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    4803 results match your criteria American Journal of Physiology - Gastrointestinal and Liver Physiology [Journal]

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    Mature gastric chief cells are not required for the development of metaplasia.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 18. Epub 2018 Jan 18.
    University of japan.
    During human gastric carcinogenesis, intestinal metaplasia (IM) is frequently seen in the atrophic stomach. In mice, a distinct type of metaplasia known as spasmolytic polypeptide-expressing metaplasia (SPEM) is found in several inflammatory and genetically engineered models. Given the diversity of long- and short-term models of mouse SPEM, it remains unclear whether all models have a shared or distinct molecular mechanism. Read More

    Establishment of a surgical bile duct injection technique giving direct access to the bile ducts for studies of the murine biliary tree.
    Am J Physiol Gastrointest Liver Physiol 2017 Dec 6. Epub 2017 Dec 6.
    NoPSC, Norway.
    Cholangiopathies are progressive disorders with largely unknown pathoetiology and limited treatment options. We aimed to develop a novel surgical technique with direct access to the bile ducts that would complement existing mouse models of cholestasis, biliary inflammation and fibrosis, and present a new route of administration for testing of potential treatment strategies. We developed a surgical technique to access the murine biliary tree by injection of different solvents through catheterization of the gall bladder with simultaneous clamping of the common bile duct. Read More

    β-PIX plays important role in regulation of intestinal epithelial restitution by interacting with GIT1 and Rac1 after wounding.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 30:ajpgi002962017. Epub 2017 Nov 30.
    2 University of Maryland School of Medicine, Baltimore Veterans Affairs Medical Center.
    Early gut mucosal restitution is a process by which intestinal epithelial cells (IECs) migrate over the wounded area, and its defective regulation occurs commonly in various critical pathological conditions. This rapid reepithelialization is mediated by different activating small GTP-binding proteins, but exact mechanism underlying this process remains largely unknown. Recently, it has been reported that interaction between p21-activated kinase-interacting exchange factor (β-PIX) and G-protein-coupled receptor kinase-interacting protein 1 (GIT1) activates small GTPases and plays important role in the regulation of cell motility. Read More

    Genetic deletion of the circadian clock transcription factor BMAL1 and chronic alcohol consumption differentially alter hepatic glycogen in mice.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 30:ajpgi002812017. Epub 2017 Nov 30.
    3 UAB.
    Multiple metabolic pathways exhibit time-of-day dependent rhythms that are controlled by the molecular circadian clock. We have shown that chronic alcohol is capable of altering the molecular clock and diurnal oscillations in several elements of hepatic glycogen metabolism. Herein, we sought to determine whether genetic disruption of the hepatocyte clock differentially impacts hepatic glycogen content in chronic alcohol-fed mice. Read More

    Loss of cellular FLICE-inhibitory protein promotes acute cholestatic liver injury and inflammation from bile duct-ligation.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 30. Epub 2017 Nov 30.
    University Medical Center of the Johannes Gutenberg University Mainz.
    Background: Cholestatic liver injury results from impaired bile flow or metabolism and promotes hepatic inflammation and fibrogenesis. Toxic bile acids that accumulate in cholestasis induce apoptosis and contribute to early cholestatic liver injury, which is amplified by accompanying inflammation. Aim of the current study was to evaluate the role of the anti-apoptotic caspase 8-homologue cellular FLICE-inhibitory (cFLIP) protein during acute cholestatic liver injury. Read More

    Medullary raphe nuclei activate the lumbosacral defecation center through the descending serotonergic pathway to regulate colorectal motility in rats.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 22:ajpgi003172017. Epub 2017 Nov 22.
    1 Gifu University.
    Colorectal motility is regulated by two defecation centers located in the brain and spinal cord. In previous studies, we have shown that administration of serotonin into the lumbosacral spinal cord causes enhancement of colorectal motility. Since spinal serotonin is derived from neurons of the medullary raphe nuclei including the raphe magnus, raphe obscurus and raphe pallidus, we examined whether stimulation of the medullary raphe nuclei enhances colorectal motility via the lumbosacral defecation center. Read More

