cellules épithéliales/effets des médicaments et des substances chimiques , Organoïdes/métabolisme , Organoïdes/microbiologieRÉSUMÉ
OBJECTIVE: Data regarding Helicobacter pylori (H. pylori)-associated mucosa-associated lymphoid tissue (MALT) lymphoma in children are lacking. We aimed to characterize the diagnosis, management, and outcome of H. pylori-associated MALT lymphoma in pediatric patients. STUDY DESIGN: A retrospective multicenter case series of the pediatric patients with H. pylori-associated MALT lymphoma who were diagnosed during 2010-2022. RESULTS: Five children, of them three females, were identified. The mean age at diagnosis was 14.6 ± 2.4 years. The clinical presentation included abdominal pain (5/5), nausea (3/5), weight loss, night sweats, recurrent fever (1/5), and iron deficiency anemia (2/5). Endoscopic findings in both the stomach antrum and body included a fragile and hyperemic mucosa, large ulcers, extensive nodularity, and exudate. All the biopsies from the gastric mucosa were consistent with MALT lymphoma, and positive for H. pylori (by Giemsa stain). All the patients received triple therapy (amoxicillin, nitroimidazole, or a macrolide, and a proton pump inhibitor, for 14 days), and achieved H. pylori eradication. All had complete resolution of histological findings at the last follow-up. In one patient, the histology of MALT lymphoma persisted 12 months after H. pylori eradication, and only the 18-month-biopsy was free of residual disease. CONCLUSIONS: In this series of pediatric MALT lymphoma, complete resolution of disease occurred in all the patients, yet histological remission was delayed in one. This supports the importance of endoscopic follow-up.
Sujet(s)
Infections à Helicobacter , Helicobacter pylori , Lymphome B de la zone marginale , Humains , Lymphome B de la zone marginale/microbiologie , Lymphome B de la zone marginale/anatomopathologie , Lymphome B de la zone marginale/traitement médicamenteux , Lymphome B de la zone marginale/complications , Femelle , Mâle , Infections à Helicobacter/traitement médicamenteux , Infections à Helicobacter/complications , Infections à Helicobacter/microbiologie , Infections à Helicobacter/anatomopathologie , Études rétrospectives , Adolescent , Enfant , Helicobacter pylori/effets des médicaments et des substances chimiques , Helicobacter pylori/isolement et purification , Muqueuse gastrique/anatomopathologie , Muqueuse gastrique/microbiologie , Antibactériens/usage thérapeutique , Résultat thérapeutique , BiopsieRÉSUMÉ
BACKGROUND: The requirement for routine biopsy sampling in esophagogastroduodenoscopy (EGD) with normal endoscopic findings is a subject of debate. In this study, patients who had normal endoscopic findings in EGD and underwent biopsy sampling were retrospectively analyzed. METHODS: This single-center retrospective cohort study included 671 patients who underwent EGD between 2021 and 2023 in the Sisli Hamidiye Etfal Training and Research Hospital Surgical Endoscopy Unit. All patients had normal endoscopic findings and a sampling biopsy was performed on all patients included. Patients were evaluated based on demographic and clinicopathologic findings. This study was registered to ClinicalTrials.gov (NCT06269380). RESULTS: Two hundred sixty patients (38.7%) have abnormal histopathologic findings. Helicobacter pylori positivity was detected in 200 (29.8%) patients. Intestinal metaplasia (IM) was present in 80 of 260 patients (30.8%). The frequency of IM was higher in older age groups and cases with mild gastritis ( P <0.001). The frequency and severity of gastritis were associated with increased H. pylori positivity and density ( P <0.001). CONCLUSIONS: The biopsy sampling may contribute to the diagnosis and treatment process in cases where normal endoscopic findings are observed during EGD.
