Chief cell plasticity is the origin of metaplasia following acute injury in the stomach mucosa

ObjectiveMetaplasia arises from differentiated cell types in response to injury and is considered a precursor in many cancers. Heterogeneous cell lineages are present in the reparative metaplastic mucosa with response to injury, including foveolar cells, proliferating cells and spasmolytic polypeptide-expressing metaplasia (SPEM) cells, a key metaplastic cell population. Zymogen-secreting chief cells are long-lived cells in the stomach mucosa and have been considered the origin of SPEM cells; however, a conflicting paradigm has proposed isthmal progenitor cells as an origin for SPEM.DesignGastric intrinsic factor (GIF) is a stomach tissue-specific gene and exhibits protein expression unique to mature mouse chief cells. We generated a novel chief cell-specific driver mouse allele, GIF-rtTA. GIF-GFP reporter mice were used to validate specificity of GIF-rtTA driver in chief cells. GIF-Cre-RnTnG mice were used to perform lineage tracing during homoeostasis and acute metaplasia development. L635 treatment was used to induce acute mucosal injury and coimmunofluorescence staining was performed for various gastric lineage markers.ResultsWe demonstrated that mature chief cells, rather than isthmal progenitor cells, serve as the predominant origin of SPEM cells during the metaplastic process after acute mucosal injury. Furthermore, we observed long-term label-retaining chief cells at 1 year after the GFP labelling in chief cells. However, only a very small subset of the long-term label-retaining chief cells displayed the reprogramming ability in homoeostasis. In contrast, we identified chief cell-originating SPEM cells as contributing to lineages within foveolar cell hyperplasia in response to the acute mucosal injury.ConclusionOur study provides pivotal evidence for cell plasticity and lineage contributions from differentiated gastric chief cells during acute metaplasia development.

Notch Signaling Ligand Jagged1 Enhances Macrophage-Mediated Response to Helicobacter pylori

Helicobacter pylori (H. pylori) is one of the gram-negative bacteria that mainly colonize the stomach mucosa and cause many gastrointestinal diseases, such as gastritis, peptic ulcer, and gastric cancer. Macrophages play a key role in eradicating H. pylori. Recent data have shown that Notch signaling could modulate the activation and bactericidal activities of macrophages. However, the role of Notch signaling in macrophages against H. pylori remains unclear. In the present study, in the co-culture model of macrophages with H. pylori, the inhibition of Notch signaling using γ-secretase decreased the expression of inducible nitric oxide synthase (iNOS) and its product, nitric oxide (NO), and downregulated the secretion of pro-inflammatory cytokine and attenuated phagocytosis and bactericidal activities of macrophages to H. pylori. Furthermore, we identified that Jagged1, one of Notch signaling ligands, was both upregulated in mRNA and protein level in activated macrophages induced by H. pylori. Clinical specimens showed that the number of Jagged1+ macrophages in the stomach mucosa from H. pylori-infected patients was significantly higher than that in healthy control. The overexpression of Jagged1 promoted bactericidal activities of macrophages against H. pylori and siRNA-Jagged1 presented the opposite effect. Besides, the addition of exogenous rJagged1 facilitated the pro-inflammatory mediators of macrophages against H. pylori, but the treatment of anti-Jagged1 neutralizing antibody attenuated it. Taken together, these results suggest that Jagged1 is a promoting molecule for macrophages against H. pylori, which will provide insight for exploring Jagged1 as a novel therapeutic target for the control of H. pylori infection.

BACTERIAL SYMBIOSIS IN COMPLICATED ULCERS: THE PATHOGENETIC HYPOTHESIS

Aim of this paper is to estimate crystallogenic properties of gastric mucosa in connection with its microbial contamination. We investigated crystallogenic properties of some biological substrata (gastric mucosa, gastric mucosal layer homogenates) in 12 healthy individuals and 30 patients with ulcer disease complicated in 12 cases by perforation, bleeding or penetration. Biological substrata were received at fibrogastroduodenoscopy. Estimation of crystallogenic properties of biological material was accomplished by classic crystalloscopy. Biological substrata crystalloscopic investigation was accompanied by its traditional microbiological study for Helicobacter pylori and detection of other microorganisms. Our data allow to suppose dual contamination of stomach mucosa both by Helicobacter pylori and Providencia or Morganella. This combination caused elevation of gastric mucosa crystallogenic properties that provoked formation of ulcer. Procrystallogenic potential of this symbiosis may be an important link to the pathogenesis of ulcer disease which realized through microorganism-associated mucosal damage and the progression of complications.