    Epigenetic Modulation of Intestinal Na+/H+ Exchanger-3 Expression.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 22:ajpgi002932017. Epub 2017 Nov 22.
    3 Jesse Brown VA Medical Center/University of Illinois at Chicago.
    Na+/H+ exchanger-3 (NHE3) is crucial for intestinal Na+ absorption and its reduction has been implicated in infectious and Inflammatory Bowel Diseases (IBD)-associated diarrhea. Epigenetic mechanisms such as DNA methylation are involved in the pathophysiology of IBD. Whether changes in DNA methylation are involved in modulating intestinal NHE3 gene expression is not known. Read More

    Exocrine pancreas glutamate secretion help to sustain enterocyte nutritional needs under protein restriction.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 22:ajpgi001352017. Epub 2017 Nov 22.
    1 University of Zurich.
    Glutamine (Gln) is the most concentrated amino acid in blood and considered conditionally essential. Its requirement is increased during physiological stress, such as malnutrition or illness, despite its production by muscle and other organs. In the malnourished state Gln has been suggested to have a trophic effect on the exocrine pancreas and small intestine. Read More

    Irritable bowel syndrome (IBS) patients have SCN5A channelopathies that lead to decreased NaV1.5 current and mechanosensitivity.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 22:ajpgi000162017. Epub 2017 Nov 22.
    1 Mayo Clinic.
    The SCN5A-encoded voltage-gated mechanosensitive sodium (Na+) channel NaV1.5 is expressed in human GI smooth muscle cells and interstitial cells of Cajal. NaV1. Read More

    Cross-organ sensitisation between the colon and bladder: To pee, or not to pee?
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 16:ajpgi002722017. Epub 2017 Nov 16.
    2 Flinders University, Adelaide.
    Chronic abdominal and pelvic pain are common, debilitating clinical conditions experienced by millions of patients around the globe. The origin of such pain commonly arises from the intestine and bladder, which share common primary roles; the collection, storage and expulsion of waste. These visceral organs are located in close proximity to one another, and also share common innervation from spinal afferent pathways. Read More

    Functional role and therapeutic targeting of microRNAs in Inflammatory Bowel Disease.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 16:ajpgi002682017. Epub 2017 Nov 16.
    2 UCLA.
    Inflammatory Bowel Diseases (IBD) are chronic inflammatory gastrointestinal diseases, primarily consisting of Ulcerative Colitis (UC) and Crohn's Disease (CD). The complex nature of the disease, as well as the limited therapeutic options characterized by low efficiency and major side effects, shows the importance of developing novel strategies of therapeutic intervention in IBD. Susceptibility loci related to IBD are present only in a small percentage of IBD patients, implying that epigenetic modifications could influence the pathogenesis of the disease. Read More

    Epithelial immunity: priming defensive responses in the intestinal mucosa.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 16:ajpgi002152016. Epub 2017 Nov 16.
    2 Vall d'Hebron Institut de Recerca.
    As the largest interface between the outside and internal milieu, the intestinal epithelium constitutes the first structural component facing potential luminal threats to homeostasis. This single-cell layer is the epicenter of a tightly-regulated communication network between external and internal factors which converge to prime defensive responses aimed at limiting antigen penetration and the maintenance of intestinal barrier function. The defensive role developed by intestinal epithelial cells (IEC) relies largely on the variety of receptors they express at both extracellular (apical and basolateral) and intracellular compartments, and the capacity of IEC to communicate with immune and nervous systems. Read More

    Frontline defenders: Goblet cell mediators dictate host-microbe interactions in the intestinal tract during health and disease.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 9:ajpgi001812017. Epub 2017 Nov 9.
    2 University of British Columbia.
    Goblet cells (GC)s are the predominant secretory epithelial cells lining the luminal surface of the mammalian gastrointestinal (GI) tract. Best known for their apical release of the mucin Muc2, which is critical in the formation of the intestinal mucus barrier, GCs have often been overlooked for their active contributions to intestinal protection and host defense. In part, this oversight reflects the limited tools available to study their function, but also because GCs have long been viewed as relatively passive players in promoting intestinal homeostasis and host defense. Read More

