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The mucosa of the body of the stomach (ie, the gastric corpus) uses 2 overlapping, depth-dependent mechanisms to respond to injury. Superficial injury heals via surface cells with histopathologic changes like foveolar hyperplasia. Deeper, usually chronic, injury/inflammation, most frequently induced by the carcinogenic bacteria Helicobacter pylori, elicits glandular histopathologic alterations, initially manifesting as pyloric (also known as pseudopyloric) metaplasia. In this pyloric metaplasia, corpus glands become antrum (pylorus)-like with loss of acid-secreting parietal cells (atrophic gastritis), expansion of foveolar cells, and reprogramming of digestive enzyme-secreting chief cells into deep antral gland-like mucous cells. After acute parietal cell loss, chief cells can reprogram through an orderly stepwise progression (paligenosis) initiated by interleukin-13-secreting innate lymphoid cells (ILC2s). First, massive lysosomal activation helps mitigate reactive oxygen species and remove damaged organelles. Second, mucus and wound-healing proteins (eg, TFF2) and other transcriptional alterations are induced, at which point the reprogrammed chief cells are recognized as mucus-secreting spasmolytic polypeptide-expressing metaplasia cells. In chronic severe injury, glands with pyloric metaplasia can harbor both actively proliferating spasmolytic polypeptide-expressing metaplasia cells and eventually intestine-like cells. Gastric glands with such lineage confusion (mixed incomplete intestinal metaplasia and proliferative spasmolytic polypeptide-expressing metaplasia) may be at particular risk for progression to dysplasia and cancer. A pyloric-like pattern of metaplasia after injury also occurs in other gastrointestinal organs including esophagus, pancreas, and intestines, and the paligenosis program itself seems broadly conserved across tissues and species. Here we discuss aspects of metaplasia in stomach, incorporating data derived from animal models and work on human cells and tissues in correlation with diagnostic and clinical implications., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Oxidative stress is directly implicated in the loss of intestinal epithelial barrier function (IEBF) induced by non-steroidal anti-inflammatory drugs (NSAIDs). Previous studies by our research team demonstrated that 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone (BZF), a quercetin oxidation metabolite that naturally occurs in onion peels, exhibits an antioxidant potency notably higher than quercetin. Thus, we assessed the potential of BZF and a BZF-rich onion peel aqueous extract (OAE) to protect against the loss of IEBF in Caco-2 cell monolayers and in rats exposed to indomethacin. In vitro, pure BZF and OAE standardized in BZF (100 nM), protected against the drop in transepithelial electrical resistance by 70 - 73%. Likewise, it prevented the increase in fluorescein-isothiocyanate labelled dextran (FITC-dextran) paracellular transport by 74% and oxidative stress by 84 - 86%. In vivo, BZF, given orally at a dose 80 µg/Kg bw as OAE, totally abolished a 30-fold increase in FITC-dextran serum concentration induced by indomethacin. This effect was dose-dependent and largely conserved (85%) when OAE was given 180-min prior to indomethacin. The IEBF-protective effect of OAE was accompanied by a full prevention of the NF-ĸB activation, and the increases in interleukine-8 secretion and myeloperoxidase activity induced by indomethacin. The protection was also associated with a 21-fold increase in Nrf2, and a 7-fold and 9-fold increase in heme oxygenase-1 and NAD(P)H-quinone oxidoreductase 1, respectively. The IEBF-protecting effect of OAE involves, most likely, its dual capacity to activate Nrf2 while inhibiting NF-ĸB activation. The extremely low doses of BZF needed to promote such actions warrants extending its IEBF-protective effects to other NSAIDs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Energy homeostasis is is determined by food intake and energy expenditure, which are partly regulated by the cross-talk between central and peripheral hormonal signals. Phoenixin (PNX) is a recently discovered pleiotropic neuropeptide with isoforms of 14 (PNX-14) and 20 (PNX-20) amino acids. It is a potent reproductive peptide in vertebrates, regulating the hypothalamo-pituitary-gonadal axis (HPG). It has been identified as a regulator of food intake during light phase when injected intracerebroventricularly in rats. In addition, plasma levels of PNX also increased after food intake in rats, suggesting that it might have possible roles in energy homeostasis. We hypothesized that gut is a source and site of action of PNX in mice. Immunoreactivity for PNX and its putative receptor, super-conserved receptor expressed in brain (SREB3; also known as the G-protein coupled receptor 173/GPR 173) was found in the stomach and intestine of male C57/BL6 J mice, and in MGN3-1 (mouse stomach endocrine) cells and STC-1 (mouse enteroendocrine) cells. In MGN3-1 cells, PNX-20 significantly upregulated ghrelin (10 nM) and ghrelin-O-acyl transferase (GOAT) mRNAs (1000 nM) at 6 h. In STC-1 cells, it significantly suppressed CCK (100 nM) at 2 h. No effects were found on other intestinal hormones tested (glucagon like peptide-1, glucose dependent insulinotropic polypeptide, and peptide YY). Together, these results indicate that PNX-20 is produced in the gut, and it could act directly on gut cells to regulate metabolic hormones., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Lipopolysaccharide (LPS) of Helicobacter pylori (Hp) bacteria causes disintegration of gastric tissue cells in vitro. It has been suggested that interleukin (IL)-33 is involved in healing gastric injury., Aim: To elucidate whether Hp LPS affects regeneration of gastric barrier initiated by IL-33., Methods: Primary gastric epithelial cells or fibroblasts from Caviae porcellus were transfected with siRNA IL-33. Such cells, not exposed or treated with LPS Hp, were sub-cultured in the medium with or without exogenous IL-33. Then cell migration was assessed in conjunction with oxidative stress and apoptosis, activation of extracellular signal-regulated kinase (Erk), production of collagen I and soluble ST2 (IL-33 decoy)., Results: Control cells not treated with LPS Hp migrated in the presence of IL-33. The pro-regenerative activity of IL-33 was related to stimulation of cells to collagen I production. Wound healing by cells exposed to LPS Hp was inhibited even in the presence of IL-33. This could be due to increased oxidative stress and apoptosis in conjunction with Erk activation, sST2 elevation and modulation of collagen I production., Conclusions: The recovery of gastric barrier cells during Hp infection potentially can be affected due to downregulation of pro-regenerative activity of IL-33 by LPS Hp.

The enteric nervous system (ENS) is the largest division of the peripheral nervous system and closely resembles components and functions of the central nervous system. Although the central role of the ENS in congenital enteric neuropathic disorders, including Hirschsprung disease and inflammatory and functional bowel diseases, is well acknowledged, its role in systemic diseases is less understood. Evidence of a disordered ENS has accumulated in neurodegenerative diseases ranging from amyotrophic lateral sclerosis, Alzheimer disease and multiple sclerosis to Parkinson disease as well as neurodevelopmental disorders such as autism. The ENS is a key modulator of gut barrier function and a regulator of enteric homeostasis. A 'leaky gut' represents the gateway for bacterial and toxin translocation that might initiate downstream processes. Data indicate that changes in the gut microbiome acting in concert with the individual genetic background can modify the ENS, central nervous system and the immune system, impair barrier function, and contribute to various disorders such as irritable bowel syndrome, inflammatory bowel disease or neurodegeneration. Here, we summarize the current knowledge on the role of the ENS in gastrointestinal and systemic diseases, highlighting its interaction with various key players involved in shaping the phenotypes. Finally, current flaws and pitfalls related to ENS research in addition to future perspectives are also addressed.

