Search Results (27)

Global warming represents one of the most pressing environmental challenges to cold-water fish farming. Heat stress markedly alters the mucosal symbiotic microbiota and intestinal microbial metabolites in fish, posing substantial barriers to the healthy artificial breeding of rainbow trout (Oncorhynchus mykiss). However, the relationship between mucosal commensal microbiota, intestinal metabolites, and host environmental adaptability under heat stress remains poorly understood. In this study, rainbow trout reared at optimal temperature (16 °C) served as controls, while those exposed to maximum tolerated temperature (24 °C, 21 d) comprised the heat stress group. Using 16S rRNA amplicon sequencing and ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS), we analysed the mucosal commensal microbiota—including gastrointestinal digesta, gastrointestinal mucosa, skin mucus, and gill mucosa—and intestinal metabolites of rainbow trout under heat stress conditions to explore adaptive and regulatory mechanisms. Analysis of microbial composition and diversity revealed that heat stress exerted the greatest impact on the diversity of gill and skin mucus microbiota, followed by gastrointestinal digesta, with relatively minor effects on the gastrointestinal mucosa. At the phylum level, Proteobacteria, Firmicutes, and Bacteroidetes were predominant in the stomach, intestine, and surface mucosa. At the genus level, Acinetobacter showed the greatest increase in abundance in skin and gill mucosa under heat stress, while Enterobacteriaceae exhibited the most pronounced increase in intestinal digesta, gastric digesta, and gastric mucosa. Differential metabolites in the intestinal digesta under heat stress were predominantly enriched in pathways associated with amino acid metabolism, particularly tryptophan metabolism. This study provides a comprehensive characterisation of microbiota and metabolic profile alterations in rainbow trout under heat stress condition, offering a theoretical foundation for understanding the response mechanisms of fish commensal microbiota to thermal stress. Full article

When the protective mechanisms of the gastroesophageal mucosa are overwhelmed by injurious factors, the structural and functional mucosal integrity is compromised, resulting in a wide spectrum of disorders. Poliprotect has recently been shown to be non-inferior to standard-dose omeprazole for the treatment of endoscopy-negative patients with heartburn and/or epigastric pain or burning. Here, we provide preclinical data describing the mechanism of action of the Poliprotect formulation, a 100% natural, biodegradable, and environmental friendly medical device according to EU 2017/745 and containing UVCB (unknown or variable composition, complex-reaction products, or biological materials) substances of botanical and mineral origin, according to the REACH and European Chemical Agency definitions. Different in vitro assays demonstrated the capability of Poliprotect to adhere to mucus-secreting gastric cells and concomitantly deliver a local barrier with buffering and antioxidant activity. In studies conducted in accordance with systems biology principles, we evaluated the effects of this barrier on human gastric cells exposed to acidic stress. Biological functions identified via Ingenuity Pathway Analysis highlighted the product’s ability to create a microenvironment that supports the mucosal structural and functional integrity, promotes healing, and restores a balanced mucosal inflammatory status. Additionally, transepithelial electrical resistance and an Ussing chamber showed the product’s capability of preserving the integrity of the gastric and esophageal epithelial barriers when exposed to an acid solution. Two in vivo models of erosive gastropathy further highlighted its topical protection against ethanol- and drug-induced mucosal injury. Overall, our findings sustain the feasibility of a paradigm shift in therapeutics R&D by depicting a very innovative and desirable mode of interaction with the human body based on the emerging biophysical, rather than the pharmacological properties of these therapeutic agents. Full article

Excessive alcohol consumption has led to the prevalence of gastrointestinal ailments. Alleviating gastric disorders attributed to alcohol-induced thinning of the mucus layer has centered on enhancing mucin secretion as a pivotal approach. In this study, foxtail millet bran polyphenol BPIS was divided into two components with MW < 200 D and MW > 200 D by molecular interception technology. Combined with MTT, cell morphology observation, and trypan blue staining, isoferulic acid (IFA) within the MW < 200 D fraction was determined as the effective constituent to mitigate ethanol-induced damage of gastric epithelial cells. Furthermore, a Wistar rat model with similar clinical features to alcohol-induced gastric mucosal injury was established. Then, gastric morphological observation, H&E staining, and assessments of changes in gastric hexosamine content and gastric wall binding mucus levels were carried out, and the results revealed that IFA (10 mg/Kg) significantly ameliorated alcohol-induced gastric mucosal damage. Finally, we applied techniques including Co-IP, molecular docking, and fluorescence spectroscopy and found that IFA inhibited the alcohol-induced downregulation of N-acetylgalactosamintransferase 2 (GALNT2) activity related to mucus synthesis through direct interaction with GALNT2 in gastric epithelial cells, thus promoting mucin synthesis. Our study lays a foundation for whole grain dietary intervention tailored to individuals suffering from alcoholic gastric mucosal injury. Full article

