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    4791 results match your criteria American Journal of Physiology - Gastrointestinal and Liver Physiology [Journal]

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    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:ajpgi.00181.2017. Epub 2017 Nov 9.
    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:ajpgi.00276.2017. Epub 2017 Nov 2.
    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:ajpgi.00242.2017. Epub 2017 Nov 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 (15)N test meal in minipigs with pancreatic exocrine insufficiency.
    Am J Physiol Gastrointest Liver Physiol 2017 Oct 26:ajpgi.00218.2017. Epub 2017 Oct 26.
    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 (15)N 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:ajpgi.00204.2017. Epub 2017 Oct 26.
    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 2017 Oct 26:ajpgi.00103.2017. Epub 2017 Oct 26.
    Rush University Medical Center.
    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 if there are differences in alcohol-induced intestinal barrier dysfunction after an alcohol binge at different times of day and if 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 four weeks. 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:ajpgi.00094.2017. Epub 2017 Oct 26.
    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:ajpgi.00239.2017. Epub 2017 Oct 19.
    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 2017 Oct 19:ajpgi.00233.2017. Epub 2017 Oct 19.
    Thomas Jefferson University
    In these studies, we developed a novel approach of in vivo magnetofection for localized delivery of nucleic acids such as micro-RNA-139-p (miR-139-5p, 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 pin-pointed areas of the rat perianal region, and then incubated for 20 minutes 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:ajpgi.00208.2017. Epub 2017 Oct 19.
    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 2017 Oct 12:ajpgi.00378.2016. Epub 2017 Oct 12.
    University of Louisville, Louisville VA Medical Center.
    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:ajpgi.00249.2017. Epub 2017 Oct 12.
    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:ajpgi.00241.2017. Epub 2017 Oct 12.
    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:Rack1(fl/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-ER(T2):Rack1(fl/fl) Within 5-10 days of the initial tamoxifen treatment, the mice lost over 20% of their body weight, developed severe diarrhea that for some was bloody, became critically ill and died, if not euthanized. 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 2017 Oct 12:ajpgi.00229.2017. Epub 2017 Oct 12.
    University of South Carolina
    We examined the role of macrophages in inflammation associated 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 at weeks 1, 4, and 7, respectively. Read More

    Apelin-13 inhibits gastric motility through vagal cholinergic pathway in rats.
    Am J Physiol Gastrointest Liver Physiol 2017 Oct 12:ajpgi.00223.2017. Epub 2017 Oct 12.
    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 2017 Oct 12:ajpgi.00093.2017. Epub 2017 Oct 12.
    Harvard University.
    Fatty liver disease (FLD), the most common chronic liver disease in the US, 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 2017 Sep 28:ajpgi.00228.2017. Epub 2017 Sep 28.
    Tohoku University Graduate School of Medicine
    The Keap1-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 chained amino acids in patients with liver disease independent of type 2 diabetes.
    Am J Physiol Gastrointest Liver Physiol 2017 Sep 28:ajpgi.00216.2017. Epub 2017 Sep 28.
    University of Copenhagen.
    Patients with type 2 diabetes (T2D) and patients with non-alcoholic fatty liver disease (NAFLD) frequently exhibit elevated plasma concentrations of glucagon (hyperglucagonemia). Hyperglucagonemia and alpha-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:ajpgi.00188.2017. Epub 2017 Sep 28.
    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:ajpgi.00023.2017. Epub 2017 Sep 28.
    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 2017 Sep 21:ajpgi.00240.2017. Epub 2017 Sep 21.
    Stanford University
    Previously we showed that Rack1 (Receptor for Activated C Kinase) 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. Following radiation injury, the morphology of Rack1-deleted small bowel was strikingly abnormal with development of large polypoid structures that contained many partly formed villi, numerous back-to-back elongated and regenerating crypts, and high-grade dysplasia in surface epithelia. Read More

    Am J Physiol Gastrointest Liver Physiol 2017 Sep 21:ajpgi.00234.2017. Epub 2017 Sep 21.
    Flinders University
    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:ajpgi.00210.2017. Epub 2017 Sep 21.
    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

    Neuro-immune interaction and the regulation of intestinal immune homeostasis.
    Am J Physiol Gastrointest Liver Physiol 2017 Sep 14:ajpgi.00425.2016. Epub 2017 Sep 14.
    KU Leuven.
    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 neuro-immune 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 post-transcriptional regulation of the intestinal riboflavin transporter-3.
    Am J Physiol Gastrointest Liver Physiol 2017 Sep 14:ajpgi.00238.2017. Epub 2017 Sep 14.
    UCI/VA Medical Center
    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 (NHE3).
    Am J Physiol Gastrointest Liver Physiol 2017 Sep 7:ajpgi.00225.2017. Epub 2017 Sep 7.
    University of Illinois at Chicago.
    The Na(+)/H(+) exchanger isoform-3 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 IBD or enteric infections. Our previous studies revealed transcriptional regulation of NHE3 by various agents such as TNF-, IFN-γ and butyrate involving the 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 Sep 7:ajpgi.00221.2017. Epub 2017 Sep 7.
    University of Utah.
    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 auto-digestion 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 2017 Sep 7:ajpgi.00165.2017. Epub 2017 Sep 7.
    Michigan State University
    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 (BSO) impacts neuronal survival and inflammation. Read More

