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The Turkish Journal of Gastroenterology... Apr 2023The polymorphisms in the region between 58 and 62 amino acids of the 194-amino acid CagL protein (CagL hypervariable motif) affect the binding affinity of CagL to...
BACKGROUND
The polymorphisms in the region between 58 and 62 amino acids of the 194-amino acid CagL protein (CagL hypervariable motif) affect the binding affinity of CagL to integrin α5β1 (ITGA5B1) receptor in host epithelial cells and have an effect on the development of various gastrointestinal diseases. We aimed to evaluate the associations of gastroduodenal pathologies, with the polymorphisms of cagL gene of Helicobacter pylori (H. pylori) and also associations between vacA genotypes and cagL polymorphisms.
METHODS
A total of 19 gastric cancer, 16 duodenal ulcer, and 26 non-ulcer dyspepsia patients were included in this case-control study. All cases had H. pylori. A fragment of 651 bp from gene cagL (hp0539) and cagA, vacA genes was amplified by polymerase chain reaction. Purified polymerase chain reaction products were sequenced by Sanger sequencing, and nucleotide sequences were translated into amino acid sequences.
RESULTS
All of the H. pylori strains had cagL and cagA genes. In the 16 (84%) gastric cancer cases, the D58 amino acid polymorphism was significant than the 4 (15.4%) duodenal ulcer cases (P = .029), and the D58/K59 amino acid polymorphism was significant in 12 (63.1%) of the gastric cancer cases than 1 (3.85%) duodenal ulcer case (P = .008). D58/K59 and DKIGQ (n = 10; 52.63%) were the most common polymorphisms in the gastric cancer and were associated with the vacA genotype s1/m2, respectively (P = .022 and P = .008). The D58/K59 amino acid polymorphism was found to have a significant Odds Ratio (OR) value of 8.9 (P = .0017) in multivariate logistic regression analysis.
CONCLUSIONS
The risk of gastric cancer development is 8.9 times higher with D58/K59 polymorphism.
Topics: Humans; Bacterial Proteins; Helicobacter pylori; Duodenal Ulcer; Stomach Neoplasms; Case-Control Studies; Genotype; Amino Acids; Helicobacter Infections; Antigens, Bacterial
PubMed: 36789984
DOI: 10.5152/tjg.2023.22274 -
Journal of Ethnopharmacology Oct 2023Ruda-6 (RD-6), a typical traditional Mongolian medicine formulae consisting of 6 herbs, has been traditionally used in treating gastric disorders. Even though it has...
ETHNOPHARMACOLOGICAL RELEVANCE
Ruda-6 (RD-6), a typical traditional Mongolian medicine formulae consisting of 6 herbs, has been traditionally used in treating gastric disorders. Even though it has been shown to protect against gastric ulcers (GU) in animal models, the gut microbiome and serum metabololite-related mechanisms that prevent GU are not well understood.
AIM OF THE STUDY
This study was conducted to evaluate the gastroprotective mechanism of RD-6 associated with the alteration of the gut microbiome and serum metabolic profiles in GU rats.
MATERIALS AND METHODS
RD-6 (0.27, 1.35 and 2.7 g/kg) or ranitidine (40 mg/kg) were orally administered in rats for three weeks before the induction of gastric ulcer using indomethacin (30 mg/kg, single oral dose). The gastric ulcer index, ulcer area, H&E staining, and the levels of TNF-α, iNOS, MPO and MDA were quantified to evaluate the ulcer inhibitory effects of RD-6. Then, 16S rRNA gene sequencing combined with LC-MS metabolic profiling was performed to investigate the effect of RD-6 on the gut microbiota and serum metabolites in rats. Moreover, a spearman analysis was used to calculate the correlation coefficient between the different microbiota and the metabolites.
RESULTS
RD-6 inhibited the gastric lesion damage caused by indomethacin in rats, decreased the ulcer index by 50.29% (p < 0.05), reduced the levels of TNF-α, iNOS, MDA and MPO in gastric tissue. Additionally, RD-6 reshaped the diversity and microbial composition, and reversed the reduced bacteria including [Eubacterium]_xylanophilum group, Sellimonas, Desulfovibrio, and UCG-009, and the increased bacteria Aquamicrobium caused by indomethacin induction. Furthermore, RD-6 regulated the levels of metabolites including amino acids and organic acids, and these affected metabolites were involved in taurine and hypotaurine metabolism and tryptophan metabolism. Spearman analysis revealed that the perturbed gut microbiota were closely related to the changes in differential serum metabolites.