A network of myenteric interstitial cells of Cajal in the corpus of the stomach serves as its "pacemaker", continuously generating a ca 0.05 Hz electrical slow wave, which is transmitted to the brain chiefly by vagal afferents. A recent study combining resting-state functional MRI (rsfMRI) with concurrent surface electrogastrography (EGG), with cutaneous electrodes placed on the epigastrium, found 12 brain regions with activity that was significantly phase-locked with this gastric basal electrical rhythm. Therefore, we asked whether fluctuations in brain resting state networks (RSNs), estimated using a spatial independent component analysis (ICA) approach, might be synchronized with the stomach. In the present study, in order to determine whether any RSNs are phase-locked with the gastric rhythm, an individual participant underwent 22 scanning sessions; in each, two 15-minute runs of concurrent EGG and rsfMRI data were acquired. EGG data from three sessions had weak gastric signals and were excluded; the other 19 sessions yielded a total of 9.5 hours of data. The rsfMRI data were analyzed using group ICA; RSN time courses were estimated; for each run, the phase-locking value (PLV) was computed between each RSN and the gastric signal. To assess statistical significance, PLVs from all pairs of "mismatched" data (EGG and rsfMRI data acquired on different days) were used as surrogate data to generate a null distribution for each RSN. Of a total of 18 RSNs, three were found to be significantly phase-locked with the basal gastric rhythm, namely, a cerebellar network, a dorsal somatosensory-motor network, and a default mode network. Disruptions to the gut-brain axis, which sustains interoceptive feedback between the central nervous system and the viscera, are thought to be involved in various disorders; manifestation of the infra-slow rhythm of the stomach in brain rsfMRI data could be useful for studies in clinical populations., Competing Interests: The authors have declared that no competing interests exist.

Spasmolytic polypeptide/trefoil factor 2 (TFF2)-expressing metaplasia (SPEM) is a mucous-secreting reparative lineage that emerges at the ulcer margin in response to gastric injury. Under conditions of chronic inflammation with parietal cell loss, SPEM has been found to emerge and evolve into neoplasia. Cluster-of-differentiation gene 44 (CD44) is known to coordinate normal and metaplastic epithelial cell proliferation. In particular, CD44 variant isoform 9 (CD44v9) associates with the cystine-glutamate transporter xCT, stabilizes the protein, and provides defense against reactive oxygen species (ROS). xCT stabilization by CD44v9 leads to defense against ROS by cystine uptake, glutathione (GSH) synthesis, and maintenance of the redox balance within the intracellular environment. Furthermore, p38 signaling is a known downstream ROS target, leading to diminished cell proliferation and migration, two vital processes of gastric epithelial repair. CD44v9 emerges during repair of the gastric epithelium after injury, where it is coexpressed with other markers of SPEM. The regulatory mechanisms for the emergence of CD44v9 and the role of CD44v9 during the process of gastric epithelial regeneration are largely unknown. Inflammation and M2 macrophage infiltration have recently been demonstrated to play key roles in the induction of SPEM after injury. The following review proposes new insights into the functional role of metaplasia in the process of gastric regeneration in response to ulceration. Our insights are extrapolated from documented studies reporting oxyntic atrophy and SPEM development and our current unpublished findings using the acetic acid-induced gastric injury model.

In clinical medicine, indomethacin (IND, a non-steroidal anti-inflammatory drug) is used variously in the treatment of severe osteoarthritis, rheumatoid arthritis, gouty arthritis or ankylosing spondylitis. A common complication found alongside the therapeutic characteristics is gastric mucosal damage. This complication is mediated through apoptosis and autophagy of the gastrointestinal mucosal epithelium. Apoptosis and autophagy are critical homeostatic pathways catalysed by caspases downstream of the gastrointestinal mucosal epithelial injury. Both act through molecular signalling pathways characterized by the initiation, mediation, execution and regulation of the cell regulatory cycle. In this study we hypothesized that dysregulated apoptosis and autophagy are associated with IND-induced gastric damage. We examined the spectra of in vivo experimental gastric ulcers in male Sprague-Dawley rats through gastric gavage of IND. Following an 18-hour fast, IND was administered to experimental rats. They were sacrificed at 3-, 6- and 12-hour intervals. Parietal cells (H + , K + -ATPase β-subunit assay) and apoptosis (TUNEL assay) were determined. The expression of apoptosis-signalling caspase (caspases 3, 8, 9 and 12), DNA damage (anti-phospho-histone H2A.X) and autophagy (MAP-LC3, LAMP-1 and cathepsin B)-related molecules in gastric mucosal cells was examined. The administration of IND was associated with gastric mucosal erosions and ulcerations mainly involving the gastric parietal cells (PCs) of the isthmic and upper neck regions and a time-dependent gradual increase in the number of apoptotic PCs with the induction of both apoptotic (upregulation of caspases 3 and 8) cell death and autophagic (MAP-LC3-II, LAMP-1 and cathepsin B) cell death. Autophagy induced by fasting and IND 3 hours initially prompted the degradation of caspase 8. After 6 and 12 hours, damping down of autophagic activity occurred, resulting in the upregulation of active caspase 8 and its nuclear translocation. In conclusion we report that IND can induce time-dependent apoptotic and autophagic cell death of PCs. Our study provides the first indication of the interactions between these two homeostatic pathways in this context., (© 2020 Company of the International Journal of Experimental Pathology (CIJEP).)

The identity of embryonic gastric epithelial progenitors is unknown. We used single-cell RNA-sequencing, genetic lineage tracing and organoid assays to assess whether Axin2 - and Lgr5 -expressing cells are gastric progenitors in the developing mouse stomach. We show that Axin2 + cells represent a transient population of embryonic epithelial cells in the forestomach. Lgr5 + cells generate both glandular corpus and squamous forestomach organoids ex vivo Only Lgr5 + progenitors give rise to zymogenic cells in culture. Modulating the activity of the WNT, BMP and Notch pathways in vivo and ex vivo , we found that WNTs are essential for the maintenance of Lgr5 + epithelial cells. Notch prevents differentiation of the embryonic epithelial cells along all secretory lineages and hence ensures their maintenance. Whereas WNTs promote differentiation of the embryonic progenitors along the zymogenic cell lineage, BMPs enhance their differentiation along the parietal lineage. In contrast, WNTs and BMPs are required to suppress differentiation of embryonic gastric epithelium along the pit cell lineage. Thus, coordinated action of the WNT, BMP and Notch pathways controls cell fate determination in the embryonic gastric epithelium., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

The structurally-related peptides, gastrin and cholecystokinin (CCK), were originally discovered as humoral stimulants of gastric acid secretion and pancreatic enzyme release, respectively. With the aid of methodological advances in biochemistry, immunochemistry, and molecular biology in the past several decades, our concept of gastrin and CCK as simple gastrointestinal hormones has changed considerably. Extensive in vitro and in vivo studies have shown that gastrin and CCK play important roles in several cellular processes including maintenance of gastric mucosa and pancreatic islet integrity, neurogenesis, and neoplastic transformation. Indeed, gastrin and CCK, as well as their receptors, are expressed in a variety of tumor cell lines, animal models, and human samples, and might contribute to certain carcinogenesis. In this review, we will briefly introduce the gastrin and CCK system and highlight the effects of gastrin and CCK in the regulation of cell proliferation and apoptosis in both normal and abnormal conditions. The potential imaging and therapeutic use of these peptides and their derivatives are also summarized., (Copyright © 2020 Zeng, Ou, Wang and Guo.)

Background : Gastric glands grow and cells reach differentiation at weaning in rats. By considering that early weaning (EW) can affect the timing of development, we aimed to compare molecular and cellular markers of differentiation in pups and adults. Methods : Wistar rats were separated into suckling-control (S) and EW groups at 15 days. Stomachs were collected at 15, 18, and 60 days for RNA and protein extraction, and morphology. Results : After EW, the expression of genes involved in differentiation ( Atp4b , Bhlha15 and Pgc ) augmented (18 days), and Atp4b and Gif were high at 60 days. EW increased the number of zymogenic cells (ZC) in pups and adults and augmented mucous neck cells only at 18 days, whereas parietal and transition cells (TC) were unchanged. Conclusions : EW affected the gastric mucosa mostly in a transient manner as the changes in gene expression and distribution of differentiated cells that were detected in pups were not fully maintained in adults, except for the size of ZC population. We concluded that though most of EW effects were immediate, such nutritional change in the infancy might affect part of gastric digestive functions in a permanent manner, as some markers were kept unbalanced in the adulthood.

