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Frontiers in Endocrinology 2021Spexin (SPX), a neuropeptide with diverse functions, is a novel satiety factor in fish models and its role in feeding control has been recently confirmed in mammals. In...
Spexin (SPX), a neuropeptide with diverse functions, is a novel satiety factor in fish models and its role in feeding control has been recently confirmed in mammals. In mouse, food intake was shown to trigger SPX expression in glandular stomach with parallel rise in serum SPX and these SPX signals could inhibit feeding central actions within the hypothalamus. However, the mechanisms for SPX regulation by food intake are still unclear. To examine the role of insulin signal caused by glucose uptake in SPX regulation, the mice were IP injected with glucose and insulin, respectively. In this case, serum SPX was elevated by glucose but not altered by insulin. Meanwhile, SPX transcript expression in the glandular stomach was up-regulated by glucose but the opposite was true for insulin treatment. Using hybridization, the differential effects on SPX gene expression were located in the gastric mucosa of glandular stomach. Co-injection experiments also revealed that glucose stimulation on serum SPX and SPX mRNA expressed in glandular stomach could be blocked by insulin. In gastric mucosal cells prepared from glandular stomach, the opposite effects on SPX transcript expression by glucose and insulin could still be noted with similar blockade of the stimulatory effects of glucose by insulin. In this cell model, SPX gene expression induced by glucose was mediated by glucose uptake GLUT, ATP synthesis by glycolysis/respiratory chain, and subsequent modulation of K channel activity, but the voltage-sensitive Ca channels were not involved. The corresponding inhibition by insulin, however, was mediated by PI3K/Akt, MEK/ERK, and P cascades coupled to insulin receptor but not IGF-1 receptor. Apparently, glucose uptake in mice can induce SPX expression in the glandular stomach through ATP synthesis glucose metabolism and subsequent modification of K channel activity, which may contribute to SPX release into circulation to act as the satiety signal after food intake. The insulin rise caused by glucose uptake, presumably originated from the pancreas, may serve as a negative feedback to inhibit the SPX response by activating MAPK and PI3K/Akt pathways in the stomach.
Topics: Animals; Cells, Cultured; Eating; Gene Expression; Glucose; Insulin; Male; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Peptide Hormones; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Stomach; Mice
PubMed: 34025589
DOI: 10.3389/fendo.2021.681648 -
Nature Reviews. Gastroenterology &... May 2018Subjected to countless daily injuries, the stomach still functions as a remarkably efficient digestive organ and microbial filter. In this Review, we follow the lead of... (Review)
Review
Subjected to countless daily injuries, the stomach still functions as a remarkably efficient digestive organ and microbial filter. In this Review, we follow the lead of the earliest gastroenterologists who were fascinated by the antiseptic and digestive powers of gastric secretions. We propose that it is easiest to understand how the stomach responds to injury by stressing the central role of the most important gastric secretion, acid. The stomach follows two basic patterns of adaptation. The superficial response is a pattern whereby the surface epithelial cells migrate and rapidly proliferate to repair erosions induced by acid or other irritants. The stomach can also adapt through a glandular response when the source of acid is lost or compromised (that is, the process of oxyntic atrophy). We primarily review the mechanisms governing the glandular response, which is characterized by a metaplastic change in cellular differentiation known as spasmolytic polypeptide-expressing metaplasia (SPEM). We propose that the stomach, like other organs, exhibits marked cellular plasticity: the glandular response involves reprogramming mature cells to serve as auxiliary stem cells that replace lost cells. Unfortunately, such plasticity might mean that the gastric epithelium undergoes cycles of differentiation and de-differentiation that increase the risk of accumulating cancer-predisposing mutations.
Topics: Animals; Cell Plasticity; Cellular Reprogramming; Gastric Acid; Gastric Mucosa; Humans; Stomach; Stomach Neoplasms
PubMed: 29463907
DOI: 10.1038/nrgastro.2018.5 -
Animals : An Open Access Journal From... Oct 2022Studies of equine stomach prenatal development are very rare, and descriptions usually focus on the processes taking place in the embryonic period. Only general...
