Lactobacillus acidophilus NCFM and Lactiplantibacillus plantarum Lp-115 inhibit Helicobacter pylori colonization and gastric inflammation in a murine model.

Purpose: To determine the role of Lactobacillus strains and their combinations in inhibiting the colonization of H. pylori and gastric mucosa inflammation. Methods: Human gastric adenocarcinoma AGS cells were incubated with H. pylori and six probiotic strains (Lactobacillus acidophilus NCFM, L. acidophilus La-14, Lactiplantibacillus plantarum Lp-115, Lacticaseibacillus paracasei Lpc-37, Lacticaseibacillus rhamnosus Lr-32, and L. rhamnosus GG) and the adhesion ability of H. pylori in different combinations was evaluated by fluorescence microscopy and urease activity assay. Male C57BL/6 mice were randomly divided into five groups (uninfected, H. pylori, H. pylori+NCFM, H. pylori+Lp-115, and H. pylori+NCFM+Lp-115) and treated with two lactobacilli strains (NCFM and Lp-115) for six weeks. H. pylori colonization and tissue inflammation statuses were determined by rapid urease test, Hematoxylin-Eosin (HE) staining, immunohistochemistry, and qRT-PCR and ELISA. Results: L. acidophilus NCFM, L. acidophilus La-14, L. plantarum Lp-115, L. paracasei Lpc-37, L. rhamnosus Lr-32, and L. rhamnosus GG reduced H. pylori adhesion and inflammation caused by H. pylori infection in AGS cells and mice. Among all probiotics L. acidophilus NCFM and L. plantarum, Lp-115 showed significant effects on the H. pylori eradication and reduction of inflammation in-vitro and in-vivo. Compared with the H. pylori infection group, the mRNA and protein expression levels of IL-8 and TNF-α in the six Lactobacillus intervention groups were significantly reduced. The changes in the urease activity (ureA and ureB) for 1-7h in each group showed that L. acidophilus NCFM, L. acidophilus La-14, L. plantarum Lp-115, and L. rhamnosus GG effectively reduced the colonization of H. pylori. We observed a higher ratio of lymphocyte and plasma cell infiltration into the lamina propria of the gastric mucosa and neutrophil infiltration in H. pylori+NCFM+Lp-115 mice. The infiltration of inflammatory cells in lamina propria of the gastric mucosa was reduced in the H. pylori+NCFM+Lp-115 group. Additionally, the expression of IFN-γ was decreased significantly in the NCFM and Lp-115 treated C57BL/6 mice. Conclusions: L. acidophilus NCFM and L. plantarum Lp-115 can reduce the adhesion of H. pylori and inhibit the gastric inflammatory response caused by H. pylori infection.

Residual Level Of Deltamethrin Induced Gastritis And Preventive Role Of Curcumin On Stomach Mucosa.

BACKGROUND: Benefits of Curcumin for health have been explained by different experimental models and clinical trials. It is a very potent antioxidant. Curcumin was found to play a preventive and curative role in both acute and chronic gastritis. Deltamethrin is a useful pesticide when applied with caution to crops. However, it also has noxious effects on gastric mucosa once ingested with sprayed crops. Its maximum permissible limit, MRL (Maximum Residual Level) as pesticide food residues is 5 mg/kg body weight as defined by WHO. However, there is still a potential to cause harm at these levels and maybe a serious potential health hazard. The present study aimed to: (a) determine the prevalence and severity of gastritis induced by deltamethrin when administered at MRL doses and (b) To observe the preventive effect on gastric mucosa against the action of Deltamethrin present as a residual pesticide in different vegetables and fruits. METHODS: In this two-phase subacute toxicity study of seven weeks, forty Sprague Dawley rats were divided into eight subgroups. Control groups were kept on a normal diet and sesame oil. Out of the two treatment groups, one group was given deltamethrin (5 mg/kg body weight) orally along with curcumin 100 mg/kg body weight. The second group was first given deltamethrin (5mg/kg body weight) and curcumin (200mg/kg). All were culled at its end. The stomach samples were collected and processed to obtain histology slides for analysis via microscopy and micrometry. Grading was done to look for changes according to the "Visual Analogue Scale and Operative Link on Gastritis Assessment (OLGA)". RESULTS: The experimental deltamethrin group when compared to control groups, revealed mild changes in stomach histomorphology while curcumin-treated both groups; Group D (100 mg/kg) and Group E (200 mg/kg) showed no changes. CONCLUSIONS: Administration of Deltamethrin even in maximum residual dose (permissible) is proven to be toxic. Curcumin is hence proven to protect the gastric mucosa against the toxic effects of deltamethrin ingested in residual form.