Purpose of Review: The gastroduodenal mucosal layer is a complex and dynamic system that functions in an interdependent manner to resist injury. We review and summarize the most updated knowledge about gastroduodenal defense mechanisms and specifically address (a) the mucous barrier, (b) membrane and cellular properties, and vascular, hormonal, and (c) gaseous mediators., Recent Findings: Trefoil factor family peptides play a crucial role in cellular restitution by increasing cellular permeability and expression of aquaporin channels, aiding cellular migration and tissue repair. Additionally, evidence suggests that the symptoms of functional dyspepsia may be attributed to alterations in the duodenum, including low-grade inflammation and increased mucosal permeability. The interaction of the various mucosal protective components helps maintain structural and functional homeostasis. There is increasing evidence suggesting that the upper GI microbiota plays a crucial role in the defense mechanisms. However, this warrants further investigation.

Fructo-oligosaccharides are commonly administered as prebiotics to horses in order to reduce the risk of disruption of microbial populations in the hindgut. Their microbial degradation to SCFA already begins in the stomach potentially resulting in increased gastric concentrations of SCFA such as butyric acid. The impact of butyric acid on the squamous mucosa is postulated to be detrimental, its effects on the glandular mucosa are yet unknown. Thus, the aim of this study was to determine the effects of butyric acid exposure on the functional integrity and morphology of the equine nonglandular and glandular gastric mucosa using butyric acid concentrations equivalent to the ones found in horses subjected to prebiotic fructo-oligosaccharides feeding. Gastric mucosal samples of healthy horses were exposed to butyric acid using the in vitro Ussing chamber technique. Electrophysiological parameters were continuously monitored, mucosal samples were blinded and histomorphological analysis was performed using a scoring system for assessment of histopathologic changes. Exposure to butyric acid resulted in pathohistomorphological changes in the glandular mucosa and in impairment of functional mucosal integrity in the squamous and the glandular mucosa as documented by significant changes in tissue conductances (G t ). Administration of fructo-oligosaccharides as a preventive prebiotic measure to horses should therefore be carefully considered, particularly in horses known to be at risk of developing EGUS., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Helicobacter suis is the most prevalent non-Helicobacter pylori Helicobacter species in the human stomach and is associated with chronic gastritis, peptic ulcer disease, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. H. suis colonizes the gastric mucosa of 60-95% of pigs at slaughter age, and is associated with chronic gastritis, decreased weight gain, and ulcers. Here, we show that experimental H. suis infection changes the mucin composition and glycosylation, decreasing the amount of H. suis-binding glycan structures in the pig gastric mucus niche. Similarly, the H. suis-binding ability of mucins from H. pylori-infected humans is lower than that of noninfected individuals. Furthermore, the H. suis growth-inhibiting effect of mucins from both noninfected humans and pigs is replaced by a growth-enhancing effect by mucins from infected individuals/pigs. Thus, Helicobacter spp. infections impair the mucus barrier by decreasing the H. suis-binding ability of the mucins and by decreasing the antiprolific activity that mucins can have on H. suis. Inhibition of these mucus-based defenses creates a more stable and inhabitable niche for H. suis. This is likely of importance for long-term colonization and outcome of infection, and reversing these impairments may have therapeutic benefits.

Background: Peptic ulcer disease (PUD) is a common disease worldwide moreover known as stomach ulcer or peptic ulcer. Increased the number of T CD4 + helper cells in response to gastric infection by Helicobacter pylori (H. pylori) play an important role in the development of PUD. The aim of this study was to determine the frequency of T-bet + cells in H. pylori-infection, its interaction with Th17/Treg cells and its association with the clinical consequences of the infection., Methods: A total of 63 patients with PUD, 89 patients with gastritis and 48 H. pylori-negative subjects were enrolled in this study. The number of T-bet + cells were determined by immunohistochemistry., Results: The numbers of T-bet + cells and INF-γ expression in infected patients were significantly higher than uninfected. Moreover, the number of T-bet + cells and INF-γ expression in infected patients with PUD were significantly higher than infected patients with gastritis. Additionally, the number of T-bet + cells and INF-γ expression were found to be inversely correlated with degree of H. pylori density and chronic inflammation score (CIS) in infected patients with gastritis disease, but this correlation was positive in the infected patients with PUD. The number of T-bet + cells was found to be positively correlated with the number of Th17 cells and inversely correlated with the number of Treg cells in infected patients with gastritis and PUD., Conclusion: Abnormal hyper-activation of T-bet + cells during H. pylori-infection may lead to tissue damage caused by immunopathologic reactions., (Copyright © 2019 IMSS. Published by Elsevier Inc. All rights reserved.)

OBJECTIVE To assess the feasibility of esophageal insufflation CT (EICT) for evaluation of the esophagus in dogs. ANIMALS 7 clinically normal adult Beagles. PROCEDURES Each dog was anesthetized twice with 1 week between anesthesia sessions. Dogs were positioned in sternal recumbency during all CT scans. During the first anesthesia session, a CT scan was performed before the esophagus was insufflated (insufflation pressure, 0 mm Hg) and unenhanced and contrast-enhanced EICT scans were performed after CO 2 was insufflated into the esophageal lumen to achieve a pressure of 5 mm Hg. For the contrast-enhanced scan, each dog received iohexol (600 mg/kg, IV), and the scan was performed 30 seconds later. During the second anesthesia session, unenhanced and contrast-enhanced EICT scans were performed in the same manner except the insufflation pressure achieved was 10 mm Hg. The esophageal luminal cross-sectional area and wall thickness were measured at each of 5 segments, and mean values were compared among the 3 insufflation pressures and between unenhanced and contrast-enhanced images. RESULTS Mean esophageal luminal cross-sectional area increased and esophageal wall thickness decreased as insufflation pressure increased. Measurements did not differ significantly between unenhanced and contrast-enhanced images. The stomach became distended with CO 2 at an insufflation pressure of 10 mm Hg but not at 5 mm Hg. No adverse effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested EICT was feasible for esophageal evaluation in dogs. Further research is necessary to determine the optimal insufflation pressure for the procedure and its diagnostic efficacy in diseased patients.

Oxidative stress contributes to the progression of non-steroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) cell apoptosis. In our previous study, we reported that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a protective role against ketoprofen-induced GI mucosal oxidative injury. Recent reports suggest that Nrf2 could exhibit antioxidative and antiapoptosis responses through up-regulation of DJ-1 (PARK7). In the current study, we proposed that induction of DJ-1 expression by protocatechuic acid (PCA) might provide a potential therapeutic approach for treating oxidative stress-associated GI ulcer diseases. The results indicated that PCA increased mRNA expression of glutathione peroxidase and heme oxygenase-1 through up-regulation of DJ-1 followed by Nrf2 translocation. Furthermore, PCA protected Int-407 cells against ketoprofen-induced oxidative stress by regulating the DJ-1, PI3K, and mTOR pathways. Pretreatment with PCA inhibited mitochondrial ROS generation, up-regulated the mitochondrial membrane potential, and down-regulated pro-apoptotic Bax as well as downstream caspase-8, caspase-9, and caspase-3 activity, and reversed impaired DJ-1 and anti-apoptotic Bcl-2 protein expression in Int-407 cells induced by ketoprofen. Similar to the in vitro results, SD rats treated with PCA before administration of ketoprofen exhibited decreased caspase-3 protein expression as well as oxidative damage, and impairment of the antioxidant system and DJ-1 protein expression in the GI mucosa were reversed. The administration of lansoprazole, a type of proton pump inhibitor (PPI), strongly inhibited ketoprofen-induced GI mucosal injuries via up-regulation of DJ-1, indicating that DJ-1 is essential for the dietary antioxidant- and PPI drug-mediated mechanism of ulcer therapy. These results suggest that DJ-1 could be a novel target for protection against ketoprofen-induced GI ulcers due to its antioxidant and anti-apoptosis characteristics., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The human body is often used for illegal drug trafficking around the world. This may be done by concealing the drugs inside the body, so-called "body packing". This can lead to life-threatening conditions, mainly by leakage of the illegal substances in lethal amounts into the circulation system, which may cause fatal consequences due to acute drug overdose. Most of these cases present as sudden unexpected deaths. However, we present herein a case in which the death of an unidentified victim, which was notified as a case of seawater drowning in a non-suspicious manner, but later proved to be the death of a body packer as a result of drowning due to a morphine overdose. This case highlights the importance of investigating deaths even in unidentified bodies and the different presentations of fatal consequences of a body packer, which previously have not been described in literature.

