Number Of Parietal Cells Research Articles

Impact of Autoimmune Gastritis on Occurrence of Metachronous Gastric Neoplasms after Endoscopic Resection for Gastric Neoplasms.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Autoimmune gastritis (AIG) is characterized by antibody production against the gastric parietal cells, reducing the number of functional parietal cells. It is also associated with an increased susceptibility to gastric neuroendocrine tumors and gastric cancer. Endoscopic resection (ER) is an effective treatment for early gastric cancer; however, metachronous gastric neoplasms (MGN) can develop. This study aimed to evaluate the clinical effect of AIG on the occurrence of MGN after ER for gastric neoplasms. We retrospectively analyzed patients who underwent ER for gastric neoplasms. Patients with multiple lesions, recurrent lesions, or a history of partial gastrectomy were excluded. The presence of AIG was determined using anti-parietal cell antibody (APCA) testing. Follow-up endoscopy and metachronous tumor occurrence rates were compared between the AIG and non-AIG groups. Of the 569 patients, 282 underwent APCA testing and 20 (7.1%) were diagnosed with AIG. The incidence of MGN was significantly higher in the AIG group than in the non-AIG group (45.0% vs. 18.3%); however, the MGN occurrence pattern was similar between the two groups. Multivariate analysis revealed that AIG (HR 3.32, 95% CI 1.55-7.10, p = 0.002) and a higher body mass index (HR 1.16, 95% CI 1.06-1.27, p = 0.002) were independent factors significantly associated with the occurrence of MGN. Patients with AIG have a higher risk of metachronous lesion occurrence after ER for gastric neoplasms. Positive results of APCA testing have independent clinical implications for predicting MGN. Proper monitoring and management are essential for early detection and treatment of recurrent lesions in patients with AIG.

The effects of curcumin and sertraline on stress-induced changes in the stomach tissues of rats.

Exposure to stressors can cause functional disorders and structural damage to the stomach. Sertraline (SER) is an antidepressant and curcumin (CUR) is a natural compound with many properties. The current study aimed to investigate the impacts of stress, SER, and CUR on the stomach tissue using stereological methods. In total, 24 male and 24 female Sprague-Dawley rats were divided into four groups. In the control group, the rats were not exposed to stress. However, the animals in stress, SER and, CUR groups were exposed to daily stress and were orally fed with distilled water, SER (10mg/kg/day), and CUR (100mg/kg/day), respectively. The volume, surface area, and number of nerve, parietal, and chief cells were evaluated by stereological methods. Results showed that stress increased the stomach and its mucosa and submucosa volumes, while it decreased the surface area of the mucosa. Furthermore, this disorder increased the number of neurons in the submucosa and myenteric plexuses while it decreased the number of parietal and chief cells. However, treating stressed rats with SER or CUR could prevent these changes. The results showed that the consumption of SER or CUR could be used as a preventive or adjunctive treatment for stressful situations.

Repair stimulator alpha-glutamyl-tryptophan in the complex therapy of chronic atrophic gastritis: results of histological examination

To study the effect of the repair stimulator alpha-glutamyl-tryptophan on the morphological characteristics of the gastric mucosa and the expression of CXCL-12 and CDX-2 in chronic atrophic gastritis associated with Helicobacter pylori. Biopsy samples of 116 patients with a verified diagnosis of chronic atrophic gastritis associated with Helicobacter pylori were analyzed in a multicenter double-blind randomized placebo-controlled study. During the morphological study, the parameters characterizing the process of atrophy were evaluated: the number of glands per 1 mm2 of the gastric mucosa, the depth of the gastric mucosa glands, the number of parietal cells per 100 epithelial cells of the gastric mucosa, and the presence of signs of intestinal metaplasia. Primary antibodies Anti-CXCL-12 (MA5-23759) and Anti-CDX-2 (EP25) were used to set up immunohistochemical reactions to verify the expression of CXCL-12 and CDX-2. In patients taking the studied drug, a statistically significant increase in the number of glands per 1 mm2 of the gastric mucosa was revealed when compared with the initial screening indicators by 26.1% (p=0.028) and with the placebo group (p=0.026), a tendency to decrease the signs of intestinal metaplasia was determined. There was a statistically significant increase in the expression in the relative area of CXCL-12 expression in patients taking placebo when compared with the parameters of the initial data (p=0.045) and the absence of statistically significant changes in the main group. A statistically significant increase in the relative area of the CDX-2 expression was revealed in the group taking alpha-glutamyl-tryptophan in comparison with the baseline data (p=0.015), no statistically significant dynamics of this indicator was found in the placebo group. A statistically significant positive effect of the study drug on regenerative mechanisms leading to stabilization and/or improvement of the histological picture in the atrophic area of the gastric mucosa was found in comparison with the control of the initial state and with placebo. The results of an immunohistochemical study to increase CDX-2 expression while taking the study drug can also be regarded as an indicator of improvement in reparative processes.

