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Patients affected by microgastria, severe gastroesophageal reflux, or those who have undergone subtotal gastrectomy, have commonly described reporting dumping syndromes or other symptoms that seriously impair the quality of their life. Gastric tissue engineering may offer an alternative approach to treating these pathologies. Decellularization protocols have great potential to generate novel biomaterials for large gastric defect repair. There is an urgency to define more reliable protocols to foster clinical applications of tissue-engineered decellularized gastric grafts.
Maintenance of progenitor cell properties in development is required for proper organogenesis of most organs, including those derived from the endoderm. FGF10 has been shown to play a role in both lung and pancreatic development. Here we find that FGF10 signaling controls stomach progenitor maintenance, morphogenesis and cellular differentiation. Through a characterization of the initiation of terminal differentiation of the three major gastric regions in the mouse, forestomach, corpus and antrum, we first describe the existence of a "secondary transition" event occurring in mouse stomach between E15.5 and E16.5. This includes the formation of terminally differentiated squamous cells, parietal, chief and gastric endocrine cells from a pre-patterned gastric progenitor epithelium. Expression analysis of both FGF and Notch signaling components suggested a role of these networks in such progenitors, which was tested through ectopically expressing FGF10 in the developing posterior stomach. These data provide evidence that gastric gland specification and progenitor cell maintenance is controlled by FGF10. The glandular proliferative niche was disrupted in pPDX-FGF10(FLAG) mice leading to aberrant gland formation, and endocrine and parietal cell differentiation was attenuated. These effects were paralleled by changes in Hes1, Shh and Wnt6 expression, suggesting that FGF10 acts in concert with multiple morphogenetic signaling systems during gastric development.
The stomach is an important digestive organ with various biological functions. However, because of the complexity of its cellular and glandular composition, its precise cellular biology has yet to be elucidated. In this study, we conducted single-cell RNA sequencing (scRNA-seq) and subcellular-level spatial transcriptomics analysis of the human stomach and constructed the largest dataset to date: a stomach encyclopedia. This dataset consists of approximately 380,000 cells from scRNA-seq and the spatial transcriptome, enabling integrated analyses of transcriptional and spatial information of gastric and metaplastic cells. This analysis identified LEFTY1 as an uncharacterized stem cell marker, which was confirmed through lineage tracing analysis. A wide variety of cell-cell interactions between epithelial and stromal cells, including PDGFRA+BMP4+WNT5A+ fibroblasts, was highlighted in the developmental switch of intestinal metaplasia. Our extensive dataset will function as a fundamental resource in investigations of the stomach, including studies of development, aging, and carcinogenesis.
In this study, we established a radioimmunoassay (RIA) specific for ghrelin from the bullfrog Rana catesbeiana using a novel antibody raised against the C-terminal amino acid sequence of bullfrog ghrelin [13-28]. We also examined the distribution of ghrelin-producing cells in the stomachs of bullfrogs using this antibody and a cRNA probe specific for the bullfrog ghrelin gene. Ghrelin levels in plasma and stomach extracts were approximately 150 fmol/ml and 83-135 fmol/mg wet tissue, respectively. Reverse-phase high performance liquid chromatographic analysis, combined with bullfrog ghrelin RIA, revealed that ghrelin immunoreactivity in the stomach was composed of non-acylated ghrelin (des-acyl ghrelin) and several acylated forms of ghrelin bearing different fatty acid modifications, which could induce increases in intracellular Ca2+ in cells expressing the rat GH secretagogue receptor. In the stomach, the major storage form was acylated ghrelin. In bullfrog plasma, however, the majority of ghrelin immunoreactivity was des-acyl ghrelin and C-terminal fragments of frog ghrelin. Acylated ghrelin forms comprised only minor peaks. Ghrelin-immunopositive and ghrelin mRNA-expressing cells were observed within the mucosal layer of the stomach. Following starvation, significant increases in plasma ghrelin levels and stomach ghrelin mRNA levels were observed as early as 10 days after starvation. These results indicate that ghrelin is present in the stomach and plasma of the bullfrog, which can be detected with our novel antibody. Interestingly, the primary storage form of ghrelin in the stomach differed from the circulating form dominating in the plasma. Furthermore, increases in ghrelin levels in plasma and mRNA levels in the stomach after starvation suggest the possible involvement of ghrelin in energy homeostasis in the bullfrog.