Gastric proton pump (H + ,K + -ATPase) which is responsible for H + secretion of gastric acid (HCl) in gastric parietal cells is the major therapeutic target for treatment of acid-related diseases. H + ,K + -ATPase consists of two subunits, a catalytic α-subunit (αHK) and a glycosylated β-subunit (βHK). N-glycosylation of βHK is essential for trafficking and stability of αHK in apical membrane of gastric parietal cells. Terminal sialic acid residues on sugar chains have an important role in various cellular functions. Recently, we succeeded in visualizing the sialylation and desialylation dynamics of βHK using a fluorescence bioimaging nanoprobe consisting of biocompatible polymers conjugated with lectins for detecting sialic acid. In H + ,K + -ATPase-expressing cell lines, rat gastric mucosa, and primary culture of rat gastric parietal cells, fluorescence imaging of sialic acid with the nanoprobe showed that sialylation of βHK is regulated by intragastric pH and that inhibition of gastric acid secretion induces desialylation of βHK. In biochemical and pharmacological studies, we revealed that enzyme activity of αHK is negatively regulated by desialylation of βHK. Our studies uncovered a novel negative-feedback mechanism of H + ,K + -ATPase in which sialic acids of βHK positively regulates H + ,K + -ATPase activity, and acidic pH decreases the pump activity by cleaving sialic acids of βHK. In this topic, we introduce the overview of our research using the bioimaging nanoprobe.

High-performance submucosal injection materials (SIMs) contribute to the success of endoscopic therapy for early-stage gastrointestinal neoplasms. This study aimed to identify the most important factor (viscoelastic parameter) that determines SIM performance and the ease of injection. To determine the ideal viscoelastic parameters of SIMs, submucosal elevation heights (SEHs) and the ease of submucosal injection [characterized by injection pressures (IPs)] were evaluated using a newly developed ex vivo model, in which a constant tension was applied to the studied specimen. The strongest positive correlation was observed between the loss modulus determined at an oscillation frequency of 0.1 rad/s and SEH (correlation coefficient > 0.9) and between the loss modulus at 10 rad/s and IP (correlation coefficient > 0.9). SIMs with high loss moduli (0.1 rad/s) also contributed to maintenance of the submucosal elevation. Moreover, the SEHs of pseudoplastic fluid SIMs (whose loss moduli increased slightly with increasing angular frequency) were greater than those of Newtonian fluid SIMs (whose loss modulus increased drastically with increasing angular frequency). In this study, the ideal viscoelastic SIM parameters were clarified. The loss modulus (0.1 rad/s) was the most important viscoelastic factor affecting SIM performance. Additionally, the development of pseudoplastic fluid SIMs may lead to the creation of next-generation SIMs, with a performance superior to that of sodium hyaluronate, which is currently used widely in endoscopic treatments., (Copyright © 2018 Elsevier B.V. All rights reserved.)

DNA methylation is a regulatory mechanism in epigenetics that is frequently altered during human carcinogenesis. To detect critical methylation events associated with gastric cancer (GC), we compared three DNA methylomes from gastric mucosa (GM), intestinal metaplasia (IM), and gastric tumor (GT) cells that were microscopically dissected from an intestinal-type early gastric cancer (EGC) using methylated DNA binding domain sequencing (MBD-seq) and reduced representation bisulfite sequencing (RRBS) analysis. In this study, we focused on differentially methylated promoters (DMPs) that could be directly associated with gene expression. We detected 2,761 and 677 DMPs between the GT and GM by MBD-seq and RRBS, respectively, and for a total of 3,035 DMPs. Then, 514 (17%) of all DMPs were detected in the IM genome, which is a precancer of GC, supporting that some DMPs might represent an early event in gastric carcinogenesis. A pathway analysis of all DMPs demonstrated that 59 G protein-coupled receptor (GPCR) genes linked to the hypermethylated DMPs were significantly enriched in a neuroactive ligand-receptor interaction pathway. Furthermore, among the 59 GPCRs, six GI hormone receptor genes (NPY1R, PPYR1, PTGDR, PTGER2, PTGER3, and SSTR2) that play an inhibitory role in the secretion of gastrin or gastric acid were selected and validated as potential biomarkers for the diagnosis or prognosis of GC patients in two cohorts. These data suggest that the loss of function of gastrointestinal (GI) hormone receptors by promoter methylation may lead to gastric carcinogenesis because gastrin and gastric acid have been known to play a role in cell differentiation and carcinogenesis in the GI tract.

The role of the actin cytoskeleton in the sequence of physiological epithelial repair in the intact epithelium has yet to be elucidated. Here, we explore the role of actin in gastric repair in vivo and in vitro gastric organoids (gastroids). In response to two-photon-induced cellular damage of either an in vivo gastric or in vitro gastroid epithelium, actin redistribution specifically occurred in the lateral membranes of cells neighboring the damaged cell. This was followed by their migration inward to close the gap at the basal pole of the dead cell, in parallel with exfoliation of the dead cell into the lumen. The repair and focal increase of actin was significantly blocked by treatment with EDTA or the inhibition of actin polymerization. Treatment with inhibitors of myosin light chain kinase, myosin II, trefoil factor 2 signaling or phospholipase C slowed both the initial actin redistribution and the repair. While Rac1 inhibition facilitated repair, inhibition of RhoA/Rho-associated protein kinase inhibited it. Inhibitors of focal adhesion kinase and Cdc42 had negligible effects. Hence, initial actin polymerization occurs in the lateral membrane, and is primarily important to initiate dead cell exfoliation and cell migration to close the gap., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Helicobacter pylori (H. pylori) infections are very serious health problem that are further worsened by increasing/developing resistance to the current antibiotics. Therefore, new therapeutic agents are needed for H. pylori eradication. Use of a CD46 derived peptide (P3) as bactericidal agent against H. pylori has shown high activity rate in vivo and this study examines the changes in H. pylori features in response to effect of P3 treatment.AGS cells were infected with H. pylori wild type strain 67:21 and its mice passage strains (P3 treated and untreated strains) and further examined using immunoblotting assay, FACS and Urease activity analysis. Comparatively we found increased level of Urease alpha subunit A (UreA) and alkyl hydroperoxide reductase C (AhpC) proteins for P3 treated strain of H. pylori than its wild type or untreated strain after infection of AGS cells. Conclusion These results suggest that there might be a high rate of adherence to host cells for the P3 treated passage strain than untreated or wild type strain. Our findings also indicate that either adhesins are being changed or H. pylori interaction to the host cells is affected after P3 treatment.

Background: Gastric motility is controlled by the autonomic and enteric nervous systems and by interstitial cells of Cajal (ICCs). Although histamine is known to be released from enterochromaffin-like cells in the gastric mucosa, its regulatory roles in gastric motility are still controversial. Therefore, we investigated the functional roles of histamine in gastric motility., Methods: Stomach preparations from hamsters were used because the stomach of hamsters can be easily separated into the forestomach and the glandular stomach. A whole preparation of the stomach was mounted in a Magnus tube, and mechanical responses were recorded using a force transducer., Key Results: Exogenous application of histamine had little effect on contractile activity of the glandular stomach. In contrast, the monoamine evoked regular, periodic contractions in the forestomach. An H1 receptor agonist reproduced the contractile responses and an H1 receptor antagonist blocked histamine-evoked contractions. Atropine and tetrodotoxin did not affect the histamine-evoked contractions. Pretreatment with drugs that inhibit the activity of ICCs abolished the effects of histamine., Conclusion & Inferences: The findings suggest that histamine regulates gastric motility by acting on ICCs via H1 receptors in the hamster. The remarkable ability of histamine to induce rhythmic contractions would be useful for treatment of gastric dysmotility., (© 2017 John Wiley & Sons Ltd.)