Sujet(s)
Endoscopie digestive , Gastrite , Infections à Helicobacter , Helicobacter pylori , Humains , Études rétrospectives , Femelle , Mâle , Adulte d'âge moyen , Biopsie/méthodes , Endoscopie digestive/méthodes , Infections à Helicobacter/anatomopathologie , Infections à Helicobacter/diagnostic , Helicobacter pylori/isolement et purification , Adulte , Gastrite/anatomopathologie , Gastrite/microbiologie , Gastrite/diagnostic , Sujet âgé , Antre pylorique/anatomopathologie , Antre pylorique/microbiologie , Métaplasie/anatomopathologie , Jeune adulteRÉSUMÉ
OBJECTIVE: Colonic diverticulosis might be caused by low-fiber dietary habits, gastrointestinal motility disorders, and colonic wall resistance changes, which might also affect the upper gastrointestinal system mucosa. Therefore, the present study aims to answer whether the gastric histopathological findings of the cases with diverge from those without. METHODS: This retrospective cross-sectional study included 184 cases who underwent both upper and lower gastrointestinal endoscopy procedures between January 2020 and December 2022. Notably, 84 cases were colonic diverticulosis, while the rest of the study group was control. Their demographic, laboratory, and histopathological findings were compared meticulously. RESULTS: The median ages for the colonic diverticulosis and control were 67.07±8.14 and 66.29±15.83 years, respectively, and no statistical difference concerning the age and gender distribution between them was recognized. The median levels of white blood cells, neutrophils, glucose, creatinine, and aspartate aminotransferase in colonic diverticulosis were significantly increased compared to control. As for pathological comparison, colonic diverticulosis had a higher prevalence of Helicobacter pylori (45.2 vs. 38%), while atrophy and intestinal metaplasia prevalence were nearly the same in the groups, without significance regarding Helicobacter pylori. CONCLUSION: Consequently, colonic diverticulosis should not be overlooked, particularly when the abovementioned laboratory parameters are augmented in a dyspeptic patient. A correlation might be raised between Helicobacter pylori and colonic diverticulosis. Eradication therapy might help attenuate the risk of colonic diverticulosis when Helicobacter pylori has emerged in a patient.
Sujet(s)
Diverticulose colique , Infections à Helicobacter , Helicobacter pylori , Humains , Femelle , Mâle , Études transversales , Études rétrospectives , Helicobacter pylori/isolement et purification , Infections à Helicobacter/anatomopathologie , Infections à Helicobacter/complications , Diverticulose colique/anatomopathologie , Sujet âgé , Adulte d'âge moyen , Sujet âgé de 80 ans ou plus , Études cas-témoinsRÉSUMÉ
Helicobacter pylori (HP) infection initiates and promotes gastric carcinogenesis. ONECUT2 shows promise for tumor diagnosis, prognosis, and treatment. This study explored ONECUT2's role and the specific mechanism underlying HP infection-associated gastric carcinogenesis to suggest a basis for targeting ONECUT2 as a therapeutic strategy for gastric cancer (GC). Multidimensional data supported an association between ONECUT2, HP infection, and GC pathogenesis. HP infection upregulated ONECUT2 transcriptional activity via NFκB. In vitro and in vivo experiments demonstrated that ONECUT2 increased the stemness of GC cells. ONECUT2 was also shown to inhibit PPP2R4 transcription, resulting in reduced PP2A activity, which in turn increased AKT/ß-catenin phosphorylation. AKT/ß-catenin phosphorylation facilitates ß-catenin translocation to the nucleus, initiating transcription of downstream stemness-associated genes in GC cells. HP infection upregulated the reduction of AKT and ß-catenin phosphorylation triggered by ONECUT2 downregulation via ONECUT2 induction. Clinical survival analysis indicated that high ONECUT2 expression may indicate poor prognosis in GC. This study highlights a critical role played by ONECUT2 in promoting HP infection-associated GC by enhancing cell stemness through the PPP2R4/AKT/ß-catenin signaling pathway. These findings suggest promising therapeutic strategies and potential targets for GC treatment.
