Chronic gastritis is a kind of chronic gastric mucosal inflammation caused by many factors.Intestinal metaplasia refers to the transformation of gastric mucosal epithelial cells into small/large intestinal mucosal epithelium containing Panette or goblet cells.Chronic gastritis has the highest incidence among stomach diseases,while intestinal metaplasia is the serious manifestation of chronic gastritis.In this experiment,the therapeutic effect of modified Zhengqi Powder on mild intestinal metaplasia in chronic gastritis and on patients' quality of life and inflammatory reaction was investigated to analyze the efficacy and mechanism of traditional Chinese medicine prescription.From April 2016 to April 2017,120 patients of chronic gastritis with mild intestinal metaplasia were selected and divided into two groups according to the envelope method.The control group(60 cases) was treated with famoxetine.After one month of continuous treatment,the total effective rate of treatment in the observation group was 93.3%,which was much higher than 80.0% in the control group.Health questionnaire(SF-36),serum C-reactive protein(CRP),interleukin-8(IL-8) and tumor necrosis factor-α(TNF-α) levels were significantly higher than those in the control group(P<0.05).The results showed that modified Zhengqi Powder has a significant efficacy in treat chronic gastritis with mild intestinal metaplasia,and can obviously alleviate clinical symptoms and intestinal metaplasia,remove inflammatory factors and improve the quality of life of patients,and is worth promotion.
C-Reactive Protein ; analysis ; Drugs, Chinese Herbal ; therapeutic use ; Gastric Mucosa ; drug effects ; Gastritis, Atrophic ; drug therapy ; Humans ; Interleukin-8 ; blood ; Metaplasia ; drug therapy ; Quality of Life ; Tumor Necrosis Factor-alpha ; blood

Proton pump inhibitors (PPIs) are commonly used to lessen symptoms in patients with gastroesophageal reflux disease (GERD). However, the effects of PPI therapy on the gastrointestinal microbiota in GERD patients remain unclear. We examined the association between the PPI usage and the microbiota present in gastric mucosal and fecal samples from GERD patients and healthy controls (HCs) using 16S rRNA gene sequencing. GERD patients taking PPIs were further divided into short-term and long-term PPI user groups. We showed that PPI administration lowered the relative bacterial diversity of the gastric microbiota in GERD patients. Compared to the non-PPI-user and HC groups, higher abundances of Planococcaceae, Oxalobacteraceae, and Sphingomonadaceae were found in the gastric microbiota from the PPI-user group. In addition, the Methylophilus genus was more highly abundant in the long-term PPI user group than in the short-term PPI-user group. Despite the absence of differences in alpha diversity, there were significant differences in the fecal bacterial composition of between GERD patients taking PPIs and those not taking PPIs. There was a higher abundance of Streptococcaceae, Veillonellaceae, Acidaminococcaceae, Micrococcaceae, and Flavobacteriaceae present in the fecal microbiota from the PPI-user group than those from the non-PPI-user and HC groups. Additionally, a significantly higher abundance of Ruminococcus was found in GERD patients on long-term PPI medication than that on short-term PPI medication. Our study indicates that PPI administration in patients with GERD has a significant effect on the abundance and structure of the gastric mucosal microbiota but only on the composition of the fecal microbiota.
Adult ; Aged ; Bacteria ; genetics ; isolation & purification ; Feces ; microbiology ; Female ; Gastric Mucosa ; microbiology ; Gastroesophageal Reflux ; drug therapy ; microbiology ; Gastrointestinal Microbiome ; drug effects ; Humans ; Male ; Microbiota ; Middle Aged ; Proton Pump Inhibitors ; therapeutic use ; RNA, Ribosomal, 16S ; genetics

Restraint water-immersion stress (RWIS), a compound stress model, has been widely used to induce acute gastric ulceration in rats. A wealth of evidence suggests that the central nucleus of the amygdala (CEA) is a focal region for mediating the biological response to stress. Different stressors induce distinct alterations of neuronal activity in the CEA; however, few studies have reported the characteristics of CEA neuronal activity induced by RWIS. Therefore, we explored this issue using immunohistochemistry and in vivo extracellular single-unit recording. Our results showed that RWIS and restraint stress (RS) differentially changed the c-Fos expression and firing properties of neurons in the medial CEA. In addition, RWIS, but not RS, induced the activation of corticotropin-releasing hormone neurons in the CEA. These findings suggested that specific neuronal activation in the CEA is involved in the formation of RWIS-induced gastric ulcers. This study also provides a possible theoretical explanation for the different gastric dysfunctions induced by different stressors.
Action Potentials ; drug effects ; physiology ; Analysis of Variance ; Animals ; Central Amygdaloid Nucleus ; pathology ; Corticotropin-Releasing Hormone ; metabolism ; Disease Models, Animal ; Gastric Mucosa ; pathology ; Gene Expression Regulation ; physiology ; Neurons ; physiology ; Patch-Clamp Techniques ; Proto-Oncogene Proteins c-fos ; metabolism ; Rats ; Rats, Wistar ; Stress, Physiological ; physiology ; Stress, Psychological ; etiology ; physiopathology

OBJECTIVEVigna subterranea is widely consumed as a traditional staple food in Nigeria and some West African countries. The ethanolic seed extract of V. subterranea (EEVS) was investigated for its gastroprotective effects on aspirin plus pylorus ligation-induced gastric ulcerated rats using an in vivo assay.