Genetic and epigenetic alterations are both involved in carcinogenesis, and their low-level accumulation in normal tissues constitutes cancer risk. However, their relative importance has never been examined, as measurement of low-level mutations has been difficult. Here, we measured low-level accumulations of genetic and epigenetic alterations in normal tissues with low, intermediate, and high cancer risk and analyzed their relative effects on cancer risk in the esophagus and stomach. Accumulation of genetic alterations, estimated as a frequency of rare base substitution mutations, significantly increased according to cancer risk in esophageal mucosae, but not in gastric mucosae. The mutation patterns reflected the exposure to lifestyle risk factors. In contrast, the accumulation of epigenetic alterations, measured as DNA methylation levels of marker genes, significantly increased according to cancer risk in both tissues. Patients with cancer (high-risk individuals) were precisely discriminated from healthy individuals with exposure to risk factors (intermediate-risk individuals) by a combination of alterations in the esophagus (odds ratio, 18.2; 95% confidence interval, 3.69-89.9) and by only epigenetic alterations in the stomach (odds ratio, 7.67; 95% confidence interval, 2.52-23.3). The relative importance of epigenetic alterations upon genetic alterations was 1.04 in the esophagus and 2.31 in the stomach. The differential impacts among tissues will be critically important for effective cancer prevention and precision cancer risk diagnosis., Competing Interests: Conflict of interest statement: S.Y. and T.U. made a patent application with Sysmex Corporation.

Helicobacter pylori (H. pylori) infection is the major cause for gastritis, peptic ulcer, and gastric cancer. Elevated oxidative stress, mitochondrial dysfunction and apoptotic death of gastric epithelial cells are typical hallmarks of H. pylori infection. Ascorbic Acid 2-Glucoside (AA2G) is a stable version of Vitamin C, that binds glucose to conventional vitamin C. AA2G has free radical scavenging activities and anti-apoptotic abilities. However, the protective effect of AA2G against H. pylori-infection in gastric epithelial cells is yet unknown. In this study, we investigated the effects of AA2G in human H. pylori-infected gastric epithelial cells. AA2G could remarkably ameliorate H. pylori-induced oxidative stress, including the levels of intracellular reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE). Importantly, AA2G treatment also improved mitochondrial function by restoring the level of ATP and mitochondrial membrane potential (MMP). Furthermore, AA2G reduced apoptosis induced by H. pylori through modulation of mitochondria-dependent apoptotic pathways. Our findings suggest that AA2G has a protective effect against H. pylori infection in gastric epithelial cells., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

It is well known that protein ingestion immediately after exercise greatly stimulates muscle protein synthesis during the postexercise recovery phase. However, immediately after strenuous exercise, the gastrointestinal (GI) mucosa is frequently injured by hypoperfusion in the organ/tissue, possibly resulting in impaired GI function (e.g., gastric emptying; GE). The aim of this study was to examine the effect of GI blood flow on the GE rate. Eight healthy young subjects performed an intermittent supramaximal cycling exercise for 30 min, which consisted of a 120% V̇o 2peak for 20 s, followed by 20 W for 40 s. The subjects ingested 300 ml of a nutrient drink containing carbohydrate-protein at either 5 min postexercise in one trial (PE-5) or 30 min postexercise in another trial (PE-30). In the control trial (Con), the subjects ingested the same drink without exercise. The celiac artery blood flow (CABF) and superior mesenteric artery blood flow (SMABF) and GE rate were assessed by ultrasonography. Before drink ingestion in PE-5, CABF significantly decreased from baseline, whereas in PE-30, it returned to baseline. Following drink ingestion in PE-5, CABF did not change from baseline, but it significantly increased in PE-30 and Con. SMABF increased significantly later in PE-5 than in PE-30 and Con. The GE rate was consistently slower in PE-5 than in PE-30 and Con. In conclusion, the CABF response after exercise seems to modulate the subsequent GE rate and SMABF response. NEW & NOTEWORTHY A carbohydrate-protein drink was ingested at either 5 min (i.e., profoundly decreased celiac artery blood flow; CABF) or 30 min (i.e., already recovered CABF) postexercise. In the 5-min postexercise trial, the gastric emptying (GE) rate and superior mesenteric artery blood flow (SMABF) response were slower than those in the 30-min postexercise trial. The GE rate and SMABF response may be altered depending on the postexercise CABF response., (Copyright © 2017 the American Physiological Society.)

Single-cell analysis of heterogeneity has become the cutting-edge technology for profound understandings of relationships between cell populations. At present, common methods used in single cellular genomic research are mainly microfluidic technologies (Fluidigm) or based on microwells, both requiring a uniform size of cells at the entrance. However, the size of cells in specific tissues can vary from type to type. To address this issue, we need to establish a method to identify genomic features of individual cells of different sizes. In this paper, we developed a robust method in the analysis of single cellular genomic mutations among gastric tissues. Briefly, the single gastric gland was isolated from the whole tissue, and further enzymatically digested into single cells of various sizes by trypsin. These single cells were then spread on the polyethylene naphthalene slides and selected by the laser microdissection method. Whole genome amplification (WGA) and capillary electrophoresis were performed subsequently to detect single cell microsatellite. This method enabled us to detect the existence of microsatellite instability (MSI) of each single cell within the intestinal metaplasia, and to carry out a flexible and fine analysis of single cells with different sizes in tissues and glands. This reliable and practical method is well performed in both low and high-throughput genome analysis when combined with cell labeling methods, thus providing a novel and highly flexible way to study tissue heterogeneity on the single cell scale.

The CD44 gene encodes several protein isoforms due to alternative splicing and post translational modifications. Given that CD44 variant isoform 9 (CD44v9) is expressed within Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) glands during repair, CD44v9 may be play a funcitonal role during the process of regeneration of the gastric epithelium. Here we hypothesize that CD44v9 marks a regenerative cell lineage responsive to infiltrating macrophages during regeneration of the gastric epithelium. Ulcers were induced in CD44-deficient (CD44KO) and C57BL/6 (BL6) mice by a localized application of acetic acid to the serosal surface of the stomach. Gastric organoids expressing CD44v9 were derived from mouse stomachs and transplanted at the ulcer site of CD44KO mice. Ulcers, CD44v9 expression, proliferation and histology were measured 1, 3, 5 and 7-days post-injury. Human-derived gastric organoids were generated from stomach tissue collected from elderly (>55 years) or young (14-20 years) patients. Organoids were transplanted into the stomachs of NOD scid gamma (NSG) mice at the site of injury. Gastric injury was induced in NRG-SGM3 (NRGS) mice harboring human-derived immune cells (hnNRGS) and the immune profile anlayzed by CyTOF. CD44v9 expression emerged within regenerating glands the ulcer margin in response to injury. While ulcers in BL6 mice healed within 7-days post-injury, CD44KO mice exhibited loss of repair and epithelial regeneration. Ulcer healing was promoted in CD44KO mice by transplanted CD55v9-expressing gastric organoids. NSG mice exhibited loss of CD44v9 expression and gastric repair. Transplantation of human-derived gastric organoids from young, but not aged stomachs promoted repair in NSG mouse stomachs in response to injury. Finally, compared to NRGS mice, huNRGS animals exhibited reduced ulcer sizes, an infiltration of human CD162+ macrophages and an emergence of CD44v9 expression in SPEM. Thus, during repair of the gastic epithelium CD44v9 emerges within a regenerative cell lineage that coincides with macrophage inflitration within the injured mucosa. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background: Helicobacter pylori (HP) infection induces methylation silencing of specific genes in gastric epithelium. Various stimuli activate the nonselective cation channel TRPV4, which is expressed in gastric epithelium where it detects mechanical stimuli and promotes ATP release. As CpG islands in TRPV4 are methylated in HP-infected gastric epithelium, we evaluated HP infection-dependent changes in TRPV4 expression in gastric epithelium., Materials and Methods: Human gastric biopsy samples, a human gastric cancer cell line (AGS), and a normal gastric epithelial cell line (GES-1) were used to detect TRPV4 mRNA and protein expression by RT-PCR and Western blotting, respectively. Ca 2+ imaging was used to evaluate TRPV4 ion channel activity. TRPV4 methylation status was assessed by methylation-specific PCR (MSP). ATP release was measured by a luciferin-luciferase assay., Results: TRPV4 mRNA and protein were detected in human gastric biopsy samples and in GES-1 cells. MSP and demethylation assays showed TRPV4 methylation silencing in AGS cells. HP coculture directly induced methylation silencing of TRPV4 in GES-1 cells. In human samples, HP infection was associated with TRPV4 methylation silencing that recovered after HP eradication in a time-dependent manner., Conclusion: HP infection-dependent DNA methylation suppressed TRPV4 expression in human gastric epithelia, suggesting that TRPV4 methylation may be involved in HP-associated dyspepsia., (© 2016 The Authors. Helicobacter Published by John Wiley & Sons Ltd.)