Sujet(s)
Infections à Helicobacter , Helicobacter pylori , Cellules souches tumorales , Protéines proto-oncogènes c-akt , Tumeurs de l'estomac , Animaux , Femelle , Humains , Mâle , Souris , bêta-Caténine/métabolisme , Lignée cellulaire tumorale , Régulation de l'expression des gènes tumoraux , Infections à Helicobacter/métabolisme , Infections à Helicobacter/microbiologie , Infections à Helicobacter/complications , Infections à Helicobacter/anatomopathologie , Souris de lignée BALB C , Souris nude , Cellules souches tumorales/métabolisme , Cellules souches tumorales/anatomopathologie , Phosphorylation , Protein Phosphatase 2/métabolisme , Protein Phosphatase 2/génétique , Protéines proto-oncogènes c-akt/métabolisme , Transduction du signal , Tumeurs de l'estomac/anatomopathologie , Tumeurs de l'estomac/microbiologie , Tumeurs de l'estomac/métabolisme , Tumeurs de l'estomac/génétiqueRÉSUMÉ
BACKGROUND: Integrin-linked kinase (ILK) is crucial in solid tumors by regulating the Hippo-Yes-associated protein 1 (YAP) pathway. This study aimed to uncover how Helicobacter pylori influences ILK levels and its role in regulating YAP during H. pylori-induced gastric cancer. MATERIALS AND METHODS: GES-1 cells with stable Ilk knockdown and overexpression and a mouse carcinogenesis model for H. pylori infection were constructed. And ILK, the phosphorylated mammalian STE20-like protein kinase 1 (MST1), large tumor suppressor 1 (LATS1; S909, T1079), and YAP (S109, S127) were detected in cells, and mice by western blotting, as well as fluorescence intensity of YAP were assayed by immunofluorescence. YAP downstream genes Igfbp4 and Ctgf, the pathological changes and tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1ß), and nitric oxide (NO) levels in mice gastric tissues were detected by real-time PCR, H&E, and ELISA assays. RESULTS: In this study, stable Ilk knockdown cells exhibited significantly higher phosphorylated levels of MST1, LATS1, and YAP, as well as increased YAP in the nuclei of GES-1 cells. Conversely, cells with Ilk overexpression showed opposite results. H. pylori infection led to decreased ILK levels in gastric epithelial cells but increased ILK levels in gastric cancer cell lines (MGC803, SGC7901) and gastric cancer tissues in mice. Treatment with the ILK inhibitor OST-T315 elevated the phosphorylated MST, LATS1, and YAP levels, and inhibited the mRNA levels of Igfbp4 and Ctgf at 44, 48 week-aged mice. OST-T315 also reduced the release of TNF-α, IL-6, IL-1ß, and NO, as well as the progression of gastric cancer caused by H. pylori and N-Nitroso-N-methylurea (NMU) treatment. CONCLUSION: Upon initiation of gastric tumorigenesis signals, H. pylori increases ILK levels and suppresses Hippo signaling, thereby promoting YAP activation and gastric cancer progression. ILK can serve as a potential prevention target to impede H. pylori-induced gastric cancer.
Sujet(s)
Infections à Helicobacter , Helicobacter pylori , Protein-Serine-Threonine Kinases , Tumeurs de l'estomac , Protein-Serine-Threonine Kinases/métabolisme , Protein-Serine-Threonine Kinases/génétique , Animaux , Tumeurs de l'estomac/microbiologie , Tumeurs de l'estomac/anatomopathologie , Tumeurs de l'estomac/métabolisme , Tumeurs de l'estomac/génétique , Infections à Helicobacter/microbiologie , Infections à Helicobacter/anatomopathologie , Souris , Humains , Modèles animaux de maladie humaine , Lignée cellulaire , MâleRÉSUMÉ
Aim: Understanding molecular mechanisms of Helicobacter pylori (H. pylori)-induced inflammation is important for developing new therapeutic strategies for gastrointestinal diseases.Materials & methods: We designed an H. pylori-neutrophil infection model and explored the effects of H. pylori infection on neutrophils.Results: H. pylori infected neutrophils showed a low level of apoptosis. H. pylori stimulation activated the NACHT/LRR/PYD domain-containing protein 3 (NLRP3)-gasdermin-D (GSDMD) pathway for interleukin (IL)-1ß secretion. However, IL-1ß secretion was not completely dependent on GSDMD, as inhibition of autophagy significantly reduced IL-1ß release, and autophagy-related molecules were significantly upregulated in H. pylori-infected neutrophils.Conclusion: Therefore, H. pylori infection inhibits neutrophils apoptosis and induces IL-1ß secretion through autophagy. These findings may be utilized to formulate therapeutic strategies against H. pylori mediated chronic gastritis.
[Box: see text].