Tauroursodeoxycholic Acid Inhibits Nuclear Factor Kappa B Signaling in Gastric Epithelial Cells and Ameliorates Gastric Mucosal Damage in Mice.

Background/Aims: Previous studies have reported the protective effects of tauroursodeoxycholic acid (TUDCA) on gastric epithelial cells in some animal models, but the precise mechanisms are unclear. This study examined the effects of TUDCA on NF-κB signaling in gastric epithelial cells. Moreover, the protective effects of TUDCA in experimental gastritis models induced by ethanol and NSAID were evaluated and compared with ursodeoxycholic acid (UDCA). Methods: After a pretreatment with TUDCA or UDCA, human gastric epithelial MKN-45 cells were stimulated with tumor necrosis factor (TNF)-α to activate NF-κB signaling. A real-time PCR (RT-PCR) for human interleukin (IL)-1 mRNA was performed. An electrophoretic mobility shift assay (EMSA) and immunoblot analyses were carried out. In murine models, after a pretreatment with TUDCA or UDCA, ethanol and indomethacin were administered via oral gavage. Macroscopic and microscopic assessments were performed to evaluate the preventive effects of TUDCA and UDCA on murine gastritis. Results: A pretreatment with TUDCA downregulated the IL-1α mRNA levels in MKN-45 cells stimulated with TNF-α, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-α-induced NF-κB DNA binding activity. A pretreatment with TUDCA inhibited IκBα phosphorylation induced by TNF-α, as assessed by immunoblot analysis. TUDCA attenuated the ethanol-induced and NSAID-induced gastritis in murine models, as determined macroscopically and microscopically. Conclusions: TUDCA inhibited NF-κB signaling in gastric epithelial cells and ameliorated ethanol- and NSAID-induced gastritis in murine models. These results support the potential of TUDCA for the prevention of gastritis in humans.

Uncut Roux-en-Y might reduce the rate of reflux gastritis after radical distal gastrectomy: An evidence mapping from a systematic review.

BACKGROUND: To evaluate the efficacy, safety, technical feasibility, and effect of reducing the incidence of reflux gastritis from uncut Roux-en-Y (URY) reconstruction after radical distal gastrectomy (RDG) for gastric cancer. METHODS: A literature search was conducted in PubMed, EMBASE, Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure, and WanFang databases until June 30, 2020, to identify studies comparing URY reconstruction with other gastrointestinal tract reconstruction methods after RDG. The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration's risk for bias assessment tool were used to assess the risk of bias. The study was performed using review manager RevMan 5.3.0 software. RESULTS: A total of 35 original studies (six randomized clinical trials (RCTs) and 29 cohort studies) were included in this analysis with a total of 4100 patients. For reflux gastritis, URY anastomosis was significantly superior to the other four types of anastomoses (Billroth-I (odds ratio (OR) = 0.16 [0.10, 0.27], P < 0.00001); Billroth-II (OR = 0.32 [0.20, 0.51], P < 0.00001); Billroth-II with Braun (OR = 0.14 [0.007, 0.26], P < 0.00001), and Roux-en-Y (OR = 0.59 [0.38, 0.91], P = 0.02)). Furthermore, URY anastomosis was better than Billroth-II with Braun (OR = 0.07, 95%confidence interval (CI): [0.02, 0.28], P = 0.0001) and Billroth-II (OR = 0.14, 95%CI: [0.09, 0.24], P < 0.00001) anastomoses for preventing bile reflux. In addition, for anastomotic leakage, URY anastomosis was significantly superior to Roux-en-Y (OR = 0.34, 95%CI: [0.13, 0.87], P = 0.02) anastomosis, and no statistically significant difference between URY and the other three reconstruction methods was found. The postoperative hospital stay of patients receiving URY anastomosis was substantially shorter than those receiving Billroth-II with Braun (MD: 2.84, 95%CI: [-3.16, -1.80], P < 0.00001), Bollroth-II (MD: 1.23, 95%CI: [-2.10, -0.37], P = 0.005) and Roux-en-Y (MD: 1.98, 95%CI: [-2.17, -1.78], P < 0.00001) anastomoses. CONCLUSION: URY reconstruction significantly reduce the rate of reflux gastritis after RDG, and it was a more favorable reconstruction method after RDG for its operative simplicity, safety, and reduced postoperative complications especially in Roux-en-Y stasis syndrome. Large sample size cohort studies and well-designed RCTs are needed for further confirmation of our findings. OTHER: This work was supported by the National Nature Science Foundation of China (No.81871962), Industry-University-Research Innovation Fund in the Ministry of Education of the People's Republic of China (No. 2018A01013) and the Autonomous Intelligent Unmanned System (No. 62088101). This study was registered with PROSPERO (CRD42020200906).