This study investigated the morphological, histological, and histochemical characteristics of the digestive tract of the marbled flounder (Pseudopleuronectes yokohamae). The relative length of the gut of the marbled flounder digestive tract was 1.54 ± 0.10 (n = 20), and it had a simple stomach and 6–9 pyloric caeca. The mucosal folds of the marbled flounder digestive tract exhibited a general branched morphology. The thickness and mucosal fold length of the intestinal muscularis externa showed similar aspects in all areas. The thickness of the intestinal muscularis externa was the thickest in the posterior intestine portion, and the length of mucosal folds was the longest in the anterior intestine portion. It was indicated that food digested by gastric acid in the stomach moves to the anterior portion (including pyloric caeca) and mid portion of the intestine, ensuring effective stimulation of cholecystokinin (CCK)-producing cells. In addition, the distribution pattern of CCK-producing cells in the intestine was very similar to that of mucus-secreting goblet cells. The CCK-producing cells and goblet cells in the marbled flounder were well-adapted to promote optimal control of the digestive process. Based on the morphological and histochemical studies, it was concluded that the marbled flounder displays a digestive tract comparable to that of fish species with carnivorous habits. Full article

The European beaver is a herbivorous rodent whose diet changes seasonally, and in winter consists of large quantities of woody plants. It is distinguished among other mammals by a unique organization of the stomach that comprises the cardiogastric gland and by the unusual process of mucus formation in the gastric mucosa. The aim of study was to (i) characterize the structure of the beaver esophagus with particular attention to the mucosal epithelium; (ii) compare the histological structure of the esophagi collected in spring, summer, and winter; (iii) provide preliminary data on the structure of the esophagus in beaver fetuses. The study was conducted on esophagi of 18 adult beavers captured in Poland in April, August, and December, and on 3 fetal organs. The results obtained in adults show that the mucosa is lined with thick stratified squamous keratinized epithelium with a structure similar to that of the skin epidermis. Ultrastructural studies reveal the presence of multiple lamellar and non-lamellar bodies in granular cells, whose morphology and location gradually change while reaching the upper epithelial layers. The muscularis mucosa comprises a layer of longitudinally oriented bundles of smooth muscle cells. Both mucosa and submucosa do not comprise any glands. The thick muscularis externa consists mainly of internal circular and external longitudinal layers of striated muscle fibers. The keratinized layer of mucosa epithelium was 2-3-fold thicker in esophagi collected in winter than in those collected in spring and summer, while the epithelial cell layer thickness remained unchanged regardless of the season. Immunolabeling for proliferating cell nuclear antigen shows a higher index of epithelium proliferation in esophagi collected in winter than in spring and summer. No seasonal differences were noted in other layers of the esophagus. Fetal organs have epithelium covered with a keratinized layer, thinner than in adults, and the muscularis externa comprises both striated and smooth muscle cells. Full article