CONCLUSION
In view of the 16S rRNA gene sequencing and LC-MS metabolic results, the present study suggests the mechanism of RD-6 ameliorating GU via modulating intestinal microbiota and their metabolites.
Topics: Rats; Animals; Indomethacin; Gastrointestinal Microbiome; Stomach Ulcer; Medicine, Mongolian Traditional; Ulcer; Tumor Necrosis Factor-alpha; RNA, Ribosomal, 16S; Metabolomics
PubMed: 37196816
DOI: 10.1016/j.jep.2023.116545 -
Annals of the Royal College of Surgeons... Jan 2022Intestinal intussusception is uncommon in adults. As a retroperitoneal structure, gastroduodenal intussusception is extremely rare. The leading cause of intussusception...
Intestinal intussusception is uncommon in adults. As a retroperitoneal structure, gastroduodenal intussusception is extremely rare. The leading cause of intussusception is reported to be a tumour, either benign or malignant. The case presented may be the first of gastroduodenal intussusception resulting from severe peptic ulcer. A 64-year-old man was admitted with epigastralgia, appetite loss and melena for 1 week. He had history of peptic ulcer and reflux esophagitis for 9 years, caused by infection; eradication therapy had been performed 5 years previously. This time, an abdominal computed tomography scan showed duodenogastric intussusception and gastric outlet obstruction. Preoperative biopsy failed for complete obstruction; thus, the patient underwent Whipple procedure for complete resection under impression of malignancy. The postoperative course was uneventful. Pathological findings for the specimen showed gastric and duodenal ulcer. Progressive peptic ulcer after eradication therapy is rarely seen, and eradication therapy is used widely to treat infection. The eradication rate is extremely high in Taiwan for lower first-line antibiotic as clarithromycin resistance is low due to a policy restricting antimicrobial usage. Early eradication therapy is highly recommended for patients with infection. We emphasise the importance of regular follow-up for the non-significant correlation of severity of gastric ulcer with clinical symptoms. When ulceration progresses or non-invasive treatments fail early surgical interventions should be applied to these anatomic alterations.
Topics: Duodenal Ulcer; Humans; Intussusception; Male; Middle Aged; Stomach Diseases
PubMed: 34730406
DOI: 10.1308/rcsann.2021.0067 -
Scientific Reports Feb 2021Although the type 4 secretion system of the integrating and conjugative elements (tfs ICE) is common in Helicobacter pylori, its clinical association with the cag...
Although the type 4 secretion system of the integrating and conjugative elements (tfs ICE) is common in Helicobacter pylori, its clinical association with the cag pathogenicity island (cagPAI) have not yet been well-investigated. In this study, Vietnamese patient H. pylori samples (46 duodenal ulcer (DU), 51 non-cardia gastric cancer (NCGC), 39 chronic gastritis (CG)) were fully sequenced using next-generation sequencing and assembled into contigs. tfs3, tfs4, and cagPAI genes were compared with the public database. Most (94%) H. pylori strains possessed a complete cagPAI, which was the greatest risk factor for clinical outcomes, while the prevalences of tfs3 and tfs4 were 45% and 77%, respectively. Complete tfs3 and tfs4 were found in 18.3% and 17.6% of strains, respectively. The prevalence of H. pylori strains with complete tfs3 ICE in DU patients was significantly higher than that in NCGC patients (30.4% vs 11.7%, P < 0.05). In addition, the prevalence of strains with complete tfs3 ICE and cagPAI was significantly higher in DU patients than that in NCGC (28.4% vs 9.8%, P = 0.038) and CG patients (28.2% vs 7.7%, P = 0.024). cagPAI and complete tfs3 increased the risk of DU compared to NCGC (OR = 3.56, 95%CI: 1.1-14.1, P = 0.038) and CG (OR = 4.64, 95%CI: 1.1-27.6, P = 0.024). A complete cluster of tfs3 ICE was associated with gastroduodenal diseases in Vietnam. However, there was a low prevalence of the dupA/complete dupA cluster (15.4%) in the Vietnam strains. The prevalence of cagPAI in Vietnam strains was significantly higher than in US (P = 0.01) and Indonesia (P < 0.0001); the prevalence of the dupA cluster was also higher in the Vietnam strains than in the Indonesian strains (P < 0.05). In addition, the prevalence of ctkA, an accessory gene of tfs3, was significantly different between Vietnam and US strains (28% vs 2%, P = 0.0002). In summary, the acquisition of tfs3/4 ICE was common in H. pylori strains in patients with gastroduodenal disease in Vietnam, and the complete cluster of tfs3 ICE was a reliable marker for the severity of disease in the H. pylori infected population.