Preventive Anti-inflammatory Diet to Reduce Gastrointestinal Inflammation in Familial Adenomatous Polyposis Patients: A Prospective Pilot Study.

Familial adenomatous polyposis (FAP) is an autosomal-dominant hereditary condition associated with germline mutations in the adenomatous polyposis coli gene. Patient management involves prophylactic surgery and intensive life-long endoscopic surveillance. Diet is a major concern for patients with FAP, who are generally free of symptoms before surgery but tend to have issues related to bowel function postoperatively. We hypothesized that a low-inflammatory diet based on the principles and recipes of the Mediterranean diet would reduce markers of local and systemic inflammation. Twenty-eight patients with FAP over 18 years of age who underwent rectum-sparing prophylactic colectomy and were included in our surveillance program participated in a pilot dietary intervention study. Blood and stool samples at baseline (T0), at the end of the dietary intervention (T1, three months), and at the end of the study (T2, six months after T0) were collected. Gastrointestinal inflammation markers including fecal calprotectin, cyclooxygenase-2, and 15-hydroxyprostaglandin dehydrogenase were evaluated. Serum calprotectin, insulin, insulin-like growth factor-1, C-reactive protein, and glycated hemoglobin were also assessed. Significant changes in serum calprotectin, insulin, and insulin-like growth factor-1 levels occurred over time. Borderline significant changes were observed in the neutrophil-lymphocyte ratio. These changes were noticeable immediately at the end of the 3-month active dietary intervention (T1). A significant increase in 15-hydroxyprostaglandin dehydrogenase expression in the normal crypts of matched samples was also observed between T0 and T2. This pilot study supports the hypothesis that a low-inflammatory diet can modulate gastrointestinal markers of inflammation in individuals with FAP. PREVENTION RELEVANCE: Cancer is known to be related to inflammatory conditions. This study suggests that anti-inflammatory dietary intervention may potentially prevent adenomas and cancer in FAP patients by reducing systemic and tissue inflammatory indices.

Association Between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: A Swedish Population-Based Cohort Study.

BACKGROUND AND AIMS: Biliary tract cancer is a group of highly aggressive malignant disorders, yet risk factors are poorly understood. In this study, we aim to assess whether prolonged use of proton pump inhibitors (PPIs) increases the risk of incident biliary tract carcinoma in a nation-wide population-based cohort in Sweden. APPROACH AND RESULTS: Using nation-wide registries, we identified all adults who received maintenance PPIs (≥180 days) according to the Swedish Prescribed Drug Register from 2005 through 2012. Data on incident biliary tract cancer were retrieved from the Swedish Cancer, Death and Outpatient Registers. Risk of biliary tract cancer in persons who received PPI treatment was compared with the general population of the corresponding age, sex, and calendar year yielding standardized incidence ratios (SIRs) with 95% CIs. Of 738,881 PPI users (median follow-up of 5.3 years), 206 (0.03%) developed gallbladder cancer and 265 (0.04%) extrahepatic and 131 (0.02%) intrahepatic bile duct cancer corresponding to SIRs of 1.58 (95% CI, 1.37-1.81), 1.77 (95% CI, 1.56-2.00), and 1.88 (95% CI, 1.57-2.23), respectively. In sensitivity analyses restricted to persons without a history of gallstones or chronic liver or pancreatic diseases, SIRs were 1.36 (95% CI, 1.17-1.57) and 1.47 (95% CI, 1.19-1.80) for extra- and intrahepatic duct cancer, respectively. The risk remained higher than the corresponding general population with ≥5 years of PPIs use, ruling out confounding by indication. CONCLUSIONS: In this study, long-term use of PPIs was associated with an increased risk of gallbladder, intrahepatic, and extrahepatic bile duct cancer compared with the general population.