Sujet(s)
Apoptose , Autophagie , Infections à Helicobacter , Helicobacter pylori , Inflammation , Interleukine-1 bêta , Granulocytes neutrophiles , Granulocytes neutrophiles/immunologie , Granulocytes neutrophiles/métabolisme , Infections à Helicobacter/microbiologie , Infections à Helicobacter/immunologie , Infections à Helicobacter/anatomopathologie , Interleukine-1 bêta/métabolisme , Humains , Inflammation/métabolisme , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Protéines de liaison aux phosphates/métabolisme , Protéines de liaison aux phosphates/génétique , Protéines et peptides de signalisation intracellulaire/métabolisme , Protéines et peptides de signalisation intracellulaire/génétique , Gastrite/microbiologie , Gastrite/anatomopathologie , Gastrite/immunologie , AnimauxRÉSUMÉ
CagA, a virulence factor of Helicobacter pylori (H. pylori), is known to drive inflammation in gastric epithelial cells and is typically degraded through autophagy. However, the molecular mechanism by which CagA evades autophagy-mediated degradation remains elusive. This study found that H. pylori inhibits autophagic flux by upregulating the expression of AU-rich element RNA-binding factor 1 (AUF1). We confirmed that AUF1 does not affect autophagy initiation but instead hampers lysosomal clearance, as evidenced by treatments with 3-MA, CQ and BafA1. Upregulated AUF1 stabilizes CagA protein levels by inhibiting the autolysosomal degradation of intracellular CagA in H. pylori-infected gastric epithelial cells. Knocking down AUF1 promotes CagA degradation, an effect that can be reversed by the lysosome inhibitor BafA1 and CQ. Transcriptome analysis of AUF1-knockdown gastric epithelial cells infected with H. pylori indicated that AUF1 regulates the expression of lysosomal-associated hydrolase genes, specifically CTSD, to inhibit autolysosomal degradation. Moreover, we observed that knockdown of AUF1 enhanced the stability of CTSD mRNA and identified AUF1 binding to the 3'UTR region of CTSD mRNA. AUF1-mediated downregulation of CTSD expression contributes to CagA stability, and AUF1 overexpression leads to an increase in CagA levels in exosomes, thus promoting extracellular inflammation. In clinical gastric mucosa, the expression of AUF1 and its cytoplasmic translocation are associated with H. pylori-associated gastritis, with CagA being necessary for the translocation of AUF1 into the cytoplasm. Our findings suggest that AUF1 is a novel host-positive regulator of CagA, and dysregulation of AUF1 expression increases the risk of H. pylori-associated gastritis.
Sujet(s)
Antigènes bactériens , Autophagie , Protéines bactériennes , Cellules épithéliales , Muqueuse gastrique , Infections à Helicobacter , Helicobacter pylori , Ribonucléoprotéine nucléaire hétérogène D0 , Ribonucléoprotéine nucléaire hétérogène D , Lysosomes , Antigènes bactériens/métabolisme , Antigènes bactériens/génétique , Ribonucléoprotéine nucléaire hétérogène D0/métabolisme , Helicobacter pylori/métabolisme , Helicobacter pylori/génétique , Protéines bactériennes/métabolisme , Protéines bactériennes/génétique , Humains , Lysosomes/métabolisme , Lysosomes/microbiologie , Infections à Helicobacter/microbiologie , Infections à Helicobacter/métabolisme , Infections à Helicobacter/anatomopathologie , Ribonucléoprotéine nucléaire hétérogène D/métabolisme , Ribonucléoprotéine nucléaire hétérogène D/génétique , Cellules épithéliales/microbiologie , Cellules épithéliales/métabolisme , Muqueuse gastrique/microbiologie , Muqueuse gastrique/métabolisme , Inflammation/métabolisme , Inflammation/microbiologie , Facteurs de virulence/métabolisme , Facteurs de virulence/génétique , Lignée cellulaireRÉSUMÉ
BACKGROUND: Chronic gastritis caused by Helicobacter pylori (Hp) infection is a common gastrointestinal disorder. Despite the high prevalence of Hp infection and chronic gastritis in the Tibetan Plateau, there is a lack of studies elucidating the influence of plateau hypoxia on Hp-induced gastritis. This study aimed to investigate the impact of high-altitude hypoxia on Hp-induced gastritis, particularly focusing on pathological manifestations and inflammatory responses. METHODS: This study was conducted from July 2023 to March 2024 at the Department of Gastroenterology, Affiliated Hospital of Qinghai University. Ninety patients diagnosed with chronic gastritis were enrolled in the study and divided into four groups based on their residential altitude and Hp infection status. Data on endoscopic and pathological characteristics were collected, along with serum oxidative stress and inflammatory markers. RESULTS: Patients with Hp gastritis exhibit distinctive features in the gastric mucosa, including diffuse erythema, enlarged folds, and white turbid mucus during endoscopy. Notably, individuals with Hp gastritis at high altitudes show a higher prevalence of diffuse erythema and enlarged folds. Pathological analysis reveals that these patients have elevated gastric mucosal inflammation scores and increased chronic and active inflammation. Furthermore, individuals with Hp gastritis at high altitudes demonstrate elevated levels of serum TNF-α, IL-1ß, IL-6, and MDA, as well as reduced serum SOD and GSH-Px activities. CONCLUSIONS: High-altitude hypoxia may exacerbate gastric mucosal damage by enhancing oxidative stress and inflammatory response induced by Hp infection.