METHODSGastric mucosal ulceration was induced experimentally in Groups 2 to 5 using aspirin plus pylorus ligation. Rats in Group 1 were orally pretreated with 3% Tween 80 only as normal control. Groups 2 to 5 were pretreated with 3% Tween 80 (ulcer group), 20 mg/kg of omeprazole (positive group), and 200 and 400 mg/kg of EEVS (experimental groups), respectively, once daily for 21 days before ulcer induction. Parameters including those for gastric secretions, ulcerated areas and gastric wall histology were assessed. Levels of superoxide dismutase (SOD), glutathione peroxidase (GP), and malondialdehyde (MDA) in the gastric tissue homogenate were also determined.

RESULTSPretreatment with EEVS significantly (P < 0.05) reduced the ulcer index, gastric volume and total acidity in rats with aspirin plus pylorus ligation-induced ulcer. The pH and mucus of gastric content increased significantly (P < 0.05) while the levels of SOD and GP were observed to be elevated with a reduced amount of MDA. Significant severe gastric mucosal injury was exhibited in the ulcer group and EEVS or omeprazole offered significant (P < 0.05) protection against mucosal ulceration. Histologically, the gastric submucosal layer showed remarkable decrease in edema and leucocytes infiltration compared with ulcer group.

CONCLUSIONThe study suggests that EEVS offered a protective action against aspirin plus pylorus ligation-induced gastric ulcers in Wistar rats. The protective effect might be mediated via antisecretory, cytoprotective and antioxidative mechanisms.

Animals ; Anti-Ulcer Agents ; pharmacology ; therapeutic use ; Antioxidants ; pharmacology ; therapeutic use ; Aspirin ; Edema ; Gastric Mucosa ; drug effects ; metabolism ; pathology ; Gastrointestinal Agents ; pharmacology ; therapeutic use ; Glutathione Peroxidase ; metabolism ; Hydrogen-Ion Concentration ; Leukocytes ; Male ; Malondialdehyde ; metabolism ; Mucus ; metabolism ; Nuts ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Severity of Illness Index ; Stomach Ulcer ; chemically induced ; drug therapy ; metabolism ; prevention & control ; Superoxide Dismutase ; metabolism ; Vigna

Gastric dysplasia is a neoplastic lesion and a precursor of gastric cancer. The Padova, Vienna, and World Health Organization classifications were developed to overcome the discrepancies between Western and Japanese pathologic diagnoses and to provide a universally accepted classification of gastric epithelial neoplasia. At present, the natural history of gastric dysplasia is unclear. Much evidence suggests that patients with high-grade dysplasia are at high risk of progression to carcinoma or synchronous carcinoma. Therefore, endoscopic resection is required. Although patients with low-grade dysplasia have been reported to be at low risk of progression to carcinoma, due to the marked histologic discrepancies between forceps biopsy and endoscopic specimens, endoscopic resection for this lesion is recommended, particularly in the presence of other risk factors (large size; depressed gross type; surface erythema, unevenness, ulcer, or erosion; and tubulovillous or villous histology). Helicobacter pylori eradication in patients with dysplasia after endoscopic resection appear to reduce the incidence of metachronous lesions.
Anti-Bacterial Agents/therapeutic use ; Biopsy ; Carcinoma in Situ/classification/microbiology/*pathology/*surgery ; Disease Progression ; *Gastrectomy/adverse effects/methods ; Gastric Mucosa/microbiology/*pathology/*surgery ; Gastroscopy ; Helicobacter Infections/drug therapy/microbiology ; Helicobacter pylori/drug effects ; Humans ; Neoplasm Grading ; Precancerous Conditions/classification/microbiology/*pathology/*surgery ; Predictive Value of Tests ; Risk Factors ; Stomach Neoplasms/classification/microbiology/*pathology/*surgery ; Treatment Outcome

OBJECTIVETo study the effects of Weipixiao (胃痞消, WPX) on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions (GPL).

