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American Journal of Physiology. Gastrointestinal and Liver Physiology

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https://www.readbyqxmd.com/read/28526690/emerging-concepts-in-biliary-repair-and-fibrosis
#1
Luca Fabris, Carlo Spirli, Massimiliano Cadamuro, Romina Fiorotto, Mario Strazzabosco
Chronic diseases of the biliary tree (cholangiopathies) represent one of the major unmet needs in clinical hepatology and a significant knowledge gap in liver pathophysiology. The common theme in cholangiopathies is that the target of the disease is the biliary tree. After damage to the biliary epithelium, inflammatory changes stimulate a reparative response with proliferation of cholangiocytes and restoration of the biliary architecture, owing to the re-activation of a variety of morphogenetic signals. Chronic damage and inflammation, will ultimately result in pathologic repair, with generation of biliary fibrosis and clinical progression of the disease...
May 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28526689/long-non-coding-rna-neat1-promotes-hepatocellular-carcinoma-cell-proliferation-through-the-regulation-of-mir-129-5p-vcp-i%C3%AE%C2%BAb
#2
Luo Fang, Jiao Sun, Zongfu Pan, Yu Song, Like Zhong, Yiwen Zhang, Yujia Liu, Xiaowei Zheng, Ping Huang
BACKGROUND: Long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) plays an important role in the pathogenesis and development of several types of cancer. However, the functional mechanism of NEAT1 in hepatocellular carcinoma (HCC) remains unclear. METHODS: The NEAT1 and miR-129-5p expression in HCC tissues and cell lines were quantified by means of qPCR. The effects of NEAT1 expression inhibition or up-regulation in HCC cell lines were analyzed in terms of cell viability and apoptosis...
May 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28526688/loss-of-the-anion-exchanger-dra-slc26a3-or-pat1-slc26a6-alters-sulfate-transport-by-the-distal-ileum-and-overall-sulfate-homeostasis
#3
Jonathan M Whittamore, Marguerite Hatch
The ileum is considered the primary site of inorganic sulfate (SO4(2-)) absorption. In the present study, we explored the contributions of the apical chloride/bicarbonate (Cl(-)/HCO3(-)) exchangers DRA (Slc26a3), and PAT1 (Slc26a6), to the underlying transport mechanism. Transepithelial (35)SO4(2-) and (36)Cl(-) fluxes were determined across isolated, short-circuited segments of the distal ileum from wild-type (WT), DRA-knockout (KO) and PAT1-KO mice, together with measurements of urine and plasma sulfate. The WT distal ileum supported net sulfate absorption (197...
May 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28526687/ffa2-activation-combined-with-ulcerogenic-cox-inhibition-induces-duodenal-mucosal-injury-via-the-5-ht-pathway-in-rats
#4
Yasutada Akiba, Koji Maruta, Kazuyuki Narimatsu, Hyder Said, Izumi Kaji, Ayaka Kuri, Ken-Ichi Iwamoto, Atsukazu Kuwahara, Jonathan D Kaunitz
Serotonin (5-HT), predominantly synthesized and released by enterochromaffin cells, is implicated in gastrointestinal symptoms such as emesis, abdominal pain and diarrhea. Since luminal short-chain fatty acids (SCFAs) release 5-HT from enterochromaffin cells, which express the SCFA receptor FFA2 in rat duodenum, we examined the effects of the selective FFA2 agonist phenylacetamide-1 (PA1) on duodenal 5-HT release with consequent bicarbonate secretion (DBS) and on indomethacin (IND)-induced enteropathy. Intestinal injury was induced by IND (10 mg/kg, sc) with or without PA1...