Plant-Based Meat Analogues Weaken Gastrointestinal Digestive Function and Show Less Digestibility Than Real Meat in Mice.

Real meat and plant-based meat analogues have different in vitro protein digestibility properties. This study aims to further explore their in vivo digestion and absorption and their effects on the gastrointestinal digestive function of mice. Compared with the real pork and beef, plant-based meat analogues significantly reduced the number of gastric parietal cells, the levels of gastrin/CCKBR, acetylcholine/AchR, Ca2+, CAMK II, PKC, and PKA, the activity of H+, K+-ATPase, and pepsin, the duodenal villus height, and the ratio of villus height to crypt depth and downregulated the expression of most nitrogen nutrient sensors. Peptidomics revealed that plant-based meat analogues released fewer peptides during in vivo digestion and increased the host- and microbial-derived peptides. Moreover, the real beef showed better absorption properties. These results suggested that plant-based meat analogues weaken gastrointestinal digestive function of mice, and their digestion and absorption performance in vivo is not as good as the real meat.

Cellular composition of gastric glands in chronic gastritis among children

Objective. To establish the features of the cellular composition of gastric mucosa glands in chronic Hp-associated gastritis among children to improve its diagnostics. Material and methods. Morphometric analysis of fundal and pyloric gland cell populations was performed in 214 children aged 615 years with Hp-associated chronic gastritis. For this purpose, the number of main, parietal, endocrine and additional cells was calculated in the materials of gastrobiopsy of the gastric mucosa, the result was expressed in (per 1000 epithelial cells). Results. It was found that as the severity of inflammation in the fundal glands increases, the number of main cells decreases, the number of parietal, accessory and especially endocrine cells grows. In the pyloric glands, a reduction of the parietal pool, a decrease in the population of additional cells and a sharp increase in endocrinocytes is registered. With a decrease in the severity of inflammation, positive changes in the cellular composition of the glands are observed, but its full normalization does not occur 6 months after the course of antihelicobacter therapy. A significant proportion of patients, shows morphological signs of gastric mucosa atrophy, which is associated with inflammation and is uncertain. Its presence does not significantly affect the cellular composition of the gastric glands, and the regression of the inflammatory process is accompanied by a decrease in the degree of atrophy or complete disappearance of signs of the latter. Conclusions. The addition of a standard study of gastrobioptates with a quantitative morphometric analysis of the cellular composition of the fundal and pyloric glands in chronic gastritis among children objectifies the data of morphological assessment of pathohistological picture of gastric mucosa.

FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell Distribution.

BACKGROUND AND AIMS:Stomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdxl over-expression. Enteroendocrine cells can be similarly made to produce insulin by the deletion of FOXO1. Characteristics and functional properties of FOXO1-expressing stomach cells are not known.METHODS:Using mice bearing a FOXO1-GFP knock-in allele and primary cell cultures, we examined the identity of FOXO1-expressing stomach cells and analyzed their features through loss-of-function studies with red-to-green fluorescent reporters.RESULTS:FOXO1 localizes to a subset of Neurog3 and parietal cells. FOXO1 deletion ex vivo or in vivo using Neurog3-cre or Atp4b-cre increased numbers of parietal cells, generated insulin- and C-peptide-immunoreactive cells, and raised Neurog3 messenger RNA. Gene expression and ChIP- seq experiments identified the cell cycle regulator cyclin E1 (CCNE1) as a FOXO1 target.CONCLUSION:FOXO1 is expressed in a subset of stomach cells. Its ablation increases parietal cells and yields insulin-immunoreactive cells, consistent with a role in lineage determination.