METHODSSprague Dawley rats were randomly divided into control, model, vitacoenzyme (0.2 g·kg(-1)·day(-1)), WPX high-dose (H-WPX, 15 g·kg(-1)·day(-1)), WPX medium-dose (M-WPX, 7.5 g·kg(-1)·day(-1)) and WPX low-dose (L-WPX, 3.75 g·kg(-1)·day(-1)) groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-proteincoupled receptor 5 (Lgr5), matrix metalloproteinase-7 (MMP-7), Wnt1, Wnt3a, and β-catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software.

RESULTSGastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wnt1, Wnt3a and β-catenin than those of the control group(P<0.01). Interestingly, we also observed Lgr5+ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wnt1, and β-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups (P<0.05). A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups (P>0.05).

CONCLUSIONOur findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wnt1, β-catenin and the aberrant activation of Wnt/β-catenin pathway.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Gastric Mucosa ; pathology ; Immunohistochemistry ; Male ; Matrix Metalloproteinase 7 ; metabolism ; Precancerous Conditions ; drug therapy ; pathology ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; metabolism ; Staining and Labeling ; Stomach Neoplasms ; drug therapy ; pathology ; Wnt Proteins ; metabolism ; Wnt Signaling Pathway ; drug effects ; beta Catenin ; metabolism

BACKGROUNDCurrent knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions.

METHODSWe recruited aspirin takers as the exposed group and healthy volunteers as the control group. The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy, including erosion, ulcer or bleeding of the esophagus, stomach, or duodenum; subgroup B as no injury of the gastric mucosa was detected by gastroscopy. Clinical information was collected, and 53 single nucleotide polymorphisms were evaluated.

RESULTSAmong 385 participants, 234 were in the aspirin-exposed group. According to gastroscopy, 82 belonged to subgroup A, 91 belonged to subgroup B, and gastroscopic results of 61 participants were not available. Using the Chi-square test and logistic regression, we found that peptic ulcer history (odds ratio [OR] = 5.924, 95% confidence intervals [CI]: 2.115-16.592), dual anti-platelet medication (OR = 3.443, 95% CI: 1.154-10.271), current Helicobacter pylori infection (OR = 2.242, 95% CI: 1.032-4.870), male gender (OR = 2.211, 95% CI: 1.027-4.760), GG genotype of rs2243086 (OR = 4.516, 95% CI: 1.180-17.278), and AA genotype of rs1330344 (OR = 2.178, 95% CI: 1.016-4.669) were more frequent in subgroup A than subgroup B. In aspirin users who suffered from upper gastrointestinal bleeding, the frequency of the TT genotype of rs2238631 and TT genotype of rs2243100 was higher than in those without upper gastrointestinal bleeding.

CONCLUSIONSPeptic ulcer history, dual anti-platelet medication, H. pylori current infection, and male gender were possible clinical risk factors for aspirin-induced gastric mucosal injury. GG genotype of rs2243086 and AA genotype of rs1330344 were possible genetic risk factors. TT genotype of rs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in aspirin users.

Aged ; Aspirin ; adverse effects ; Female ; Gastric Mucosa ; drug effects ; injuries ; Genotype ; Helicobacter Infections ; physiopathology ; Humans ; Male ; Middle Aged ; Peptic Ulcer ; physiopathology ; Platelet Aggregation Inhibitors ; adverse effects ; Polymorphism, Single Nucleotide ; genetics ; Risk Factors

BACKGROUND/AIMS: The interaction between nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori remains controversial. We retrospectively investigated whether H. pylori infection exacerbates severe gastric mucosal injury among chronic NSAID users. METHODS: From January 2010 to December 2013, a total of 245 long-term NSAID (including low-dose aspirin) users who had undergone an esophagogastroduodenoscopy and had been evaluated for H. pylori infection were enrolled at Okayama University Hospital and Tsuyama Chuo Hospital. The degree of gastric mucosal injury was assessed according to the modified Lanza score (MLS). Severe gastric mucosal injury was defined as an MLS > or =4. Univariate and multivariate logistic regression analyses were performed. RESULTS: In the univariate analysis, age > or =75 years (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3 to 4.2), H. pylori-positivity (OR, 2.0; 95% CI, 1.2 to 3.5), and the concomitant use of proton pump inhibitors (PPIs) (OR, 0.48; 95% CI, 0.26 to 0.86) were significantly associated with severe gastric mucosal injury. The multivariate analysis was adjusted by age and sex and demonstrated that H. pylori-positivity (OR, 1.8; 95% CI, 1.0 to 3.3) and the concomitant use of PPIs (OR, 0.53; 95% CI, 0.28 to 0.99) significantly contributed to severe gastric mucosal injury. CONCLUSIONS: H. pylori infection exacerbates severe gastric mucosal injury among chronic NSAID users.
Aged ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Case-Control Studies ; *Disease Progression ; Endoscopy, Digestive System ; Female ; Gastric Mucosa/*drug effects/*microbiology ; Helicobacter Infections/*complications/microbiology/pathology ; *Helicobacter pylori/drug effects ; Humans ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Proton Pump Inhibitors/adverse effects ; Retrospective Studies