May 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28495802/a-common-nhe3-single-nucleotide-polymorphism-has-normal-function-and-sensitivity-to-regulatory-ligands
#5
Jianyi Yin, Chung-Ming Tse, Boyoung Cha, Rafiqual Sarker, Xinjun C Zhu, Anna Walentinsson, Peter J Greasley, Mark Donowitz
Na(+)/H(+) exchanger NHE3 mediates the majority of intestinal and renal electroneutral sodium absorption. Dysfunction of NHE3 is associated with a variety of diarrheal diseases. We previously reported that the NHE3 gene (SLC9A3) has more than 400 single nucleotide polymorphisms (SNPs) but few non-synonymous polymorphisms. Among the latter, one polymorphism (rs2247114-G>A), which causes a substitution from arginine to cysteine at amino acid position 799 (p.R799C), is common in Asian populations. To improve our understanding of the population distribution and potential clinical significance of the NHE3-799C variant, we investigated the frequency of this polymorphism in different ethnic groups using bioinformatics analyses, and in a cohort of Japanese patients with cardiovascular or renal disease...
May 11, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28473332/cd151-supports-vcam-1-mediated-lymphocyte-adhesion-to-liver-endothelium-and-is-upregulated-in-chronic-liver-disease-and-hepatocellular-carcinoma
#6
James C R Wadkin, Daniel A Patten, Sivesh Kamarajah, Emma L Shepherd, Vera Novitskaya, Fedor Berditchevski, David H Adams, Chris J Weston, Shishir Shetty
CD151, a member of the tetraspanin family of receptors, is a lateral organizer and modulator of activity of several families of transmembrane proteins. It has been implicated in the development and progression of several cancers but its role in chronic inflammatory disease is less well understood. Here we show that CD151 is up-regulated by distinct microenvironmental signals in a range of chronic inflammatory liver diseases and in primary liver cancer where it supports lymphocyte recruitment. CD151 was highly expressed in endothelial cells of the hepatic sinusoids and neovessels developing in fibrotic septa and tumour margins...
May 4, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28473331/the-emerging-role-of-mast-cells-in-liver-disease
#7
Veronica Jarido, Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Joanne Thomson, Kristen Stephenson, Heather Francis
The depth of our knowledge regarding mast cells has widened exponentially in the last 20 years. Once thought to be only important for allergy-mediated events, mast cells are now recognized to be important regulators of a number of pathological diseases. The revelation that mast cells can influence organs, tissues, and cells has increased interest in mast cell research during liver disease. The purpose of this review is to refresh the reader on the development, type, and location of mast cells and to review recent work that demonstrates the role of hepatic mast cells during diseased states...
May 4, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28450278/from-sensing-to-shaping-microbiota-insights-into-the-role-of-nod2-in-intestinal-homeostasis-and-progression-of-crohn-s-disease
#8
Iyshwarya Balasubramanian, Nan Gao
NOD2 was the first susceptibility gene identified for Crohn's disease (CD), one of the major forms of inflammatory bowel disease (IBD). The field of NOD2 research has opened up many questions critical to understanding the complexities of microbiota-host interactions. In addition to sensing its specific bacterial components as a cytosolic pattern recognition receptor, NOD2 also appears to shape the colonization of intestinal microbiota. Activated NOD2 triggers downstream signaling cascades exampled by the NF-κB pathway to induce anti-microbial activities, however defective or loss of NOD2 functions incur a similarly activated inflammatory response...
April 27, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28450277/absence-of-the-nod2-protein-renders-epithelia-more-susceptible-to-barrier-dysfunction-due-to-mitochondrial-dysfunction
#9
Alpana Saxena, Fernando Lopes, Karen K H Poon, Derek M McKay
Irregular mitochondria structure and reduced ATP in some patients with IBD suggests that metabolic stress contributes to disease. Loss-of-function mutations in the NOD2 gene is a major susceptibility trait for IBD. Hence, we assessed if loss of NOD2 further impairs the epithelial barrier function instigated by disruption of mitochondrial ATP synthesis via the hydrogen ionophore, dinitrophenol (DNP). NOD2 protein (virtually undetectable in epithelia under basal conditions) was increased in T84 (human colon cell line) cells treated with non-invasive E...