Geranium koreanum, a medicinal plant Geranii Herba, ameliorate the gastric mucosal injury in gastritis-induced mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Geranii Herba, the traditional medicinal plants Korean and northeast China, has been used in the healing of a variety of gastrointestinal inflammation disorders. Geranium koreanum is a congeneric origin plant of Geranii Herba that can be used as medicinal plants with Geranium thunbergii, Geranium sibiricum, Geranium carolinianum, Geranium nepalense, and Geranium japonicam. However, research on the biological activity of Geranium koreanum is currently insufficient. AIM OF THE STUDY: Gastritis is typically characterized by inflammation and irritation, and it is commonly caused by factors such as stress, alcohol consumption, smoking, and the use of anti-inflammatory drugs. In particular, excessive ethanol ingestion is an important cause of gastric disease mediated by mucosal damage by inflammatory cells infiltration. In this study, we investigated whether Geranium koreanum, the well-known traditional medicinal plant, could have a protective effect on gastric mucosal damage in an HCl/EtOH-induced gastritis model by analyzing the inflammation response in gastric tissue. MATERIAL AND METHODS: The cytotoxicity and anti-inflammatory effects of Geranium koreanum were analyzed by determining cell viability and nitric oxide (NO) production, as well as the levels of nuclear factor (NF)-κB proteins in lipopolysaccharide (LPS)-induced cells. Additionally, we measured the damage ratio, conducted histopathological assay by H&E and PAS staining, and determined the levels of pro-inflammation mediator proteins in gastric tissue after induction of gastritis by HCl/EtOH administration in order to analyze the gastro-protective effects of Gerranium koreanum. RESULTS: The ulcer ratio and inflammatory cell infiltration in gastric mucosa were reduced by treatment with Geranium koreanum. Additionally, the expression of inflammatory mediators in gastric tissue was effectively decreased by extracts administrated at 200 mg/kg, as compared to the gastritis control. CONCLUSIONS: We demonstrated that Geranium koreanum could have ameliorating effects against HCl/EtOH-induced gastritis through the anti-inflammatory response, which indicates the potential use of this plant as a natural preventive medicine for gastritis treatment.

Gentiopicroside ameliorates ethanol-induced gastritis via regulating MMP-10 and pERK1/2 signaling.

BACKGROUND: Excessive ethanol consumption results in gastric mucosa damage, which could further develop into chronic gastritis, peptic ulcer, and gastric cancer in humans. Gentiopicroside (GPS), a major active component of Gentianae Macrophyllae radix, was reported to play a critical role in anti-inflammation. In the study, we aimed to investigate the functional role and underlying mechanism of GPS in ethanol-induced gastritis. METHODS: A model of gastritis was created by ethanol in C57BL/6 mice. Enzyme-linked immunosorbent assay was used to determine the concentration of TNF-α, IL-1ß, IL-8, and IL-10. RESULTS: We found that GPS treatment significantly ameliorated ethanol-induced gastritis in mice, with lower production of pro-inflammatory cytokine TNF-α, IL-1ß, and IL-8 and higher levels of anti-inflammatory cytokine IL-10. The anti-inflammatory effect of GPS was further confirmed in vitro in ethanol-treated human gastric mucosal GES cells. Mechanistically, we demonstrated that GPS regulated matrix metallopeptidase expression and pERK1/2 signaling. Knockdown of matrix metallopeptidase 10 (MMP-10) greatly improved cell survival and suppressed inflammatory response in ethanol-treated GES cells. Moreover, inhibition of pERK1/2 signaling using U0126 decreased the expression of MMP-10 in ethanol-induced gastritis. U0126 treatment also suppressed the expression of TNF-α, IL-1ß, and IL-8, and enhanced IL-10 expression in mice gastric mucosa. CONCLUSIONS: Taken together, our findings suggest that GPS ameliorates ethanol-induced gastritis via regulating MMP-10 and pERK1/2 signaling, which might provide a promising therapeutic drug for ethanol-induced gastritis.

Protective Effects of Wheat Peptides against Ethanol-Induced Gastric Mucosal Lesions in Rats: Vasodilation and Anti-Inflammation.