Gastric endoscopy is a golden standard in the clinical process that enables medical practitioners to diagnose various lesions inside a patient's stomach. If a lesion is found, a success in identifying the location of the found lesion relative to the global view of the stomach will lead to better decision making for the next clinical treatment. Our previous research showed that the lesion localization could be achieved by reconstructing the whole stomach shape from chromoendoscopic indigo carmine (IC) dye-sprayed images using a structure-from-motion (SfM) pipeline. However, spraying the IC dye to the whole stomach requires additional time, which is not desirable for both patients and practitioners. Our objective is to propose an alternative way to achieve whole stomach 3D reconstruction without the need of the IC dye. We generate virtual IC-sprayed (VIC) images based on image-to-image style translation trained on unpaired real no-IC and IC-sprayed images, where we have investigated the effect of input and output color channel selection for generating the VIC images. We validate our reconstruction results by comparing them with the results using real IC-sprayed images and confirm that the obtained stomach 3D structures are comparable to each other. We also propose a local reconstruction technique to obtain a more detailed surface and texture around an interesting region. The proposed method achieves the whole stomach reconstruction without the need of real IC dye using SfM. We have found that translating no-IC green-channel images to IC-sprayed red-channel images gives the best SfM reconstruction result. Clinical impact We offer a method of the frame localization and local 3D reconstruction of a found gastric lesion using standard endoscopy images, leading to better clinical decision.
Stomach adenocarcinoma (STAD) is a common malignant tumor in the world and its prognosis is poor, miRNA plays a role mainly by influencing the expression of mRNAs, and participates in the occurrence and development of tumors. However, reliable miRNA prognostic models for stomach adenocarcinoma remain to be identified.
Stomach cancer (SC) is a type of cancer, which is derived from the stomach mucous membrane. As there are non-specific symptoms or no noticeable symptoms observed at the early stage, newly diagnosed SC cases usually reach an advanced stage and are thus difficult to cure. Therefore, in this study, we aimed to develop an integrated database of SC.
Tularemia with peritonitis developed in a 50-year-old man soon after diagnosis of stomach cancer with metastasis. The ascites grew Francisella tularensis subsp. holarctica, which was identified by sequencing analysis of the 16S rDNA. The infection resolved with antimicrobial treatment. Antibodies detected 4 weeks after onset disappeared after chemotherapy-associated lymphopenia.
We report the second case of a malignant paraganglioma of the stomach in a 56-year-old female patient. However, our case is the first investigated by immunohistochemistry and electron-microscopy. The tumour was characterized immunohistochemically by the presence of neurofilament protein, glial fibrillary acidic protein, S-100 protein, neuron-specific enolase, chromogranin A, ACTH, leu-enkephalin and vasoactive intestinal polypeptide, and ultrastructurally by demonstration of neurosecretory granules and paranuclear intermediate filament whorls. Despite massive metastatic spread in the abdominal cavity, the patient is still alive 4 years after initial diagnosis.
The strengths, directions and coupling of the movements of the stomach depend on the organisation of its musculature. Although the rat has been used as a model species to study gastric function, there is no detailed, quantitative study of the arrangement of the gastric muscles in rat. Here we provide a descriptive and quantitative account, and compare it with human gastric anatomy. The rat stomach has three components of the muscularis externa, a longitudinal coat, a circular coat and an internal oblique (sling) muscle in the region of the gastro-oesophageal junction. These layers are similar to human. Unlike human, the rat stomach is also equipped with paired muscular oesophago-pyloric ligaments that lie external to the longitudinal muscle. There is a prominent muscularis mucosae throughout the stomach and strands of smooth muscle occur in the mucosa, between the glands of the corpus and antrum. The striated muscle of the oesophageal wall reaches to the stomach, unlike the human, in which the wall of the distal oesophagus is smooth muscle. Thus, the continuity of gastric and oesophageal smooth muscle bundles, that occurs in human, does not occur in rat. Circular muscle bundles extend around the circumference of the stomach, in the fundus forming a cap of parallel muscle bundles. This arrangement favours co-ordinated circumferential contractions. Small bands of muscle make connections between the circular muscle bundles. This is consistent with a slower conduction of excitation orthogonal to the circular muscle bundles, across the corpus towards the distal antrum. The oblique muscle merged and became continuous with the circular muscle close to the gastro-oesophageal junction at the base of the fundus, and in the corpus, lateral to the lesser curvature. Quantitation of muscle thickness revealed gradients of thickness of both the longitudinal and circular muscle. This anatomical study provides essential data for interpreting gastric movements.
The present study was planned to investigate miR-143 expression during stomach cancer. The study explored the relationship between miR-143 expression and clinicopathological characteristics including proliferation, migration and apoptosis of stomach cancer cells. Sixty-three samples from each of stomach cancer tissue and surrounding tissue were obtained. Total RNA was extracted. The expression levels of miR-143 from stomach cancer tissue as well as from surrounding tissue were measured by semi-quantitative PCR. The effects of miR-143 overexpression on the migration of stomach cancer cells were examined by Transwell assay. The effects of miR-143 overexpression on the apoptosis of stomach cancer cells were examined by flow cytometer. The expression level of miR-143 was significantly decreased in stomach cancer tissues in comparison to surrounding tissues (P<0.01). Moreover, the expression of miR-143 related well with the tumor size, TNM stage, lymphatic metastasis and relapse (P<0.01). On the other hand, stomach cancer cell line with overexpression of miR-143, showed significant decline in proliferation rate and migration rate comparison to control cells (P<0.01). However, it showed significant higher in apoptosis rate (P<0.01). The present study concluded that expression of miR-143 is low during stomach cancer. Further, higher expression levels of miR-143 have the ability to decline proliferation and migration of stomach cancer cells. In this manner, the expression level of miR-143 could be used as an important factor to determine the severity of stomach cancer.
