Hyperplasia Of Gastric Mucosa Research Articles

Effectiveness of the Sellick maneuver for painless gastroscopy in patients with esophageal hiatal hernia: A randomized, self‑control trial.

The Sellick maneuver is used for endotracheal intubation to prevent the occurrence of gastroesophageal reflux. The aim of the present study was to observe the effect of the Sellick maneuver on safety, esophageal closure status, gastric mucosal fold extension status, and positive detection rate of lesions in patients with esophageal hiatal hernia under painless gastroscopy. A total of 40 patients with esophageal hiatal hernia who underwent painless gastroscopy were screened for the use of the Sellick maneuver, in which the operator applied pressure to the cervical cricoid cartilage during the examination. The status of esophageal closure at the are pressed, examination time, gastric mucosal fold extension score, positive rate of lesion detection, and reflux of gastric juice or gastric contents, amongst other parameters were assessed. After using the Sellick maneuver, the state of esophageal closure during gastroscopy was significantly better than the no-Sellick maneuver group (P<0.05), and the extension scores of the greater curvature folds of the gastric body, the lateral folds of the lesser curvature of the gastric body, and the mucosal folds of the fundus were significantly higher than that of the no-Sellick maneuver (all P<0.05). The number of gastric polyps and gastric lesions (gastric ulcers and mucosal hyperplasia, amongst others) examined with the Sellick maneuver was significantly higher than the no-Sellick maneuver group (P<0.01). The Sellick maneuver effectively improved the extension of gastric mucosal folds during gastroscopy in patients with esophageal hiatal hernia, increased the positive detection rate of gastric lesions, and shortened the endoscopy time.

Prognostic factors in the treatment of gastric mucosal atypical hyperplasia by endoscopic submucosal dissection

BackgroundEndoscopic submucosal dissection (ESD) is becoming increasingly popular as a treatment for precancerous lesions and early cancers of the stomach. However, there have been few studies on the factors associated with the recurrence of precancerous lesions after ESD.MethodsTo investigate the prognostic factors of gastric intraepithelial neoplasia, we retrospectively analyzed 115 patients who were treated with ESD between February 2018 and January 2020. Chi-square test and Fisher’s extract test were used to select factors for further investigation, and prognostic analysis was carried out with the Kaplan–Meier method and a Cox regression model.ResultsPlatelet counts (P = 0.027) and albumin levels (P = 0.011) were both lower in patients with recurrence than in patients without recurrence of gastric mucosal atypical hyperplasia after ESD.ConclusionsThis study reveals that low platelet counts and albumin levels were probably unfavorable prognostic factors in mucosal atypical hyperplasia of the stomach.

Study on molecular biological mechanism of Chinese herbal medicines for the treatment of gastric precancerous lesions based on data mining and network pharmacology.