    Both NHERF3 and NHERF2 are necessary for multiple aspects of acute regulation of NHE3 by elevated Ca(2+), cGMP and lysophosphatidic acid.
    Am J Physiol Gastrointest Liver Physiol 2017 Sep 7:ajpgi.00140.2017. Epub 2017 Sep 7.
    Johns Hopkins University School of Medicine
    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 C-terminus that include the four multi-PDZ domain containing NHERF family proteins. Because the roles of each NHERF appear to vary based on the cell model or intestinal segment studied and because of our recent finding that a NHERF3-NHERF2 heterodimer appears important for NHE3 regulation in Caco-2 cells, we examined the role of NHERF3 and NHERF2 in homozygous C57BL/6 NHERF2 and NHERF3 KO mouse jejunum. Read More

    Zinc strengthens the jejunal barrier by reversibly tightening the paracellular route.
    Am J Physiol Gastrointest Liver Physiol 2017 Sep 1:ajpgi.00355.2016. Epub 2017 Sep 1.
    Charité - Universitätsmedizin Berlin
    During the post weaning 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 zinc 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 Sep 1:ajpgi.00027.2017. Epub 2017 Sep 1.
    The Catholic University of America
    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 2017 Sep 1:ajpgi.00019.2017. Epub 2017 Sep 1.
    Kawasaki Medical School
    Background: 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).

    Methods: First, we enrolled 22 healthy men (mean age: 59. Read More

    Age Related External Anal Sphincter Muscle Dysfunction & Fibrosis: Possible Role of Wnt-β Catenin Signaling Pathways.
    Am J Physiol Gastrointest Liver Physiol 2017 Aug 24:ajpgi.00209.2017. Epub 2017 Aug 24.
    University of California, San Diego.
    Studies show an age-related increase in the prevalence of anal incontinence and sphincter muscle atrophy. Wnt-β catenin signaling pathway has been recently recognized as the major molecular pathway involved in the age-related skeletal muscle atrophy and fibrosis. The goals of our study were to evaluate: (i) impact of normal aging on the EAS muscle length-tension (L-T) function & morphology; and (ii) specifically examine the role of Wnt signaling pathways in anal sphincter muscle fibrosis. Read More

    Ammonia modifies enteric neuromuscular transmission through glial gamma-aminobutyric acid signaling.
    Am J Physiol Gastrointest Liver Physiol 2017 Aug 24:ajpgi.00154.2017. Epub 2017 Aug 24.
    Michigan State University
    Objective: 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.

    Design: 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 Aug 24:ajpgi.00145.2017. Epub 2017 Aug 24.
    University of South Florida Morsani College of Medicine
    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 (PAT), ZDHHC21, in mediating signaling events required for gut hyperpermeability induced by inflammation. Read More

    Effects of NK1 receptors on gastric motor functions and satiation in healthy humans: results from a controlled trial with the NK1 antagonist aprepitant.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 16;313(5):G505-G510. Epub 2017 Aug 16.
    Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota
    Aprepitant, an NK1 receptor antagonist, is approved for the treatment of chemotherapy-induced or postoperative emesis by blocking NK1 receptors in the brain stem vomiting center. The effects of NK1 receptors on gastric functions and postprandial symptoms in humans are unclear; a single, crossover study did not show a significant effect of aprepitant on gastrointestinal transit. Our aim was to compare, in a randomized, double-blind, placebo-controlled, parallel-group study (12 healthy volunteers per group), the effects of aprepitant vs. Read More

    A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 10;313(5):G492-G504. Epub 2017 Aug 10.
    Biochemistry and Molecular Genetics Department, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain;
    Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Read More

    Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 10;313(5):G511-G523. Epub 2017 Aug 10.
    Department of Nutritional Science & Toxicology, University of California, Berkeley, California.
    Iron homeostasis is tightly regulated, and the peptide hormone hepcidin is considered to be a principal regulator of iron metabolism. Previous studies in a limited number of mouse strains found equivocal sex- and strain-dependent differences in mRNA and serum levels of hepcidin and reported conflicting data on the relationship between hepcidin (Hamp1) mRNA levels and iron status. Our aim was to clarify the relationships between strain, sex, and hepcidin expression by examining multiple tissues and the effects of different dietary conditions in multiple inbred strains. Read More

    Enteric serotonin and oxytocin: endogenous regulation of severity in a murine model of necrotizing enterocolitis.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 3;313(5):G386-G398. Epub 2017 Aug 3.
    Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York; and.
    Necrotizing enterocolitis (NEC), a gastrointestinal inflammatory disease of unknown etiology that may also affect the liver, causes a great deal of morbidity and mortality in premature infants. We tested the hypothesis that signaling molecules, which are endogenous to the bowel, regulate the severity of intestinal and hepatic damage in an established murine NEC model. Specifically, we postulated that mucosal serotonin (5-HT), which is proinflammatory, would exacerbate experimental NEC and that oxytocin (OT), which is present in enteric neurons and is anti-inflammatory, would oppose it. Read More

