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American Journal of Physiology. Gastrointestinal and Liver Physiology

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https://www.readbyqxmd.com/read/30406699/molecular-characterization-of-a-precision-cut-rat-liver-slice-model-for-the-evaluation-of-anti-fibrotic-compounds
#1
Xinqiang Huang, Hong Cai, Ron Ammar, Yan Zhang, Yihe Wang, Kandasamy Ravi, John Ryan Thompson, Gabor Jarai
Precision-cut liver tissue slice (PCLS) contains all major cell types of the liver parenchyma and preserves the original cell-cell and cell-matrix contacts. It represents a promising ex vivo model to study liver fibrosis and test the anti-fibrotic effect of experimental compounds in a physiologic environment. In this study using RNAquencing we demonstrated that various pathways functionally related to fibrotic mechanisms were dysregulated in PCLSs derived from rats subjected to bile duct ligation. The Alk5 inhibitor SB525334, nintedanib and sorafenib each reversed a subset of genes dysregulated in fibrotic PCLSs and of those genes we identified 608 genes whose expression was reversed by all three compounds...
November 8, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30406698/zinc-ameliorates-intestinal-barrier-dysfunctions-in-shigellosis-by-reinstating-claudin-2-and-4-on-the-membranes
#2
Paramita Sarkar, Tultul Saha, Irshad Ali Sheikh, Subhra Chakraborty, Joydeep Aoun, Manoj Kumar Chakrabarti, Vazhaikkurichi M Rajendran, Nadia A Ameen, Shanta Dutta, Kazi Mirajul Hoque
Whether zinc(Zn2+ ) regulates barrier functions by modulating tight junction (TJ) proteins when pathogens such as Shigella alter epithelial permeability is still un-resolved. We investigated the potential benefits of Zn2+ in restoring impaired barrier function in vivo in Shigella infected mouse tissue and in vitro T84 cell monolayers. Basolateral Shigella infection triggered time dependent decrease in trans-epithelial resistance (TER) followed by an increase in paracellular permeability of FITC-labelled dextran and altered ion selectivity...
November 8, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30406697/lgr4-protects-hepatocytes-from-injury-in-mouse
#3
Ziru Li, Shiying Liu, Jianing Lou, Michael W Mulholland, Weizhen Zhang
Leucine-rich repeat G-protein-coupled receptors (LGRs) and their endogenous ligands R-spondin1-4 (Rspo) are critical in embryonic development and in maintenance of stem cells. The functions of the Rspo-LGR system in differentiated cells remain uncharacterized. In this study, the expression profiles of LGRs and Rspos were characterized in mature hepatocytes. A liver-specific knockout of LGR4 in mouse was generated and used to study hepatic ischemia and reperfusion induced injury (HIRI) as well as LPS/D-Gal induced liver injury...
November 8, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30383414/lipid-mediators-of-liver-injury-in-nonalcoholic-fatty-liver-disease
#4
Suthat Liangpunsakul, Naga Chalasani
Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of histopathological phenotypes ranging from simple steatosis to more severe liver disease associated with cell injury including nonalcoholic steatohepatitis (NASH), advanced fibrosis and cirrhosis. Only a subset of patients with NAFLD develop NASH from yet incompletely understood mechanisms. Emerging data suggest lipid species other than triglycerides as contributors to the pathogenesis of NASH. In this mini review, we focus on the recent data on the mechanisms of NASH focusing on these lipid mediators and their potential as therapeutic targets in NASH...
November 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30383413/absence-of-the-sulfate-transporter-sat-1-slc26a1-has-no-impact-on-oxalate-handling-by-mouse-intestine-and-does-not-cause-hyperoxaluria-or-hyperoxalemia
#5
Jonathan M Whittamore, Christine Elizabeth Stephens, Marguerite Hatch
The anion exchanger SAT-1 (Sulfate Anion Transporter 1; Slc26a1), is considered an important regulator of oxalate and sulfate homeostasis but the mechanistic basis of these critical roles remain undetermined. Previously, characterization of the SAT-1 knockout (KO) mouse suggested the loss of SAT-1 mediated oxalate secretion by the intestine was responsible for the hyperoxaluria, hyperoxalemia and calcium oxalate urolithiasis reportedly displayed by this model. To test this hypothesis, we compared the transepithelial fluxes of 14 C-oxalate, 35 SO4 2- and 36 Cl- across isolated, short-circuited segments of the distal ileum, cecum and distal colon from wild-type (WT) and SAT-1 KO mice...
