Organoids as ex vivo culture system to investigate infection-host interaction in gastric pre-carcinogenesis.

Advancements in stem cell research have enabled the establishment of three-dimensional (3D) primary cell cultures, known as organoids. These culture systems follow the organization of an in vivo organ, as they enclose the different epithelial cell lines of which it is normally composed. Generation of these 3D cultures has bridged the gap between in vitro models, made up by two-dimensional (2D) cancer cell lines cultures, and in vivo animal models, that have major differences with human diseases. Organoids are increasingly used as a model to study colonization of gastric mucosa by infectious agents and to better understand host-microbe interactions and the molecular events that lead to infection, pathogen-epithelial cells interactions and mechanisms of gastric mucosal injury. In this review we will focus on the role of organoids as a tool to investigate molecular interactions of Helicobacter (H.) pylori and Epstein Barr Virus (EBV) and gastric mucosa and how these infections, that affect ≈ 45% of the world population, might progress to gastric cancer, a highly prevalent cancer and the third leading cause of cancer death.

Activation of dopamine D2 receptor promotes pepsinogen secretion by suppressing somatostatin release from the mouse gastric mucosa

In vivo administration dopamine (DA) receptor (DR)-related drugs modulates gastric pepsinogen secretion. However, DRs on gastric pepsinogen-secreting chief cells and DA D2 receptor (D2R) on somatostatin-secreting D cells were subsequently acquired. In this study, we aimed to further investigate the local effect of DA on gastric pepsinogen secretion through DRs expressed on chief cells or potential D2Rs expressed on D cells. To elucidate the modulation of DRs in gastric pepsinogen secretion, immunofluorescence staining, ex vivo incubation of gastric mucosa isolated from normal and D2R-/- mice were conducted, accompanied by measurements of pepsinogen or somatostatin levels using biochemical assays or enzyme-linked immunosorbent assays. D1R, D2R, and D5R-immunoreactivity (IR) were observed on chief cells in mouse gastric mucosa. D2R-IR was widely distributed on D cells from the corpus to the antrum. Ex vivo incubation results showed that DA and the D1-like receptor agonist SKF38393 increased pepsinogen secretion, which was blocked by the D1-like receptor antagonist SCH23390. However, D2-like receptor agonist quinpirole also significantly increased pepsinogen secretion, and D2-like receptor antagonist sulpiride blocked the promotion of DA. Besides, D2-like receptors exerted an inhibitory effect on somatostatin secretion, in contrast to their effect on pepsinogen secretion. Furthermore, D2R-/- mice showed much lower basal pepsinogen secretion but significantly increased somatostatin release and an increased number of D cells in gastric mucosa. Only SKF38393, not quinpirole, increased pepsinogen secretion in D2R-/- mice. DA promotes gastric pepsinogen secretion directly through D1-like receptors on chief cells and indirectly through D2R-mediated suppression of somatostatin release.

Peculiarities of the relationship between aggressive and protective factors of the gastric mucosa in patients with esophagogastroduodenal pathology with impaired adaptive potential and autonomic homeostasis (according to PRECISE-diagnostics)

Background. An imbalance of interaction between the sympathetic and parasympathetic links of the autonomic nervous system leads to autonomic dysregulation of the heart rate resulting in insufficient stress resistance, impaired adaptation and depletion of the protective mechanisms of the gastric mucosa. Therefore, the purpose of our research was to study adaptive potential of the body depending on the aggressive and protective factors of the gastric juice. Materials and methods. Seventy-one patients with esophagogastroduodenal pathology were examined using the method of PRECISE-diagnostics. The level of pH, pepsin, glycoproteins, fucose and sialic acids in the gastric contents was determined. The patients were divided into 3 representative groups: I — 30 individuals with hiatal hernia; II — 20 patients with achalasia cardia; III — 21 people with duodenal ulcer disease complicated by stenosis. Results. An imbalance of sympathetic and parasympathetic links of autonomic system was detected in 85.2 % of patients. The sympathetic mechanisms dominated in 71.3 % of cases. At the same time, most patients with achalasia cardia had vagotonia. The adaptive and compensatory mechanisms were identified after studying the relationship between the aggressive and protective factors of the gastric mucosa. When analyzing the correlation of aggressive and protective factors of gastric juice, the following adaptive and compensatory options were revealed: 1) hyperreactive, with simultaneous increase in the factors of both aggression and protection; 2) compensatory (an increase in the level of aggressive factors against the background of normal protective indicators); 3) decompensatory (an increase in the level of aggressive factors simultaneously with a decrease in protective factors). Conclusions. The adaptive potential of the body in 85.2 % of surgical patients, mostly those with hiatal hernia and achalasia cardia, according to PRECISE-diagnostics was defined as reduced, in the form of impaired adaptation in decompensatory type of the relationship between aggressive and protective factors of gastric juice.