Studies of equine stomach prenatal development are very rare, and descriptions usually focus on the processes taking place in the embryonic period. Only general information about gastric organogenesis in the fetal period is available in embryology textbooks on domestic mammals. The material for our study included twenty half-breed horse fetuses divided into three age groups on the basis of known fetal age (verified using the CRL method). Our study consists of the topographical, morphological, and morphometrical description of stomach development between the 4th and 11th months of gestation. Even though the skeletotopy, syntopy, and holotopy of the stomach in the fetal period seems to be relatively unchanged, the organ shape and the proportions between its anatomical parts differed in fetuses from the three age groups. The achieved results were statistically elaborated to estimate the dynamics of the stomach shape. This can be described as changing from medium-wide to wide and from slightly bent to sharply bent. A nonlinear correlation of all metric values with CRL in all age groups was observed. A positive allometric growth rate of different intensity was seen in all metric parameters. All the values increased as the fetal period progressed. Only the parietal surface growth rate gradually changed from strongly positive allometric in the first age group to strongly negative allometric in the third age group. A difference between the non-glandular and glandular mucosa of the stomach was visible in the first group. Development of a well-distinguishable plicated edge margin began in the second age group together with gastric pits and gastric areas. The third age group showed a well-developed gastric groove and angular incisura.
PubMed: 36359095
DOI: 10.3390/ani12212966 -
Journal of Veterinary Internal Medicine Sep 2021The role of the gastric microbiome in development or persistence of equine glandular gastric disease (EGGD) remains to be investigated.
BACKGROUND
The role of the gastric microbiome in development or persistence of equine glandular gastric disease (EGGD) remains to be investigated.
HYPOTHESIS/OBJECTIVES
The objective was to characterize the glandular mucosal and gastric fluid microbiomes of horses with and without EGGD. It was hypothesized that differences in the mucosal microbiome are associated with EGGD.
ANIMALS
Twenty-four horses were enrolled.
METHODS
Gastroscopy was performed and EGGD scores recorded (score 0, n = 6; score 1, n = 8; score ≥2, n = 10). Gastric fluid and pinch biopsies of healthy glandular mucosa and EGGD lesions were collected via gastroscope. 16S rRNA amplicon sequencing of the gastric fluid and glandular mucosal biopsies was performed. Relationships between gastric fluid and mucosal microbial community composition were evaluated among EGGD score groups (EGGD 0-BX, EGGD 1-BX, EGGD ≥2-BX) and among endoscopic appearances: controls from horses without EGGD and normal areas, hyperemic areas, and lesions from horses with EGGD.
RESULTS
Microbial community structure of mucosal biopsies differed among EGGD score groups (Jaccard similarity index; P = .009). Principal coordinate analysis showed separate clusters for EGGD 0-BX and EGGD ≥2-BX.
CONCLUSIONS AND CLINICAL IMPORTANCE
A modest difference was detected in the community structure of the gastric glandular mucosal microbiome in association with EGGD score.
Topics: Animals; Gastric Mucosa; Gastrointestinal Microbiome; Horse Diseases; Horses; RNA, Ribosomal, 16S; Stomach Diseases; Stomach Ulcer
PubMed: 34351018
DOI: 10.1111/jvim.16241 -
Animals : An Open Access Journal From... Nov 2022Histological and morphometrical analysis of the stomach wall was performed during the foetal period divided into three age groups (4th-11th month of gestation). The...
Histological and morphometrical analysis of the stomach wall was performed during the foetal period divided into three age groups (4th-11th month of gestation). The material was taken from non-glandular (the blind ventricular sac) and glandular parts (the plicated edge margin/cardiac part, the body of stomach and the pyloric part) of the stomach. It was preserved and prepared according to the standard protocol. The histological slides were stained (H-E, Masson-Goldner and PAS). The analyses were performed using the light microscope. All measurements were statistically elaborated. The crown-rump length growth rate was estimated as isometric. The blind ventricular sac growth rate was lower than CRL (negative allometric) and the partition of stomach mucosa into non-glandular and glandular part occurred in the 1st age group. The plicated edge margin/cardiac part and the pyloric part shoved similar tendencies. Only the body of stomach demonstrated a higher growth rate than CRL (positive allometric), which can be explained due to the strongest development of fundic glands. Moreover, comparing the adult reference group to the three parts of the foetal period, all metric values were lower than those achieved prenatally. The blind ventricular sac was covered with the multiple plane epithelium. The glandular parts of stomach that formed the superficial concave areas were covered with the simple columnar epithelium in the 1st age group, which developed to the cardiac, fundic, and pyloric glands in the 2rd and 3rd age groups. The was built with the mesenchyme, which differentiated later to the loose connective tissue. The muscular layer of mucosa was not clearly distinguishable in the 1st age group. The muscular layer of the stomach wall was formed with myoblasts in the 1st age group and later in the 2nd and the 3rd age groups built with fusiform myocytes divided into internal and external layers. The non-differentiated cells of glandular epithelium transformed into the parietal and chief cells. The first were visible in the gastric glands of the 2nd age group. Both of them were present in the 3rd age group gastric mucosa. The PAS staining proved a moderate PAS-positive reaction in the 2rd age group, while it was estimated as intense Pas-positive in the gastric glands in the 3rd age group and was comparable to postnatal observation (the adult reference group).