Alcohol consumption increases the risk of gastritis and gastric ulcer. Nutritional alternatives are considered for relieving the progression of gastric mucosal lesions instead of conventional drugs that produce side effects. This study was designed to evaluate the gastroprotective effects and investigate the defensive mechanisms of wheat peptides against ethanol-induced acute gastric mucosal injury in rats. Sixty male Sprague-Dawley rats were divided into six groups and orally treated with wheat peptides (0.1, 0.2, 0.4 g/kgbw) and omeprazole (20 mg/kgbw) for 4 weeks, following absolute ethanol administration for 1 h. Pretreatment with wheat peptides obviously enhanced the vasodilation of gastric mucosal blood vessels via improving the gastric mucosal blood flow and elevating the defensive factors nitric oxide (NO) and prostaglandin E2 (PGE2), and lowering the level of vasoconstrictor factor endothelin (ET)-1. Wheat peptides exhibited anti-inflammatory reaction through decreasing inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-6, and increasing trefoil factor 1 (TFF1) levels. Moreover, wheat peptides significantly down-regulated the expression of phosphorylated nuclear factor kappa-B (p-NF-κB) p65 proteins in the NF-κB signaling pathway. Altogether, wheat peptides protect gastric mucosa from ethanol-induced lesions in rats via improving the gastric microcirculation and inhibiting inflammation mediated by the NF-κB signaling transduction pathway.

Loratadine, an antihistamine drug, exhibits anti-inflammatory activity through suppression of the NF-kB pathway.

Loratadine is an antihistamine drug that shows promise as an anti-inflammatory drug, but supportive studies are lacking. We elucidated the effects and mechanisms by which loratadine inhibits inflammatory responses. Molecular components were evaluated in macrophages by nitric oxide assay, polymerase chain reaction, luciferase assay, immunoblotting, overexpression strategies and cellular thermal shift assay. At the molecular level, loratadine reduced the levels of nitric oxide, iNOS, IL-1ß, TNF-α, IL-6, and COX-2 in RAW264.7 cells treated with lipopolysaccharide. Loratadine also specifically inhibited the NF-kB pathway, targeting the Syk and Src proteins. Furthermore, loratadine bound Src in the bridge between SH2 and SH3, and bound Syk in the protein tyrosine kinase domain. The NF-kB signaling pathway was assessed along with putative binding sites through a docking approach. The anti-inflammatory effect of loratadine was tested using mouse models of gastritis, hepatitis, colitis, and peritonitis. Stomach tissue histopathology, liver morphology, and colon length in the loratadine group were improved over the group without loratadine treatment. Taken together, loratadine inhibited the inflammatory response through the NF-kB pathway by binding with the Syk and Src proteins.

Pretreatment with Lactobacillus fermentum XY18 Relieves Gastric Injury Induced by HCl/Ethanol in Mice via Antioxidant and Anti-Inflammatory Mechanisms.

AIM: Lactobacillus fermentum XY18 (LF-XY18) is a bacterial strain with satisfactory antioxidant properties in vitro that we previously isolated from Xinjiang yogurt. This article will explore the preventive effect of LF-XY18 on acute gastric injury and provide the basis for the innovative development and application of lactic acid bacteria (LAB). METHODS: Kunming mice underwent gastric injury induced by hydrochloric acid and ethanol. LF-XY18 isolated from yogurt in Xinyuan County in the Yili region of Xinjiang was subsequently administered intragastrically to mice for 2 weeks to explore the mechanism of LF-XY18 in preventing gastric injury via its antioxidant effects. RESULTS: There was decreased gastric juice volume, gastric injury area, and formation of gastric mucosal lesions in the LF-XY18 mice as compared to those in the control mice, while LF-XY18 prevented the decrease in the gastric juice pH value in mice. Compared with the gastric injury model group mice, LF-XY18 reduced the serum levels of motilin, substance P, interleukin-6, interleukin-12, tumor necrosis factor-α, and interferon-γ but increased the serum levels of somatostatin and vasoactive intestinal peptide. The activities of superoxide dismutase, glutathione peroxidase, glutathione, and nitric oxide were increased in the gastric tissue of the LF-XY18 mice compared with the control mice, but malondialdehyde activity was decreased in the LF-XY18 mice. Quantitative polymerase chain reaction analysis illustrated that in the gastric tissue of LF-XY18 mice, the messenger RNA (mRNA) expression of occludin, epidermal growth factor (EGF), EGF receptor, vascular EGF, inhibitor kappa-B-α, neuronal nitric oxide synthase, endothelial nitric oxide synthase, cuprozinc superoxide dismutase, manganese superoxide dismutase, and catalase was stronger than that in the control mice, but the mRNA expression of activated B cells (NF-κB), inducible nitric oxide synthase, and cyclooxygenase-2 was weaker than in the control mice. CONCLUSION: These results indicate that LF-XY18 has a potential role in the prevention of gastric injury through antioxidant effects, and a high concentration (1.0 × 109 CFU/kg b.w.) of LF-XY18 has a stronger anti-gastric injury effect than a low concentration (1.0 × 108 CFU/kg b.w.).