To explore the molecular biological mechanisms of Chinese herbal medicines for the treatment of gastric precancerous lesions by data mining and network pharmacology. The keywords "gastric precancerous lesions""gastric precancerous disease""gastric mucosal intraepithelial neoplasia""gastric mucosal heterogeneous hyperplasia""gastric precancerous state""chronic gastritis, atrophic""combined Chinese and Western medicine""Chinese medicine therapy""efficacy evaluation" "randomized controlled trial"were searched in China Journal Full-text Database, Wanfang Data, VIP database, PubMed and Embase from 2001 to 2021. The information was extracted from the literature which met the inclusion and exclusion criteria, and the database was constructed to identify the high-frequency herbal medicines. The top six Chinese herbal medicines were analyzed by the network pharmacology methods, including the acquisition of herbs compounds and gastric precancerous lesions targets using Pharmacology Database and Analysis Platform and GeneCards databases, construction of protein-protein interaction network, and screening of core targets, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of core targets through Metascape platform, etc., to elucidate their active components, targets and pathways. A total of 482 compound prescriptions with 603 herbal medicines were included, and the top 6 herbal medicines with higher application frequency were Ume plum (63.35%), Curcuma longa (58.54%), Paeonia lactiflora (54.06%), Salvia miltiorrhiza (49.92%), Rhizoma alba (46.43%), and Astragalus membranaceus (45.44%). The results of the network pharmacological analysis showed that the active ingredients were 4 types from Ume plum, 3 from Curcuma longa, 9 from Paeonia lactiflora, 13 from Salvia miltiorrhiza, 7 from Astragalus alba, and 9 from Astragalus; 77 predicted targets were in Ume plum, 11 in Curcuma longa, 33 in Paeonia lactiflora, 58 in Salvia miltiorrhiza, 65 in Astragalus alba and 89 in Astragalus; and 98 crossover genes were obtained after these targets were compared with the disease genes, among which HSP90AA1, AKT1, TP53, STAT3, MAPK1 and TNF had higher relevance to the treatment of gastric precancerous lesions. The results of the GO enrichment analysis showed that the active ingredients of high frequency Chinese medicine mostly acted through biological processes such as response to inorganic substance, response to hormone, gland development, positive regulation of cell migration, positive regulation of cell motility, etc. The targets include cellular components such as vesicle lumen, secretory granule lumen, cytoplasmic vesicle lumen, transcription regulator complex, and with molecular functions such as kinase binding, protein kinase binding and DNA-binding transcription factor binding. The results of the KEGG pathway enrichment analysis showed that Paeonia lactiflora, Ulmus lucidus, Salvia miltiorrhiza and Astragalus mainly act through the cancer pathway and PI3K-AKT pathway; Curcuma longa and Rhizoma alba mainly act through the cancer pathway and proteoglycans in cancer, and all six herbs were involved in the cancer pathway and five herbs are involved in the PI3K-AKT pathway. In this study, we obtained the top 6 high-frequency Chinese herbal medicines in the treatment of gastric precancerous lesions by data mining method, and revealed that their mechanisms are involved in cell proliferation, differentiation, immunity, inflammation and other processes mainly through cancer pathway, PI3K-AKT signaling pathway, proteoglycans in cancer.

Gut Microbiota Dysbiosis in the Development and Progression of Gastric Cancer.

Objectives This study aims to explore gut microbiota dysbiosis in the histological stages of gastric cancer (GC). Methods Feces samples and clinical characteristics were collected from patients with different stages of GC, including 15 superficial gastritis (SG), 13 atrophic gastritis (AG), 8 gastric mucosal atypical hyperplasia (GMAH), and 15 advanced GC cases. The diversity and composition of gut microbiota among the four groups were determined by sequencing the V4 region of bacterial 16S rRNA genes. Results Reduced gut microbial alpha diversity and altered dissimilarity of the microbial community structure were found among the four groups. In addition, 18 species, 6 species, 6 species, and 16 species of bacteria were enriched in the SG, AG, GMAH, and GC groups, respectively, using the linear discriminant analysis (LDA) effect size (LEfSe) analyses. Besides, we found that two new genera, Scardovia and Halomonas, are associated with GC and the metabolic pathways of Genetic information processing and Circulatory System were more abundant in the GC group compared with noncancer groups. Conclusions We identified differences in microbial compositional changes across stages of GC. Six genera and two metabolic pathways were more abundant in the GC group than noncancer groups, suggesting that these findings may contribute to the therapy strategies in GC in the near feature.

Astaxanthin Inhibits Helicobacter pylori-induced Inflammatory and Oncogenic Responses in Gastric Mucosal Tissues of Mice.

