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Annals of Surgical Oncology Mar 2024Gastric neuroendocrine tumors (G-NET) are rare tumors arising from enterochromaffin-like cells of the gastric mucosa. They belong to a larger group called... (Review)
Review
Gastric neuroendocrine tumors (G-NET) are rare tumors arising from enterochromaffin-like cells of the gastric mucosa. They belong to a larger group called gastroenteropancreatic neuroendocrine tumors and are classified as low, intermediate, or high-grade tumors based on their proliferative indices. They are further categorized into three subtypes based on their morphologic characteristics, pathogenesis, and behavior. Types 1 and 2 tumors are characterized by elevated serum gastrin and are usually multifocal. They typically occur in the setting of atrophic gastritis or MEN1/Zollinger Ellison syndrome, respectively. Type 2 tumors are associated with the most symptoms, such as abdominal pain and diarrhea. Type 3 tumors are associated with normal serum gastrin, are usually solitary, and occur sporadically. This type has the most aggressive phenotype and metastatic potential. Treatment and prognosis for G-NET is dependent on their type, size, and stage. Type 1 has the best prognosis, and Type 3 has the worst. This review discusses the presentation, workup, and surgical management of these tumors.
Topics: Humans; Gastrins; Neuroendocrine Tumors; Zollinger-Ellison Syndrome; Pancreatic Neoplasms; Gastric Mucosa; Stomach Neoplasms
PubMed: 38062290
DOI: 10.1245/s10434-023-14712-9 -
Internal and Emergency Medicine Sep 2023The intestinal mucosa represents the most extensive human barrier having a defense function against microbial and food antigens. This barrier is represented externally... (Review)
Review
The intestinal mucosa represents the most extensive human barrier having a defense function against microbial and food antigens. This barrier is represented externally by a mucus layer, consisting mainly of mucins, antimicrobial peptides, and secretory immunoglobulin A (sIgA), which serves as the first interaction with the intestinal microbiota. Below is placed the epithelial monolayer, comprising enterocytes and specialized cells, such as goblet cells, Paneth cells, enterochromaffin cells, and others, each with a specific protective, endocrine, or immune function. This layer interacts with both the luminal environment and the underlying lamina propria, where mucosal immunity processes primarily take place. Specifically, the interaction between the microbiota and an intact mucosal barrier results in the activation of tolerogenic processes, mainly mediated by FOXP3 regulatory T cells, underlying intestinal homeostasis. Conversely, the impairment of the mucosal barrier function, the alteration of the normal luminal microbiota composition (dysbiosis), or the imbalance between pro- and anti-inflammatory mucosal factors may result in inflammation and disease. Another crucial component of the intestinal barrier is the gut-vascular barrier, formed by endothelial cells, pericytes, and glial cells, which regulates the passage of molecules into the bloodstream. The aim of this review is to examine the various components of the intestinal barrier, assessing their interaction with the mucosal immune system, and focus on the immunological processes underlying homeostasis or inflammation.
Topics: Humans; Immunity, Mucosal; Endothelial Cells; Intestinal Mucosa; Inflammation; Homeostasis
PubMed: 37402104
DOI: 10.1007/s11739-023-03329-1 -
Frontiers in Immunology 2023Invariant natural killer T (iNKT) cells, a subset of unconventional T cells that recognize glycolipid antigens in a CD1d-dependent manner, are crucial in regulating... (Review)
Review
Invariant natural killer T (iNKT) cells, a subset of unconventional T cells that recognize glycolipid antigens in a CD1d-dependent manner, are crucial in regulating diverse immune responses such as autoimmunity. By engaging with CD1d-expressing non-immune cells (such as intestinal epithelial cells and enterochromaffin cells) and immune cells (such as type 3 innate lymphoid cells, B cells, monocytes and macrophages), iNKT cells contribute to the maintenance of immune homeostasis in the intestine. In this review, we discuss the impact of iNKT cells and CD1d in the regulation of intestinal inflammation, examining both cellular and molecular factors with the potential to influence the functions of iNKT cells in inflammatory bowel diseases such as Crohn's disease and ulcerative colitis.
Topics: Humans; Natural Killer T-Cells; Immunity, Innate; Lymphocytes; Macrophages; Inflammation
PubMed: 38274786
DOI: 10.3389/fimmu.2023.1343718 -
Journal of Animal Science and... Aug 2023Serotonin is an important signaling molecule that regulates secretory and sensory functions in the gut. Gut microbiota has been demonstrated to affect serotonin...
BACKGROUND
Serotonin is an important signaling molecule that regulates secretory and sensory functions in the gut. Gut microbiota has been demonstrated to affect serotonin synthesis in rodent models. However, how gut microbes regulate intestinal serotonin production in piglets remains vague. To investigate the relationship between microbiota and serotonin specifically in the colon, microbial composition and serotonin concentration were analyzed in ileum-cannulated piglets subjected to antibiotic infusion from the ileum when comparing with saline infusion. Microbes that correlated positively with serotonin production were isolated from piglet colon and were further used to investigate the regulation mechanisms on serotonin production in IPEC-J2 and a putative enterochromaffin cell line RIN-14B cells.