The role of bacteria other than Helicobacter pylori (HP) in the stomach remains elusive. We characterized the gastric microbiota in individuals with different histological stages of gastric carcinogenesis and after receiving HP eradication therapy. Endoscopic gastric biopsies were obtained from subjects with HP gastritis, gastric intestinal metaplasia (IM), gastric cancer (GC) and HP negative controls. Gastric microbiota was characterized by Illumina MiSeq platform targeting the 16 S rDNA. Apart from dominant H. pylori, we observed other Proteobacteria including Haemophilus, Serratia, Neisseria and Stenotrophomonas as the major components of the human gastric microbiota. Although samples were largely converged according to the relative abundance of HP, a clear separation of GC and other samples was recovered. Whilst there was a strong inverse association between HP relative abundance and bacterial diversity, this association was weak in GC samples which tended to have lower bacterial diversity compared with other samples with similar HP levels. Eradication of HP resulted in an increase in bacterial diversity and restoration of the relative abundance of other bacteria to levels similar to individuals without HP. In conclusion, HP colonization results in alterations of gastric microbiota and reduction in bacterial diversity, which could be restored by antibiotic treatment.

By virtue of their cardiovascular anatomy, reptiles and amphibians can shunt blood away from the pulmonary or systemic circuits, but the functional role of this characteristic trait remains unclear. It has been suggested that right-to-left (R-L) shunt (recirculation of systemic blood within the body) fuels the gastric mucosa with acidified and CO 2 -rich blood to facilitate gastric acid secretion during digestion. However, in addition to elevating P CO 2 , R-L shunt also reduces arterial O 2 levels and would compromise O 2 delivery during the increased metabolic state of digestion. Conversely, arterial P CO 2  can also be elevated by lowering ventilation relative to metabolism (i.e. reducing the air convection requirement, ACR). Based on a mathematical analysis of the relative roles of ACR and R-L shunt on O 2 and CO 2 levels, we predict that ventilatory modifications are much more effective for gastric CO 2 supply with only modest effects on O 2 delivery. Conversely, elevating CO 2 levels by means of R-L shunt would come at a cost of significant reductions in O 2 levels. The different effects of altering ACR and R-L shunt on O 2 and CO 2 levels are explained by the differences in the effective blood capacitance coefficients., (© 2017. Published by The Company of Biologists Ltd.)

Background: Non-steroidal anti-inflammatory drugs are the oldest and most widely used medicines. However, their untoward effects, especially gastrointestinal toxicity, remain the main obstacle to their application. Because of their mechanism of action, cycloxygenase (COX) inhibition, in combination with the weekly acidic character of most of them, major protective mechanisms of the gastrointestinal system are suppressed and deregulated., Objective: In this review, several compounds designed to retain anti-inflammatory activity, but devoid of gastrointestinal side effects, are presented. Thus, gastro-protective drugs, selective COX-2 inhibitors, nitric monoxide- and hydrogen sulphide-releasing agents, prodrugs, lipoxygenase (LOX) inhibitors and dual COX/LOX inhibitors are presented. Their mechanism of action, as well as their advantages and disadvantages are discussed., Conclusion: Efforts, aiming to the development of safe non-steroidal anti-inflammatory agents, are evolving, however there are still several problems concerning gastro-protection to be efficiently solved, thus, design of effective and safe agents for the treatment of inflammatory conditions still remains a major challenge., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

BACKGROUND The purpose of this study was to determine the effect of mild hypothermia therapy on gastric mucosa after cardiopulmonary resuscitation (CPR) and the underlying mechanism. MATERIAL AND METHODS Ventricular fibrillation was induced in pigs. After CPR, the surviving pigs were divided into mild hypothermia-treated and control groups. The changes in vital signs and hemodynamic parameters were monitored before cardiac arrest and at intervals of 0.5, 1, 2, 4, 6, 12, and 24 h after restoration of spontaneous circulation. Serum IL-6 was determined at the same time, and gastroscopy was performed. The pathologic changes were noted, and the expression of IL-6 was determined by hematoxylin and eosin (HE) staining and immunohistochemistry under light. RESULTS The heart rate, mean arterial blood pressure, and cardiac output in both groups did not differ significantly. The gastric mucosa ulcer index evaluated by gastroscopy 2 h and 24 h after restoration of spontaneous circulation (ROSC) in the mild hypothermic group was lower than that the control group (P<0.05). The inflammatory pathologic score of gastric mucosa in the mild hypothermic group 6-24 h after ROSC was lower than that in the control group (P<0.05). Serum and gastric mucosa IL-6 expression 0.5-4 h and 6, 12, and 24 h after ROSC was lower in the mild hypothermic group than in the control group (P<0.05). CONCLUSIONS Mild hypothermia treatment protects gastric mucosa after ROSC via inhibiting IL-6 production and relieving the inflammatory reaction., Competing Interests: There are no conflict of interests associated with this study.

The chief motor functions of human stomach, namely receiving, storing, mixing and emptying, influence the absorption of ingested food and hence determine the glycemic response to the meal. However, among these functions, the gastric emptying pattern of the stomach is essentially regulated by the meal characteristics such as particle size, volume, nutrient composition and viscosity. Understanding the complex relationship between the stomach motor functions and the physicochemical characteristics of meal on glycemic control needs more attention in the formulation of functional foods. Hence, the objective of this study is to employ the magnetic resonance imaging (MRI) technique in ten healthy human volunteers to elucidate the relationship between the motor functions of the stomach and the glycemic response to fibre rich foods. For this, wheat and oat based breakfast meals were selected as fibre rich foods with low (0.042 Pa s) and high (0.266 Pa s) viscosity, respectively. Although wheat meal had a lower viscosity compared to oatmeal, the gastric emptying was found to be delayed for the former due to its high caloric density. This was reflected in the glycemic response as well, with wheat meal having a lower area under the curve (AUC) value than oatmeal. The antral contraction frequency is significantly reduced (P < 0.05) with delayed gastric emptying in the case of high nutrient wheat meal. Overall, the study demonstrated the synergistic effect of gastric emptying, stomach motor functions and physicochemical characteristics of food on the glycemic response to a meal. This information will aid in the development of functional foods with specific end applications.

Ezrin, an adaptor protein that cross-links plasma membrane-associated proteins with the actin cytoskeleton, is concentrated on apical surfaces of epithelial cells, especially in microvilli of the small intestine and stomach. In the stomach, ezrin is predominantly expressed on the apical canalicular membrane of parietal cells. Transgenic ezrin knockdown mice in which the expression level of ezrin was reduced to <7% compared with the wild-type suffered from achlorhydria because of impairment of membrane fusion between tubulovesicles and apical membranes. We observed, for the first time, hypergastrinemia and foveolar hyperplasia in the gastric fundic region of the knockdown mice. Dilation of fundic glands was observed, the percentage of parietal and chief cells was reduced, and that of mucous-secreting cells was increased. The parietal cells of knockdown mice contained dilated tubulovesicles and abnormal mitochondria, and subsets of these cells contained abnormal vacuoles and multilamellar structures. Therefore, lack of ezrin not only causes achlorhydria and hypergastrinemia but also changes the structure of gastric glands, with severe perturbation of the secretory membranes of parietal cells.