Interplay of Biochemical, Genetic, and Immunohistochemical Factors in the Etio-Pathogenesis of Gastric Ulcer in Rats: A Comparative Study of the Effect of Pomegranate Loaded Nanoparticles Versus Pomegranate Peel Extract

BackgroundFew data are available about the role of herbal extract loaded nanoparticles as an alternative safe medicine for the management of a gastric ulcer.AimThis work is targeted at exploring the physiological effects of pomegranate loaded nanoparticles (PLN) against an indomethacin IND-induced gastric ulcer and comparing the results with traditional pomegranate peel extract (PPE).MethodsTwenty-four rats were equally distributed into four groups: control, IND-treated, PLN-treated, and PPE-treated groups. Gross examination of gastric mucosa, and the calculation of ulcer and inhibition indices were done. Serum malondialdehyde (MDA), total antioxidant capacity (TAC), interleukin 2 (IL-2), IL-6, IL-10, gastric homogenate prostaglandin E2 (PGE2), and nitric oxide (NO) were estimated. Mucosal endothelial nitric oxide synthase (eNOS mRNA) expression was identified by qPCR. Histological and immuno-histochemical staining of Tumor necrosis factor-α (TNF-α) and eNOS of stomach mucosa were performed.ResultsIn comparison with the control group, IND-treated rats showed visible multiple ulcers with ulcer index, serum MDA, IL-2 and IL-6 were elevated while IL-10, PGE2, NO, and eNOS mRNA expression were significantly reduced. Damaged surface epithelium with disrupted glandular architecture and heavy leucocyte infiltration of lamina propria was noticed. Immunohistochemical staining of stomach mucosa revealed marked increased TNF-α and reduced eNOS. Oral administration of PLN and PPE succeeded in improving the gross mucosal picture, and all biochemical, histological, and immunohistochemical alterations.ConclusionBoth PLN and PPE potently alleviated IND-induced gastric ulceration via increasing TAC, PGE2, NO, eNOS mRNA, and protein expression. However, the healing effect of PLN was obviously greater than PPE-treated rats.

Detection of Helicobacter suis bacteria in pigs of different age groups

Currently, the pathogenesis of gastric ulcer in pigs remains largely unexplored. The origin of this pathology is most often associated with the type and the technologies of feeding, stresses and disorders of homeostasis of the animal body. The possible involvement of bacteria of the genus Helicobacter in the development of chronic gastritis and gastric ulcer disease in pigs was suggested by the researchers relatively recently. The article comprises the results of investigations aimed at detection of Helicobacter suis bacteria and the contamination degree of porcine gastric mucosa in pigs of different age groups. The stomachs, obtained from suckling pigs, fattening pigs and sows in the slaughterhouse of the Mari El Republic, were examined. The study determined the dependence of pathomorphological changes in the gastric mucosa of pigs on the detection of H. suis in microscopic and biochemical tests as well as in PCR. Thus, no pathomorphological changes in the gastric mucosa of suckling pigs were detected. Severe hyperkeratosis, erosions, and ulcers were found on the stomach mucosa of fattening pigs and sows that were infected with H. suis bacteria. Sows also had ulcerative lesions in the non-glandular region of esophagus. In the biomaterial of suckling piglets the DNA of H. suis bacteria was found only in the pyloric region of the stomach, while in fattening pigs, the DNA of these bacteria was most often isolated from the fundal region, and in sows – from the fundal and cardial regions. This indicates a shift in colonization by helicobacters of the mucous membrane of the stomach from the pyloric to the cardiac sectionincreased with animal age. The obtained research data provide the additional evidence of the etiological role of H. suis in the pathogenesis of gastric ulcer in pigs.