Foxtail millet has been traditionally considered to possess gastroprotective effects, but studies evaluating its use as a treatment for gastric ulcers are lacking. Here, we assessed the antiulcer effects of foxtail millet protein hydrolysate (FPH) and explored its mechanism by using blocking agents. In a mouse model of ethanol-induced gastric ulcers, pretreatment with FPH reduced the ulcerative lesion index, downregulated the expression of inflammatory cytokines in the gastric tissue, increased the activity of antioxidant enzymes, and improved the oxidative status. FPH increased constitutive the activity of nitric oxide synthase (cNOS), NO levels, and mucin expression in gastric mucosa, and inhibited the activation of the ET-1/PI3K/Akt pathway. In a mouse model of pyloric ligation-induced gastric ulcers, FPH inhibited gastric acid secretion and decreased the activity of gastric protease. Pretreatment of mice with the sulfhydryl blocker NEM and the NO synthesis inhibitor L-NAME abolished the gastroprotective effect of FPH, but not the KATP channel blocker glibenclamide and the PGE2 synthesis blocker indomethacin. Among the peptides identified in FPH, 10 peptides were predicted to have regulatory effects on the gastric mucosa, and the key sequences were GP and PG. The results confirmed the gastroprotective effect of FPH and revealed that its mechanism was through the regulation of gastric mucosal mucus and NO synthesis. This study supports the health effects of a millet-enriched diet and provides a basis for millet protein as a functional food to improve gastric ulcers and its related oxidative stress. Full article

Papaver decaisnei (P. decaisnei) has been used as folkloric medicine for many health issues including gastric problems. The current study investigates the gastroprotective roles of P. decaisnei against ethanol-induced ulcers in rodents. Sprague Dawley rats (30) were separated into five groups: the normal group (G1) and the ulcer control group (G2) were orally administered 0.5% carboxymethylcellulose (CMC); the reference group (G3) was administered 20 mg/kg of Omeprazole; two experimental groups were fed with 200 mg/kg (G4) and 400 mg/kg (G5) of the P. decaisnei extract (PDE), respectively. Next, the rats were given absolute ethanol and sacrificed for the analysis of the gastric mucosal injury through microscopic, enzymatic, histologic, and immunohistochemistry assays. The ulcer controls showed significant superficial hemorrhagic gastric mucosal lesions, with a decreased gastric wall mucus and edema production, whereas fewer were found for the reference and plant-treated rats. Furthermore, the PDE pre-treated rats had a significantly reduced the periodic acid-Schiff (PAS) staining intensity, produced the upregulation of the HSP70 protein, and the downregulation of the Bax protein expressions in the stomach epithelium. P. decaisnei displayed a significant role in the upregulation of endogenous antioxidant enzymes (SOD, CAT, and PGE2), significantly reduced malondialdehyde (MDA), TNF-a, IL-6, and upraised the IL-10 levels. Based on the positive impacts, the PDE can be proposed as the protective/treatment agent against gastric ulcers and stomach lesions. Full article

The incidence of gastric cancer in Okinawa Prefecture is the lowest in Japan, which is attributed to differences in strains of Helicobacter pylori in Okinawa and other prefectures in Japan. Our aim was to compare the endoscopic findings of H. pylori-infected gastric mucosa in Okinawa and Tokyo. Patients who underwent upper gastrointestinal endoscopy (UGI) at Northern Okinawa Medical Center (Okinawa group) and Juntendo University Hospital (Tokyo group) from April 2019 to March 2020 were included. Patients diagnosed with H. pylori-infected gastric mucosa were retrospectively compared between the Okinawa and Tokyo groups according to the Kyoto Classification of Gastritis. The numbers of subjects (Okinawa/Tokyo) were 435/352, male/female ratio was 247:188/181:171, and age was 53.3 ± 14.7/64.6 ± 14.3 (mean ± standard deviation) years. Regarding the Kyoto Classification of Gastritis, the prevalence (Okinawa/Tokyo) of the closed type of atrophic gastritis was 73%/37% (p < 0.001), diffuse redness 80%/84% (p = 0.145), mucosal swelling 46%/46% (p = 0.991), enlarged fold 26%/32% (p = 0.048), spotty redness 77%/68% (p = 0.002), sticky mucus 17%/36% (p < 0.001), and intestinal metaplasia 32%/42% (p < 0.001). Age analysis also revealed that closed-type atrophy and spotty redness were more frequent in the Okinawa group than in the Tokyo group. There may be regional differences in endoscopic findings of H. pylori-infected gastric mucosa between Okinawa and Tokyo. Full article