Myths and reality about the effects of glutamate. Compilation of scientific data of modern world literature

The aim of our scientific work was to study the existing experimental models of glutamate effects on the body and to understand the mechanisms of this effect and its possible consequences. To achieve this goal, we have studied different sources of scientific medical literature. Results. In a healthy body, glutamic acid is secreted by brain neurons in the required amount as a neurotransmitter and participates in the main information flows of human body. Sodium glutamate, which enters the body with food in large quantities, affects the body, causing general toxic effects and has a local effect on the stomach, intestines, salivary glands and pancreas and so on. Based on the scientific literature, experimental models that study the effects of glutamate are divided into two types: models in which glutamate enters the body orally and when glutamate is administered subcutaneously and intraperitoneally in the neonatal period of life. In the first route of administration, glutamate causes a toxic effect, which is manifested in increased catalytic activity in the blood serum of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltranspeptidase in 2.5; 1.6; and 1.5 times, respectively, while the activity of alkaline phosphatase remained at control levels, indicating a pronounced hepatotoxic effect of monosodium glutamate as a dietary supplement. It causes an increase in content of total and tyrosine-containing peptides in the blood serum, increase of substances of low and medium molecular weight, as well as an increase in the values of intoxication, which indirectly indicates a violation of the detoxification of endogenous metabolites in the liver of experimental animals. Ingestion of sodium glutamate within the recommended doses has not been shown to cause marked pathological changes in the mucous, muscular and serous membranes of the gastric wall, but there is a slight fullness of the vessels of the submucosal membrane. It has been found that in high doses, sodium glutamate has a local pathogenic effect on the tissues of the stomach, which consists in thinning all layers of its wall, desquamation of the mucous membrane and its disorganization by reducing the size of gastric glands, increasing the number of vessels and their fullness with blood. One of the mechanisms of pathogenic effect of sodium glutamate is the contact local and free radical oxidizing effect on gastric tissues. In the oral route of administration of glutamate there are no phenomena of fat growth (obesity) as epidermal, which is characteristic of the abdominal form of obesity, so and pararectal, parallelic, pararenal and retroperitoneal, which is characteristic for the visceral form of obesity. In the subcutaneous and intraperitoneal routes of administration of glutamate in the neonatal period of life in experimental animals, glutamate causes hypersecretion of hydrochloric acid, the development of lesions manifested by hemorrhage, erosions and ulcers in the gastric mucosa and obesity. Prolonged administration of monosodium glutamate significantly enhances the striking effects of stress on the gastric mucosa. Morphological studies of the submandibular salivary glands of rats on the background of glutamate-induced obesity confirm the development of pathological changes, as evidenced by the detected vacuolar dystrophy in the acinar region, perivascular and periductal edema. On the background of abdominal obesity, dystrophic processes were found in the acinuses and minor dystrophic changes in the intraparticle inserts. Conclusion. In the subcutaneous and intraperitoneal routes of administration of glutamate in the neonatal period of life in experimental animals, glutamate causes hypersecretion of hydrochloric acid, the development of lesions manifested by hemorrhage, erosions and ulcers in the gastric mucosa and obesity. Prolonged administration of monosodium glutamate significantly enhances the striking effects of stress on the gastric mucosa. Morphological studies of the submandibular salivary glands of rats on the background of glutamate-induced obesity confirm the development of pathological changes, as evidenced by the detected vacuolar dystrophy in the acinar region, perivascular and periductal edema. On the background of abdominal obesity, dystrophic processes were found in the acinuses and minor dystrophic changes in the intraparticle inserts. There is no doubt in the fact, which is based on the results of numerous experimental studies and covered in professional scientific litefrature, that the abdominal form of glutamate-induced obesity is possible only with subcutaneous and intraperitoneal routes of its administration in the neonatal period of life and while intraorall way of administration does not occur.

Gastroprotective Mechanisms

Gastric ulcer (GU), a common type of peptic ulcer, results from an imbalance in the action of protective and aggressive agents. Gastroprotective mechanisms are mucus layer, gastric epithelium, gastric blood flow, gastric neurons, mucosal repair capacity, and immune system. Thus, the aim of this chapter was to provide an update on gastroprotective mechanisms. It was carried out through searches in PubMed covering the years 2016–2021 using several keywords. This survey resulted in 428 articles, of which 110 were cited in this chapter. It was reviewed the status of gastroprotective mechanisms and highlighted that mucins can act as a filter; gastric epithelial defenses are composed of the cell barrier, stem cells, and sensors on the mucosal surface; nitric oxide (NO) and hydrogen sulfide (H2S) act for gastric blood flow homeostasis (GBF); the main effector neurons in the gastric mucosa are cholinergic, nitrergic and VIPergic, and oxytocin can activate neurons; repair of the gastric mucosa requires complex biological responses; the immune system regulates the entry of antigens and pathogens. The main knowledge about gastroprotective mechanisms remains unchanged. However, we conclude that there has been progressing in this area.

Gastroprotective Effect of Conocarpus Erectus Plus Omega-3 on Experimentally Induced Ulcer in Rats

There has been a dearth of research on the gastroprotective effect of Conocarpus erectus in the literature so the current study was designed to estimate the ability of Conocarpus erectus (C. erectus) leaves extract alone and in combination with omega-3 regarding gastroprotective effects. A total of 30 male rats were divided into five groups (n = 6). All animals induced gastric ulcer by 80 mg/kg of naproxen orally twice a day for three consecutive days. At the same time, the animals treated orally with 175 mg/kg omega-3, 250 mg/kg C. erectus, 80 mg omega-3 + 150 mg C. erectus, 10 mg/kg of lansoprazole, and 2 ml/kg of DMSO were named T1, T2, T3, T4, and TC, respectively. The obtained results of the present study indicated the presence of flavonoids, saponin, and tannin as active ingredients in C. erectus leaves extract. Consequently, C. erectus seemed to have the potential of chelating metals in a concentration-dependent manner. Gross and histopathology findings showed the highly protective capability of C. erectus and omega-3 against ulcerative lesion, compared to the time each was used alone. The outcomes of the current study indicated that using C. erectus alone or plus omega-3 can protect the gastric mucosa from the ulceration induced by naproxen, and the chelating properties of C. erectus.

The thin red line between pathological and physiological inflammatory background in the gastric mucosa

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