Protective Effect of Prunus Dulcis Against Acetylsalicylic Acid Injury on Gastric Parietal Cells

Background: Acetylsalicylic acid is in common clinical use but has the side effect of causing gastric mucosal erosions and selective injury to parietal cells. Aim: To explore if prior treatment with Prunus dulcis (almond) had a protective effect against acetylsalicylic acid induced injury. Study design: Experimental study. Methodology: Albino mice weighing 30 to 40 grams were given two drops of almond oil without peel and 300 mg of finely ground whole almond kernel by oral gavage for sixty days followed by 400 mg/kg body weight of acetylsalicylic acid orally. Gastric mucosal damage was observed and recorded as ulcer index. The number of parietal cells/ sq. micrometer and area of parietal cells were observed and recorded under microscope in formalin fixed H and E stained sections. Data analyzed by SPSS 22.0v. Results: Mucosal damage, distortion of gastric glands and damage to parietal cells was pronounced in the positive control animals. The number of surviving parietal cells after acetylsalicylic acid insult in animals given almond oil was significantly higher when compared with positive control animals (p<0.001) and even better in animals receiving whole ground almond kernel. The area of parietal cells was also similarly larger in the treated animals. Conclusion: This study concluded Prunus dulcis offers protection against acute gastric mucosal injury and damage to the gastric parietal cells caused by acetylsalicylic acid in mice. Keywords: Prunus Dulcis, Parietal Cells, Gastric Erosions and Acetylsalicylic Acid.

Castrated autoimmune glomerulonephritis mouse model shows attenuated glomerular sclerosis with altered parietal epithelial cell phenotype.

Sex hormones help in maintaining proper immunity as well as renal homeostasis in mammals, and these multi-functional properties characterize the onset of sex-dependent diseases. To clarify the contribution of sex hormones to autoimmune disease-related renal pathogenesis, BXSB/MpJ-Yaa was investigated as a murine autoimmune glomerulonephritis model. BXSB/MpJ-Yaa and its wild-type, BXSB/MpJ-Yaa+ were castrated or sham-operated at three weeks and examined until six months of age. Both castrated strains showed significantly lower serum testosterone levels and body weights than sham-operated mice. Castration did not change the disease phenotypes in BXSB/MpJ-Yaa+. At three months, both sham-operated and castrated BXSB/MpJ-Yaa manifested splenomegaly, autoantibody production, and glomerulonephritis, and castrated BXSB/MpJ-Yaa tended to show heavier spleen weights than the sham-operated group. At six months, both the treated BXSB/MpJ-Yaa showed equivalent autoimmune disease conditions; however, castrated mice clearly showed milder glomerular sclerotic lesions than the sham-operated groups. Urinary albumin excretion in castrated BXSB/MpJ-Yaa was significantly milder than in sham-operated mice at four months, but those of both the treated BXSB/MpJ-Yaa were comparable at six months. The examined renal histopathological indices in parietal epithelial cells were remarkably altered by castration. Briefly, castration decreased the height of parietal epithelial cells and total parietal epithelial cell number in BXSB/MpJ-Yaa at six months. For immunostaining, parietal epithelial cells facing the injured glomeruli of BXSB/MpJ-Yaa expressed CD44, an activated parietal epithelial cell marker, and CD44-positive parietal epithelial cells showed nuclear localization of the androgen receptor and proliferation marker Ki67. CD44- or Ki67-positive parietal epithelial cells were significantly fewer in castrated group than in sham-operated BXSB/MpJ-Yaa at six months. Further, quantitative indices for CD44-positive parietal epithelial cell number and frequency in renal corpuscles positively correlated with glomerular sclerotic severity in BXSB/MpJ-Yaa. In conclusion, androgen seemed to have an effect on both systemic immunity and renal morpho-function; however, the effect on the latter could be more clearly observed in BXSB/MpJ-Yaa, as parietal epithelial cell activation resulted in glomerular sclerosis.

Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis- and autophagy-associated molecules.

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.

Increased expression of hypoxia inducible factor-1 alpha and vascular endothelial growth factor is associated with diabetic gastroparesis

BackgroundGastroparesis is a recognized complication of diabetes but its pathogenic mechanism incompletely understood. Our aim was to determine whether HIF-1α and VEGF are secreted from gastric tissue is a fundamental factor that drives diabetic gastroparesis.MethodsDiabetes was induced in Sprague-Dawley by a single intraperitoneal injection of 65 mg/kg streptozotocin. After 4 and 12 weeks, rats were euthanized for assaying body weight, blood glucose, gastric acid secretion and gastric emptying. Morphologic changes in gastric mucosa were observed by the light microscope. Expression of HIF-1α and VEGF were assessed using immunohistochemistry, RT-PCR and Western blot analyses.ResultsCompared with control group, blood glucose were significantly increased and body weight were markedly decreased in streptozotocin-induced diabetes. Gastric emptying was significantly decreased in diabetic rats compared to the control group at different times. The number of parietal cells was obviously decreased, and vacuolated degeneration in diabetic rats. Gastric acid secretion in diabetic group was significantly decreased, and expression of HIF-1α and VEGF were significantly increased in the diabetic group.ConclusionThese results indicated that overexpression of HIF-1α and VEGF in the gastric mucosa and played a pivotal role in the progression of diabetic gastroparesis.

Light and Electron Microscopic Studies on the Possible Protective Effect of Ginger on the Gastric Fundic Mucosa of Adult Male Albino Rats Treated with 5- Fluorouracil

Introduction: 5-fluorouracil is a potent antimetabolite chemotherapeutic medication used for treatment of various malignancies . Using this agent result in toxic effect mainly in the lining of digestive tract. To ameliorate 5 FU toxic effect ginger was implicated in this study.Aim of the Work: To evaluate the microscopic effect of 5-fluorouracil on gastric fundus mucosa in rat models . and to study the possible beneficial role of ginger in the ameliorations of these changes. Material and Methods: Forty-eight adult male albino rates were divided into four groups: group I (control), group II received ginger orally in a dose of 200 mg/kg/day , group III received 5-fluorouracil (15 mg/kg) intraperitoneally and group IV received 5 FU and Ginger as previous doses for 5 days. The fundic part of stomach was excised and subjected to light and electron microscopic studies.Results: In 5 FU treated group, the fundic gastric mucosa showed multiple areas of tissue loss , congested dilated blood vessels and extravasated red blood cells and mononuclear infiltration were seen between fundic gland cells. Parietal cells showed ballooned appearance, vacuolated cytoplasm, and pykontic nuclei. PAS/ Alcian blue stained sections showed marked reduction in both alcian blue and PAS positive reaction. There was strong positive cytoplasmic reaction in the apical and middle parts of the fundic glands for caspase 3 while large number of parietal cells were stained positive for Cox 2. These histological findings were improved after ginger administration. Histomorphometric study revealed significant weight reduction, increased mucosal ulcer depth, decreased mucosal thickness and increased number of parietal cells in 5 FU treated group when compared to control group. Conclusion: 5FU causes gastric damage in rat model. Ginger supplementation could be used to alleviate the damaging pathological effect on gastric fundus.