Junctional epithelia are common sites for pathological transformations. In mice, the stratified epithelium of the forestomach joins the simple glandular epithelium of the cardia at the limiting ridge. We previously demonstrated the expression of vitamin A receptors in the gastric stem/progenitor cells and their progeny and found that excess retinoic acid enhances cellular dynamics of gastric epithelium. This study examines how deficiency of vitamin A would alter gastric epithelial stem cell lineages. Three-week-old mice of both genders were weaned and fed with a vitamin A deficient (VAD) diet for 4 or 8 months. Sex- and weight-matched littermate mice received a standard (control) diet. To label S-phase cells, all mice received a single intraperitoneal injection of 5-bromo-2-deoxyuridine before being euthanized. Stomach tissues were processed for microscopic examination and protein analysis to investigate stem cell lineages using different stains, lectins, or antibodies. The Student’s t-test was used to compare quantified data showing differences between control and VAD groups. Eight-month-vitamin-A deficiency caused enlarged forestomach and overgrowth of the squamocolumnar junction with metaplastic and dysplastic cardiac glands, formation of intramucosal cysts, loss of surface mucosal integrity, increased amount of luminal surface mucus, and upregulation of trefoil factor 1 and H⁺,K⁺-ATPase. These changes were associated with decreased cell proliferation and upregulation of p63. In conclusion, vitamin A is necessary for maintaining gastric epithelial integrity and its deficiency predisposes the mouse stomach to precancerous lesions. Full article

Nowadays, an increased interest in natural compounds with preventive or therapeutic potential for various diseases has been observed. Given the involvement of oxidative stress in the pathogenesis of gastric ulcer (GU) and the wide range of bioactive compounds isolated from snails, this study aimed to investigate the protective effect of Cornu aspersum (Müller, 1774) mucus on ethanol-induced GUs. Male albino mice were divided into Control, Ethanol, Mucus + Ethanol and Mucus + Omeprazole treated groups. The GUs were induced by administration of 96% ethanol (10 mL/kg, per os). One hour before ulcer induction, the mice of Mucus + Ethanol group were pretreated with mucus (20 mg/kg, per os), and the mice of Mucus + Omeprazole group were pretreated with omeprazole (20 mg/kg, per os). Ethanol administration caused grave lesions of gastric mucosa and a significant decrease of glutathione (GSH) and superoxide dismutase (SOD), catalase, and glutathione reductase (GR) activities. In the animals with mucus or omeprazole pre-administration compared to the Ethanol group, the following were observed: only a small number of hemorrhagic fields, significantly reduced GU index with calculated 73% protection by mucus and 78% protection by omeprazole, and significant recovery of mucosal GSH and SOD and GR activities. In addition, the mucus inhibited Helicobacter pylori growth. Thus, the protective effect of C. aspersum mucus on both gastric mucosa and gastric antioxidant potential in ethanol-induced GU model suggests that it may serve as a good tool for prevention of this disease. Full article

The prevalence of gastric ulcers has increased in recent years, mainly because of non-steroidal anti-inflammatory drug utilization. Therefore, the current study investigates the gastroprotective effect of p-Cymene on absolute ethanol-induced acute gastric mucosal hemorrhagic lesions in rats. Thirty Sprague Dawley rats were randomly separated into five groups: normal control, ulcer control, reference, and two experimental groups. The normal and ulcer control groups were orally fed with 0.5% carboxymethylcellulose (CMC). The reference group was fed orally with 20 mg/kg omeprazole. The experimental groups were fed with 30 mg/kg and 60 mg/kg p-Cymene, respectively. After one hour, the normal group was fed with 0.5% CMC, and groups 2–5 were given absolute alcohol. After another hour all rats were sacrificed. The ulcer control group showed severe superficial hemorrhagic gastric mucosal lesions with decreased gastric mucus secretion and pH of gastric content. p-Cymene significantly reduced ethanol-induced gastric lesions, as evidenced by increased mucus and pH of gastric content, decreased ulcer area, reduced or absence of edema, and leucocyte infiltration of the subcutaneous layer. In gastric mucosal homogenate, p-Cymene displayed a significant increase in superoxide dismutase (SOD), catalase (CAT) activities, prostaglandin E2 (PGE2), and significantly reduced the malondialdehyde (MDA) level. In addition, p-Cymene increased the intensity of periodic acid–Schiff (PAS) stain of the gastric epithelium, and produced up-regulation of the HSP 70 protein and down-regulation of the Bax protein of the stomach epithelium, as well as a reduction in the levels of tumor necrotic factor-alpha and interleukin-6, while the level of interleukin-10 was increased. p-Cymene decreased the level of TNF-a and IL-6, and increased the level of IL-10. Acute toxicity with a higher dose of 500 mg/kg p-Cymene did not manifest any toxicological signs in rats and could enhance defensive mechanisms against gastric mucosal lesions. p-Cymene showed gastroprotective effects that could be attributed to its antioxidant nature, or its ability to increase mucus secretion, increase endogenous enzymes (SOD, CAT, PGE2), reduce MDA level, up-regulate HSP 70 protein, down-regulate Bax protein, and modulate inflammatory cytokines. Full article