    Customization of bilio-pancreatic limb length to modulate and sustain anti-diabetic effect of gastric bypass surgery.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 2:ajpgi002762017. Epub 2017 Nov 2.
    3 Brigham & Women's Hospital.
    Background: Although Roux-en-Y Gastric Bypass (RYGB) remains the most effective treatment for obesity and Type 2 Diabetes (T2D), many patients fail to achieve remission, or relapse. Increasing intestinal limb lengths of RYGB may improve outcomes, but the mechanistic basis for this remains unclear. We hypothesize Bilio-Pancreatic (BP) limb length modulates the anti-diabetic effect of RYGB. Read More

    LncRNA-MIAT promoted proliferation and invasion of HCC cells via sponging miR-214.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 2:ajpgi002422017. Epub 2017 Nov 2.
    2 The First Affiliated Hospital of Nanjing Medical University.
    Background: The aberrant expression of lncRNAs has been involved in various human tumors including hepatocellular carcinoma (HCC). Our study aimed to investigate the potential molecular mechanism of lncRNA-MIAT in HCC.

    Methods: The expression of MIAT and miR-214 in HCC tissues and cells was examined by qRT-PCR, and the levels of EZH2 and β-catenin were detected by western blot assay. Read More

    Metabolic markers of protein maldigestion after a 15N test meal in minipigs with pancreatic exocrine insufficiency.
    Am J Physiol Gastrointest Liver Physiol 2017 Oct 26:ajpgi002182017. Epub 2017 Oct 26.
    1 AgroParisTech/INRA/Université Paris Saclay.
    The effect of pancreatic exocrine insufficiency (PEI) on protein malabsorption is little documented, partly due to methodological barriers. We aimed to validate biomarkers of protein malabsorption using a 15N test meal in a minipig model of PEI. Six pancreatic duct-ligated minipigs were used as a model of PEI and four non-operated animals as a control. Read More

    Animal Models of Chemotherapy-induced Mucositis: Translational Relevance and Challenges.
    Am J Physiol Gastrointest Liver Physiol 2017 Oct 26:ajpgi002042017. Epub 2017 Oct 26.
    2 Hans Christian Andersen Children's Hospital.
    Chemotherapy for cancer patients induces damaging tissue reactions along the epithelium of the gastrointestinal tract (GIT). This chemotherapy-induced mucositis (CIM) is a serious side effect of cytotoxic drugs and several animal models of CIM have been developed to help understand the progression of CIM, and how to prevent it. Animal models allow highly controlled experimental conditions, detailed organ (e. Read More

    Diurnal variations in intestinal barrier integrity and liver pathology in mice: implications for alcohol binge.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 14;314(1):G131-G141. Epub 2017 Nov 14.
    Section of Gastroenterology, Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush University Medical Center , Chicago, Illinois.
    Recent studies suggest that circadian rhythms regulate intestinal barrier integrity, but it is not clear whether there are daily variations in barrier integrity. This study investigated daily variations in intestinal barrier integrity, including whether there are differences in alcohol-induced intestinal barrier dysfunction after an alcohol binge at different times of day and whether this is associated with concurrent liver injury. C57BL6/J male mice were fed a standard chow diet, an alcohol-containing liquid diet, or an alcohol control diet for 4 wk. Read More

    Transjugular intrahepatic portosystemic shunt: impact on systemic haemodynamics and renal and cardiac function in patients with cirrhosis.
    Am J Physiol Gastrointest Liver Physiol 2017 Oct 26:ajpgi000942017. Epub 2017 Oct 26.
    1 Copenhagen University Hospital Hvidovre.
    Background And Aims: Transjugular intrahepatic portosystemic shunt (TIPS) alleviates portal hypertension and possibly increases central blood volume (CBV). Moreover, renal function often improves; however, its effects on cardiac function are unclear. The aims of our study were to examine the effects of TIPS on hemodynamics and renal and cardiac function in patients with cirrhosis. Read More