Gastrointestinal risk factors for anemia in children with celiac disease

With oral intake, iron absorption in patients with celiac disease (CD) is reduced due to the decreased absorption surface of the atrophic small intestine mucous membrane. Besides, there are additional risk factors for anemia whose mechanisms are unclear.The aimof this study was to evaluate gastrointestinal risk factors for anemia in children.
 Materialsand methods.The first group consisted of 58 children with newly diagnosed CD who did not adhere to the gluten-free diet(GFD). The second group included 49 children with CD who hasnt been adhering to the GFD. The third group included 69children with chronic gastritis (CG) without CD. In addition to the standard examination, which includes the determination of antibodies to tissue transglutaminase and histological examination of the duodenum mucous membrane, a histological evaluation of the gastric mucosa, determination of pepsinogen 1 and 2 and their ratio, antibodies to Castles intrinsic factor were performed.
 Results.The mean level of hemoglobin in the group 1114,71120,10125,50g/l, in the group 2124,37128,74133,10g/l, in the group 3130,12133,78137,43g/l (p1,2=0.013;p1,3=0,000;p2,3=0.083). A correlation analysis of the hemoglobin level and morphological parameters of the duodenal mucosa among the studied patients revealed an inverse moderate correlation between the hemoglobin level and the degree of the small intestinal atrophy according to Marshr=0.331,p=0,000, crypt depthr=0,439,p=0,000, and a moderate direct with the ratio of villi:cryptr=0.417,p=0.000, with the height of the villir=0.366,p=0,000. Additionally, a moderate direct correlation between the level of hemoglobin and the number of parietal cells was found to ber=0.354,p=0.037. In group 1, a significant inverse correlation between the level of hemoglobin and the level of antibodies to Castles factorr=0.529,p=0.006, was obtained for the level of antibodies in the Castles factor.
 Conclusion.Autoimmune gastritis may be an additional risk factor in combination with malabsorption, as a possible cause of anemia in children with CD.

Glomeruli from patients with nephrin mutations show increased number of ciliated and poorly differentiated podocytes

BackgroundPodocytes are postmitotic, highly specialized cells which maintain the glomerular filtration barrier (GFB). Their injury is characterized by foot processes effacement and change in protein expression leading to proteinuria and end-stage kidney disease. MethodsOur study focuses on the morphological and immunohistochemical changes of human podocytes during normal development and postnatal period, compared to congenital nephrotic syndrome of the Finnish type (CNF). Kidney tissues taken from 17 human conceptuses 8th–38th weeks old, two healthy and three CNF kidneys were embedded in paraffin for immunohistochemical or double immunofluorescence methods, or were embedded in resin for electron microscopy. Paraffin sections were stained with markers for proliferation (Ki-67), proteins nephrin and nestin, and alpha-tubulin. Quantification of positive cells were performed using Mann Whitney and Kruskal–Wallis test. ResultsTissue analysis showed that proliferation of podocytes gradually decreased during development and disappeared in postnatal period. Decrease in number of ciliated glomerular cells and visceral podocytes (from 47% to 3%), and parietal epithelial cells (from 32% to 7%) characterized normal development. Nestin and nephrin co-expressed in developing podocytes in different cellular compartments. During development, nephrin expression increased (from 17% to 75%) and postnatally changed its pattern, while nestin positive glomerular cells decreased from 98% to 40%. CNF glomeruli displayed increased number of immature ciliated podocytes (6%) and parietal epithelial cells (9%). ConclusionChanges in cytoplasmic alpha-tubulin expression and reduced nephrin expression (20%) indicating association of incomplete podocyte maturation with failure of GFB function and appearance of prenatal proteinuria in CNF patients.

Abstract A34: EGF receptor-activated Notch signaling contributes to pathogenesis of premalignant gastric lesions