The objective of this trial was to study the influence of dietary fiber sources on the gastrointestinal fermentation, digestive enzyme activity, and mucosa morphology of growing Greylag geese. In total, 240 Greylag geese (28-day-old) were allocated to 4 treatments (15 pens/treatment) differing in dietary fiber source: corn straw silage (CSS group), steam-exploded corn straw (SECS group), steam-exploded wheat straw (SEWS group), or steam-exploded rice straw (SERS group). At 112 days of age, 15 birds per group were euthanized to collect samples. No difference (P > 0.05) was found on all the gastrointestinal pH values and ammonia-nitrogen concentrations between the groups. The CSS and SERS groups had a lower (P < 0.05) proportion of acetic acid in the gizzard than the SECS and SEWS groups. The CSS group had a higher VFA concentration in the jejunum (P < 0.05) and acetic acid proportion (P < 0.01) in the ceca, and a lower (P < 0.01) butyric acid proportion than the other groups except for the SECS group. The SECS group had a higher (P < 0.01) acetic acid proportion and lower (P < 0.05) proportions of propionic acid and valeric acid in the ceca than the SEWS and SERS groups. Different fiber sources resulted in different VFA profiles, especially in the gizzard and ceca. Almost all gastrointestinal protease activities of the CSS group were higher (P < 0.05) than the other groups, along with lower (P < 0.01) amylase activities in the duodenum, jejunum, ileum, and ceca. Lipase activity in proventriculus was highest (P < 0.01) in the SEWS group and its cecal activity was lower (P < 0.01) in the SECS and SEWS groups than the CSS and SERS groups with a higher (P < 0.01) lipase activity in the CSS group than the SERS group. The SECS and SERS groups had a higher cellulase activity in the ceca than the CSS and SEWS groups, with a higher (P < 0.01) rectal cellulase activity in the SERS group than the other groups. There was no significant effect (P > 0.05) on the intestinal mucosa morphology. These results suggest that corn straw silage improves protein digestion while steam-exploded straw provides more energy., (© 2015 Poultry Science Association Inc.)

Objective: To explore the ettect and mechanisms of bone marrow mesenchymal stem cells (BMSCs) on healing quality of acetic acid-induced gastric ulcer., Methods: Forty-eight clean grade male Wistar rats were used to establish the model of gastric ulcer with acetic acid and were randomly divided into 3 groups after 3 days of modeling, 16 rats each group. After the abdominal cavity was open and stomach was pulled out, no treatment was given in group A, 150 µL phosphate buffered saline (PBS) and 150 µL BMSCs at passage 4+PBS (1 x 10(8) cells/100 µL) were injected into the gastric wall surrounding the ulcer at 5 different points in groups B and C respectively. After 10 days, the ulcer area was measured, the mucosal thickness and the number of dilated glands were tested in the regenerative mucosa by histological method. And the expression of vascular endothelial growth factor (VEGF) was detected at ulcerative margin by immunohistochemical method., Results: The ulcer area in group C was significantly smaller than that of groups A and B (P < 0.01), but no significant difference was found between groups A and B (P > 0.05). HE staining showed that group C had thicker regenerative gastric mucosa, less dilated glands, and more regular mucosal structure than groups A and B, showing significant differences in regenerative gastric mucosa thickness and dilated glands number (P < 0.01), but no significant difference between groups A and B (P > 0.05). Immunohistochemical staining showed that the positive expression of VEGF in the ulcer margin mucosa of group C was significantly higher than that of groups A and B. The integral absorbance (IA) value of VEGF expression in group C was significantly higher than that in groups A and B (P < 0.01), but no significant difference between groups A and B (P > 0.05)., Conclusion: BMSCs can accelerate ulcer healing by the secretion of VEGF, and improve the quality of ulcer healing.

Electrotaxis, directional cell movement in response to an electric potential, has been demonstrated in a wide range of cell types including lymphocytes. Exoelectrogens, microorganisms capable of generating electrical currents, have been identified in microbial fuel cells. However, no studies have investigated exoelectrogenic microbes in fresh feces or the effects of an exoelectrogenic microbiota on the host organism. Here we show that commensal gut microbial populations differ in their capacity for electrical current production by exoelectrogens and that those differences are predictive of increased lymphocyte trafficking to the gut in vivo, despite the lack of increased production of canonical lymphocyte-specific chemokines. Additionally, we demonstrate that the difference in current production between mice purchased from different commercial sources correlates reproducibly with the presence or absence of segmented filamentous bacteria, and while our data do not support a direct role for segmented filamentous bacteria in ex vivo current production, an exoelectrogenic microbiota can be transferred in vivo via mucosa-associated bacteria present in the ileum. Moreover, we detect upregulation of microbial genes associated with extracellular electron transfer in feces of mice colonized with exoelectrogenic microbiota containing segmented filamentous bacteria. While still correlative, these results suggest a novel means by which the gut microbiota modulates the recruitment of cells of the immune system to the gut., (Copyright © 2015 the American Physiological Society.)

A specific device and system has been developed and tested for clinical monitoring of gastric mucosal reactance in the critically ill as an early warning of splanchnic hypoperfusion associated with shock and sepsis. This device has been proven effective in clinical trials and is expected to become commercially available next year. The system uses a combination nasogastric tube and impedance spectroscopy probe as a single catheter. Because this device has a double function, the question is: Does enteral feeding or suction affect the gastric reactance measurements? This study was designed to evaluate the effect of feeding and suction on the measurement of gastric impedance spectroscopy in healthy volunteers. Impedance spectra were obtained from the gastric wall epithelia of 18 subjects. The spectra were measured for each of the following conditions: postinsertion of gastric probe, during active suction, postactive suction, and during enteral feeding (236 ml of nutritional supplement). Impedance spectra were reproducible in all volunteers under all conditions tested. There was a slight increase in impedance parameters after suction, and a decrease in impedance after feeding; however, these observed differences were insignificant compared to patient-to-patient variability, and truly negligible compared with previously observed changes associated with splanchnic ischemia in critically ill patients. Our results demonstrate that suction or feeding when using the impedance spectro-metry probe/nasogastric tube does not significantly interfere with gastric impedance spectrometer measurements.

The structural and functional integrity of the gastric and duodenal mucosa represents equilibrium between aggressive factors and protective mechanisms. Mucus-buffers-phospholipid layer as pre-epithelial barrier, enhanced by prostaglandins and epidermal growth factor, remains a vanguard of mucosal protection. It maintains a neutral pH at the surface epithelial luminal interface, facing luminal pH dropping to 1.0, i.e., hydrogen ion concentration gradient equal 1,000,000. The surface epithelial cells, elaborating mucins, buffers, phospholipids, prostaglandins, trefoil peptides, peptide growth factor and their receptors, heat shock proteins, cathelicidins, and β-defensins form the second line of defense. Endothelium exerts mucosal protection through production of potent vasodilators like nitric oxide and prostacyclins and through release of angiogenic growth factors, securing adequate blood flow and representing the third and an ultimate line of mucosal protection. This microcirculation is instrumental for supply of oxygen, nitric oxide, hydrogen sulfide and removal of ad hoc generated toxic substances as well as for continuous mucosal cell renewal from progenitor cells, secured by growth factors accompanied by survivin preventing early apoptosis.

Aims and Methods: Heat shock protein A4 (HSPA4, also called Apg-2), a member of the HSP110 family, regulates the immune response in the gut. Here, we assessed the involvement of HSPA4 in gastric ulcer healing by using fibroblasts from wild-type and HSPA4-deficient mice, a murine gastric ulcer model, and samples from 65 patients with gastric cancer., Results: HSPA4 expression was inversely correlated with gastric ulcer healing following endoscopic resection of gastric cancer. In the human gastric mucosa, the expression of HSPA4 was inversely correlated with the expression of stromal cell-derived factor 1 (SDF-1), its cognate receptor CXC chemokine receptor 4 (CXCR4), the stromal cell marker vimentin, and the epithelial-mesenchymal transition regulator Twist. HSPA4 was overexpressed in stromal cells as well as in human gastric cancer cells. HSPA4 deficiency increased the expression of SDF-1 and CXCR4, as well as the number of fibroblast-specific protein 1-positive cells, leading to accelerated ulcer healing in the murine gastric ulcer model. Deletion of HSPA4 promoted cell migration in mouse fibroblasts through increased expression of SDF-1 and Twist., Conclusion: HSPA4 regulates the expression of SDF-1 and Twist in fibroblasts, thereby controlling gastric ulcer healing.