Topics: Biomarkers; Duodenal Diseases; Genes, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Severity of Illness Index; Stomach Diseases; Type IV Secretion Systems; Vietnam
PubMed: 33633144
DOI: 10.1038/s41598-021-83862-1 -
Medicine Nov 2022Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy and safety of first-line therapy, the choice of individual PPIs or vonoprazan in the treatment of EE remains controversial. This study aimed to evaluate the efficacy and safety of vonoprazan and PPIs in healing esophageal mucosal injury in patients with EE.
METHODS
Relevant databases were searched to collect randomized controlled trials of proton pump inhibitors and vonoprazan in the treatment of reflux esophagitis up to December 2021. Studies on standard-dose PPIs or vonoprazan that were published in Chinese or English and assessed healing effects in EE were included in the analysis. Stata16.0 was used to conduct a network Meta-analysis to evaluate the efficacy and safety of the treatment.
RESULTS
A total of 41 literatures were included with 11,592 enrolled patients. For the endoscopic cure rate, all the PPIs and vonoprazan significantly improve compared to Placebo; Based on the surface under the cumulative ranking curve, Ilaprazole ranked first, followed by esomeprazole, vonoprazan, pantoprazole, lansoprazole, omeprazole, rabeprazole and placebo therapy ranked the last. For the rate of adverse events, there was no significant difference among all the PPIs, vonoprazan, and placebo.
CONCLUSIONS
Ilaprazole, esomeprazole and vonoprazan have more advantages in mucosal erosion healing, there was no significant difference in the comparative safety among all interventions.
Topics: Humans; Proton Pump Inhibitors; Esomeprazole; Network Meta-Analysis; Peptic Ulcer; Rabeprazole; Esophagitis, Peptic; Abdominal Injuries
PubMed: 36451489
DOI: 10.1097/MD.0000000000031807 -
Nutrients Jan 2023Genetic and environmental factors are associated with developing and progressing duodenal ulcer (DU) risk. However, the exact nature of the disease pathophysiology and...
Genetic and environmental factors are associated with developing and progressing duodenal ulcer (DU) risk. However, the exact nature of the disease pathophysiology and the single nucleotide polymorphism (SNP)-lifestyle interaction has yet to be determined. The purpose of the present study was to examine the SNPs linked to DU risk and their interaction with lifestyles and diets in a large hospital-based cohort of Asians. Based on an earlier diagnosis, the participants were divided into the DU (case; n = 1088) and non-DU (control, n = 56,713) groups. The SNP associated with DU risk were obtained from a genome-wide association study (GWAS), and those promoted genetic impact with SNP-SNP interactions were identified with generalized multifactor dimensionality reduction analysis. The interaction between polygenic risk score (PRS) calculated from the selected genetic variants and nutrient were examined. They were related to actin modification, immune response, and cell migration by modulating leucine-rich repeats (LRR) domain binding, Shaffer interferon regulatory factor 4 (IRF4) targets in myeloma vs. mature B lymphocyte, and Reactome runt-related transcription factor 3 (RUNX3). Among the selected SNPs, rs11230563 (R225W) showed missense mutation and low binding affinity with different food components in the autodock analysis. Glycyrrhizin, physalin B, janthitrem F, and casuarinin lowered it in only wild CD6 protein but not in mutated CD6. Plastoquinone 8, solamargine, saponin D, and matesaponin 2 decreased energy binding affinity in mutated CD6 proteins. The PRS of the 5-SNP and 6-SNP models exhibited a positive association with DU risk (OR = 3.14). The PRS of the 5-SNP PRS model interacted with irregular eating habits and smoking status. In participants with irregular eating habits or smokers, DU incidence was much higher in the participants with high PRS than in those with low PRS. In conclusion, the genetic impact of DU risk was mainly in regulating immunity, inflammation, and actin modification. Adults who are genetically susceptible to DU need to eat regularly and to be non-smokers. The results could be applied to personalize nutrition.