    Relationship of gastric emptying or accommodation with satiation, satiety, and postprandial symptoms in health.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 3;313(5):G442-G447. Epub 2017 Aug 3.
    Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
    The contributions of gastric emptying (GE) and gastric accommodation (GA) to satiation, satiety, and postprandial symptoms remain unclear. We aimed to evaluate the relationships between GA or GE with satiation, satiety, and postprandial symptoms in healthy overweight or obese volunteers (total n = 285, 73% women, mean BMI 33.5 kg/m(2)): 26 prospectively studied obese, otherwise healthy participants and 259 healthy subjects with previous similar GI testing. Read More

    Overactivation of intestinal sterol response element-binding protein 2 promotes diet-induced nonalcoholic steatohepatitis.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 3;313(5):G376-G385. Epub 2017 Aug 3.
    Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois;
    Nonalcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver that may progress to hepatic fibrosis and nonalcoholic steatohepatitis (NASH). Mechanisms underlying NAFLD and NASH are not yet fully understood. Dietary cholesterol was recently shown to be a risk factor for the development of NASH, suggesting a role for intestinal handling of cholesterol. Read More

    Role of G protein-coupled receptors-microRNA interactions in gastrointestinal pathophysiology.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 3;313(5):G361-G372. Epub 2017 Aug 3.
    Center for Inflammatory Bowel Diseases, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; and
    G protein-coupled receptors (GPCRs) make up the largest transmembrane receptor superfamily in the human genome and are expressed in nearly all gastrointestinal cell types. Coupling of GPCRs and their respective ligands activates various phosphotransferases in the cytoplasm, and, thus, activation of GPCR signaling in intestine regulates many cellular and physiological processes. Studies in microRNAs (miRNAs) demonstrate that they represent critical epigenetic regulators of different pathophysiological responses in different organs and cell types in humans and animals. Read More

    PARP2 deficiency affects invariant-NKT-cell maturation and protects mice from concanavalin A-induced liver injury.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 27;313(5):G399-G409. Epub 2017 Jul 27.
    Institut National de la Santé et de la Recherche Médicale, Institut de Recherche Santé Environnement et Travail, Rennes, France;
    Excessive or persistent inflammation and hepatocyte death are the key triggers of liver diseases. The poly(ADP-ribose) polymerase (PARP) proteins induce cell death and inflammation. Chemical inhibition of PARP activity protects against liver injury during concanavalin A (ConA)-induced hepatitis. Read More

    Melatonin inhibits hypothalamic gonadotropin-releasing hormone release and reduces biliary hyperplasia and fibrosis in cholestatic rats.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 27;313(5):G410-G418. Epub 2017 Jul 27.
    Research, Central Texas Veterans Health Care System, Temple, Texas;
    Melatonin is a hormone produced by the pineal gland with increased circulating levels shown to inhibit biliary hyperplasia and fibrosis during cholestatic liver injury. Melatonin also has the capability to suppress the release of hypothalamic gonadotropin-releasing hormone (GnRH), a hormone that promotes cholangiocyte proliferation when serum levels are elevated. However, the interplay and contribution of neural melatonin and GnRH to cholangiocyte proliferation and fibrosis in bile duct-ligated (BDL) rats have not been investigated. Read More

    A simple, cost-effective method for generating murine colonic 3D enteroids and 2D monolayers for studies of primary epithelial cell function.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 27;313(5):G467-G475. Epub 2017 Jul 27.
    Department of Physiology and Pharmacology and Gastrointestinal Research Group, University of Calgary, Calgary, Alberta, Canada;
    Cancer cell lines have been the mainstay of intestinal epithelial experimentation for decades, due primarily to their immortality and ease of culture. However, because of the inherent biological abnormalities of cancer cell lines, many cellular biologists are currently transitioning away from these models and toward more representative primary cells. This has been particularly challenging, but recent advances in the generation of intestinal organoids have brought the routine use of primary cells within reach of most epithelial biologists. Read More

    Adaptive regulation of pancreatic acinar mitochondrial thiamin pyrophosphate uptake process: possible involvement of epigenetic mechanism(s).
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 20;313(5):G448-G455. Epub 2017 Jul 20.
    Department of Medical Research, Veterans Affairs Medical Center, Long Beach, California; and Departments of Medicine and Physiology/Biophysics, University of California, Irvine, California
    The essentiality of thiamin stems from its roles as a cofactor [mainly in the form of thiamin pyrophosphate (TPP)] in critical metabolic reactions including oxidative energy metabolism and reduction of cellular oxidative stress. Like other mammalian cells, pancreatic acinar cells (PAC) obtain thiamin from their surroundings and convert it to TPP; mitochondria then take up TPP by a carrier-mediated process that involves the mitochondrial TPP (MTPP) transporter (MTPPT; product of SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the MTPP uptake process, but little is known about its possible adaptive regulation. Read More

    Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.
    Am J Physiol Gastrointest Liver Physiol 2017 Nov 20;313(5):G434-G441. Epub 2017 Jul 20.
    Department of Neural and Behavioral Sciences, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania
    Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e. Read More

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