Baicalin protects against ethanol-induced chronic gastritis in rats by inhibiting Akt/NF-κB pathway.

AIMS: Currently, chronic gastritis is a high incidence of digestive diseases, along with loss of appetite, abdominal pain and diarrhea. Baicalin belongs to the major bioactive flavonoids compounds from Scutellariae Radix, it exhibited anti-inflammatory and anti-bacteria activities. Nonetheless, the protective effects of baicalin on ethanol-induced gastritis have not been completely clarified. Our study was designed to evaluate the protective activity of baicalin on ethanol-induced chronic gastritis. MAIN METHODS: Rat with chronic gastritis model was induced by the administration of 56% ethanol for four weeks. Baicalin (50 and 100 mg/kg) were orally administered for seven days to evaluate its curative effect, respectively. The production of TNF-α, interleukin (IL)-8, IL-1ß, NO, ET-1, PGE2, LDH and COX-2 were determined by ELISA. The activities of Akt, p-Akt, IκBα, p-IκBα, NF-κBp65 and NF-κBp-p65 were tested by western blot. Immunofluorescence staining was employed to assess the location of NF-κBp65. KEY FINDINGS: The changes of the histopathological analysis and the levels of NO, ET-1, PGE2, LDH and COX-2 demonstrated that baicalin treatment ameliorated ethanol-induced gastritis. ELISA analysis showed that baicalin inhibited the levels of TNF-α, IL-8 and IL-1ß. Besides, Akt, p-Akt, IκBα, p-IκBα, NF-κBp65 and NF-κBp-p65 expression were significantly suppressed by baicalin. Meanwhile, baicalin suppressed the translocation of NF-κBp65 to the cell nucleus through immunofluorescence staining, molecular docking analysis showed that baicalin had affinity with Akt and NF-κBp65. SIGNIFICANCE: All results demonstrated that baicalin effectively alleviated chronic gastritis via suppressing the levels of inflammatory regulators and inhibiting Akt/NF-κB activation.

Analysis of A4gnt Knockout Mice Reveals an Essential Role for Gastric Sulfomucins in Preventing Gastritis Cystica Profunda.

Gastric adenocarcinoma cells secrete sulfomucins, but their role in gastric tumorigenesis remains unclear. To address that question, we generated A4gnt/Chst4 double-knockout (DKO) mice by crossing A4gnt knockout (KO) mice, which spontaneously develop gastric adenocarcinoma, with Chst4 KO mice, which are deficient in the sulfotransferase GlcNAc6ST-2. A4gnt/Chst4 DKO mice lack gastric sulfomucins but developed gastric adenocarcinoma. Unexpectedly, severe gastric erosion occurred in A4gnt/Chst4 DKO mice at as early as 3 weeks of age, and with aging these lesions were accompanied by gastritis cystica profunda (GCP). Cxcl1, Cxcl5, Ccl2, and Cxcr2 transcripts in gastric mucosa of 5-week-old A4gnt/Chst4 DKO mice exhibiting both hyperplasia and severe erosion were significantly upregulated relative to age-matched A4gnt KO mice, which showed hyperplasia alone. However, upregulation of these genes disappeared in 50-week-old A4gnt/Chst4 DKO mice exhibiting high-grade dysplasia/adenocarcinoma and GCP. Moreover, Cxcl1 and Cxcr2 were downregulated in A4gnt/Chst4 DKO mice relative to age-matched A4gnt KO mice exhibiting adenocarcinoma alone. These combined results indicate that the presence of sulfomucins prevents severe gastric erosion followed by GCP in A4gnt KO mice by transiently regulating a set of inflammation-related genes, Cxcl1, Cxcl5, Ccl2, and Cxcr2 at 5 weeks of age, although sulfomucins were not directly associated with gastric cancer development.