Topics: Adult; Humans; Actins; Duodenal Ulcer; Feeding Behavior; Genetic Predisposition to Disease; Genome-Wide Association Study; Inflammation; Polymorphism, Single Nucleotide; Risk Factors; Multifactorial Inheritance
PubMed: 36678166
DOI: 10.3390/nu15020296 -
Gastroenterology Feb 2022Gastroesophageal reflux disease (GERD) is associated with an increased risk of cancer of the upper gastrointestinal tract. This study aimed to assess whether and to what...
BACKGROUND AND AIMS
Gastroesophageal reflux disease (GERD) is associated with an increased risk of cancer of the upper gastrointestinal tract. This study aimed to assess whether and to what extent a negative upper endoscopy in patients with GERD is associated with decreased incidence and mortality in upper gastrointestinal cancer (ie, esophageal, gastric, or duodenal cancer).
METHODS
We conducted a population-based cohort study of all patients with newly diagnosed GERD between July 1, 1979 and December 31, 2018 in Denmark, Finland, Norway, and Sweden. The exposure, negative upper endoscopy, was examined as a time-varying exposure, where participants contributed unexposed person-time from GERD diagnosis until screened and exposed person-time from the negative upper endoscopy. The incidence and mortality in upper gastrointestinal cancer were assessed using parametric flexible models, providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs).
RESULTS
Among 1,062,740 patients with GERD (median age 58 years; 52% were women) followed for a mean of 7.0 person-years, 5324 (0.5%) developed upper gastrointestinal cancer and 4465 (0.4%) died from such cancer. Patients who had a negative upper endoscopy had a 55% decreased risk of upper gastrointestinal cancer compared with those who did not undergo endoscopy (HR, 0.45; 95% CI, 0.43-0.48), a decrease that was more pronounced during more recent years (HR, 0.34; 95% CI, 0.30-0.38 from 2008 onward), and was otherwise stable across sex and age groups. The corresponding reduction in upper gastrointestinal mortality among patients with upper endoscopy was 61% (adjusted HR, 0.39; 95% CI, 0.37-0.42). The risk reduction after a negative upper endoscopy in incidence and mortality lasted for 5 and at least 10 years, respectively.
CONCLUSIONS
Negative upper endoscopy is associated with strong and long-lasting decreases in incidence and mortality in upper gastrointestinal cancer in patients with GERD.
Topics: Adult; Aged; Duodenal Neoplasms; Endoscopy, Digestive System; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Proportional Hazards Models; Risk Assessment; Stomach Neoplasms
PubMed: 34627859
DOI: 10.1053/j.gastro.2021.10.003 -
Scientific Reports Apr 2022We aimed to explore factors associated with prognosis in patients with metastatic small bowel adenocarcinoma (SBA) as well as to develop and validate nomograms to...
We aimed to explore factors associated with prognosis in patients with metastatic small bowel adenocarcinoma (SBA) as well as to develop and validate nomograms to predict overall survival (OS) and cancer-specific survival (CSS). Relevant information of patients diagnosed between 2004 and 2016 was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms for predicting 1- and 3-year OS and CSS were established with potential risk factors screened from multivariate cox regression analysis. The discrimination and accuracy of the nomograms were assessed by concordance index (C-index), calibration plots, and the area under receiver operating characteristic curve (AUC). In total, 373 SBA patients with M1 category were enrolled. Multivariate analysis revealed that age, size and grade of primary tumor, primary tumor surgery, and chemotherapy were significant variables associated with OS and CSS. The C-index values of the nomogram for OS were 0.715 and 0.687 in the training and validation cohorts, respectively. For CSS, it was 0.711 and 0.690, respectively. Through AUC, decision curve analysis (DCA) and calibration plots, the nomograms displayed satisfactory prognostic predicted ability and clinical application both in the OS and CSS. Our models could be served as a reliable tool for prognostic evaluation of patients with metastatic SBA, which are favorable in facilitating individualized survival predictions and clinical decision-making.