Helicobacter pylori is recognized as a risk factor for gastric carcinogenesis. The chronic exposure of gastric epithelium to H. pylori induces a prolonged inflammatory state that may progress to gastric cancer. Astaxanthin, a pinkish antioxidant carotenoid, abundant in marine organisms, is known for its protective effect against inflammation and multiple types of cancer. The purpose of this study was to examine the effect of astaxanthin on H. pylori-induced oxidative injury, inflammation, and oncogene expression in gastric mucosal tissues of the infected mice. Mice were inoculated using oral gavage with H. pylori suspension (108 colony forming unit of H. pylori/0.1 mL) for three days, after which they were fed astaxanthin-supplemented diet (5 mg/kg body weight/day for seven weeks). The effects of astaxanthin on H. pylori-induced increase in lipid peroxide (LPO) production, myeloperoxidase (MPO) activity, expression of the inflammatory cytokine IFN-γ and oncogenes (c-myc and cyclin D1), and the accompanying histologic changes in gastric mucosal tissues were evaluated. H. pylori infection increased the level of LPO, MPO activity, and the expression of IFN-γ, c-myc, and cyclin D1 in gastric mucosal tissues of mice. H. pylori infection induced neutrophil infiltration and hyperplasia of gastric mucosa. Astaxanthin supplementation attenuated these effects. In conclusion, consumption of astaxanthin-rich foods may prevent H. pylori-associated oxidative damage and inflammatory and oncogenic responses in gastric mucosal tissues.

TAZ Controls Helicobacter pylori-Induced Epithelial-Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties.

Helicobacter pylori infection, the main risk factor for gastric cancer (GC), leads to an epithelial–mesenchymal transition (EMT) of gastric epithelium contributing to gastric cancer stem cell (CSC) emergence. The Hippo pathway effectors yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) control cancer initiation and progression in many cancers including GC. Here, we investigated the role of TAZ in the early steps of H. pylori-mediated gastric carcinogenesis. TAZ implication in EMT, invasion, and CSC-related tumorigenic properties were evaluated in three gastric epithelial cell lines infected by H. pylori. We showed that H. pylori infection increased TAZ nuclear expression and transcriptional enhancer TEA domain (TEAD) transcription factors transcriptional activity. Nuclear TAZ and zinc finger E-box-binding homeobox 1 (ZEB1) were co-overexpressed in cells harboring a mesenchymal phenotype in vitro, and in areas of regenerative hyperplasia in gastric mucosa of H. pylori-infected patients and experimentally infected mice, as well as at the invasive front of gastric carcinoma. TAZ silencing reduced ZEB1 expression and EMT phenotype, and strongly inhibited invasion and tumorsphere formation induced by H. pylori. In conclusion, TAZ activation in response to H. pylori infection contributes to H. pylori-induced EMT, invasion, and CSC-like tumorigenic properties. TAZ overexpression in H. pylori-induced pre-neoplastic lesions and in GC could therefore constitute a biomarker of early transformation in gastric carcinogenesis.

Gastric Corpus Mucosal Hyperplasia and Neuroendocrine Cell Hyperplasia, but not Spasmolytic Polypeptide-Expressing Metaplasia, Is Prevented by a Gastrin Receptor Antagonist in H+/K+ATPase Beta Subunit Knockout Mice.

Proton pump inhibitor use is associated with an increased risk of gastric cancer, which may be mediated by hypergastrinemia. Spasmolytic polypeptide-expression metaplasia (SPEM) has been proposed as a precursor of gastric cancer. We have examined the effects of the gastrin receptor antagonist netazepide (NTZ) or vehicle on the gastric corpus mucosa of H+/K+ATPase beta subunit knockout (KO) and wild-type (WT) mice. The gastric corpus was evaluated by histopathology, immunohistochemistry (IHC), in situ hybridization (ISH) and whole-genome gene expression analysis, focusing on markers of SPEM and neuroendocrine (NE) cells. KO mice had pronounced hypertrophy, intra- and submucosal cysts and extensive expression of SPEM and NE cell markers in the gastric corpus, but not in the antrum. Numerous SPEM-related genes were upregulated in KO mice compared to WT mice. NTZ reduced hypertrophia, cysts, inflammation and NE hyperplasia. However, NTZ neither affected expression of SPEM markers nor of SPEM-related genes. In conclusion, NTZ prevented mucosal hypertrophy, cyst formation and NE cell hyperplasia but did not affect SPEM. The presence of SPEM seems unrelated to the changes caused by hypergastrinemia in this animal model.

Panax ginseng C.A. Meyer (Rg3) Ameliorates Gastric Precancerous Lesions in Atp4a-/- Mice via Inhibition of Glycolysis through PI3K/AKT/miRNA-21 Pathway.