Immunity and Vaccine Development Against Helicobacter pylori.

Helicobacter pylori is a highly-adapted gastrointestinal pathogen of humans and the immunology of this chronic infection is extremely complex. Despite the availability of antibiotic therapy, the global incidence of H. pylori infection remains high, particularly in low to middle-income nations. Failure of therapy and the spread of antibiotic resistance among the bacteria are significant problems and provide impetus for the development of new therapies and vaccines to treat or prevent gastric ulcer, and gastric carcinoma. The expansion of knowledge on gastric conventional and regulatory T cell responses, and the role of TH17 in chronic gastritis from studies in mouse models and patients have provided valuable insights into how gastritis is initiated and maintained. The development of human challenge models for testing candidate vaccines has meant a unique opportunity to study acute infection, but the field of vaccine development has not progressed as rapidly as anticipated. One clear lesson learned from previous studies is that we need a better understanding of the immune suppressive mechanisms in vivo to be able to design vaccine strategies. There is still an urgent need to identify practical surrogate markers of protection that could be deployed in future field vaccine trials. Important developments in our understanding of the chronic inflammatory response, progress and problems arising from human studies, and an outlook for the future of clinical vaccine trials will be discussed.

Preventive Effect of Anji White Tea Flavonoids on Alcohol-Induced Gastric Injury through Their Antioxidant Effects in Kunming Mice.

Anji white tea (Camellia sinensis) is a traditional Chinese tea beverage, which is classified as green tea and contains an abundant amount of flavonoids. In this study, the preventive effect of Anji white tea flavonoids (AJWTFs) on ethanol/hydrochloric acid-induced gastric injury in mice was evaluated. The serum and gastric tissues of mice were analyzed using a biochemical kit and by quantitative polymerase chain reaction (qPCR). Observation of the appearance of the stomach indicated that AJWTFs could effectively reduce the area of gastric injury caused by ethanol/hydrochloric acid, and the inhibition rate of AJWTF on gastric injury increased with an increase in AJWTF concentration. The Anji white tea flavonoids could also reduce the volume and pH of gastric juice in mice with gastric injury. Biochemical results showed that AJWTFs could increase the superoxide dismutase (SOD) and glutathione (GSH) activities, as well as decrease the malondialdehyde (MDA) level, in the serum and liver of mice with gastric injury. Pathological observation confirmed that AJWTFs could inhibit the tissue damage caused by ethanol/hydrochloric acid in the stomach of mice. Further qPCR experiments also showed that AJWTFs could inhibit the decreases in neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), copper/zinc superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD), catalase (CAT), and the increase in inducible nitric oxide synthase (iNOS) expression in the gastric tissue of mice caused by gastric injury. As observed, AJWTFs exerted a good preventive effect on alcohol-induced gastric injury in mice induced by ethanol/hydrochloric acid, and the effect is close to that of ranitidine. Anji white tea flavonoids present good antioxidant effect, which allows them to effectively prevent alcoholic gastric injury and be used as biologically active substances with a broad range of applications.

Endogenous glucocorticoids prevent gastric metaplasia by suppressing spontaneous inflammation.

In the stomach, chronic inflammation causes metaplasia and creates a favorable environment for the evolution of gastric cancer. Glucocorticoids are steroid hormones that repress proinflammatory stimuli, but their role in the stomach is unknown. In this study, we show that endogenous glucocorticoids are required to maintain gastric homeostasis. Removal of circulating glucocorticoids in mice by adrenalectomy resulted in the rapid onset of spontaneous gastric inflammation, oxyntic atrophy, and spasmolytic polypeptide-expressing metaplasia (SPEM), a putative precursor of gastric cancer. SPEM and oxyntic atrophy occurred independently of lymphocytes. However, depletion of monocytes and macrophages by clodronate treatment or inhibition of gastric monocyte infiltration using the Cx3cr1 knockout mouse model prevented SPEM development. Our results highlight the requirement for endogenous glucocorticoid signaling within the stomach to prevent spontaneous gastric inflammation and metaplasia, and suggest that glucocorticoid deficiency may lead to gastric cancer development.

Lactobacillus reuteri DSM 17938 Protects against Gastric Damage Induced by Ethanol Administration in Mice: Role of TRPV1/Substance P Axis.