Sujet(s)
Altitude , Gastrite , Infections à Helicobacter , Helicobacter pylori , Stress oxydatif , Humains , Gastrite/microbiologie , Gastrite/anatomopathologie , Mâle , Infections à Helicobacter/complications , Infections à Helicobacter/anatomopathologie , Femelle , Adulte , Adulte d'âge moyen , Hypoxie , Inflammation , Jeune adulte , Muqueuse gastrique/anatomopathologie , Muqueuse gastrique/microbiologie , Tibet/épidémiologieRÉSUMÉ
INTRODUCTION: Cytokeratins (CKs) have been associated with precancerous and cancerous gastric lesions in patients with Helicobacter pylori-associated chronic gastritis, making them useful for diagnosing epithelial tumors. METHODOLOGY: A retrospective study was conducted utilizing 200 formalin-fixed paraffin-embedded gastric biopsy samples collected from the lesser curvature of the stomach. Samples from the control group, patients with H. pylori infection, and patients with H. pylori-associated gastritis, with complete and incomplete intestinal metaplasia (IM) were immunostained. Monoclonal antibodies were utilized to determine the expression of CK7, CK20, and Ki-67. RESULTS: Patients infected with H. pylori had strong CK20 expression on the surface, and weak CK7 expression on the surface and deep glands; while non-specific chronic gastritis patients had weak focal CK7 expression and strong CK20 expression. The normal gastric mucosa of patients in the control group had relatively weak CK7 expression, restricted to a few cells in the neck and deep glands. CK20 showed diffuse strong reactivity on the surface. On the other hand, patients with complete IM showed a CK7 staining pattern that was either negative or weakly focal on the surface and crypts associated with diffuse surface CK20 and focal crypt staining corresponding to gastric type IM. The Ki67 proliferating index was low (≤ 15%) in H. pylori infected patients, high (> 30%) in patients with incomplete IM, and intermediate (16-30%) in patients with complete IM. CONCLUSIONS: These results indicate a significant link between the expressions of CK7/CK20 and Ki67 in patients afflicted with H. pylori and IM.
Sujet(s)
Gastrite , Infections à Helicobacter , Helicobacter pylori , Kératine-20 , Kératine-7 , Antigène KI-67 , Métaplasie , Humains , Antigène KI-67/métabolisme , Études rétrospectives , Métaplasie/anatomopathologie , Métaplasie/microbiologie , Infections à Helicobacter/anatomopathologie , Infections à Helicobacter/microbiologie , Kératine-20/métabolisme , Kératine-7/métabolisme , Gastrite/microbiologie , Gastrite/anatomopathologie , Immunohistochimie , Mâle , Femelle , Muqueuse gastrique/anatomopathologie , Muqueuse gastrique/microbiologie , Muqueuse gastrique/métabolisme , Adulte d'âge moyen , Biopsie , Adulte , Sujet âgéRÉSUMÉ
BACKGROUND: Helicobacter pylori infection-associated gastric adenocarcinoma is influenced by various factors, including the digestive microbiota. Lactic acid bacteria role in digestive carcinogenesis has been discussed, and some Lactobacillaceae family species have been shown to act against H. pylori-induced inflammation and colonization. However, their effects on H. pylori-related carcinogenesis have not yet been studied. Lactobacillaceae family effects on the epithelial-to-mesenchymal transition (EMT), emergence of cells with cancer stem cell (CSC) properties and the pro-inflammatory response of gastric epithelial cells to H. pylori infection were investigated. MATERIALS AND METHODS: A co-culture model of AGS gastric epithelial cells infected with a carcinogenic strain of H. pylori associated with 18 different probiotic strains candidates were used. Different EMT indicators and CSC properties were studied, including quantification of the mesenchymal phenotype, tumorsphere formation, EMT marker expression, and tight junction evaluation with immunofluorescence microscopy. The effect of the strains on the pro-inflammatory response to H. pylori was also evaluated by quantifying interleukin-8 (IL-8) production using ELISA. RESULTS: Among the strains tested, Lactobacillus gasseri BIO6369 and Lacticaseibacillus rhamnosus BIO5326 induced a 30.6% and 38.4% reduction in the mesenchymal phenotype, respectively, caused a significant decrease in Snail and Zeb1 EMT marker expression and prevented the loss of tight junctions induced by H. pylori infection. A separate co-culture with a Boyden chamber maintained the effects induced by the two strains. H. pylori-induced IL-8 production was also significantly reduced in the presence of L. gasseri BIO6369 and L. rhamnosus BIO5326. CONCLUSION: Lactobacillus gasseri BIO6369 and L. rhamnosus BIO5326 strains decreased epithelial-to-mesenchymal transition and inflammation induced by H. pylori infection, suggesting that these species may have a protective effect against H. pylori-induced gastric carcinogenesis.