PubMed: 36359171
DOI: 10.3390/ani12213047 -
Archives of Razi Institute Aug 2023The equine stomach consists of two separate non-glandular and glandular sections. Despite the incidence of most lesions in the non-glandular region, both stomach parts...
The equine stomach consists of two separate non-glandular and glandular sections. Despite the incidence of most lesions in the non-glandular region, both stomach parts are prone to lesions. In this study, 41 hybrid-native horses, including 24 stallions and 17 mares, were examined over five years. In total, 27 horses (65.85%) that were sampled had lesions, including erosion, granuloma, or both on the glandular region of the stomach. Occurrence of gastric erosive and granulomatous lesions had no significant relationship with the age and gender of horses or the sampling season (>0.05). Moreover, parasites and were mainly the primary cause of gastric erosive and granulomatous lesions respectively. In Periodic Acid Schiff (PAS) stained tissue sections, the inflammation severity in granulomatous lesions was higher and statistically significant, compared to erosive lesions (<0.05). Immunohistochemistry revealed negative expression of glial cell line-derived neurotrophic factor in gastric lesions, while its expression was relatively positive in normal stomachs. Interestingly, based on counting cells and evaluation of expression intensity, Chromogranin A expression in neuroendocrine glandular cells had a significant relationship with the increase of severity and depth of the lesions (<0.05). The results indicated that the glial cell line-derived neurotrophic factor does not affect the pathogenesis of equine gastric lesions while confirming the role of increment of gastric neuroendocrine cells in lesion progress. Furthermore, the increased expression of Ki67 and p53 proteins in granulomatous lesions, compared to other groups, may be associated with the proliferation and control process of the cells in measures regarding the formation and healing of the lesion.
Topics: Horses; Animals; Male; Female; Glial Cell Line-Derived Neurotrophic Factor; Chromogranin A; Stomach Ulcer; Horse Diseases
PubMed: 38226378
DOI: 10.32592/ARI.2023.78.4.1365 -
Experimental Cell Research Nov 2011Contiguous regions along the mammalian gastrointestinal tract, from the esophagus to the rectum, serve distinct digestive functions. Some organs, such as the esophagus... (Review)
Review
Contiguous regions along the mammalian gastrointestinal tract, from the esophagus to the rectum, serve distinct digestive functions. Some organs, such as the esophagus and glandular stomach or the small bowel and colon, are separated by sharp boundaries. The duodenal, jejunal and ileal segments of the small intestine, by contrast, have imprecise borders. Because human esophageal and gastric cancers frequently arise in a background of tissue metaplasia and some intestinal disorders are confined to discrete regions, it is useful to appreciate the molecular and cellular basis of boundary formation and preservation. Here we review the anatomy and determinants of boundaries and transitions in the alimentary canal with respect to tissue morphology, gene expression, and, especially, transcriptional control of epithelial identity. We discuss the evidence for established and candidate molecular mechanisms of boundary formation, including the solitary and combinatorial actions of tissue-restricted transcription factors. Although the understanding remains sparse, genetic studies in mice do provide insights into dominant mechanisms and point the way for future investigation.
Topics: Animals; Body Patterning; Colon; Duodenum; Esophagus; Gastrointestinal Tract; Humans; Intestine, Small; Mice; Models, Biological; Stomach
PubMed: 21802415
DOI: 10.1016/j.yexcr.2011.07.011 -
Toxicologic Pathology Jan 2010Cancers of the stomach and large intestine (LI) are the second and fourth leading causes of human cancer mortality. A review of the National Toxicology Program (NTP)... (Review)
Review
Cancers of the stomach and large intestine (LI) are the second and fourth leading causes of human cancer mortality. A review of the National Toxicology Program (NTP) database and the Carcinogenic Potency Database (CPDB) reveals that chemically induced neoplasms of the gastrointestinal tract (GIT) are relatively common. Within the GIT, epithelial tumors of the forestomach in mice and rats and LI of the rat are most common. Generally, there is a high species concordance for forestomach with at least 26 chemicals inducing tumors in both species. Glandular stomach tumors are rare, and the few reported are usually neuroendocrine tumors (carcinoids) originating from the enterochromaffin-like (ECL) cells. Of 290 carcinogenic agents identified by the NTP, 19 (7%) caused intestinal neoplasia, 14 in the rat and 5 in the mouse. Neoplasms occurred in both males and females, exclusively in the small intestine (SI) of the mouse and in the LI or both SI and LI in the rat. Enteric carcinogens (NTP) frequently induced neoplasms at other alimentary sites (oral cavity, esophagus, and stomach). In conclusion, the most common induced GIT tumors are squamous neoplasms of the forestomach, glandular neoplasms of the stomach are rare, and rats appear more prone to developing LI (colorectal) cancer compared to mice.