Abstract Ménétrier's disease is a rare acquired protein-losing premalignant hypertrophic gastropathy characterized by giant gastric rugal folds, decreased acid secretion, increased gastric mucus production, and hypoalbuminemia. Microscopically, it is characterized by massive foveolar hyperplasia, oxyntic gland atrophy, and repatterning of cell specification. Spasmolytic polypeptide-expressing metaplasia (SPEM) is a more widely prevalent premalignant gastric lesion, and it is associated with chronic inflammatory conditions such as Helicobacter pylori infection. SPEM is microscopically similar to Ménétrier's disease except for absence of massive foveolar hyperplasia. We previously reported transgenic mice overexpressing the EGF receptor (EGFR) ligand, TGF-α, phenocopy Ménétrier's disease, that TGF-α is overexpressed in the stomach of Ménétrier's disease patients, and that the EGFR-neutralizing monoclonal antibody (mAb), cetuximab, is the first effective medical therapy for Ménétrier's disease. In a proteomic analysis of gastric tissue of Ménétrier's disease patients, we observed decreased levels of the Notch ligand, Jagged1, after cetuximab treatment. The aim of this study was to examine whether Notch signaling is a downstream target of EGFR signaling and whether it contributes to the pathogenesis of Ménétrier's disease and/ or SPEM. TGF-α transgenic mice (MT-TgfaTg) were used as a Ménétrier's disease mouse model. High-dose tamoxifen injection (5 mg intraperitoneal tamoxifen injection per 20 g body weight for 3 days) was used as a SPEM mouse model. Egfr protein reporter mouse line (EgfrEmgfp/Emgfp) was used to investigate the distribution of endogenous Egfr. Chief cell-specific reporter mouse line (Mist1CreERT2/+; Rosa26mTmg/+) was crossed with MT-TgfaTg for chief cell lineage tracing. We tested whether Notch signaling is activated in the stomach of Ménétrier's disease and SPEM mouse models by Hes-1 immunofluorescent staining. Then we tested whether Notch activation is reduced by MM-151, a cocktail of EGFR mAbs that blocks mouse EGFR, and/ or dibenzazepine (DBZ), a γ-secretase inhibitor in the gastric mucosa of MT-TgfaTg mice. We also examined the level of foveolar hyperplasia and proliferation, and the number of parietal and chief cells in the MT-TgfaTg mice using markers: UEA1 (foveolar pit cell), Ki-67 (proliferation), H+/K+ ATPase (parietal cell), GSII (neck cell), and gastric intrinsic factor (chief cell). Expression levels and distribution of endogenous Egfr protein were increased in the gastric mucosa of both Ménétrier's disease and SPEM mouse models. Nuclear Hes-1 expression was upregulated in the pit, isthmus, and neck compartments in the stomach of both mouse models compared to wild-type mice. Lineage tracing of chief cells in MT-TgfaTg mice showed that they were also positive for neck cell marker, GSII, which is a characteristic of SPEM. Number of nuclear Hes-1 positive cells was decreased by MM-151 and/ or DBZ treatment in MT-TgfaTg mice. Also, MM-151 and/ or DBZ treatment led to decreased foveolar hyperplasia and proliferation, and increased numbers of parietal and chief cells in the gastric mucosa of MT-TgfaTg mice. This study shows that the gastric mucosa of MT-TgfaTg mice also has a characteristic of SPEM for the first time. Both Ménétrier's disease and SPEM mouse models show increased EGFR and Notch signaling in the stomach. It was also shown that the activation of EGFR signaling is sufficient and necessary for the activation of Notch signaling in MT-TgfaTg mice. This study suggests that Notch signaling activated by EGFR signaling contributes, at least in part, to the pathogenesis of Ménétrier's disease and SPEM. Moreover, these findings suggest that blockade of Notch signaling may be a novel therapeutic strategy for Ménétrier's disease and SPEM. Citation Format: Won Jae Huh, Robert J. Coffey. EGF receptor-activated Notch signaling contributes to pathogenesis of premalignant gastric lesions [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A34.

Retinoic acid improves nephrotoxic serum–induced glomerulonephritis through activation of podocyte retinoic acid receptor α

Proliferation of glomerular epithelial cells, including podocytes, is a key histologic feature of crescentic glomerulonephritis. We previously found that retinoic acid (RA) inhibits proliferation and induces differentiation of podocytes by activating RA receptor-α (RARα) in a murine model of HIV-associated nephropathy. Here, we examined whether RA would similarly protect podocytes against nephrotoxic serum-induced crescentic glomerulonephritis and whether this effect was mediated by podocyte RARα. RA treatment markedly improved renal function and reduced the number of crescentic lesions in nephritic wild-type mice, while this protection was largely lost in mice with podocyte-specific ablation of Rara (Pod-Rara knockout). At a cellular level, RA significantly restored the expression of podocyte differentiation markers in nephritic wild-type mice, but not in nephritic Pod-Rara knockout mice. Furthermore, RA suppressed the expression of cell injury, proliferation, and parietal epithelial cell markers in nephritic wild-type mice, all of which were significantly dampened in nephritic Pod-Rara knockout mice. Interestingly, RA treatment led to the coexpression of podocyte and parietal epithelial cell markers in a small subset of glomerular cells in nephritic mice, suggesting that RA may induce transdifferentiation of parietal epithelial cells toward a podocyte phenotype. Invitro, RA directly inhibited the proliferation of parietal epithelial cells and enhanced the expression of podocyte markers. Invivo lineage tracing of labeled parietal epithelial cells confirmed that RA increased the number of parietal epithelial cells expressing podocyte markers in nephritic glomeruli. Thus, RA attenuates crescentic glomerulonephritis primarily through RARα-mediated protection of podocytes and in part through the inhibition of parietal epithelial cell proliferation and induction of their transdifferentiation into podocytes.