RESULTS
Antibiotic infusion increased quantities of Lactobacillus amylovorus (LA) that positively correlated with increased serotonin concentrations in the colon, while no effects observed for Limosilactobacillus reuteri (LR). To understand how microbes regulate serotonin, representative strains of LA, LR, and Streptococcus alactolyticus (SA, enriched in feces from prior observation) were selected for cell culture studies. Compared to the control group, LA, LR and SA supernatants significantly up-regulated tryptophan hydroxylase 1 (TPH1) expression and promoted serotonin production in IPEC-J2 cells, while in RIN-14B cells only LA exerted similar action. To investigate potential mechanisms mediated by microbe-derived molecules, microbial metabolites including lactate, acetate, glutamine, and γ-aminobutyric acid were selected for cell treatment based on computational and metabolite profiling in bacterial supernatant. Among these metabolites, acetate upregulated the expression of free fatty acid receptor 3 and TPH1 while downregulated indoleamine 2,3-dioxygenase 1. Similar effects were also recapitulated when treating the cells with AR420626, an agonist targeting free fatty acid receptor 3.
CONCLUSIONS
Overall, these results suggest that Lactobacillus amylovorus showed a positive correlation with serotonin production in the pig gut and exhibited a remarkable ability to regulate serotonin production in cell cultures. These findings provide evidence that microbial metabolites mediate the dialogue between microbes and host, which reveals a potential approach using microbial manipulation to regulate intestinal serotonin biosynthesis.
PubMed: 37542282
DOI: 10.1186/s40104-023-00903-7 -
BioRxiv : the Preprint Server For... Jan 2024Enteroendocrine cells (EECs), which secrete serotonin (enterochromaffin cells, EC) or a dominant peptide hormone, serve vital physiologic functions. As with any adult...
Enteroendocrine cells (EECs), which secrete serotonin (enterochromaffin cells, EC) or a dominant peptide hormone, serve vital physiologic functions. As with any adult human lineage, the basis for terminal cell diversity remains obscure. We replicated human EEC differentiation , mapped transcriptional and chromatin dynamics that culminate in discrete cell types, and studied abundant EEC precursors expressing selected transcription factors (TFs) and gene programs. Before expressing the pre-terminal factor NEUROD1, non-replicating precursors oscillated between epigenetically similar but transcriptionally distinct and cell states. Loss of either factor substantially accelerated EEC differentiation and disrupted EEC individuality; ASCL1 or NEUROD1 deficiency had opposing consequences on EC and hormone-producing cell features. Expressed late in EEC differentiation, the latter TFs mainly bind -elements that are accessible in undifferentiated stem cells and tailor the subsequent expression of TF combinations that specify EEC types. Thus, TF oscillations retard EEC maturation to enable accurate EEC diversification.
PubMed: 38260422
DOI: 10.1101/2024.01.09.574746 -
Frontiers in Oncology 2023The prevalence of gastric cancer has markedly declined, but due to the high mortality rates associated with gastric cancer, it is still a serious disease. The preferred... (Review)
Review
The prevalence of gastric cancer has markedly declined, but due to the high mortality rates associated with gastric cancer, it is still a serious disease. The preferred classification of gastric cancer is according to Lauren into either the intestinal type, which has a glandular growth pattern, or the diffuse type, which does not have glandular structures. Both types have been classified as adenocarcinomas, with the latter type based on periodic acid-Schiff (PAS) positivity presumed to reflect mucin. However, the presence of mucin in the diffuse type, in contrast to neuroendocrine/enterochromaffin-like (ECL) cell markers, has not been confirmed by immunohistochemistry and hybridization. The ECL cells are probably prone to becoming cancerous because they do not express E-cadherin. Gastric cancer is unique in that a bacterium, , is thought to be its main cause. predisposes infected individuals to cancer only after having caused oxyntic atrophy leading to gastric hypoacidity and hypergastrinemia. No single factor has been convincingly proved to be carcinogenic. It is probable that gastrin is the pathogenetic factor for gastric cancer due to , autoimmune gastritis, and long-term prolonged inhibition of gastric acid secretion. Hypergastrinemia induces ECL cell hyperplasia, which develops into neuroendocrine tumors (NETs) and then into neuroendocrine carcinomas in rodents, a sequence that has also been described in humans. During carcinogenesis, the tumor cells lose specific traits, requiring that sensitive methods be used to recognize their origin. Gastric cancer occurrence may hopefully be prevented by eradication at a young age, and by the reduced use of inhibitors of acid secretion and use of a gastrin antagonist in those with previous long-term infection and those with autoimmune gastritis.
PubMed: 37941554
DOI: 10.3389/fonc.2023.1176673 -
Comprehensive Physiology Jun 2023Although it is most well-known for its roles in central nervous system (CNS) function, the vast majority of serotonin, or 5-hydroxytryptamine (5-HT), is produced in the...
Although it is most well-known for its roles in central nervous system (CNS) function, the vast majority of serotonin, or 5-hydroxytryptamine (5-HT), is produced in the gastrointestinal (GI) tract. 5-HT is synthesized mostly by enterochromaffin (EC) cells of the GI epithelium and, in small part, by neurons of the enteric nervous system (ENS). The GI tract contains an array of broadly distributed 5-HT receptors, which participate in functions such as motility, sensation, inflammation, and neurogenesis. The roles of 5-HT in these functions are reviewed, as well as its role in the pathophysiology of disorders of gut-brain interaction (DGBIs) and inflammatory bowel diseases (IBD). © 2023 American Physiological Society. Compr Physiol 13:4851-4868, 2023.
Topics: Humans; Serotonin; Gastrointestinal Motility; Receptors, Serotonin; Inflammation; Gastrointestinal Tract
PubMed: 37358510
DOI: 10.1002/cphy.c220024