Sujet(s)
Cellules épithéliales , Transition épithélio-mésenchymateuse , Infections à Helicobacter , Helicobacter pylori , Lacticaseibacillus rhamnosus , Lactobacillus gasseri , Probiotiques , Tumeurs de l'estomac , Humains , Infections à Helicobacter/microbiologie , Infections à Helicobacter/anatomopathologie , Helicobacter pylori/physiologie , Helicobacter pylori/pathogénicité , Tumeurs de l'estomac/microbiologie , Tumeurs de l'estomac/anatomopathologie , Lacticaseibacillus rhamnosus/physiologie , Cellules épithéliales/microbiologie , Techniques de coculture , CarcinogenèseRÉSUMÉ
Plasma cells known as "Mott cells" present non-secretable accumulations of immunoglobulins called "Russell bodies". Its presence is related to hematological neoplasms, but it can appear in chronic inflammatory processes. The most common occurrence within the digestive tract is the gastric antrum associated with H. pylori infection. Our patient is added the rare extragastric cases where the association with H. pylori is inconsistent. We have found a frequent appearance of lower digestive and urological neoplasms in relation to these cases, justified by the expression of circulating cytokines in the tumor area that lead to the overactivation of plasma cells. This possible association could lead us to know data about the tumor environment and serve us for early diagnosis or future therapeutic targets.
Sujet(s)
Duodénite , Infections à Helicobacter , Helicobacter pylori , Humains , Duodénite/anatomopathologie , Duodénite/microbiologie , Infections à Helicobacter/complications , Infections à Helicobacter/anatomopathologie , Plasmocytes/anatomopathologieRÉSUMÉ
The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs. IMPORTANCE: Our study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.
Sujet(s)
Helicobacter pylori , Tumeurs de l'estomac , Humains , Tumeurs de l'estomac/microbiologie , Tumeurs de l'estomac/anatomopathologie , Helicobacter pylori/génétique , Helicobacter pylori/isolement et purification , Helicobacter pylori/pathogénicité , Mâle , Femelle , Adulte d'âge moyen , Études rétrospectives , Sujet âgé , Infections à Helicobacter/microbiologie , Infections à Helicobacter/épidémiologie , Infections à Helicobacter/anatomopathologie , Microbiome gastro-intestinal/génétique , Bouche/microbiologie , Microbiote/génétiqueRÉSUMÉ
OBJECTIVE: To investigate the association between Helicobacter pylori infection and GDF6 expression in gastric cancer patients, and to determine its influence on prognosis and resistance to capecitabine. METHODS: Tumor and adjacent non-tumor tissues were collected from 148 gastric cancer patients who underwent surgery in our department from October 2019 to June 2022. Of these patients, 78 tested positive for Helicobacter pylori and 70 tested negative. Hematoxylin-eosin (HE) and immunofluorescence staining were utilized to quantify GDF6 expression in cancerous and adjacent tissues. Patient prognosis was monitored via follow-up. Western blotting analyzed GDF6 expression in common gastric cancer cell lines. HGC27 cells exhibiting high GDF6 expression and BGC823 cells with low expression were used to create GDF6-silenced and overexpressed cell lines. The impact of GDF6 on the proliferation, migration, invasion, and cloning abilities of gastric cancer cells was evaluated using the CCK-8 assay, scratch test, Transwell assay, and plate colony formation assay. Fluorescent quantitative PCR and Western blotting assessed the effects of GDF6 levels on epithelial-mesenchymal transition (EMT) and tumor cell stemness. RESULTS: GDF6 expression in gastric cancer tissues was significantly correlated with cancer grading and staging (P<0.05). Helicobacter pylori-positive tissues exhibited significantly higher GDF6 expression levels than negative samples (P<0.05). Kaplan-Meier survival analysis indicated that high GDF6 expression was associated with poor survival prognosis. Overexpressed GDF6 enhanced the