Morphology, histology and histochemistry of the digestive tract of the Banded tilapia, Tilapia sparrmanii (Perciformes: Cichlidae)

This study described anatomical, histological and histochemical features of the mucosal layer of the digestive tract of Tilapia sparrmanii Smith, 1840, an omnivorous freshwater fish endemic to Southern Africa. This species exhibited a short thick oesophagus with long deep longitudinal folds (466.68 ± 16.91 µm), and a thick (173.50 ± 10.92 µm) muscular layer that allow the passage of large food items. The mucosa was lined with stratified secretory epithelium rich in goblet cells that secreted neutral and acid mucins. The stomach was a sac-like structure with simple tubular glands surrounded by connective tissue. The mucosa was lined with simple columnar epithelium and the lamina propria exhibited a well-developed layer of gastric glands that occupied the entire length of the cardio-fundic region. The stomach mucosa consisted of epithelial cells with intense neutral mucin secretion which protects against gastric juice. Neck cells of gastric glands synthesized neutral and acid mucins. The intestine was highly coiled and presented a complex pattern of transversal folds internally (villi). Villi length decreased progressively from the anterior to the posterior intestine (p < 0.0001). Tunica muscularis of the mid-intestine had the thinnest thickness among all parts of the intestine (p < 0.0001). Goblet cells whose numbers increased towards the rectum secreted both acid and neutral mucins. The results indicate structural similarities of T. sparrmaniiGIT with other tilapia species and will be useful for understanding the physiology of the digestive systems as well as functional components of the GIT.

The bacterial association with oral cavity and intra-abdominal abscess after gastrectomy

Background Perioperative oral management has been reported to be effective for preventing postoperative infectious complications. In addition, severe periodontal disease was identified as the significant risk factor for complications after gastrointestinal surgery. We investigated the bacteriological association between the periodontal pocket, stomach mucosa and drainage fluid to determine whether oral bacteria directly cause intra-abdominal infection after gastrectomy. Methods Patients who were scheduled to undergo surgery for gastric cancer were prospectively enrolled. We evaluated the similarity of bacterial strains in periodontal pocket, stomach mucosa and fluid from drainage tube. Gingival crevicular fluid and dental plaque were collected from the periodontal pocket and cultured to detect bacteria. Specimens from the resected stomach were collected and used for bacterial culturing. Drainage fluid from the abdominal cavity was also cultured. Results All of 52 patients were enrolled. In the periodontal pocket, α-Streptococcus spp., Neisseria sp., and Prevotella sp. were mainly detected. Bacterial cultures in the stomach mucosa were positive in 26 cases. In 20 cases (76.9%), the detected strains were the same as those in the periodontal pocket. Six patients had the postoperative intra-abdominal infection after gastrectomy, and the same bacterial strains was detected in both of drainage fluid and periodontal pocket in two patients with severe periodontal disease. Conclusions We found the bacteriological association that same strain detected in periodontal pocket, stomach and in intra-abdominal drainage fluid after gastrectomy in patients with periodontal disease.

Morphofunctional estimation of the gastroprotective activity of the Ferulopsis hystrix dry extract in neurogenic ulcer

The purpose of the research: morphofunctional estimation of the gastroprotective activity of the dry extract from the roots and rhizomes of Ferulopsis hystrix in neurogenic ulcer.Materials and methods: The studies were carried out on white Wistar rats. The neurogenic ulcer was simulated by 24-hour immobilization of the animals. The gastroprotective effect of Ferulopsis hystrix was estimated taking into account the Pauls’ index which was calculated for bleedings, erosions and strip-like ulcers as well as taking into account the morphometric indices (the depth of erosions) of the stomach mucosa. The intensity of lipid free radical oxidation processes was estimated by malonic dialdehyde content (MDA); the state of the antioxidant system was estimated by the activity of catalase, superoxide dismutase and the reduced glutathione content.Results. The Ferulopsis hystrix extract in the doses of 100 and 150 mg/kg reduces the depth of erosions by 43% and 80% respectively, thus promoting the diminishment of destructive processes in the stomach mucosa against the background of neurogenic ulcer. The Ferulopsis hystrix extract in the given doses decreased the MDA content by 37% on average; the catalase activity was twofold increased; the reduced glutathione increases 2.6 times and SOD activity — 3.8 and 2.8 times respectively.Conclusion. Ferulopsis hystrix has the gastroprotective effect in neurogenic ulcer.