Stomach secretes estrogen in response to the blood triglyceride levels

Mammals receive body energy information to maintain energy homeostasis. Ghrelin, insulin, leptin and vagal afferents transmit the status of fasting, blood glucose, body fat, and food intake, respectively. Estrogen also inhibits feeding behavior and lipogenesis, but increases body fat mass. However, how blood triglyceride levels are monitored and the physiological roles of estrogen from the perspective of lipid homeostasis remain unsettled. Here, we show that stomach secretes estrogen in response to the blood triglyceride levels. Estrogen-secreting gastric parietal cells predominantly use fatty acids as an energy source. Blood estrogen levels increase as blood triglyceride levels rise in a stomach-dependent manner. Estrogen levels in stomach tissues increase as blood triglyceride levels rise, and isolated gastric gland epithelium produces estrogen in a fatty acid-dependent manner. We therefore propose that stomach monitors and controls blood triglyceride levels using estrogen, which inhibits feeding behavior and lipogenesis, and promotes triglyceride uptake by adipocytes.

The Involvement of CXCL17-GPR35 in Gastric Cancer Initiation and Development

Background: C-X-C motif chemokine 17 (CXCL17), a newly identified chemokine, and its possible receptor, G-protein coupled receptor 35 (GPR35) were potential proteins involved in carcinogenesis; nevertheless, their involvement in gastric cancer (GC) initiation and development, which we aimed to evaluated in this study, remains undefined.Methods and materials: CXCL17 and GPR35 expressions in normal gastric gland of non-atrophic gastritis (NAG-NOR), intestinal metaplasia of atrophic gastritis (AG-IM), IM adjacent to GC (GC-IM), and GC tissues was determined by immunohistochemistry. Their possible roles were analyzed by the Cancer Genome Atlas (TCGA) data mining and western blot.Results: Either CXCL17 or GPR35 showed a strongest expression in GC-IM among the four types of tissues: CXCL17: GC-IM vs. AG-IM (P < 0.001), GC-IM vs. GC (P < 0.001); GPR35: GC-IM vs. AG-IM (P < 0.001), GC-IM vs. GC (P < 0.01). Their expressions were positively correlated in GC tissues (Spearman r = 0.2933, P < 0.001). CXCL17 expression was negatively correlated with the depth of tumor invasion (P = 0.015) and tumor maximum diameter (P = 0.003). Higher CXCL17 expression independently predicted for better survival in GC patients. TCGA analysis suggested CXCL17 expression was positively correlated with the transcriptional level of gastric mucosal maturation indicators TFF1, TFF2, PGC and MUC5AC, but negatively with the dedifferentiation indicators CDX1 and SFRP family members. Protein-protein interaction (PPI) revealed the potential connection of GPR35-CXCL17-CCL20. Overexpressing CXCL17 in HGC27 cell line downregulated SFRP2 and CDX1, but upregulated CCL20 expression.Conclusion: CXCL17 and GPR35 may play a vital role in GC initiation and development, especially in the IM to GC process. A higher CXCL17 expression independently predicted for better survival in GC patients, with a possible role in maintaining gastric mucosa maturation.

Histogenesis of developing human fetal stomach

Background: Human stomach is a highly specialised organ with distinct types of glands and microscopic features for its physiological activity. This study aimed to assess the chronological order in the development of different layers and the cyto-differentiation of various glandular cells in 50 fetuses from 12 weeks of gestation till term.Methods: Tissue was taken from cardiac, body and pylorus to investigate with light and confocal microscopy.Results: The gastric gland formation began as an indentation of the surface epithelium, gastric pit and simultaneous development of glandular buds in the mucosa. The pyloric glands preceded the development of cardiac and gastric glands showing retro cranial sequence of development. In contrast, the muscularis externa showed the classical craniocaudal model of development with oblique layer in the cardiac region by 14 weeks and body region by 16 weeks of gestation. The parietal cells were well developed by 12 weeks and the chief cells by 16 weeks with prominent secretory granules. In addition, the pyloric sphincter was a clearly defined anatomical sphincter developed by whorling of the inner circular layer at the pyloric end of the stomach evident from 12 weeks of gestation.Conclusions: The results showed that the significant cellular morphogenesis occurred between 12-20 weeks of gestation. This aggregated data will serve as a catalyst in the understanding intricacy of embryogenesis, pathogenesis tracing of congenital anomalies and invention of new drugs.