Gastric cancer, one of the most common types of cancers, develops over a series of consecutive histopathological stages. As such, the analysis and research of the gastric precancerous lesions (GPLs) play an important role in preventing the occurrence of gastric cancer. Ginsenoside Rg3 (Rg3), an herbal medicine, plays an important role in the prevention and treatment of various cancers. Studies have demonstrated a correlation between glycolysis and gastric cancer progression. Herein, the aim of the present study was to clarify the potential role for glycolysis pathogenesis in Rg3-treated GPL in Atp4a−/− mice. The GPL mice model showed chronic gastritis, intestinal metaplasia, and more atypical hyperplasia in gastric mucosa. According to the results of HE and AB-PAS staining, it could be confirmed that GPL mice were obviously reversed by Rg3. Additionally, the increased protein levels of PI3K, AKT, mTOR, HIF-1α, LDHA, and HK-II, which are crucial factors for evaluating GPL in the aspect of glycolysis pathogenesis in the model group, were downregulated by Rg3. Meanwhile, the miRNA-21 expression was decreased and upregulated by Rg3. Furthermore, the increased gene levels of Bcl-2 and caspase-3 were attenuated in Rg3-treated GPL mice. In conclusion, the findings of this study imply that abnormal glycolysis in GPL mice was relieved by Rg3 via regulation of the expressions of PI3K, AKT, mTOR, HIF-1α, LDHA, HK-II, and miRNA-21. Rg3 is an effective supplement for GPL treatment and can be harnessed to inhibit proliferation and induce apoptosis of GPL cells.

Gastric outlet obstruction associated with congenital diaphragmatic hernia

Abstract We report an infant who developed complete gastric outlet obstruction secondary to gastric antral mucosal hyperplasia and muscular hypertrophy after CDH repair. This condition has been reported only once before when it also occurred in association with congenital diaphragmatic hernia. Other causes of gastric outlet obstruction in the newborn were excluded. The infant recovered well after undergoing a gastric antrectomy. The cause of this obscure condition is unknown. This rare condition needs to be considered in an infant who develops gastric outlet obstruction after CDH repair.

Xiao Tan He Wei Decoction reverses MNNG-induced precancerous lesions of gastric carcinoma in vivo and vitro: Regulation of apoptosis through NF-κB pathway

In recent years, Chinese medicine has played an important role in the prognosis of gastric cancer. Precancerous lesions of gastric carcinoma (PLGC) is a class of gastric cancer which is closely related to the gastric mucosal pathology changes in the role of carcinogenic incentives, and plays key role in the progression of normal gastric mucosal cells into gastric cancerous cells. In current experiment, we explore the relationship between Chinese traditional medicine (Xiao Tan He Wei Decoction) and gastric cancer in the PLGC rat animal models and epithelial-mesenchymal transitioned GES-1 cells which were induced useing 1- Methyl-3-nitro-1-nitrosoguanidine (MNNG). PLGC rat model showed significant deterioration in the gastric mucosa with terrible growth rate in body weight and more atypical hyperplasia in gastric mucosa. MC cells, MNNG induced GES-1 cells which epithelial- mesenchymal-transition (EMT)-related proteins have a great change compare with normal GES-1 cells. The cells had characteristics of malignant cells including proliferation, invasion and metastasis ability. Our research founds that Xiao Tan He Wei Decoction could inhibit cell proliferation and increased apoptosis by increase the level of pro-apoptotic proteins like Bax and caspase-3 and decreased the level of anti-apoptotic protein Bcl-2, block the cells in G0/G1 phase simultaneously. Furthermore, Xiao Tan He Wei Decoction could inhibit nuclear factor kappa-light-chain-enhancer (NF-kB) activity and inhibit its transfer from the cytoplasm to the nucleus. However, when we incubated with NF-κB activator PMA, the effect of Xiao Tan He Wei Decoction was reversed. These results suggested that Xiao Tan He Wei Decoction could be used as a method for the treatment of gastric precancerous lesions, and possibly provide a theoretical basis for the clinical treatment of gastric cancer and gastric precancerous lesions.