Topics: Animals; Carcinogenicity Tests; Female; Gastrointestinal Neoplasms; Humans; Intestinal Neoplasms; Male; Mice; Rats; Stomach Neoplasms
PubMed: 20019352
DOI: 10.1177/0192623309356452 -
Veterinary Research Jun 2022This article focuses on the pathogenic significance of Helicobacter species naturally colonizing the stomach of dogs, cats and pigs. These gastric "non-Helicobacter (H.)... (Review)
Review
This article focuses on the pathogenic significance of Helicobacter species naturally colonizing the stomach of dogs, cats and pigs. These gastric "non-Helicobacter (H.) pylori Helicobacter species" (NHPH) are less well-known than the human adapted H. pylori. Helicobacter suis has been associated with gastritis and decreased daily weight gain in pigs. Several studies also attribute a role to this pathogen in the development of hyperkeratosis and ulceration of the non-glandular stratified squamous epithelium of the pars oesophagea of the porcine stomach. The stomach of dogs and cats can be colonized by several Helicobacter species but their pathogenic significance for these animals is probably low. Helicobacter suis as well as several canine and feline gastric Helicobacter species may also infect humans, resulting in gastritis, peptic and duodenal ulcers, and low-grade mucosa-associated lymphoid tissue lymphoma. These agents may be transmitted to humans most likely through direct or indirect contact with dogs, cats and pigs. Additional possible transmission routes include consumption of water and, for H. suis, also consumption of contaminated pork. It has been described that standard H. pylori eradication therapy is usually also effective to eradicate the NHPH in human patients, although acquired antimicrobial resistance may occasionally occur and porcine H. suis strains are intrinsically less susceptible to aminopenicillins than non-human primate H. suis strains and other gastric Helicobacter species. Virulence factors of H. suis and the canine and feline gastric Helicobacter species include urease activity, motility, chemotaxis, adhesins and gamma-glutamyl transpeptidase. These NHPH, however, lack orthologs of cytotoxin-associated gene pathogenicity island and vacuolating cytotoxin A, which are major virulence factors in H. pylori. It can be concluded that besides H. pylori, gastric Helicobacter species associated with dogs, cats and pigs are also clinically relevant in humans. Although recent research has provided better insights regarding pathogenic mechanisms and treatment strategies, a lot remains to be investigated, including true prevalence rates, exact modes of transmission and molecular pathways underlying disease development and progression.
Topics: Animals; Cat Diseases; Cats; Cytotoxins; Dog Diseases; Dogs; Gastric Mucosa; Gastritis; Helicobacter; Helicobacter Infections; Helicobacter heilmannii; Helicobacter pylori; Humans; Swine; Swine Diseases; Virulence Factors
PubMed: 35692057
DOI: 10.1186/s13567-022-01059-4 -
Genes and Environment : the Official... Feb 2024Carbendazim (methyl 2-benzimidazolecarbamate, CASRN: 10605-21-7) exhibits spindle poisoning effects and is widely used as a fungicide. With respect to genotoxicity,...
BACKGROUND
Carbendazim (methyl 2-benzimidazolecarbamate, CASRN: 10605-21-7) exhibits spindle poisoning effects and is widely used as a fungicide. With respect to genotoxicity, carbendazim is deemed to be non-mutagenic in vitro, but it causes indicative DNA damage in vivo and chromosome aberrations in vitro and in vivo. In this study, we examined the mutagenicity of carbendazim in vivo.
RESULTS
MutaMice were treated with carbendazim orally at doses of 0 (corn oil), 250, 500, and 1,000 mg/kg/day once a day for 28 days. A lacZ assay was used to determine the mutant frequency (MF) in the liver and glandular stomach of mice. MutaMice were administered up to the maximum dose recommended by the Organization for Economic Co-operation and Development Test Guidelines for Chemicals No. 488 (OECD TG488). The lacZ MFs in the liver and glandular stomach of carbendazim-treated animals were not significantly different from those in the negative control animals. In contrast, positive control animals exhibited a significant increase in MFs in both the liver and glandular stomach.
CONCLUSIONS
Carbendazim is non-mutagenic in the liver and glandular stomach of MutaMice following oral treatment.
PubMed: 38378650
DOI: 10.1186/s41021-024-00299-4