Phenotype characteristics of gastric epithelial mucus in patients with different gastric diseases: from superficial gastritis to gastric cancer

Background Gastric gland mucin is important for maintaining the basic function of the gastric mucosa, protecting it from foreign substances and reducing the occurrence of gastric diseases. Exploring the phenotype of gastric gland mucus changes during the progression of gastric disease is of great clinical significance. Methods A total of 483 patients with different gastric diseases were collected in this study, including 82 superficial gastritis (SG), 81 atrophic gastritis (AG), 168 dysplasia (GD), and 152 gastric cancer (GC). Mucin staining was performed using HID-ABpH2.5-PAS method and was further grouped according to the mucin coloration. Results The phenotypic characteristics of mucin during disease progression were divided into neutral, acidic, and mucus-free types. Furthermore, acidic mucus can be divided into type I, type II, and type III. The SG group was dominated by neutral mucus (100%), and the AG was dominated by acid mucus (81.48%), which gradually increased with the severity of atrophy (P < 0.05). The GD and GC groups were dominated by mucus-free (43.45%, 78.29%), and as the degree of GD worsened, neutral and acidic mucus gradually decreased and mucus-free increased (P < 0.001). From the SG, AG, GD, and GC progression, neutral and acidic mucus gradually decreased, and mucus- free gradually increased. Acidic mucin revealed that type III (red-brown black) mucin was predominant in AG, GD, and GC, and increased with the degree of AG, GD, as well as the biological behavior of GC. In the lesion adjacent to high-grade GD or GC, type III acid mucin is predominant. Conclusion There were three mucin phenotypes in the process of gastric diseases. With the disease progression, the trend of phenotypic change was that neutral and acidic mucus gradually decreased and mucus-free increased. The appearance of type III mucin suggested a relatively serious phase of gastric diseases and may be a more suitable candidate for follow-up monitoring of patients with GC risk.

Title: pancreatic‐type mixed acinar neuroendocrine carcinoma of the stomach: a case report and review of the literature

Background The majority of gastrointestinal tumors are adenocarcinomas. Rarely, there are other types of tumors, such as acinar cell carcinoma, and these are often called pancreatic-type acinar cell carcinomas. Among these tumors, some are differentiated into neuroendocrine components. A few of them are MiNENs. Case presentation The patient was an 80-year-old male who was referred to our hospital for treatment of a pedunculated gastric tumor. It was 5 cm in diameter and detected in the upper gastric body with upper GI endoscopy conducted to investigate anemia. In the biopsy, although hyperplasia of gastric gland cells was noted, no tumor cells were found. Retrospectively, the diagnosis was misdiagnosed. An operation was arranged because bleeding from the tumor was suspected as a cause of anemia and because surgical resection was considered to be desirable for accurate diagnosis. Hence, laparoscopic and endoscopic cooperative surgery was performed. In the pathological examination, several types of epithelial cells that proliferated in the area between the mucosa and deep inside the submucosa were observed. These consisted of acinar-glandular/trabecular patterns and solid. A diagnosis of pancreatic-type acinar cell carcinoma of the stomach with NET G2 and G3 was made based on characteristic cellular findings and the results of immunostaining tests. Each of them consisted of more than 30% of the lesion; a diagnosis of pancreatic-type mixed acinar neuroendocrine carcinoma (pancreatic-type MiNEN) of the stomach or a type of gastric MiNEN was obtained. Anemia was resolved after the operation, and the patient was discharged from the hospital without perioperative complications. Conclusions Pancreatic-type ACC of the stomach that is differentiated into neuroendocrine tumors is very rare. Hence, we report this case along with a literature review.

Clinicopathological Characteristics and Differential Diagnosis of Signet-ring Cell Carcinoma of Gastric Pit Epithelium