    Rapid change of liver stiffness after variceal ligation and TIPS implantation.
    Am J Physiol Gastrointest Liver Physiol 2017 Oct 19:ajpgi002392017. Epub 2017 Oct 19.
    1 University of Heidelberg.
    Liver stiffness (LS) as measured by transient elastography is widely used to screen for liver fibrosis. However, LS also increases in response to pressure changes like congestion but no data on portal pressure are available. We here study the effect of rapid portal pressure changes on LS. Read More

    In vivo magnetofection: a novel approach for targeted topical delivery of nucleic acids for rectoanal motility disorders.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 14;314(1):G109-G118. Epub 2017 Nov 14.
    Department of Medicine, Division of Gastroenterology and Hepatology, Sidney Kimmel Medical College of Thomas Jefferson University , Philadelphia, Pennsylvania.
    In these studies, we developed a novel approach of in vivo magnetofection for localized delivery of nucleic acids such as micro-RNA-139-5p (miR-139-5p; which is known to target Rho kinase2) to the circular smooth muscle layer of the internal anal sphincter (IAS). The IAS tone is known to play a major role in the rectoanal continence via activation of RhoA-associated kinase (RhoA/ROCK2). These studies established an optimized protocol for efficient gene delivery using an assembly of equal volumes of in vivo PolyMag and miR139-5p or anti-miR-139-5p (100 nM each) injected in the circular smooth muscle layer in the pinpointed areas of the rat perianal region and then incubated for 20 min under magnetic field. Read More

    Distinct roles of intracellular heat shock protein 70 (Hsp70) in maintaining gastrointestinal homeostasis.
    Am J Physiol Gastrointest Liver Physiol 2017 Oct 19:ajpgi002082017. Epub 2017 Oct 19.
    1 University of Chicago.
    The inducible heat shock protein 70 (Hsp70) is both cytoprotective and immunomodulatory, potentially accounting for its critical role in maintaining gastrointestinal homeostasis. When levels are reduced in conditions like inflammatory bowel diseases (IBD), loss of function contributes to the severity and chronicity of these diseases, although through which cell types and mechanisms remains unclear. Here, the role of Hsp70-mediated intestinal epithelial protection and immune regulation in experimental colitis was examined by using a villin-promoter driven Hsp70 transgene in the TNBS and DSS models and in IL10/Hsp70 double knockout (IL10-/-/Hsp70-/-) mice. Read More

    Dietary copper-fructose interactions alter gut microbial activity in male rats.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 14;314(1):G119-G130. Epub 2017 Nov 14.
    Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine , Louisville, Kentucky.
    Dietary copper-fructose interactions contribute to the development of nonalcoholic fatty liver disease (NAFLD). Gut microbiota play critical roles in the pathogenesis of NAFLD. The aim of this study was to determine the effect of different dietary doses of copper and their interactions with high fructose on gut microbiome. Read More

    Hydrogen Sulfide: An Agent of Stability at the Microbiome-Mucosa Interface.
    Am J Physiol Gastrointest Liver Physiol 2017 Oct 12:ajpgi002492017. Epub 2017 Oct 12.
    1 University of Calgary.
    A diverse range of effects of the intestinal microbiota on mucosal defence and injury has become increasingly clear over the past decade. Hydrogen sulfide (H2S) has emerged as an important mediator of many physiological functions, including gastrointestinal mucosal defence and repair. Hydrogen sulfide is produced gastrointestinal tract tissues and by bacteria residing within the gut, and can influence the function of a wide range of cells. Read More

    Rack1 maintains intestinal homeostasis by protecting the integrity of the epithelial barrier.
    Am J Physiol Gastrointest Liver Physiol 2017 Oct 12:ajpgi002412017. Epub 2017 Oct 12.
    1 Stanford University.
    Previously we generated mouse models of Rack1 deficiency to identify key functions for Rack1 in regulating growth of intestinal epithelia: suppressing crypt cell proliferation and regeneration, promoting differentiation and apoptosis, and repressing development of neoplasia. However, other than low body weight, we did not detect an overt phenotype in mice constitutively deleted of Rack1 in intestinal epithelia ( vil-Cre:Rack1fl/fl mice), presumably because Rack1 was deleted in < 10% of the total surface area of the epithelia. To assess the effect of Rack1 loss throughout the entire intestinal epithelia, we generated another mouse model of Rack1 deficiency, vil-Cre-ERT2:Rack1fl/fl. Read More

