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American Journal of Physiology. Gastrointestinal and Liver Physiology

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https://www.readbyqxmd.com/read/28912251/neuro-immune-interaction-and-the-regulation-of-intestinal-immune-homeostasis
#1
Simon Verheijden, Guy E Boeckxstaens
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...
September 14, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28912250/role-of-microrna-423-5p-in-post-transcriptional-regulation-of-the-intestinal-riboflavin-transporter-3
#2
Ram Lakhan, Veedamali S Subramanian, Hamid M Said
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. Little is known, however, about how this transporter is regulated at the post-transcriptional level. We address this issue focusing on the role of microRNAs...
September 14, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28882825/hepatocyte-nuclear-factor-4%C3%AE-regulates-the-expression-of-intestinal-epithelial-na-h-exchanger-isoform-3-nhe3
#3
Saminathan Muthusamy, Jong Jin Jeong, Ming Cheng, Jessica A Bonzo, Anoop Kumar, Frank J Gonzalez, Alip Borthakur, Pradeep K Dudeja, Seema Saksena, Jaleh Malakooti
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. In silico analysis revealed that the NHE3 core promoter also contains a hepatocyte nuclear factor 4α (HNF4α) binding site that is evolutionarily conserved in several species suggesting that HNF4α has a role in NHE3 regulation...
September 7, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28882824/a-physics-based-model-for-maintenance-of-the-ph-gradient-in-the-gastric-mucus-layer
#4
Owen L Lewis, James P Keener, Aaron L Fogelson
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...
September 7, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28882823/the-antioxidant-glutathione-protects-against-enteric-neuron-death-in-situ-but-its-depletion-is-protective-during-colitis
#5
Isola Am Brown, Brian D Gulbransen
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...
September 7, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28882822/both-nherf3-and-nherf2-are-necessary-for-multiple-aspects-of-acute-regulation-of-nhe3-by-elevated-ca-2-cgmp-and-lysophosphatidic-acid
#6
Leela Rani Avula, Tiane Chen, Olga Kovbasnjuk, Mark Donowitz
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...
September 7, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28864501/zinc-strengthens-the-jejunal-barrier-by-reversibly-tightening-the-paracellular-route
#7
Silke S Zakrzewski, Michael Fromm, Joerg D Schulzke, Dorothee Günzel
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. In order to analyze the molecular mechanism whereby zinc acts on porcine intestinal barrier function, ex vivo studies on piglet jejunum and accompanying in vitro studies on a porcine jejunal epithelial cell line, IPEC-J2/PS, were performed with electrophysiological tools...
September 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28864500/kr%C3%A3-ppel-like-factor-5-is-essential-for-maintenance-of-barrier-function-in-mouse-colon
#8
Yang Liu, Martyn Chidgey, Vincent W Yang, Agnieszka B Bialkowska
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. We used an inducible and a constitutive intestine-specific Klf5 knockout mouse model (Villin-CreER(T2);Klf5(fl/fl) designated as Klf5(ΔIND) and Villin-Cre;Klf5(fl/fl) as Klf5(ΔIS) ), and studied an inducible KLF5 knockdown in Caco-2 BBe cells using a lentiviral Tet-on system (Caco-2 BBe KLF5ΔIND)...
September 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28864499/ethanol-metabolism-by-alcohol-dehydrogenase-or-cytochrome-p450-2e1-differentially-impairs-hepatic-protein-trafficking-and-growth-hormone-signaling
#9
Erin E Doody, Jennifer L Groebner, Jetta R Walker, Brittnee M Frizol, Dean J Tuma, David J Fernandez, Pamela L Tuma
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. We have also shown that enhanced protein acetylation correlates with impaired clathrin-mediated endocytosis, constitutive secretion and nuclear translocation and that the defects are likely mediated by acetaldehyde...
September 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28864498/new-ultrasonographic-screening-method-for-oropharyngeal-dysphagia-tissue-doppler-imaging
#10
Noriaki Manabe, Ken Haruma, Rui Nakato, Hiroaki Kusunoki, Tomoari Kamada, Jiro Hata
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: 59.7 years) who all underwent both US-TDI and videofluoroscopy (VF) and then esophageal high-resolution manometry (HRM) in the same week...
September 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28838988/impact-of-prevailing-thiamin-levels-on-thiamin-pyrophosphate-uptake-in-pancreatic-acinar-cells-do-the-shuttle
#11
Lindsey Kennedy, Heather Francis, Gianfranco Alpini
Editorial.
August 24, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28838987/age-related-external-anal-sphincter-muscle-dysfunction-fibrosis-possible-role-of-wnt-%C3%AE-catenin-signaling-pathways
#12
M Raj Rajasekaran, Sadhana Kanoo, Johnny Fu, My-Uyen Lilly Nguyen, Valmik Bhargava, Ravinder K Mittal
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. New Zealand White female rabbits (six young 6 months old and six old 36 months of age were anesthetized anal canal pressure was measured to determine the L- T function of EAS...