Background:To investigate the clinicopathological characteristics, immunophenotype and differential diagnosis of signet-ring cell carcinoma of gastric pit epithelium. Methods Seven cases of signet-ring cell carcinoma of gastric pit epithelium were studied by histomorphology observation, special staining, immunohistochemical staining and follow-up. Results At the initial stage, the glands proliferated and expanded, and the cells morphologically transformed into signet ring-like atypical cells and then formed clonal hyperplastic signet-ring cell carcinoma, which expanded laterally along the gastric pit, with a length of 3–6 mm. Erosion or mucosal ulcers can be formed on the surface, and the atrophy of fundus or pylorus glands leads to local depression of gastric mucosa. PAS was positive by special staining. Immunophenotype testing included MUC5AC, CKpan, CK20, CEA, villin and CDX2 with positive expression. In cytology, five cell morphologies could be seen: classic, immature, high proliferation, non-nucleus vacuole and degeneration. Three out of seven cases were accompanied by Helicobacter pylori (Hp) infection, accounting for 42.9% of the cases. Conclusion The signet-ring cell carcinoma of gastric pit epithelium originates from the proliferative region of the gastric fundus and the neck of gastric gland, which grows laterally along the gastric pit and is easy to be missed and misdiagnosed. Attention should be paid to the differential diagnosis, and the recognition level of signet-ring cell carcinoma of gastric pit epithelium should be improved.

Pancreatic-Type Mixed Acinar Neuroendocrine Carcinoma of the Stomach: A Case Report And Review of Literature

Background: A majority of gastrointestinal tumors are adenocarcinoma. Rarely, there is also a type of tumors such as acinar cell carcinoma, which are often called pancreatic-type acinar cell carcinoma. Among those, some are differentiated into neuroendocrine components. A few of them can be called MiNENs. Case presentation: The patient was an 80-year old male who was referred to our hospital for treatments of a pedunculated gastric tumor. It was 5 cm in diameter and detected in the upper gastric body with upper GI endoscopy conducted for investigation of anemia. In the biopsy, although a kind of hyperplasia of gastric gland cell was pointed out, no tumor cells were found. Retrospectively, the diagnosis was turned out to be a misdiagnosis. An operation was arranged because bleeding from the tumor was suspected as a cause of anemia and because a surgical resection was considered to be desirable for accurate diagnosis. Hence, laparoscopy and endoscopy cooperative surgery was performed. In pathological examination, several types of epithelial cells which proliferated in the area between mucosa and deep inside the submucosa were observed. These consisted of acinar-glandular/trabecular patterns and solid pattern. A diagnosis of pancreatic-type acinar cell carcinoma of the stomach with NET G2 and G3 was made based on characteristic cellular findings and the result of immunostaining tests. Each of them consisted of more than 30% of the lesion; a diagnosis of pancreatic-type mixed acinar neuroendocrine carcinoma (pancreatic-type MiNEN) of the stomach, or a type of gastric MiNEN was obtained. Anemia was resolved after operation, and the patient was discharged from the hospital without perioperative complications. Conclusions: Pancreatic-type ACC of the stomach which is differentiated into neuroendocrine tumor is very rare. Hence, we report this case along with several literature reviews.

Modulating Effect of Vitamin D on iNOS, PCNA and a-SMA Expression Against Diclofenac Sodium Induced Gastric Injury in Rats

BACKGROUND: Diclofenac sodium is a nonsteroidal anti-inflammatory prescription, widely used in the management of many inflammatory diseases but the side effects limiting its clinical use. The present work was carried out to detect the ameliorative effect of vitamin D against diclofenac sodium induced gastric injury in adult male albino rats.METHODS: Forty adult male Wistar albino rats were classified into four groups: G-I received no treatment (control group), G-II orally received 500 IU/kg of vitamin D daily, G-III intraperitoneally received 3 mg/kg of diclofenac sodium daily, and G-IV received both 500 IU/kg of vitamin D and 3 mg/kg of diclofenac sodium daily for 14 days. Specimens from rats' stomach were processed for light microscopy. Immunohistochemical examination was carried out to detect inducible nitric oxide synthase (iNOS), proliferating cell nuclear antigen (PCNA), and alpha smooth muscle actin (α-SMA). The morphometric results were analyzed statistically.RESULTS: Gastric sections of G-III displayed inflammatory cellular infiltrations and dilated congested blood vessels. Some of the gastric gland cells showed cytoplasmic vacuolation, dilated gastric pits, and cystic dilatation. There was a significant increased Masson's trichrome stain and a significant decrease in PAS. The mean area percentage of iNOS and α-SMA expression showed a statistically significant increase. The PCNA positive cells were significantly decreased in the isthmus and neck region compared with the control. While in contrast, G-IV prevented the gastric injury by increasing PAS and PCNA but decreasing Masson's trichrome stain, iNOS and α-SMA expression.CONCLUSION: Vitamin D administration prevented the structural alterations of the gastric rat induced by diclofenac sodium.KEYWORDS: diclofenac sodium, α-SMA, iNOS, PCNA, vitamin D