November 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30383412/il-6-acutely-improves-indices-of-hepatic-glucose-and-insulin-homeostasis-in-lean-and-obese-mice
#6
Willem T Peppler, Logan K Townsend, Grace M Meers, Matthew R Panasevich, Rebecca Ek MacPherson, R Scott Rector, David C Wright
Obesity can lead to impairments in hepatic glucose and insulin homeostasis, and although exercise is an effective treatment, the molecular targets remain incompletely understood. As interleukin-6 (IL-6) is an exercise-inducible cytokine, we aimed to identify if IL-6 itself influences hepatic glucose and insulin homeostasis, and if this response differs during obesity. In vivo, male mice were fed a low fat diet (LFD, 10% kcal) or high fat diet (HFD, 60% kcal) for 7 weeks, which induced obesity and hepatic lipid accumulation...
November 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30359083/asymmetric-cell-division-dominant-neutral-drift-model-for-normal-intestinal-stem-cell-homeostasis
#7
Yoshitatsu Sei, Jianying Feng, Carson C Chow, Stephen A Wank
The normal intestinal epithelium is continuously regenerated at a rapid rate from actively cycling Lgr5-expressing intestinal stem cells (ISCs) that reside at the crypt base. Recent mathematical modeling based on several lineage tracing studies in mice shows that the symmetric cell division-dominant (SCD-d) neutral drift model fits well with the observed in vivo growth of ISC clones and suggests that symmetric divisions are central to ISC homeostasis. However, other studies suggest a critical role for asymmetric cell division in the maintenance of ISC homeostasis in vivo...
October 25, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30359082/5-ht-3-receptor-signaling-in-serotonin-transporter-knockout-rats-a-female-sex-specific-animal-model-of-visceral-hypersensitivity
#8
Nadine El-Ayache, James J Galligan
The irritable bowel syndrome (IBS) is a functional gastrointestinal motor and visceral sensation disorder that is more common in women than men. Female serotonin transporter (SERT) gene knockout (KO) rats exhibit hypersensitivity to colorectal balloon distention (CRD) that mimics colonic hypersensitivity occurring in female IBS patients. Alosetron, (5-HT3 receptor antagonist), is used to treat diarrhea-predominant IBS in female patients. Other 5-HT3 receptor antagonists are ineffective in treating IBS symptoms...
October 25, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30335474/identification-of-multiple-distinct-neurogenic-motor-patterns-that-can-occur-simultaneously-in-the-guinea-pig-distal-colon
#9
Marcello C Costa, Lauren J Keightley, Lukasz Wiklendt, Timothy James Hibberd, John W Arkwright, Taher I Omari, David A Wattchow, Simon J H Brookes, Philip G Dinning, Nick J Spencer
BACKGROUND: In the guinea pig distal colon, non-propulsive neurally-mediated motor patterns have been observed in different experimental conditions. METHODS: Isolated segments of guinea pig distal colon were used to investigate these neural mechanisms by simultaneously recording wall motion, intraluminal pressure and smooth muscle electrical activity in different conditions of constant distension and in response to pharmacological agents. RESULTS: Three distinct neurally-dependent motor patterns were identified; Transient Neural Events (TNEs), Cyclic Motor Complexes (CMC) and Distal Colon Migrating Motor Complexes (DCMMC)...
October 18, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30335473/abdominal-organ-perfusion-and-inflammation-in-experimental-sepsis-a-magnetic-resonance-imaging-study
#10
Silvia Marchesi, Fracisco Ortiz Nieto, Kerstin Magdalena Ahlgren, Agneta Roneus, Ricardo Feinstein, Miklos Lipcsey, Anders Larsson, Håkan Ahlström, Goran Hedenstierna
Diffusion-weighted magnetic resonance imaging (DW-MRI) uses water as contrast and enables the study of perfusion in many organs simultaneously in situ. We used DW-MRI in a sepsis model, comparing abdominal organs perfusion with global hemodynamic measurements and inflammation. Sixteen anesthetized piglets were randomized into 3 groups: HighMAP (mean arterial pressure, MAP > 65 mmHg), LowMAP (MAP between 50 and 60 mmHg) and Healthy Controls (HC). Sepsis was obtained with endotoxin and the desired MAP maintained with noradrenaline...