    Macrophage depletion using clodronate liposomes decreases tumorigenesis and alters gut microbiota in the AOM/DSS mouse model of colon cancer.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 14;314(1):G22-G31. Epub 2017 Nov 14.
    Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina , Columbia, South Carolina.
    We examined the role of macrophages in inflammation associated with colorectal cancer (CRC). Given the emerging evidence on immune-microbiota interactions in CRC, we also sought to examine the interaction between macrophages and gut microbiota. To induce CRC, male C57BL/6 mice ( n = 32) received a single injection of azoxymethane (AOM), followed by three cycles of dextran sodium sulfate (DSS)-supplemented water in weeks 1, 4, and 7. Read More

    Apelin-13 inhibits gastric motility through vagal cholinergic pathway in rats.
    Am J Physiol Gastrointest Liver Physiol 2017 Oct 12:ajpgi002232017. Epub 2017 Oct 12.
    2 Penn State College of Medicine.
    The expression of apelin and its receptors (APJ) in central autonomic networks suggests that apelin may regulate gastrointestinal motor functions. In rodents, central administration of apelin-13 has been shown to inhibit gastric emptying, however, the mechanisms involved remain to be determined. Using male adult Sprague-Dawley rats, the aims of the present study were i) to determine the expression of APJ receptor in DVC, ii) to assess the effects central application of apelin-13 into the dorsal vagal complex (DVC) on gastric tone and motility and iii) to investigate the neuronal pathways responsible for apelin-induced alterations. Read More

    Live cell imaging of cytosolic NADH/NAD+ ratio in hepatocytes and liver slices.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 14;314(1):G97-G108. Epub 2017 Nov 14.
    Department of Neurobiology, Harvard Medical School , Boston, Massachusetts.
    Fatty liver disease (FLD), the most common chronic liver disease in the United States, may be caused by alcohol or the metabolic syndrome. Alcohol is oxidized in the cytosol of hepatocytes by alcohol dehydrogenase (ADH), which generates NADH and increases cytosolic NADH/NAD+ ratio. The increased ratio may be important for development of FLD, but our ability to examine this question is hindered by methodological limitations. Read More

    Simultaneous K-ras activation and Keap1 deletion cause atrophy of pancreatic parenchyma.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 7;314(1):G65-G74. Epub 2017 Nov 7.
    Division of Gastroenterology, Tohoku University Graduate School of Medicine , Sendai , Japan.
    The Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) system has a wide variety of effects in addition to the oxidative stress response, such as growth promotion and chemoresistance of cancer cells. Nrf2 is constitutively activated in most cancer cells. However, the activation of Nrf2 together with oncogenic mutations does not always result in cancer promotion. Read More

    Hyperglucagonemia correlates with plasma levels of non-branched-chain amino acids in patients with liver disease independent of type 2 diabetes.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 7;314(1):G91-G96. Epub 2017 Nov 7.
    Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
    Patients with type 2 diabetes (T2D) and patients with nonalcoholic fatty liver disease (NAFLD) frequently exhibit elevated plasma concentrations of glucagon (hyperglucagonemia). Hyperglucagonemia and α-cell hyperplasia may result from elevated levels of plasma amino acids when glucagon's action on hepatic amino acid metabolism is disrupted. We therefore measured plasma levels of glucagon and individual amino acids in patients with and without biopsy-verified NAFLD and with and without type T2D. Read More

    CGRPα within the Trpv1-Cre population contributes to visceral nociception.
    Am J Physiol Gastrointest Liver Physiol 2017 Sep 28:ajpgi001882017. Epub 2017 Sep 28.
    4 University of Uppsala.
    The role of Calcitonin Gene Related Peptide (CGRP) in visceral and somatic nociception is incompletely understood. CGRPα is highly expressed in sensory neurons of dorsal root ganglia (DRG) and particularly in neurons that also express the transient receptor potential cation channel subfamily V member 1 (Trpv1). Therefore, we investigated changes in visceral and somatic nociception following deletion of CGRPα from the Trpv1-Cre population using the Cre/lox system. Read More