Identification of differentially expressed proteins in the gastric mucosal atypical hyperplasia tissue microenvironment

In the present study, the interaction of proteins in the microenvironment of gastric mucosal atypical hyperplasia was analyzed. The stromata of normal gastric mucosa (NGM) and gastric mucosal atypical hyperplasia (GMAH) tissues were purified with laser capture microdissection (LCM). The differentially expressed GMAH proteins of the NGM and GMAH tissues were identified by quantitative proteomic techniques with isotope labeling. The cross-talk between differentially expressed proteins in NGM and GMAH tissues was then analyzed by bioinformatics. There were 165 differentially expressed proteins identified from the stromata of NGM and GMAH tissues. Among them, 99 proteins were upregulated and 66 were downregulated in GMAH tissue. The present study demonstrated that these proteins in gastric mucosal atypical hyperplasia were involved in cancer-associated signaling pathways, including the p53, mitogen-activated protein kinase (MAPK), cell cycle and apoptosis signaling pathways, and were involved in cellular growth, cellular proliferation, apoptosis and the humoral immune response. The results of the present study suggest that the 165 differentially expressed proteins, including S100 calcium-binding protein A6 (S100A6) and superoxide dismutase 3 (SOD3) in the microenvironment of gastric mucosal atypical hyperplasia, are involved in the p53, MAPK, cell cycle and apoptosis signaling pathways, and serve a function in the pathogenesis of gastric cancer.

Gross, histopathological and immunohistochemical study on strobilocercus of Taenia taeniaeformis infection in the liver of laboratory rats (Rattus norvegicus) in India.

We report the detailed gross, histopathological and immunohistochemical study of Strobilocercus fasciolaris infection, the metacestodal stage of Taenia taeniaeformis, in the liver of laboratory Wistar rats. Necropsy examination of seventeen rats revealed transparent or white or cream to clear, thick walled cysts, 1 to 97 in number, measuring about 2mm to 12mm on one or many of the liver lobes and containing strobilocercus of Taenia taeniaeformis. Histopathological examination revealed the presence of the cross-section of larva surrounded by a thick fibrous capsule and moderate infiltration of lymphocytes, plasma cells and a few eosinophils. Fatty degeneration of hepatocytes, gastric mucosal hyperplasia, distended gastric glands and marked increase in the mucosal epithelial cells and goblet cells in the duodenum were also observed. Contamination of feed and bedding materials seems to be the probable source in these naturally infected rats.

Leptin receptor signaling is required for high-fat diet-induced atrophic gastritis in mice.

BackgroundObesity increases the risk for malignancies in various tissues including the stomach. Atrophic gastritis with precancerous lesions is an obesity-associated disease; however, the mechanisms that underlie the development of obesity-associated atrophic gastritis are unknown. Leptin is a hormone derived from stomach as well as adipose tissue and gastric leptin is involved in the development of gastric cancer. The aim of the current study is to investigate the involvement of leptin receptor signaling in the development of atrophic gastritis during diet-induced obesity.MethodsMale C57BL/6, ob/ob and db/db mice were fed a high-fat diet (HFD) or a control diet (CD) from 1 week to 5 months. Pathological changes of the gastric mucosa and the expression of molecules associated with atrophic gastritis were evaluated in these mice.ResultsHFD feeding induced gastric mucosal hyperplasia with increased gastric leptin expression. Mucosal hyperplasia was accompanied by a higher frequency of Ki67-positive proliferating cells and atrophy of the gastric glands in the presence of inflammation, which increased following HFD feeding. Activation of ObR signaling-associated molecules such as ObR, STAT3, Akt, and ERK was detected in the gastric mucosa of mice fed the HFD for 1 week. The morphological alterations associated with gastric mucosal atrophy and the expression of Muc2 and Cdx2 resemble those associated with human intestinal metaplasia. In contrast to wild-type mice, leptin-deficient ob/ob mice and leptin receptor-mutated db/db mice did not show increased Cdx2 expression in response to HFD feeding.ConclusionTogether, these results suggest that activation of the leptin signaling pathway in the stomach is required to develop obesity-associated atrophic gastritis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-016-0066-1) contains supplementary material, which is available to authorized users.