Hollow fiber assays offer an early in vivo method of anticancer drug screening. The assays have been optimized for human cancers originating from the lung, breast, colon, ovary, and brain, but not from the stomach and liver. The current study focused on optimization of hollow fiber assays for gastric and hepatocellular carcinoma cell lines.
Adhesion of Helicobacter pylori to the gastric mucosa is a prerequisite for the pathogenesis of H. pylori related diseases. In this study, we investigated the ganglioside composition of human stomach as the target for attachment mediated by H. pylori SabA (sialic acid binding adhesin). Acid glycosphingolipids were isolated from human stomach and separated into subfractions, which were characterized by mass spectrometry and by binding of antibodies, bacteria, and Solanum tuberosum lectin. H. pylori SabA binding gangliosides were characterized as Neu5Acα3-neolactohexaosylceramide and Neu5Acα3-neolactooctaosylceramide, while the other acid human stomach glycosphingolipids characterized (sulfatide and the gangliosides GM3, GD3, GM1, Neu5Acα3-neolactotetraosylceramide, GD1a and GD1b) were not recognized by the bacteria. Defining H. pylori binding glycosphingolipids of the human gastric mucosa will be useful to specifically target this microbe-host interaction for therapeutic intervention.
The Roux-en-Y duodenal switch (RYDS) is one of the most efficient forms of bariatric surgery. However, diarrhea, malnutrition, ulcers, and internal hernias have hampered its widespread adoption. The stomach intestinal pylorus-sparing (SIPS) procedure was developed to alleviate these sequelae while retaining the same weight loss as the RYDS. In this study, we report our midterm experience with this novel technique.
The mammalian adult gastric epithelium self-renews continually through the activity of stem cells located in the isthmus of individual gland units. Mechanisms facilitating stomach stem and progenitor cell homeostasis are unknown. Here, we show that Notch signaling occurs in the mouse stomach epithelium during development and becomes restricted mainly to the isthmus in adult glands, akin to its known localization in the proliferative compartment of intestinal villi. Using genetic and chemical inhibition, we demonstrate that Notch signaling is required to maintain the gastric stem cell compartment. Activation of Notch signaling in lineage-committed stomach epithelial cells is sufficient to induce dedifferentiation into stem and/or multipotential progenitors that populate the mucosa with all major cell types. Prolonged Notch activation within dedifferentiated parietal cells eventually enhances cell proliferation and induces adenomas that show focal Wnt signaling. In contrast, Notch activation within native antral stomach stem cells does not affect cell proliferation. These results establish a role for Notch activity in the foregut and highlight the importance of cellular context in gastric tumorigenesis.
Impulsivity, defined as impaired decision making, is associated with many psychiatric and behavioral disorders, such as attention-deficit/hyperactivity disorder as well as eating disorders. Recent data indicate that there is a strong positive correlation between food reward behavior and impulsivity, but the mechanisms behind this relationship remain unknown. Here we hypothesize that ghrelin, an orexigenic hormone produced by the stomach and known to increase food reward behavior, also increases impulsivity. In order to assess the impact of ghrelin on impulsivity, rats were trained in three complementary tests of impulsive behavior and choice: differential reinforcement of low rate (DRL), go/no-go, and delay discounting. Ghrelin injection into the lateral ventricle increased impulsive behavior, as indicated by reduced efficiency of performance in the DRL test, and increased lever pressing during the no-go periods of the go/no-go test. Central ghrelin stimulation also increased impulsive choice, as evidenced by the reduced choice for large rewards when delivered with a delay in the delay discounting test. In order to determine whether signaling at the central ghrelin receptors is necessary for maintenance of normal levels of impulsive behavior, DRL performance was assessed following ghrelin receptor blockade with central infusion of a ghrelin receptor antagonist. Central ghrelin receptor blockade reduced impulsive behavior, as reflected by increased efficiency of performance in the DRL task. To further investigate the neurobiological substrate underlying the impulsivity effect of ghrelin, we microinjected ghrelin into the ventral tegmental area, an area harboring dopaminergic cell bodies. Ghrelin receptor stimulation within the VTA was sufficient to increase impulsive behavior. We further evaluated the impact of ghrelin on dopamine-related gene expression and dopamine turnover in brain areas key in impulsive behavior control. This study provides the first demonstration that the stomach-produced hormone ghrelin increases impulsivity and also indicates that ghrelin can change two major components of impulsivity-motor and choice impulsivity.
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