    S-allyl-glutathione improves experimental liver fibrosis by regulating Kupffer cell activation in rats.
    Am J Physiol Gastrointest Liver Physiol 2017 Sep 28:ajpgi000232017. Epub 2017 Sep 28.
    4 Kyoto Prefectural University.
    S-allyl-glutathione (SAG) is one of the metabolites of diallyl sulfide (DAS), a component of garlic. DAS has shown preventative effects on carcinogenesis in animal models. However, whether synthetic SAG can improve liver fibrosis has not been investigated. Read More

    Rack1 function in intestinal epithelia: regulating crypt cell proliferation and regeneration and promoting differentiation and apoptosis.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 7;314(1):G1-G13. Epub 2017 Nov 7.
    Department of Medicine, Stanford University , Stanford, California.
    Previously, we showed that receptor for activated C kinase 1 (Rack1) regulates growth of colon cells in vitro, partly by suppressing Src kinase activity at key cell cycle checkpoints, in apoptotic and cell survival pathways and at cell-cell adhesions. Here, we generated mouse models of Rack1 deficiency to assess Rack1's function in intestinal epithelia in vivo. Intestinal Rack1 deficiency resulted in proliferation of crypt cells, diminished differentiation of crypt cells into enterocyte, goblet, and enteroendocrine cell lineages, and expansion of Paneth cell populations. Read More

    Synaptic activation of putative sensory neurons by hexamethonium-sensitive nerve pathways in mouse colon.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 7;314(1):G53-G64. Epub 2017 Nov 7.
    Discipline of Human Physiology and Centre for Neuroscience, Flinders University , Adelaide South Australia.
    The gastrointestinal tract contains its own independent population of sensory neurons within the gut wall. These sensory neurons have been referred to as intrinsic primary afferent neurons (IPANs) and can be identified by immunoreactivity to calcitonin gene-related peptide (CGRP) in mice. A common feature of IPANs is a paucity of fast synaptic inputs observed during sharp microelectrode recordings. Read More

    Role of eosinophils in the initiation and progression of pancreatitis pathogenesis.
    Am J Physiol Gastrointest Liver Physiol 2017 Sep 21:ajpgi002102017. Epub 2017 Sep 21.
    1 Tulane University School of Medicine.
    Eosinophilic pancreatitis (EP) is reported in human; however, the etiology and the role of eosinophils in EP pathogenesis is a poorly understood and not excusably explored. Therefore, it is interesting to examine the role of eosinophils in the initiation and progression of pancreatitis pathogenesis. Therefore, we performed real time PCR, ELISA, western blot, anti-MBP immunostaining, Chloroesterase and Massons' trichrome analysis were performed to examine transcript and protein levels of eosinophil active cytokines, chemokines, eosinophils, mast cells and collagen tissue accumulation. Read More

    Neuroimmune interaction and the regulation of intestinal immune homeostasis.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 7;314(1):G75-G80. Epub 2017 Nov 7.
    Translational Research Center of Gastrointestinal Disorders, KU Leuven, Leuven , Belgium.
    Many essential gastrointestinal functions, including motility, secretion, and blood flow, are regulated by the autonomic nervous system (ANS), both through intrinsic enteric neurons and extrinsic (sympathetic and parasympathetic) innervation. Recently identified neuroimmune mechanisms, in particular the interplay between enteric neurons and muscularis macrophages, are now considered to be essential for fine-tuning peristalsis. These findings shed new light on how intestinal immune cells can support enteric nervous function. Read More

    Role of MicroRNA-423-5p in posttranscriptional regulation of the intestinal riboflavin transporter-3.
    Am J Physiol Gastrointest Liver Physiol 2017 Dec 14;313(6):G589-G598. Epub 2017 Sep 14.
    Departments of Medicine and Physiology/Biophysics, University of California, Irvine, California; and Department of Medical Research, Veterans Affairs Medical Center, Long Beach, California
    Riboflavin (RF) is essential for normal cellular functions and health. Humans obtain RF from exogenous sources via intestinal absorption that involves a highly specific carrier-mediated process. We have recently established that the riboflavin transporter-3 (RFVT3) is vital for the normal intestinal RF uptake process and have characterized certain aspects of its transcriptional regulation. Read More