Chronic CO 2 retention stimulates gastric acid secretion and induces gastric mucosal hyperplasia in rats

We have postulated that chronic CO2 retention (e.g., U.S. Naval submariners underway, under-ventilated workspaces, hypoventilation disorders) causes chronic vagal stimulation of gastric mucosal blood flow, gastric acid secretion & relaxation of the lower esophageal sphincter (LES) leading to ulceration and gastroesophageal reflux; see Dean's theory of gastric CO2 ventilation (2011, Resp. Physiol. & Neurobiol. 175:189-209). To test this hypothesis, male Sprague-Dawley rats (~300-450g) were exposed to chronic CO2 (3-4% CO2 in air, 1-4 weeks; Biospherix chamber). Rats were euthanized and transcardially perfused with fixative and their stomachs and distal esophagi removed for analyses. Gross stereoscopic examination of the stomach lining and esophagus revealed evidence of inflammation and visible lesions in 1/3 of rats as early as 2 weeks of hypercapnia. Histological analysis (H&E staining) revealed generalized hyperplasia of surface mucus cells, parietal cells, and chief cells, the latter displaying increased basophilic material. Our findings indicate that chronic hypercapnia induces evidence of intragastric and distal esophageal dysfunction. This supports in part the hypothesis that chronic CO2 rebreathing persistently activates gastric CO2 production and gastric CO2 ventilation (Dean 2011), secondarily resulting in gastroesophageal dysfunction from protracted release of gastric acid and LES relaxation (funded by the ONR Undersea Medicine Program).

Disruption of Primary Cilia Induces Gastric Mucosal Hyperplasia

BACKGROUND: Primary cilia are necessary for Hedgehog (Hh) signaling and other pathways. Anterograde ciliary transport is mediated by kinesin-II, a heterotrimeric protein composed of two motor subunits, KIF3A, KIF3B, and a non-motor subunit KAP3. Intraflagellar transport protein 88 (IFT88) participates in protein transport along the cilia. Conventional null mice for KIF3A and IFT88 are not viable. Sonic hedgehog (Shh) is highly expressed in gastric epithelial cells of the corpus compared to the antrum. Therefore we examined the stomach of mice conditionally null for KIF3A and IFT88 to define the role of primary cilia in this organ. METHODS: KIF3A and IFT88 mice harboring one null allele and loxP sites on the other allele on a ROSA26 reporter background were crossed to Shh-Cre mice (KIF3A-/ FL and IFT88-/FL respectively.) KIF3A+/FL, IFT88+/FL, and wild type (WT) littermates were analyzed at 6 and 8 months. Cell lineages were identified by immunohistochemistry in paraffin-sections, and by β-galactosidase (β-gal) staining for the Cre-expressing cells. Acetylated-α-tubulin was used as the marker for cilia. RESULTS: Epithelial cells in the antrum and corpus expressed primary cilia. β-gal staining confirmed variegated glandular Cre expression in all epithelial cells. Gastric epithelial cells did not express cilia in the IFT88-/FL mice, while KIF3A-/FL mice showed reduced numbers of cilia in the corpus versus controls (0.59+0.04 cilia/gland, N=8 vs. 0.72+0.06 cilia/gland, N=14), but no changes in the antrum (0.94+0.05 vs. 1.08+0.09 cilia/gland.) KIF3A-/FL and IFT88-/FL mice exhibited different phenotypes. By 6 months, KIF3A-/FL mice showed mucous pit hyperplasia in the corpus. Mucous neck and zymogenic lineages were not expanded, but parietal cells were still present. The KIF3A-/FL mice phenotype resembled the mucous pit hyperplasia observed in the Shh conditionally null mice generated with H+K+ATPase-Cre. In contrast, the phenotype of the IFT88-/FL mice showed parietal cell atrophy, and proximal corpus hyperplasia due to expansion of the mucous neck cell compartment assessed by TFF2 expression (SPEM) by 4 months of age. We have previously observed that gastrinand ghrelin-secreting cells exhibit primary cilia, but none of the mouse models showed differences in the number of these endocrine cells.CONCLUSION:The IFT88-/FLmice exhibited amore severe phenotype than the KIF3A-/FL mice even though both molecules affect primary cilia function. The phenotype of these two mouse models suggests that Hh signaling is necessary for the maintenance of the corpus epithelium. Also, gastric epithelial cilia might be important for the function but not differentiation of gastrinand ghrelin-secreting cells.