October 18, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30335469/crohn-s-disease-irgm-risk-alleles-are-associated-with-altered-gene-expression-in-human-tissues
#11
Teminioluwa Ajayi, Cynthia L Innes, Sara A Grimm, Prashant Rai, Ryan Finethy, Jörn Coers, Xuting Wang, Douglas A Bell, John A McGrath, Shepherd H Schurman, Michael B Fessler
Crohn's disease (CD) is a chronic inflammatory gastrointestinal disorder. Genetic association studies have implicated dysregulated autophagy in CD. Among risk loci identified are a promoter single nucleotide polymorphism (SNP)(rs13361189) and two intragenic SNPs (rs9637876, rs10065172) in immunity-related GTPase family M ( IRGM), a gene that encodes a protein of the autophagy initiation complex. All three SNPs have been proposed to modify IRGM expression, but reports have been divergent and largely derived from cell lines...
October 18, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30308131/the-effects-of-esophageal-acidification-on-esophageal-reflexes-controlling-the-upper-esophageal-sphincter
#12
Ivan M Lang, Bidyut K Medda, Reza Shaker
The aim of this study was to determine the effects of esophageal acid exposure on esophago-UES relaxation (EURR) and contractile (EUCR) reflexes. Cats, decerebrate (N=27) or chronic (N=4), were implanted with EMG electrodes on pharynx, larynx and esophagus. The esophagus was infused with either NaCl (0.9%) or HCl (0.1 N). The EUCR was activated by balloon distension in acute cats and slow air injection in chronic cats, and the EURR was activated by rapid air injection in both sets of cats. We found that NaCl infused for 15 or 30 minutes had no effect on EUCR or EURR in acute cats...
October 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30307745/enhanced-gastrointestinal-passive-paracellular-permeability-contributes-to-the-obesity-associated-hyperoxaluria
#13
Mohamed Bashir, Jon Meddings, Altayeb Alshaikh, Daniel Jung, Kim Le, Ruhul Amin, Sireesha Ratakonda, Sapna Sharma, Ignacio Granja, Mustafa Satti, John Asplin, Hatim Hassan
Most kidney stones (KS) are composed of calcium oxalate and small increases in urine oxalate enhance the stone risk. Obesity is a risk factor for KS and urinary oxalate excretion increases with increased body size. We previously established the obese ob/ob ( ob) mice as a model (3.3-fold higher urine oxalate) to define the pathogenesis of obesity-associated hyperoxaluria (OAH). The purpose of this study was to test the hypothesis that the obesity-associated enhanced intestinal paracellular permeability contributes to OAH by increasing passive paracellular intestinal oxalate absorption...
October 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30307739/il-23-mediates-murine-liver-transplantation-ischemia-reperfusion-injury-via-ifn-%C3%AE-irf-1-pathway
#14
John Robert Klune, Christian Bartels, Jing Luo, Shin Yokota, Qiang Du, David A Geller
Interleukin-23 (IL-23) is a pro-inflammatory cytokine initially studied in autoimmune disease which has been more recently linked to innate immunity. We observed that the expression of IL-23 is upregulated during hypoxia in hepatocyte and non-parenchymal cell (NPC) co-culture system, as well as during ischemia-reperfusion (I/R) injury in the liver. Interferon regulatory factor-1 (IRF-1) is a transcription factor that induces expression of multiple inflammatory cytokines and has been shown to play a critical role in liver I/R injury...
October 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30285481/enterotoxigenic-escherichia-coli-etec-heat-labile-enterotoxin-inhibits-intestinal-ascorbic-acid-uptake-via-a-camp-dependent-nf-%C3%AE%C2%BAb-mediated-pathway
#15
Ganapathy A Subramenium, Subrata Subai, Jonathan S Marchant, Hamid M Said, Veedamali S Subramanian
Vitamin C is an antioxidant and acts as a cofactor for many enzymatic reactions. Humans obtain vitamin C from dietary sources via intestinal absorption, a process that involves the sodium dependent vitamin C transporters-1 and -2 (SVCT1 and SVCT2). Enterotoxigenic Escherichia coli (ETEC) infection impacts intestinal absorption/secretory functions but nothing is known about its effect on ascorbic acid (AA) uptake. Here we demonstrate that infection of Caco-2 cells with ETEC led to a significant inhibition in intestinal AA uptake...