Autoimmune gastritis (AIG) is chronic atrophic gastritis caused by an autoimmune mechanism of unknown etiology and presents with various pathological conditions by causing an achlorhydria state through parietal cell damage. The most characteristic endoscopic finding in AIG is advanced corpus-dominant mucosal atrophy. A recent study that examined several cases in Japan revealed the presence of endoscopic features other than corpus-dominant advanced atrophy. Remnants of oxyntic mucosa and sticky adherent dense mucus were found in ≥30% of cases, and hyperplastic polyps were found in ≥20% of cases. In image-enhanced endoscopy (IEE), white globe appearance (WGA) was observed in 32% of AIG cases. Additionally, some reports have stated that the findings in AIG cases using IEE showed cast-off skin appearance (CSA) and foveola type mucosa; however, a consensus is yet to be achieved. These endoscopic results were found in cases of advanced-stage AIG. There have been few reports concerning early-stage AIG cases. In these few reports, all of the cases were pathologically diagnosed as early AIG. In all of the cases, the pathological findings almost always showed neither parietal cell destruction nor atrophy. Endoscopic findings such as “mosaic pattern with slight swelling of the areae gastricae”, “diffuse reddened and edematous gastric fundic gland mucosa”, and “pseudopolyp-like nodules” may be common characteristics of early images. In such early cases, high antibody titers, no atrophic changes, and few clinical abnormal findings were shown. Endoscopists are expected to update their knowledge regarding AIG diagnosis with the evolution of imaging equipment. Full article

This study was conducted to investigate the therapeutic effect of hydro-alcoholic extract of Spirulina platensis (SP), golden kiwifruit (Actinidia chinensis) flesh (KF), and golden kiwifruit peel (KP) individually or in combination (SFP) on indomethacin-induced gastric ulcer in rats. Negative control rats (GI) were orally administered distilled water in parallel with other treatments. The positive control rat group (GII) was administered 30 mg kg⁻¹ indomethacin to induce gastric ulcers. The KF and KF extracts were used individually or together with SP in treating indomethacin-induced gastric ulcerated rat groups. Gastric ulcerated rat’s groups GIII, GIV, GV, GVI, and GVII were orally administered at 30 mg kg⁻¹ rat body weight as total phenolic content (TPC) equivalent from SP, KF, KP, SPF extracts, and Lansoprazole (30 mg kg⁻¹, as reference drug) daily up to 14 days, respectively. The relevant biochemical parameters, antioxidant biomarkers, and histopathological examination were examined. Remarkably, treating rats with SP, KF, KP, and SFP extracts markedly reduced gastric juice and stomach volume expansion induced by indomethacin. The SP significantly retrieved the pH of gastric juice to a regular rate compared to GI. The ulcer index (UI) was significantly attenuated by SP, KF, KP, and SFP administration. The protection index percentage (PI %) was 80.79, 54.51, 66.08, 75.74, and 74.86% in GIII, GIV, GV, GVI, and GVII, respectively. The gastric mucin content was significantly better attenuated by 95.7 in GIII compared to its content in GI. Lansoprazole increased mucin content by 80.3%, which was considerably lower than SP and SFP. SP, KF, KP, SFP, and Lansoprazole improved the reform of gastric mucosal-increased secreted mucus by 95.6, 61.3, 64.8, 103.1, and 80.2% in GIII, GIV, GV, GVI, and GVII, respectively. Interestingly, SFP efficiently increased vit. B₁₂ level by 46.0% compared to other treatments. While Lansoprazole administrating did not significantly attenuate vit. B₁₂ level. The SP and SFP improved iron and Hemoglobin (HB) levels depending on treatment. SP, KF, KP, and SFP significantly decreased the malondialdehyde (MDA) and increased reduced glutathione (GSH) as well as superoxide dismutase (SOD) levels in blood and stomach tissues. The most potent effect was observed with SP, and SFP was even better than Lansoprazole. Histopathologically, treating rats with SP extract showed a marked reduction of gastric damage and severity changes induced by indomethacin. KP was much better than KF in lessening gastric histopathological damages caused by indomethacin. SFP significantly alleviates gastric histopathological alterations. The lansoprazole-treated group (GVII) greatly relieved the gastric histopathological changes and recorded mild focal necrosis and desquamation of the mucosa in addition to mild oedema in the serosal layer. In conclusion, the presented results proved the antiulcer potential of SP and A. chinensis extracts against an indomethacin-induced gastric ulcer in rats, which may be due to their antioxidant and anti-inflammation efficiency. Thus, these data suggested that SP, KF, KP, and SFP extracts as natural and safe alternatives have a gastroprotective potential against indomethacin-induced gastric ulceration. The antioxidative and anti-inflammatory properties are probable mechanisms. Full article