August 24, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28838986/ammonia-modifies-enteric-neuromuscular-transmission-through-glial-gamma-aminobutyric-acid-signaling
#13
David E Fried, Ralph E Watson, Simon C Robson, Brian D Gulbransen
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...
August 24, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28838985/targeting-palmitoyl-acyltransferase-zdhhc21-improves-gut-epithelial-barrier-dysfunction-resulting-from-burn-induced-systemic-inflammation
#14
Ricci J Haines, Chunyan Wang, Clement Gy Yang, Rebecca A Eitnier, Fang Wang, Mack H Wu
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...
August 24, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28814387/effects-of-nk1-receptors-on-gastric-motor-functions-and-satiation-in-healthy-humans-results-from-a-controlled-trial-with-the-nk1-antagonist-aprepitant
#15
Deepti Jacob, Irene A Busciglio, Duane D Burton, Houssam Halawi, Ibironke Oduyebo, Deborah Rhoten, Michael Ryks, W Scott Harmsen, Michael Camilleri
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. 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), effects of aprepitant vs...
August 16, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28798084/a-small-population-of-liver-endothelial-cells-undergoes-endothelial-to-mesenchymal-transition-in-response-to-chronic-liver-injury
#16
Jordi Ribera, Montse Pauta, Pedro Melgar-Lesmes, Bernat Cordoba, Anna Bosch, Maria Calvo, Daniel Rodrigo-Torres, Pau Sancho-Bru, Aurea Mira, Wladimiro Jimenez, Manuel Morales-Ruiz
BACKGROUND AND AIMS: 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. METHODS: 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...
August 10, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28798083/hamp1-mrna-and-plasma-hepcidin-levels-are-influenced-by-sex-and-strain-but-don-t-predict-tissue-iron-levels-in-inbred-mice
#17
Stela McLachlan, Kathryn E Page, Seung-Min Lee, Alex Loguinov, Erika Valore, Simon T Hui, Grace Jung, Jie Zhou, Aldons J Lusis, Brie Fuqua, Tomas Ganz, Elizabeta Nemeth, Chris D Vulpe
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. Similarly, conflicting data on the relationship between hepcidin (Hamp1) mRNA levels and iron status as assessed by transferrin saturation and tissue iron concentrations were reported. 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...
August 10, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28774871/enteric-serotonin-and-oxytocin-endogenous-regulation-of-severity-in-a-murine-model-of-necrotizing-enterocolitis
#18
Kara Gross Margolis, Jennifer Vittorio, Maria Talavera, Karen Gluck, Zhishan Li, Alina Iuga, Korey Stevanovic, Virginia Saurman, Narek Israelyan, Martha G Welch, Michael D Gershon
Necrotizing enterocolitis (NEC), a gastrointestinal inflammatory disease of unknown etiology, causes a great deal of morbidity and mortality in premature infants. The liver as well as the gut may be affected in NEC. We tested the hypothesis that signaling molecules, which are endogenous to the bowel, regulate the severity of experimental NEC in mice. Specifically, we postulated that mucosal serotonin (5-HT), which is proinflammatory, would increase the severity of NEC and that oxytocin (OT), which is present in enteric neurons and is anti-inflammatory, would oppose NEC...
August 3, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28774870/relationship-of-gastric-emptying-or-accommodation-with-satiation-satiety-and-postprandial-symptoms-in-health
#19
Houssam Halawi, Michael Camilleri, Andres Acosta, Maria I Vazquez-Roque, Ibironke Oduyebo, Duane D Burton, Irene A Busciglio, Alan R Zinsmeister
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% females, mean BMI 33.5kg/m2): 26 prospectively studied obese, otherwise healthy participants and 259 healthy subjects with previous similar GI testing. We assessed GE of solids, gastric volumes, calorie intake at buffet meal, satiation by measuring volume to comfortable fullness (VTF) and maximum tolerated volume (MTV) using Ensure® nutrient drink test (30mL/min), and symptoms 30 minutes after MTV...
August 3, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28774869/overactivation-of-intestinal-sterol-response-element-binding-protein-2-promotes-diet-induced-non-alcoholic-steatohepatitis
#20
Pooja Malhotra, Costica Aloman, Aparna Ankireddy, Hani Khadra, Kohtaro Ooka, Ravinder K Gill, Seema Saksena, Pradeep K Dudeja, Waddah A Alrefai
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. One important regulator of cholesterol homeostasis is the Sterol Response Element Binding Protein SREBP2 transcription factor. We tested the hypothesis that the overactivation of intestinal SREBP2 increases the susceptibility to diet-induced NASH...
August 3, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
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