April 27, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28450276/pregnancy-and-bile-acid-disorders
#10
Vanessa Pataia, Peter H Dixon, Catherine Williamson
During pregnancy, extensive adaptations in maternal metabolic and immunological physiology occur. Consequently, pre-existing disease may be exacerbated or attenuated and new disease susceptibility may be unmasked. Cholestatic diseases, characterized by a supraphysiological raise in bile acid levels, require careful monitoring during pregnancy. This review describes the latest advances in the knowledge of intrahepatic cholestasis of pregnancy (ICP), the commonest bile acid disorder specific to pregnancy, with a focus on the disease etiology and potential mechanisms of ICP-associated adverse pregnancy outcomes, including fetal demise...
April 27, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28428350/targeted-inactivation-of-copper-transporter-atp7b-in-hepatocytes-causes-liver-steatosis-and-obesity-in-mice
#11
Abigael Muchenditsi, Haojun Yang, James P Hamilton, Lahari Koganti, Franck Housseau, Lisa Aronov, Hongni Fan, Hannah Pierson, Ashima Bhattacharjee, Robert C Murphy, Cynthia L Sears, James J Potter, Clavia Ruth Wooton-Kee, Svetlana Lutsenko
The copper transporter ATP7B is essential for mammalian copper homeostasis. Mutations in ATP7B result in copper accumulation, especially in the liver, and cause Wilson disease (WD). The major role of hepatocytes in WD pathology is firmly established. It is less certain whether the excess Cu in hepatocytes is solely responsible for development of WD. To address this issue, we generated a mouse strain for Cre-mediated deletion of Atp7b and inactivated Atp7b selectively in hepatocytes. Atp7bΔ(Hep) mice accumulate copper in the liver, have elevated urinary copper, lack holo-ceruloplasmin, but show no liver disease for up to 30 weeks...
April 20, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28408644/human-derived-gut-microbiota-modulates-colonic-secretion-in-mice-by-regulating-5-ht3-receptor-expression-via-acetate-production
#12
Yogesh Bhattarai, Bradley A Schmidt, David R Linden, Eric D Larson, Madhusudan Grover, Arthur Beyder, Gianrico Farrugia, Purna C Kashyap
Serotonin (5-hydroxytryptamine, 5-HT), an important neurotransmitter and a paracrine messenger in the gastrointestinal (GI) tract, regulates intestinal secretion by its action primarily on 5-HT3 and 5-HT4 receptors. Recent studies highlight the role of gut microbiota in 5-HT biosynthesis. In this study we determine if human-derived gut microbiota affect host secretory response to 5-HT and 5-HT receptor expression. We used proximal colonic mucosa-submucosa preparation from age matched Swiss Webster germ free (GF) and humanized (HM; ex-GF colonized with human gut microbiota) mice...
April 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28408643/gastrin-induces-parathyroid-hormone-like-hormone-expression-in-gastric-parietal-cells
#13
Asma Al Menhali, Theresa M Keeley, Elise S Demitrack, Linda C Samuelson
Parietal cells play a fundamental role in stomach maintenance, not only by creating a pathogen-free environment through the production of gastric acid, but also by secreting growth factors important for homeostasis of the gastric epithelium. The gastrointestinal hormone gastrin is known to be a central regulator of both parietal cell function and gastric epithelial cell proliferation and differentiation. Our previous gene expression profiling studies of mouse stomach identified parathyroid hormone-like hormone (PTHLH) as a potential gastrin-regulated gastric growth factor...
April 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28408642/elevated-intrabolus-pressure-identifies-obstructive-processes-when-integrated-relaxation-pressure-is-normal-on-esophageal-high-resolution-manometry
#14
Farhan Quader, Chanakyaram Reddy, Amit Patel, C Prakash Gyawali
BACKGROUND: Elevated integrated relaxation pressure (IRP) on esophageal high resolution manometry (HRM) identifies obstructive processes at the esophagogastric junction (EGJ). AIM: To determine if intrabolus pressure (IBP) can identify structural EGJ processes when IRP is normal. METHODS: In this observational cohort study, adult patients with dysphagia and undergoing HRM were evaluated for endoscopic evidence of structural EGJ processes (strictures, rings, hiatus hernia) in the setting of normal IRP...