Long-term administration of formic acid to weaners: Influence on intestinal microbiota, immunity parameters and growth performance

The use of organic acids in diets for livestock animals is interest due to their being potentially beneficial in maintaining gut homeostasis and controlling pathogenic bacterial growth. The objective of this study was to evaluate the influence of two doses of formic acid supplementation for six weeks to weaner pigs. The long-term effects of formic acid were tested for growth performance, microbiota composition in the jejunum using 16S_rRNA, expression of marker genes of inflammation in the jejunum, and quantification of acid-secreting cells in the gastric oxyntic mucosa using immunohistochemistry. Three diets containing no (control; CO), 1.4g/kg (low formic acid; LFA) or 6.4g/kg (high formic acid; HFA) free formic acid were fed to 36 pigs for 42 d from 7 d post-weaning (7.1±1.0kg live weight) until the end of the trial (27.7±5.5kg live weight); they were housed in individual cages for six weeks. During the first three weeks, formic acid supplementation, at any of the dosage above, increased average daily gain (ADG) (P=0.004), tended to increase average daily feed intake (ADFI) (P=0.08) and tended to decrease g of feed to g of gain (F:G) (P=0.08) while no effect was observed during the last three weeks. At the end of the trial, formic acid supplementation had only a minor effect on the microbiota composition in the jejunum. A higher microbiota diversity (Chao1 index P<0.05) was found in the HFA group than in the CO group. The Control group showed a higher abundance (P<0.05) of Gemella, Lactobacillus and Parvimimoas than the HFA and LFA groups, higher levels of Acinetobacter, Fusobactrium, Leuconostoc respect to the HFA group and of Turcibacter as compared to the LFA group. The abundance of Streptococcus was lower in the CO group than in the HFA group and higher than in the LFA group. The jejunal expression of C-C Motif Chemokine Ligand 2 (CCL20) was higher in the HFA group respect to the LFA group. Formic acid intake did not affect the thickness of the gastric mucosa, the number of parietal cells and stomach weight. This study showed that the addition of formic acid to piglet diets improved growth performance during the first period after weaning and that the long-term supplementation of formic slightly affected the microbiota composition according to the dose.

Regulation of Gastric Metaplasia, Dysplasia, and Neoplasia by Bone Morphogenetic Protein Signaling

The bone morphogenetic proteins, (BMP)s are regulatory peptides that have significant effects on the growth and differentiation of gastrointestinal tissues. In addition, the BMPs have been shown to exert anti-inflammatory actions in the gut and to negatively regulate the growth of gastric neoplasms. The role of BMP signaling in the regulation of gastric metaplasia, dysplasia and neoplasia has been poorly characterized. Transgenic expression in the mouse stomach of the BMP inhibitor noggin leads to decreased parietal cell number, increased epithelial cell proliferation, and to the emergence of SPEM. Moreover, expression of noggin increases Helicobacter-induced inflammation and epithelial cell proliferation, accelerates the development of dysplasia, and it increases the expression of signal transducer and activator of transcription 3 (STAT3) and of activation-induced cytidine deaminase (AID). These findings provide new clues for a better understanding of the pathophysiological mechanisms that regulate gastric inflammation and the development of both dysplastic and neoplastic lesions of the stomach.

Impact of an Energy Drink on the Structure of Stomach and Pancreas of Albino Rat: Can Omega-3 Provide a Protection?