    Hepatocyte nuclear factor 4α regulates the expression of intestinal epithelial Na+/H+ exchanger isoform 3.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 7;314(1):G14-G21. Epub 2017 Nov 7.
    Jesse Brown Veterans Affairs Medical Center , Chicago, Illinois.
    Na+/H+ exchanger isoform 3 (NHE3) plays a key role in coupled electroneutral NaCl absorption in the mammalian intestine. Reduced NHE3 expression or function has been implicated in the pathogenesis of diarrhea associated with inflammatory bowel disease (IBD) or enteric infections. Our previous studies revealed transcriptional regulation of NHE3 by various agents such as TNF-α, IFN-γ, and butyrate involving transcription factors Sp1 and Sp3. Read More

    A physics-based model for maintenance of the pH gradient in the gastric mucus layer.
    Am J Physiol Gastrointest Liver Physiol 2017 Dec 7;313(6):G599-G612. Epub 2017 Sep 7.
    Department of Mathematics, University of Utah, Salt Lake City, Utah; and.
    It is generally accepted that the gastric mucus layer provides a protective barrier between the lumen and the mucosa, shielding the mucosa from acid and digestive enzymes and preventing autodigestion of the stomach epithelium. However, the precise mechanisms that contribute to this protective function are still up for debate. In particular, it is not clear what physical processes are responsible for transporting hydrogen protons, secreted within the gastric pits, across the mucus layer to the lumen without acidifying the environment adjacent to the epithelium. Read More

    The antioxidant glutathione protects against enteric neuron death in situ, but its depletion is protective during colitis.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 7;314(1):G39-G52. Epub 2017 Nov 7.
    Department of Physiology, Michigan State University , East Lansing, Michigan.
    Enteric glia play an important neuroprotective role in the enteric nervous system (ENS) by producing neuroprotective compounds such as the antioxidant reduced glutathione (GSH). The specific cellular pathways that regulate glial production of GSH and how these pathways are altered during, or contribute to, neuroinflammation in situ and in vivo are not fully understood. We investigated this issue using immunohistochemistry to localize GSH synthesis enzymes within the myenteric plexus and tested how the inhibition of GSH synthesis with the selective inhibitor l-buthionine sulfoximine impacts neuronal survival and inflammation. Read More

    Both NHERF3 and NHERF2 are necessary for multiple aspects of acute regulation of NHE3 by elevated Ca2+, cGMP, and lysophosphatidic acid.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 7;314(1):G81-G90. Epub 2017 Nov 7.
    Department of Medicine, the Johns Hopkins School of Medicine, Baltimore, Maryland.
    The intestinal epithelial brush border Na+/H+ exchanger NHE3 accounts for a large component of intestinal Na absorption. NHE3 is regulated during digestion by signaling complexes on its COOH terminus that include the four multi-PDZ domain-containing NHERF family proteins. All bind to NHE3 and take part in different aspects of NHE3 regulation. Read More

    Zinc strengthens the jejunal barrier by reversibly tightening the paracellular route.
    Am J Physiol Gastrointest Liver Physiol 2017 Dec 1;313(6):G537-G548. Epub 2017 Sep 1.
    Institute of Clinical Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany
    During the postweaning period, piglets are prone to gastrointestinal infections. The resulting impairment of intestinal barrier function may cause diarrhea associated with growth retardation or even death of piglets. Orally applied Zn is commonly used to prevent and treat diarrhea, but its mode of action still needs to be elucidated. Read More

    Krüppel-like factor 5 is essential for maintenance of barrier function in mouse colon.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 1;313(5):G478-G491. Epub 2017 Sep 1.
    Department of Medicine, Stony Brook University School of Medicine, Stony Brook, New York;
    Krüppel-like factor 5 (KLF5) is a member of the zinc finger family of transcription factors that regulates homeostasis of the intestinal epithelium. Previous studies suggested an indispensable role of KLF5 in maintaining intestinal barrier function. In the current study, we investigated the mechanisms by which KLF5 regulates colonic barrier function in vivo and in vitro. Read More