October 4, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30285466/knockout-of-clc-2-reveals-critical-functions-of-adherens-junctions-in-colonic-homeostasis-and-tumorigenicity
#16
Younggeon Jin, Dina R Ibrahim, Scott T Magness, Anthony T Blikslager
BACKGROUND & AIMS: Adherens junctions (AJs), together with tight junctions (TJs), form an apical junctional complex that regulates intestinal epithelial cell-to-cell adherence and barrier homeostasis. Within the AJ, membrane-bound E-cadherin binds β-catenin, which functions as an essential intracellular signaling molecule. We have previously identified a novel protein in the region of the apical junction complex, chloride channel protein 2 (ClC-2), which we have used to study TJ regulation...
October 4, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30285465/sepiapterin-alleviates-impaired-gastric-nnos-function-in-spontaneous-diabetic-female-rodents-through-nrf2-mrna-turnover-and-mirna-biogenesis-pathway
#17
Pandu R R Gangula, Kishore B Challagundla, Kalpana Ravella, Sutapa Mukhopadhyay, Vijayakumar Chinnathambi, Mukul K Mittal, K Raja Sekhar, Chethan Sampath
An impaired nitrergic system and altered redox signaling contribute to gastric dysmotility in diabetics. Our earlier studies show that NF-E2-related factor 2 (NRF2) and Phase II antioxidant enzymes play a vital role in gastric neuronal nitric oxide synthase (nNOS) function. This study aims to investigate whether supplementation of sepiapterin (SEP), a precursor for BH4 (a cofactor of NOS) via salvage pathway, restores altered nitrergic systems and redox balance in spontaneous diabetic (DB) female rats. Twelve-week spontaneous DB and age-matched, non-DB rats, with and without dietary SEP (daily 20 mg/kg body weight for 10 days) treatment, were used in this study...
October 4, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30285464/manipulating-fenestrations-in-young-and-old-liver-sinusoidal-endothelial-cells
#18
Nicholas John Hunt, Glen Lockwood, Alessandra Warren, Hong Mao, Peter McCourt, David G Le Couteur, Victoria Carroll Cogger
Fenestrations are pores within liver sinusoidal endothelial cells (LSECs) that enable the transfer of substrates (particularly insulin and lipoproteins) between blood and hepatocytes. With increasing age there are marked reductions in the frequency and diameter of fenestrations, referred to as pseudocapillarization. Currently, fenestrations are thought to be regulated by VEGF and NO pathways promoting remodelling of the actin cytoskeleton and cell membrane lipid rafts. We investigated the effects of drugs that act on these pathways on fenestrations in old (18-24m) and young mice (3-4m)...
October 4, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30260688/the-functional-role-of-protease-activated-receptors-on-contractile-responses-by-activation-of-ca-2-sensitization-pathways-in-simian-colonic-muscles
#19
Tae Sik Sung, Hongli Lu, Juno Sung, Jong Hoon Yeom, Brian A Perrino, Sang Don Koh
It has been known that activation of protease-activated receptors (PAR) affects gastrointestinal motility. In this study, we tested the effects of PAR agonists on electrical and contractile responses, and Ca2+ sensitization pathways in simian colonic muscles. The Simian colonic muscle was initially hyperpolarized by PAR agonists. After the transient hyperpolarization, simian colonic muscle repolarized to the control resting membrane potential (RMP) without a delayed depolarization. Apamin significantly reduced the initial hyperpolarization suggesting that activation of small conductance Ca2+ -activated K+ (SK) channels is involved in the initial hyperpolarization...
September 27, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/30234998/urinary-acrolein-metabolite-levels-in-severe-acute-alcoholic-hepatitis-patients
#20
Vatsalya Vatsalya, Maiying Kong, Leila Gobejishvili, Wei-Yang Chen, Sanjay Srivastava, Shirish Barve, Craig J McClain, Swati Joshi-Barve
Alcohol-associated liver disease (ALD) remains a major health concern worldwide. Alcohol consumption gives rise to reactive/toxic acrolein, a pathogenic mediator of liver injury in experimental ALD. Elevated acrolein adducts and metabolites are detectable in blood and urine. This study evaluates the major urinary acrolein metabolite, 3-hydroxypropylmercapturic acid (HPMA), in patients with acute alcoholic hepatitis (AAH), and examines its association with disease severity, and markers of hepatic inflammation and injury...
September 20, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
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