Acid Suppression by Proton Pump Inhibitors Enhances Aquaporin-4 and KCNQ1 Expression in Gastric Fundic Parietal Cells in Mouse

The widespread use of proton pump inhibitors (PPIs) is known to cause sporadic gastric fundic gland polyps (FGPs). Altered expression and localization of the water or ion transport proteins might contribute to the excess fluid secretion into the cystic lumen for the development of FGPs. We investigated the alteration of the murine gastric fundic mucosa after PPI treatment, and examined the expression of water channel aquaporin-4 (AQP4) and potassium channel KCNQ1, which are expressed only in the parietal cells in the gastric mucosa. Male 5-week-old C57BL/6J mice were administered lansoprazole (LPZ) by subcutaneous injection for 8 weeks. The expression of AQP4 and KCNQ1 were investigated by Western blotting, quantitative RT-PCR, and immunohistochemistry. The expression of mucin-6 (Muc6), pepsinogen, and sonic hedgehog (Shh) were also investigated as mucosal cell lineage markers. Gastric mucosal hyperplasia with multiple cystic dilatations, exhibiting similar histological findings to the FGPs, was observed in the LPZ-treated mice. An increase in the number of AQP4-positive parietal cells and KCNQ1-positive parietal cells was observed. The extension of the distribution of AQP4-positive cells toward the surface of the fundic glands was also observed. The expression levels of AQP4 mRNA and protein were significantly enhanced. The expression of KCNQ1 mRNA was correlated with that of AQP4 mRNA in the LPZ-treated mice. Mucous neck-to-zymogenic cell lineage differentiation was delayed in association with decreased expression of Shh in the LPZ-treated mice. PPI administration increased the number of parietal cells with enhanced expression of AQP4 and KCNQ1.

Loss of RegI in conjunction with gastrin deficiency in mice facilitates efficient gastric ulcer healing but is dispensable for hyperplasia and tumourigenesis

RegI ( Regenerating islet derived-1) was originally characterized as a growth factor involved in pancreatic islet cell regeneration. It is also considered a gastrointestinal mitogen as its expression is increased during pathologies involving aberrant cell proliferation that can lead to neoplasia. However, the absolute requirement for RegI to directly stimulate gastric mucosal cell proliferation in vivo requires further investigation. We used RegI-deficient mice to determine the requirement for RegI in normal gastric mucosal development, wound healing, hyperplasia and tumourigenesis. We found that epithelial repair of acetic acid ulcers in compound mutant RegI/gastrin-deficient mice was significantly reduced compared to wild type, RegI-deficient or gastrin-deficient mice. In contrast, RegI was dispensable for normal gastric mucosal development, hyperplasia in HKβ-deficient mice and tumourigenesis in gp130 F/F mice. Although RegI was not required for proliferation in these pathological models, expression of multiple Reg family members were increased during gp130 F/F tumourigenesis. Interestingly, loss of RegI in gp130 F/F mice resulted in decreased expression of other Reg family members. Our results indicate that RegI and gastrin may synergistically regulate gastric mucosal proliferation during certain pathological settings like wound healing while gastric epithelial proliferation in other pathologies may require coordinated expression of multiple Reg genes.