The aim of the present study was to describe age-related changes in anatomic, functional and microbial variables during the rumen development process, as affected by the feeding system (supplemental feeding v. grazing), in goats. Goats were slaughtered at seven time points that were selected to reflect the non-rumination (0, 7 and 14 d), transition (28 and 42 d) and rumination (56 and 70 d) phases of rumen development. Total volatile fatty acid (TVFA) concentration (P= 0·002), liquid-associated bacterial and archaeal copy numbers (P< 0·01) were greater for supplemental feeding v. grazing, while rumen pH (P< 0·001), acetate molar proportion (P= 0·003) and solid-associated microbial copy numbers (P< 0·05) were less. Rumen papillae length (P= 0·097) and extracellular (P= 0·093) and total (P= 0·073) protease activity potentials in supplemented goats tended to be greater than those in grazing goats. Furthermore, from 0 to 70 d, irrespective of the feeding system, rumen weight, rumen wall thickness, rumen papillae length and area, TVFA concentration, xylanase, carboxymethylcellulase activity potentials, and microbial copy numbers increased (P< 0·01) with age, while the greatest amylase and protease activity potentials occurred at 28 d. Most anatomic and functional variables evolved progressively from 14 to 42 d, while microbial colonisation was fastest from birth to 28 d. These outcomes suggest that the supplemental feeding system is more effective in promoting rumen development than the grazing system; in addition, for both the feeding systems, microbial colonisation in the rumen is achieved at 1 month, functional achievement at 2 months, and anatomic development after 2 months.

In this article, the tensile properties of gastric wall were investigated by using biomechanical test and theoretical analysis. The samples of porcine stomach strips from smaller and greater curvature of the stomach were cut in longitudinal and circumferential direction, respectively. The loading-unloading, stress relaxation, strain creep, tensile fracture tests were performed at mucosa-submucosa, serosa-muscle and intact layer, respectively. Results showed that the biomechanical properties of the porcine stomach depended on the layers, orientations and locations of the gastric wall and presented typical viscoelastic, nonlinear and anisotropic mechanical properties. During loading-unloading test, the stress of serosa-muscle layer in the longitudinal direction was 15-20% more than that in the circumferential direction at 12% stretch ratio, while it could reach about 40% for the intact layer and 50% for the mucosa-submucosa layer. The results of stress relaxation and strain creep showed that the variation degree was obviously faster in the circumferential direction than that in the longitudinal direction, and the ultimate residual values were also different for the different layers, orientations and locations. In the process of fracture test, the serosa-muscle layer fractured firstly followed by the mucosa-submucosa layer when the intact layer was tested, the longitudinal strips firstly began to fracture and the required stress value was about twice as much as that in the circumferential strips. The anisotropy and heterogeneity of mechanical characterization of the porcine stomach were related to its complicated geometry, structure and functions. The results would help us to understand the biomechanics of soft organ tissue., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Gut barrier is a functional unit organized as a multi-layer system and its multiple functions are crucial for maintaining gut homeostasis. Numerous scientific evidences showed a significant association between gut barrier leaking and gastro-intestinal/extra-intestinal diseases., Materials and Methods: In this review we focus on the relationship between gut barrier leaking and human health. At the same time we speculate on the possible new role of gut barrier protectors in enhancing and restoring gut barrier physiology with the final goal of promoting gut health., Results: The alteration of the equilibrium in gut barrier leads to the passage of the luminal contents to the underlying tissues and thus into the bloodstream, resulting in the activation of the immune response and in the induction of gut inflammation. This permeability alteration is the basis for the pathogenesis of many diseases, including infectious enterocolitis, inflammatory bowel diseases, irritable bowel syndrome, small intestinal bacterial overgrowth, celiac disease, hepatic fibrosis, food intolerances and also atopic manifestations. Many drugs or compounds used in the treatment of gastrointestinal disease are able to alter the permeability of the intestinal barrier. Recent data highlighted and introduced the possibility of using gelatin tannate, a mucosal barrier protector, for an innovative approach in the management of intestinal diseases, allowing an original therapeutic orientation with the aim of enhancing mucus barrier activity and restoring gut barrier., Conclusions: These results suggest how the mucus layer recovering, beside the gut microbiota modulation, exerted by gut barrier protectors could be a useful weapon to re-establish the physiological intestinal homeostasis after an acute and chronic injury.

Various types of neurons exhibit subthreshold resonance oscillation (preferred frequency response) to fluctuating sinusoidal input currents. This phenomenon is well known to influence the synaptic plasticity and frequency of neural network oscillation. This study evaluates the resonant properties of pacemaker pyloric dilator (PD) neurons in the central pattern generator network through mathematical modeling. From the pharmacological point of view, calcium currents cannot be blocked in PD neurons without removing the calcium-dependent potassium current. Thus, the effects of calcium (I(Ca)) and calcium-dependent potassium (I(KCa)) currents on resonant properties remain unclear. By taking advantage of Hodgkin-Huxley-type model of neuron and its equivalent RLC circuit, we examine the effects of changing resting membrane potential and those ionic currents on the resonance. Results show that changing the resting membrane potential influences the amplitude and frequency of resonance so that the strength of resonance (Q-value) increases by both depolarization and hyperpolarization of the resting membrane potential. Moreover, hyperpolarization-activated inward current (I(h)) and I(Ca) (in association with I(KCa)) are dominant factors on resonant properties at hyperpolarized and depolarized potentials, respectively. Through mathematical analysis, results indicate that I h and I(KCa) affect the resonant properties of PD neurons. However, I(Ca) only has an amplifying effect on the resonance amplitude of these neurons.

Angiotensin II, the main effector of the renin-angiotensin system (RAS), is generated from the precursor angiotensinogen by the actions of renin, angiotensin-converting enzyme, chymase and various peptidases. RAS is essential in the control of blood pressure and body fluid homeostasis but their involvement in the mechanism of the protection of gastric mucosa has not been extensively studied. On the other hand, angiotensin-(1-7) which acts on the Mas receptor, exhibits a potent vasodilatory activity and attenuates the gastric lesions induced by various ulcerogens. In this review, the mechanism of RAS, the antagonists of angiotensin AT1 and AT2 receptors and angiotensin-(1-7) in formation of gastric damage is discussed with possible translating relevance to treatment modalities in the protection against gastric mucosal injury., (Copyright © 2014. Published by Elsevier Ltd.)

Angiogenesis (also referred to as neovascularization-formation of new blood vessels from existing vessels) is a fundamental process essential for healing of tissue injury and ulcers because regeneration of blood microvessels is a critical requirement for oxygen and nutrient delivery to the healing site. This review article updates the current views on angiogenesis in gastric mucosa following injury and during ulcer healing, its sequential events, the underlying mechanisms, and the impairment of angiogenesis in aging gastric mucosa. We focus on the time sequence and ultrastructural features of angiogenesis, hypoxia as a trigger, role of vascular endothelial growth factor signaling (VEGF), serum response factor, Cox2 and prostaglandins, nitric oxide, and importin. Recent reports indicate that gastric mucosa of aging humans and experimental animals exhibits increased susceptibility to injury and delayed healing. Gastric mucosa of aging rats has increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin, and other non-steroidal anti-inflammatory drugs because of structural and functional abnormalities including: reduced gastric mucosal blood flow, hypoxia, reduced expression of vascular endothelial growth factor and survivin, and increased expression of early growth response protein 1 (egr-1) and phosphatase and tensin homolog (PTEN). Until recently, postnatal neovascularization was assumed to occur solely through angiogenesis sprouting of endothelial cells and formation of new blood vessels from pre-existing blood vessels. New studies in the last decade have challenged this paradigm and indicate that in some tissues, including gastric mucosa, the homing of bone marrow-derived endothelial progenitor cells to the site of injury can also contribute to neovascularization by a process termed vasculogenesis., (© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)