The epithelial cytokine response, associated with reactive oxygen species (ROS), is important in Helicobacter pylori (H. pylori)-induced inflammation. H. pylori induces the production of ROS, which may be involved in the activation of mitogen-activated protein kinases (MAPK), janus kinase/signal transducers and activators of transcription (Jak/Stat), and oxidant-sensitive transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), and thus, expression of interleukin-8 (IL-8) in gastric epithelial cells. alpha-lipoic acid, a naturally occurring thiol compound, is a potential antioxidant. It shows beneficial effects in treatment of oxidant-associated diseases including diabetes. The present study is purposed to investigate whether alpha-lipoic acid inhibits expression of inflammatory cytokine IL-8 by suppressing activation of MAPK, Jak/Stat, and NF-kappaB in H. pylori-infected gastric epithelial cells. Gastric epithelial AGS cells were pretreated with or without alpha-lipoic acid for 2 h and infected with H. pylori in a Korean isolate (HP99) at a ratio of 300:1. IL-8 mRNA expression was analyzed by RT-PCR analysis. IL-8 levels in the medium were determined by enzyme-linked immunosorbent assay. NF-kappaB-DNA binding activity was determined by electrophoretic mobility shift assay. Phospho-specific and total forms of MAPK and Jak/Stat were assessed by Western blot analysis. ROS levels were determined using dichlorofluorescein fluorescence. As a result, H. pylori induced increases in ROS levels, mRNA, and protein levels of IL-8, as well as the activation of MAPK [extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase 1/2 (JNK1/2), p38], Jak/Stat (Jak1/2, Stat3), and NF-kappaB in AGS cells, which was inhibited by alpha-lipoic acid. In conclusion, alpha-lipoic acid may be beneficial for prevention and/or treatment of H. pylori infection-associated gastric inflammation.
Enzyme-Linked Immunosorbent Assay ; Epithelial Cells/metabolism ; Gastric Mucosa/*drug effects/metabolism/microbiology ; Gene Expression Regulation, Bacterial ; Helicobacter Infections/immunology/*metabolism ; Helicobacter pylori/drug effects/*pathogenicity ; Humans ; Interleukin-8/genetics/*metabolism ; JNK Mitogen-Activated Protein Kinases ; Janus Kinase 1 ; Mitogen-Activated Protein Kinases/*biosynthesis ; NF-kappa B/*metabolism ; RNA, Messenger/isolation & purification/metabolism ; Reactive Oxygen Species/metabolism ; STAT3 Transcription Factor ; Stomach/metabolism/*microbiology ; Thioctic Acid/*pharmacology

NADPH oxidase produces a large amount of reactive oxygen species (ROS) in Helicobacter pylori (H. pylori)-induced gastric epithelial cells. Even though ROS mediate apoptotic cell death, direct involvement of NADPH oxidase on H. pylori-induced apoptosis remains unclear. Besides, H. pylori isolates show a high degree of genetic variability. The predominant genotype of H. pylori in Korea has been reported as cagA+, vacA s1b, m2, iceA genotype. Present study aims to investigate whether NADPH oxidase-generated ROS mediate apoptosis in human gastric epithelial AGS cells infected with H. pylori in a Korean isolate. AGS cells were pretreated with or without an NADPH oxidase inhibitor diphenyleneiodonium (DPI) and cultured in the presence of H. pylori at a bacterium/cell ratio of 300:1. Cell viability, hydrogen peroxide level, DNA fragmentation, and protein levels of p53, Bcl-2, and Bax were determined. Results showed that H. pylori inhibited cell viability with the density of H. pylori added to the cells. Inhibition of NADPH oxidase by DPI suppressed H. pylori-induced cell death, increased hydrogen peroxide, DNA fragmentation, and the ratio of Bax/Bcl-2, and p53 induction in AGS cells dose-dependently. The results suggest that targeting NADPH oxidase may prevent the development of gastric inflammation associated with H. pylori infection by suppressing abnormal apoptotic cell death of gastric epithelial cells.
Apoptosis ; Apoptosis Regulatory Proteins/metabolism ; Cell Survival ; Epithelial Cells/metabolism/microbiology ; Gastric Mucosa/metabolism ; Helicobacter Infections/*metabolism/microbiology ; Helicobacter pylori/drug effects/genetics/*isolation & purification ; Humans ; NADPH Oxidase/metabolism ; Onium Compounds/*antagonists & inhibitors/pharmacology ; Oxidative Stress/drug effects ; Reactive Oxygen Species/metabolism ; Republic of Korea ; Stomach/cytology/*metabolism/microbiology