Trefoil factor family (TFF) peptides mainly consist of characteristic TFF domains, which contain about 40 amino acid residues, including 6 conserved cysteine residues. TFF peptides possess a single (mammalian TFF1 and TFF3), two (mammalian TFF2, Xenopus laevis xP2) or four TFF domains (X. laevis xP4). They exhibit lectin activities and are characteristic exocrine products of the mucous epithelia. Here, they play different roles for mucosal protection and the innate immune defense: TFF1 is a gastric tumor suppressor; TFF2 builds a lectin complex with the mucin MUC6, physically stabilizing the inner gastric mucus layer; and TFF3 forms a disulfide-linked heterodimer with IgG Fc binding protein (FCGBP), probably preventing the infiltration of microorganisms. Minor amounts of TFF peptides are endocrine products of the immune and nervous systems. Pathologically, TFF peptides are linked to inflammation. There are increasing indications that TFF peptides can antagonize cytokine receptors, such as receptors for IL-1β, IL-6, and TNFα (thereby acting as anti-inflammatory peptides). TFF peptides can probably also activate a variety of receptors, such as CXCR4. The TFF domain is a unique shuffled module which is also present in a number of mosaic proteins, such as zona pellucida proteins, sugar degrading enzymes and frog skin mucins. Here, their function seems to be defined by a lectin activity, which might even allow a role in fertilization. Full article

Patients with gastric mucosal erosions are predisposed to chronic gastritis, ulcer or even cancer. The repair of mucosal erosions involves several events including proliferation of gastric epithelial stem cells. The aim of this study was to investigate the effects of the probiotic mixture of De Simone Formulation on gastric epithelial stem cell lineages in mouse models of gastric mucosal erosions. Gastric erosions were induced by a single oral gavage of 80% ethanol containing 15 mg/mL acetylsalicylic acid (5 mL/kg) following a daily dose of probiotic mixture (5 mg/day/mouse) for 10 days. In another protocol, erosions were induced by a daily gavage of acetylsalicylic acid (400 mg/kg/day/mouse) for 5 days before or after daily administration of probiotic mixture for 5 days. Control mice received water gavage for 10 days. All mice were injected with bromodeoxyuridine two hours before sacrifice to label S-phase cells. The stomachs of all mice were processed for histological examination, lectin binding, and immunohistochemical analysis. The results reveal that mice that received probiotics before or after the induction of erosion showed a decrease in erosion index with an increase in gastric epithelial stem/progenitor cell proliferation and enhanced production of mucus, trefoil factors, and ghrelin by mucous and enteroendocrine cell lineages. These mice also showed restoration of the amount of H⁺,K⁺-ATPase and pepsinogen involved in the production of the harsh acidic environment by parietal and chief cell lineages. In conclusion, this study demonstrates the beneficial effects of probiotics against gastric mucosal erosion and highlights the involvement and modulation of proliferative stem cells and their multiple glandular epithelial cell lineages. Full article