This study aimed to evaluate the effect of Lactobacillus reuteri DSM 17938 (DSM) on ethanol-induced gastric injury, and if its possible mechanism of action is related to inhibiting the transient receptor potential vanilloid type 1 (TRPV1). We evaluated the effect of supplementing 108 CFU•g body wt-1•day-1 of DSM on ethanol-induced gastric injury. DSM significantly reduced the ulcer area (1.940 ± 1.121 mm²) with 3 days of pretreatment. The effects of DSM supplementation were reversed by Resiniferatoxin (RTX), TRPV1 agonist (3 nmol/kg p.o.). Substance P (SP) (1 µmol/L per 20 g) plus 50% ethanol resulted in hemorrhagic lesions, and DSM supplementation did not reverse the lesion area induced by administering SP. TRPV1 staining intensity was lower, SP, malondialdehyde (MDA) and nitrite levels were reduced, and restored normal levels of antioxidant parameters (glutathione and superoxide dismutase) in the gastric mucosa in mice treated with DSM. In conclusion, DSM exhibited gastroprotective activity through decreased expression of TRPV1 receptor and decreasing SP levels, with a consequent reduction of oxidative stress.

Cost-effectiveness analysis of screen-and-treat strategy in asymptomatic Chinese for preventing Helicobacter pylori-associated diseases.

BACKGROUND: The high prevalence of Helicobacter pylori (H pylori) infection in China results in a substantial public health burden. Medical experts have not agreed on the best solution of population intervention for this problem. We presented a health economic evaluation of a population-based H pylori screen-and-treat strategy for preventing gastric cancer, peptic ulcer disease (PUD), and nonulcer dyspepsia (NUD). MATERIALS AND METHODS: Decision trees and Markov models were developed to evaluate the cost-effectiveness of H pylori screening followed by eradication treatment in asymptomatic Chinese. The modeled screen-and-treat strategy reduced the risk of gastric cancer, PUD, and NUD. The main outcomes were the costs, effectiveness, and the incremental cost-effectiveness ratio. Uncertainty was explored by one-way and probabilistic sensitivity analyses. RESULTS: For preventing gastric cancer, PUD, and NUD together in a cohort of 10 million asymptomatic Chinese at the age of 20 years, the H pylori screen-and-treat strategy saved 288.1 million dollars, 28 989 life years, and 111 663 quality-adjusted life years, and prevented 11 611 gastric cancers, 5422 deaths from gastric cancer, and 1854 deaths from PUD during life expectancy. Uncertainty of screening age from 20 to 60 did not affect the superiority of the screen-and-treat strategy over the no-screen strategy. The one-way and probabilistic sensitivity analyses confirmed the robustness of our study's results. CONCLUSIONS: Compared with the no-screen strategy, population-based screen-and-treat strategy for H pylori infection proved cheaper and more effective for preventing gastric cancer, PUD, and NUD in Chinese asymptomatic general population.

Clove oil based co-surfactant free microemulsion of flurbiprofen: Improved solubility with ameliorated drug-induced gastritis.

Flurbiprofen, an NSAID, is a water insoluble drug that is also notorious for gastric irritation and inflammation. This study was aimed at using a natural gastrprotective oil as the internal phase to develop flurbiprofen micro emulsion (ME) to improve it solubility and ameliorate its gastric side effects. Upon screening of ME components for drug solubility, clove oil, tween 80 and transcutol were identified as the oil, surfactant and co surfactant, respectively, with higher flurbiprofen solubility. Pseudo-ternary phase diagrams revealed that the ME made with surfactant only and without co-surfactant displayed the similar ME region as made with the mixture of surfactant and co-surfactant. Furthermore, drug loaded oil was also used to draw pseudo-ternary phase diagram and a very little decrease in the ME region was observed. Therefore, co-surfactant free flurbiprofen loaded ME was developed to avoid side effects associated with the use of excessive surfactant quantities. ME were found to possess size in the range of 11-41 nm with PDI <0.5 and a slightly negative charge. Conductivity, pH and refractive indices of the selected MEs were well in the range. Drug release studies indicated maximum drug release from MEs within 5 min. Analysis of the gastric mucosa of rats after oral administration of drug solution and drug loaded ME confirmed that clove oil based ME provided significant protection against the NSAIDs induced gastric damage.