proliferation, migration, and invasion abilities of gastric cancer cells, while silencing GDF6 yielded opposite results. Increased GDF6 expression upregulated TGF-ß expression and the phosphorylation levels of SMAD3, leading to an elevation in mesenchymal cell markers N-cadherin, vimentin, and a reduction in epithelial cell markers cytokeratins, E-cadherin. Moreover, high GDF6 levels contributed to increased resistance to capecitabine and enhanced the expression of tumor stem cell markers Nanog, Sox-2, Oct-4, CD44, amplifying tumor cell stemness. CONCLUSION: Helicobacter pylori infection is associated with increased GDF6 expression in gastric cancer tissue, correlating with poor survival prognosis. Elevated GDF6 expression promotes the proliferation, migration, and invasion abilities of gastric cancer cells, facilitates EMT via the TGF-ß/SMAD3 pathway, and intensifies cell stemness and capecitabine resistance. Consequently, GDF6 presents itself as a potential new target for gastric cancer treatment. DATA AVAILABILITY STATEMENT: The data that support the findings of this study are available from the corresponding author upon reasonable request.
Sujet(s)
Transition épithélio-mésenchymateuse , Infections à Helicobacter , Helicobacter pylori , Transduction du signal , Protéine Smad-3 , Tumeurs de l'estomac , Facteur de croissance transformant bêta , Tumeurs de l'estomac/anatomopathologie , Tumeurs de l'estomac/microbiologie , Tumeurs de l'estomac/métabolisme , Humains , Femelle , Mâle , Adulte d'âge moyen , Infections à Helicobacter/anatomopathologie , Infections à Helicobacter/métabolisme , Facteur de croissance transformant bêta/métabolisme , Protéine Smad-3/métabolisme , Sujet âgé , Régulation positive , Prolifération cellulaire , Pronostic , Lignée cellulaire tumorale , Capécitabine/pharmacologie , Mouvement cellulaire , Régulation de l'expression des gènes tumoraux , Résistance aux médicaments antinéoplasiques , AdulteRÉSUMÉ
Helicobacter pylori (H. pylori) infection is a well-established carcinogen that has been extensively studied in the context of gastric diseases. Recent studies suggested a potential association between H. pylori and the risk of colorectal carcinoma (CRC). However, available data remains insufficient to definitively establish a causal relationship between H. pylori infection and the development of CRC and its precursor lesions. In our study, we reviewed all patients diagnosed with CRC in 2020 at our institution. H. pylori assessment was performed in all 92 CRC specimens by immunohistochemistry. Notably, two of the three patients detected with H. pylori infection are under the age of 50. Subsequently, we reviewed a total of 52 patients under the age of 50 diagnosed with CRC at our institution from 2015 to 2022. Among these patients, H. pylori infection was detected in 7 CRC specimens (13.46â¯%). All seven patients had adenocarcinoma on the left side of the colon. In exploring the link between H. pylori infection and the risk of developing CRC precursor lesions, we analyzed 242 patients who underwent colonoscopy guided polypectomy and also had stomach biopsies from 2015 to 2022. Of these patients, 21 were proved to be positive for H. pylori infection in the stomach, while the remaining 221 were negative. Among the H. pylori-positive group, 76.19â¯% (16 patients) exhibited adenomatous polyps, compared to 33.48â¯% (74 patients) in the H. pylori-negative patients (p=0.0001). However, no H. pylori was detected in any colonic adenomatous polyps. Our findings contribute additional evidence supporting the association between H. pylori infection and the development of sporadic CRC, probably a particular association with early-onset ones. Furthermore, gastric H. pylori infection appears to be linked to the higher prevalence of colonic adenomatous polyps, suggesting that individuals with gastric H. pylori infection may benefit from closer and earlier monitoring through colonoscopy.