    Ethanol metabolism by alcohol dehydrogenase or cytochrome P450 2E1 differentially impairs hepatic protein trafficking and growth hormone signaling.
    Am J Physiol Gastrointest Liver Physiol 2017 Dec 1;313(6):G558-G569. Epub 2017 Sep 1.
    Department of Biology, The Catholic University of America, Washington, District of Columbia;
    The liver metabolizes alcohol using alcohol dehydrogenase (ADH) and cytochrome P450 2E1 (CYP2E1). Both enzymes metabolize ethanol into acetaldehyde, but CYP2E1 activity also results in the production of reactive oxygen species (ROS) that promote oxidative stress. We have previously shown that microtubules are hyperacetylated in ethanol-treated polarized, hepatic WIF-B cells and livers from ethanol-fed rats. Read More

    New ultrasonographic screening method for oropharyngeal dysphagia: tissue Doppler imaging.
    Am J Physiol Gastrointest Liver Physiol 2018 Jan 4;314(1):G32-G38. Epub 2017 Dec 4.
    Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School , Kurashiki , Japan.
    Ultrasound tissue Doppler imaging (US-TDI) has been used to diagnose regional wall motion (WM) abnormalities in coronary artery disease but has not been applied to oropharyngeal diseases. This study aimed first to validate an US-TDI method to assess cervical esophageal (CE) WM and secondly to use the method to evaluate CE WM in patients with oropharyngeal dysphagia (OD). First, we enrolled 22 healthy men (mean age: 59. Read More

    Age-related external anal sphincter muscle dysfunction and fibrosis: possible role of Wnt/β-catenin signaling pathways.
    Am J Physiol Gastrointest Liver Physiol 2017 Dec 24;313(6):G581-G588. Epub 2017 Aug 24.
    Division of Gastroenterology, Department of Medicine, Veterans Affairs San Diego Healthcare System and University of California, San Diego, California.
    Studies show an age-related increase in the prevalence of anal incontinence and sphincter muscle atrophy. The Wnt/β-catenin signaling pathway has been recently recognized as the major molecular pathway involved in age-related skeletal muscle atrophy and fibrosis. The goals of our study were to 1) evaluate the impact of normal aging on external anal sphincter (EAS) muscle length-tension (L-T) function and morphology and 2) specifically examine the role of Wnt signaling pathways in anal sphincter muscle fibrosis. Read More

    Ammonia modifies enteric neuromuscular transmission through glial γ-aminobutyric acid signaling.
    Am J Physiol Gastrointest Liver Physiol 2017 Dec 24;313(6):G570-G580. Epub 2017 Aug 24.
    Neuroscience Program and Department of Physiology, Michigan State University, East Lansing, Michigan;
    Impaired gut motility may contribute, at least in part, to the development of systemic hyperammonemia and systemic neurological disorders in inherited metabolic disorders, or in severe liver and renal disease. It is not known whether enteric neurotransmission regulates intestinal luminal and hence systemic ammonia levels by induced changes in motility. Here, we propose and test the hypothesis that ammonia acts through specific enteric circuits to influence gut motility. Read More

    Targeting palmitoyl acyltransferase ZDHHC21 improves gut epithelial barrier dysfunction resulting from burn-induced systemic inflammation.
    Am J Physiol Gastrointest Liver Physiol 2017 Dec 24;313(6):G549-G557. Epub 2017 Aug 24.
    Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, Florida
    Clinical studies in burn patients demonstrate a close association between leaky guts and increased incidence or severity of sepsis and other complications. Severe thermal injury triggers intestinal inflammation that contributes to intestinal epithelial hyperpermeability, which exacerbates systemic response leading to multiple organ failure and sepsis. In this study, we identified a significant function of a particular palmitoyl acyltransferase, zinc finger DHHC domain-containing protein-21 (ZDHHC21), in mediating signaling events required for gut hyperpermeability induced by inflammation. Read More

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