April 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28408641/gastroparesis-and-lipid-metabolism-associated-dysbiosis-in-wistar-kyoto-rats
#15
Julie E Dalziel, Karl Fraser, Wayne Young, Catherine M Lloyd-West, Shalome A Bassett, Nicole C Roy
Altered gastric accommodation and intestinal morphology suggests impaired gastrointestinal (GI) transit may occur in the Wistar Kyoto (WKY) rat strain, as common in stress-associated functional GI disorders. Because changes in GI transit can alter microbiota composition, we investigated whether these are altered in WKY rats compared with the resilient Sprague Dawley (SD) rats under basal conditions, and characterized plasma lipid and metabolite differences. Bead transit was tracked by X-ray imaging to monitor: gastric emptying (GE; 4 h), small intestine (SI) transit (9 h) and large intestine transit (12 h)...
April 13, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28385695/transient-receptor-potential-ion-channel-function-in-sensory-transduction-and-cellular-signaling-cascades-underlying-visceral-hypersensitivity
#16
Dafne Balemans, Guy E Boeckxstaens, Karel Talavera, Mira M Wouters
Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders (FGID) including functional dyspepsia, irritable bowel syndrome (IBS) and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family...
April 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28385694/phosphatidylcholine-transfer-protein-stard2-promotes-microvesicular-steatosis-and-liver-injury-in-murine-experimental-steatohepatitis
#17
Hayley Tenielle Nicholls, Jason L Hornick, David E Cohen
Mice fed a methionine and choline deficient (MCD) diet develop steatohepatitis that recapitulates key features of nonalcoholic steatohepatitis (NASH) in humans. Phosphatidylcholine is the most abundant phospholipid in the surfactant monolayer that coats and stabilizes lipid droplets within cells, and choline is required for its major biosynthetic pathway. Phosphatidylcholine-transfer protein (PC-TP), which exchanges phosphatidylcholine among membranes, is enriched in hepatocytes. PC-TP also regulates fatty acid metabolism through interactions with thioesterase superfamily member 2...
April 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28385693/expression-and-localization-of-vpac1-the-major-receptor-of-vasoactive-intestinal-peptide-along-the-length-of-the-intestine
#18
Dulari Jayawardena, Grace Guzman, Ravinder K Gill, Waddah A Alrefai, Hayat Onyuksel, Pradeep K Dudeja
Vasoactive intestinal peptide (VIP) is an endogenous neuropeptide with a broad array of physiological functions in many organs including the intestine. Its actions are mediated via G- protein coupled receptors and VPAC1 is the key receptor responsible for majority of VIP's biological activity. The distribution of VPAC1 along the length of the gastrointestinal tract and its sub cellular localization in intestinal epithelial cells has not been fully characterized. The current studies were undertaken to determine VPAC1 distribution and localization so that VIP based therapies can be targeted to specific regions of the intestine...
April 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28360031/intermediate-filament-proteins-of-digestive-organs-physiology-and-pathophysiology
#19
M Bishr Omary
Intermediate filament proteins (IFs), such as cytoplasmic keratins in epithelial cells and vimentin in mesenchymal cells and the nuclear lamins, make up one of the 3 major cytoskeletal protein families. Whether in digestive organs or other tissues, IFs share several unique features including stress-inducible overexpression, abundance, cell-selective and differentiation-state expression, and association with >80 human diseases when mutated. While most IF mutations cause disease, mutations in simple epithelial keratins 8, 18 or 19, or in lamin A/C predispose to liver disease with or without other tissue manifestations...
March 30, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28360030/old-and-new-models-for-studying-host-microbe-interactions-in-health-and-disease-c-difficile-as-an-example
#20
Vincent Bensan Young
There has been an explosion of interest in studying the indigenous microbiota, which plays an important role in human health and disease. Traditionally, the study of microbes in relationship to human health involved consideration of individual microbial species that caused classical infectious diseases. With the interest in the human microbiome, an appreciation of the influence that complex communities of microbes can have on their environment has developed. When considering either individual pathogenic microbes or a symbiotic microbial community, researchers have employed a variety of model systems with which they can study the host-microbe interaction...
March 30, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
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