Topics: Adenocarcinoma; Duodenal Neoplasms; Humans; Neoplasm Staging; Nomograms; Prognosis; Retrospective Studies; SEER Program
PubMed: 35396531
DOI: 10.1038/s41598-022-09986-0 -
United European Gastroenterology Journal May 2021Adenomatous polyposis (AP) diseases, including familial adenomatous polyposis (FAP), attenuated FAP (AFAP), and MUTYH-associated polyposis (MAP), are the second most... (Review)
Review
Adenomatous polyposis (AP) diseases, including familial adenomatous polyposis (FAP), attenuated FAP (AFAP), and MUTYH-associated polyposis (MAP), are the second most common hereditary causes of colorectal cancer. A frequent extra-colonic manifestation of AP disease is duodenal polyposis, which may lead to duodenal cancer in up to 18% of AP patients. Endoscopic surveillance is recommended at 0.5- to 5-year intervals depending on the extent of polyp growth and histological progression. Although the Spigelman classification is traditionally used to determine surveillance intervals, it lacks information on the (peri-)ampullary site, where 50% of duodenal carcinomas are located. Hence, information on the papilla has recently been added as a prognostic marker. Patients with duodenal adenoma(s) ≥10 mm and ampullary adenomas of any size are suggested to be referred to an expert center for endoscopic therapy, particularly endoscopic mucosal resection and endoscopic ampullectomy. Nonetheless, despite the logic of this approach, the long-term efficacy of endoscopic therapy is still to be demonstrated.
Topics: Adenomatous Polyposis Coli; Duodenal Neoplasms; Duodenoscopy; Endoscopic Mucosal Resection; Humans; Male; Middle Aged; Neoplasm Staging; Patient Compliance; Prognosis; Time Factors
PubMed: 34529357
DOI: 10.1002/ueg2.12071 -
Neuroendocrinology 2021Small intestinal neuroendocrine tumors (SI-NETs) are difficult to diagnose in the early stage of disease. Current blood biomarkers such as chromogranin A (CgA) and...
BACKGROUND
Small intestinal neuroendocrine tumors (SI-NETs) are difficult to diagnose in the early stage of disease. Current blood biomarkers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid have low sensitivity (SEN) and specificity (SPE). This is a first preplanned interim analysis (Nordic non-interventional, prospective, exploratory, EXPLAIN study [NCT02630654]). Its objective is to investigate if a plasma protein multi-biomarker strategy can improve diagnostic accuracy (ACC) in SI-NETs.
METHODS
At the time of diagnosis, before any disease-specific treatment was initiated, blood was collected from patients with advanced SI-NETs and 92 putative cancer-related plasma proteins from 135 patients were analyzed and compared with the results of age- and sex-matched controls (n = 143), using multiplex proximity extension assay and machine learning techniques.
RESULTS
Using a random forest model including 12 top ranked plasma proteins in patients with SI-NETs, the multi-biomarker strategy showed SEN and SPE of 89 and 91%, respectively, with negative predictive value (NPV) and positive predictive value (PPV) of 90 and 91%, respectively, to identify patients with regional or metastatic disease with an area under the receiver operator characteristic curve (AUROC) of 99%. In 30 patients with normal CgA concentrations, the model provided a diagnostic SPE of 98%, SEN of 56%, and NPV 90%, PPV of 90%, and AUROC 97%, regardless of proton pump inhibitor intake.
CONCLUSION
This interim analysis demonstrates that a multi-biomarker/machine learning strategy improves diagnostic ACC of patients with SI-NET at the time of diagnosis, especially in patients with normal CgA levels. The results indicate that this multi-biomarker strategy can be useful for early detection of SI-NETs at presentation and conceivably detect recurrence after radical primary resection.
Topics: Biomarkers; Duodenal Neoplasms; Humans; Ileal Neoplasms; Jejunal Neoplasms; Machine Learning; Neuroendocrine Tumors
PubMed: 32721955
DOI: 10.1159/000510483