Frequency, distribution of CD4+, CD8+ T cells and expression of CD38 in gastric mucosa of HIV infections

To investigate the frequencies and distribution of CD4+ T cells and CD8+ T cells as well as the changes of immune activation in gastric mucosa of HIV-infected individuals. 42 HIV-infected individuals were recruited into this investigation, and 36 patients had definite diagnosis of clinical stage. Biopsy of gastric mucosal tissues was performed by fiberoptic gastroscope including 10 normal people as a control group. Then, immunohistochemistry was used to detect expression of CD4, CD8 and CD38 in gastric mucosa, and the distinctions among three groups were analyzed with LEICA Qwin image analysis system. (1) Compared with asymptomatic HIV carriers and control group, CD4 T cells remarkably decreased in the gastric mucosa of AIDS patients (P < 0.01). In gastric mucosa of asymptomatic HIV carriers, there were still some CD4+ T cells in lymphoid follicles and stroma where CD4+ T cells were unevenly distributed, the frequency of CD4+ T cells was not significantly different between asymptomatic HIV carriers and control group (P > 0.05); (2) Phenomenon of CD8+ T cells infiltrating mucosal epithelium and gland was general in HIV-infected individuals. CD8+ T cells took on local excessive hyperplasia in gastric mucosa of some individuals. As compared with control group, CD8+ T cells markedly increased in gastric mucosa of infected individuals (P < 0.01), but the distinction of asymptomatic HIV carriers and AIDS patients was not significant (P > 0.05); (3) CD38-expressing cells mainly distributed over gastric mucosal surface to superficial layer(1/3-2/3 layer) of HIV-infected individuals, and was more intensive than control group (P < or = 0.01), but there was not noticeable difference between asymptomatic HIV carriers and AIDS patients (P > 0.05). The frequencies and distribution of gastric mucosal CD4+ T cells of HIV-infected individuals were closely correlated with progression of disease. Disfunction of mucosal immune system which was resulted from HIV infection and injury of CD4+ T cells could be an important cause of CD8+ T cells increasing and CD38-expressing enhancement.

Strobilocercus fasciolaris infection with hepatic sarcoma and gastroenteropathy in a Wistar colony

Tapeworm cysts were identified in liver of Wistar rats and it induced fibrosarcoma in liver and gastroenteropathy in stomach and intestine. The tapeworm larva was confirmed as Strobilocercus fasciolaris by PCR linked mitochondrial DNA sequencing. Light microscopy, special staining (masson trichrome) and immunoflouresence supported the diagnosis of fibrosarcoma. Infiltration of plasma cells, macrophages and eosinophils were observed in the liver section. Gastric mucosal hyperplasia, dilation of gastric glands with secretion, intestinal mucosal cell hyperplasia, proliferation of duodenal submucosal glands were confirmed by light microscopy and supported by PAS, AB staining. The concomitant development of hepatic sarcoma and gastroenteropathy by larvae of Taenia taeniaeformis ( S. fasciolaris) infection is very rare and is the first reported case in Wistar rats to our knowledge.

Loss of Runx3 function in leukocytes is associated with spontaneously developed colitis and gastric mucosal hyperplasia

RUNX transcription factors are key regulators of lineage-specific gene expression and might be involved in autoimmune diseases. Runx3 plays a role during the development of sensory neurons and T cells and regulates transforming growth factor beta (TGF-beta) signaling in dendritic cells. Here, we report that at 4 weeks of age, Runx3 knockout (KO) mice spontaneously develop inflammatory bowel disease (IBD) characterized by leukocyte infiltration, mucosal hyperplasia, formation of lymphoid clusters, and increased production of IgA. Additionally, at a considerably older age (8 months), the KO mice also develop progressive hyperplasia of the gastric mucosa associated with disturbed epithelial differentiation and cellular hyaline degeneration. Analysis of cytokines in the colonic mucosa of Runx3 KO mice revealed a mixed T helper 1/T helper 2 response. By using immunohistochemistry and RNA in situ hybridization, Runx3 expression in the gastrointestinal tract is detected in lymphoid and myeloid populations but not in the epithelium. The data indicate that loss of leukocytic cell-autonomous function of Runx3 results in IBD and gastric lesion in the KO mice. IBD in humans is viewed as a complex genetic disorder. Several susceptibility loci were identified on different human chromosomes including the chromosomal region 1p36 where RUNX3 resides. It is thus tempting to speculate that mutations in RUNX3 may constitute an IBD risk factor in humans.