Background and ObjectivesA controversy developed between the benefits of energy drinks (EDs) versus the possible health threats since its revolution. Lack of information was a call to assess the effect of chronic consumption of Power Horse (PH) as one of the EDs, on the structure of pancreas and fundic mucosa of stomach in rats, and possible protective role of Omega-3.Materials and MethodsThirty two adult male albino rats were divided equally into 4 groups; control received group which only received a standard diet, Omega-3 group, PH group which given PH and PH plus Omega-3 group received both PH plus Omega-3 for 4 weeks. Biochemical assessment of blood glucose, serum insulin, gastrin, tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthetase (iNOS) was performed. The antioxidant activity and histopathological examination of both pancreatic tissue and fundic mucosa of stomach were assessed.ResultsAdministration of PH significantly increased serum insulin and glucose levels while it significantly reduced serum gastrin level compared to control. PH also caused oxidants/antioxidants imbalance in both pancreas and fundic mucosa. The latter revealed degenerative changes and increased apoptosis which was evident by increased caspase-3 immunoexpression. Pancreas exhibited signs of β-cells overstimulation. Fundic mucosa showed reduced number of parietal cells, gastrin hormone expression compared to control group. Omega-3 administration could alleviate, to some extent, these changes. It significantly decreased TNF-α, iNOS and reduced glutathione (GSH) as well as significantly increasing superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities compared to the group which received PH alone.ConclusionPower Horse intake significantly injures islet cells, pancreatic acini as well as the glandular cells of the fundic mucosa. Omega-3 decreases these detrimental effects mostly through its antioxidant and anti-inflammatory action.

Влияние экстракта эхинацеи пурпурной на структуру слизистой оболочки и количество клеток собственных желез слизистой оболочки фундального отдела желудка крыс

The research purpose was to study the influence of echinacea purple extract on height of proper gastric glands, total amount of cells, and number of parietal cells in one proper fundus gland of rats` stomach. The experiment was conducted on sixty mature outbred white male rats, divided into two experimental groups. The first group consisted of intact rats, the second one- rats having exposed to echinacea purple extract. The proper gastric gland height measurement was carried out, and the number of all cells and parietal cells in one proper fundus gland of rats` stomach was calculated with the light-optical microscopy using a digital morphometric complex after preliminary coloring the sections with hematoxylin-eosin. The echinacea purple extract application increases the studied parameters, which remains after its action has completed.

Genetic Ablation of the ClC-2 Cl- Channel Disrupts Mouse Gastric Parietal Cell Acid Secretion.

The present studies were designed to examine the effects of ClC-2 ablation on cellular morphology, parietal cell abundance, H/K ATPase expression, parietal cell ultrastructure and acid secretion using WT and ClC-2-/- mouse stomachs. Cellular histology, morphology and proteins were examined using imaging techniques, electron microscopy and western blot. The effect of histamine on the pH of gastric contents was measured. Acid secretion was also measured using methods and secretagogues previously established to give maximal acid secretion and morphological change. Compared to WT, ClC-2-/- gastric mucosal histological organization appeared disrupted, including dilation of gastric glands, shortening of the gastric gland region and disorganization of all cell layers. Parietal cell numbers and H/K ATPase expression were significantly reduced by 34% (P<0.05) and 53% (P<0.001) respectively and cytoplasmic tubulovesicles appeared markedly reduced on electron microscopic evaluation without evidence of canalicular expansion. In WT parietal cells, ClC-2 was apparent in a similar cellular location as the H/K ATPase by immunofluorescence and appeared associated with tubulovesicles by immunogold electron microscopy. Histamine-stimulated [H+] of the gastric contents was significantly (P<0.025) lower by 9.4 fold (89%) in the ClC-2-/- mouse compared to WT. Histamine/carbachol stimulated gastric acid secretion was significantly reduced (range 84–95%, P<0.005) in ClC-2-/- compared to WT, while pepsinogen secretion was unaffected. Genetic ablation of ClC-2 resulted in reduced gastric gland region, reduced parietal cell number, reduced H/K ATPase, reduced tubulovesicles and reduced stimulated acid secretion.