Interaction of epidermal growth factor with COX-2 products and peroxisome proliferator-activated receptor gamma system in experimental rat Barrett's esophagus.
Abstract Mixed acidic-alkaline refluxate is a major pathogenic factor in chronic esophagitis progressing into Barrett's esophagus (BE) but the involvement of epidermal growth factor (EGF), COX-2 and peroxisome proliferator-activated receptor gamma (PPARg) in BE has not been extensively studied. Rats surgically prepared with esophagogastroduodenal anastomosis (EGDA) with intact or removed salivary glands to deplete salivary EGF were treated either with: 1) vehicle, 2) EGF or pioglitazone with or without tyrphostin A46 or GW9662, respectively, 3) ranitidine or pantoprazole. At three months, the esophageal damage (LI...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - January 13, 2020 Category: Physiology Authors: Majka J, Wierdak M, Szlachcic A, Magierowski M, Targosz A, Urbanczyk K, Krzysiek-Maczka G, Ptak-Belowska A, Bakalarz D, Magierowska K, Chmura A, Brzozowski T Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Myocardin and myocardin-related transcription factor-A synergistically mediate actin cytoskeletal dependent inhibition of liver fibrogenesis.
Abstract Hepatic stellate cells (HSCs) activation, characterized by development of a robust actin cytoskeleton and expression of abundant extracellular matrix (ECM) proteins such as type 1 collagen (COL.1), is a central cellular and molecular event in liver fibrosis. It has been demonstrated that HSCs express both myocardin and myocardin-related transcription factor-A (MRTF-A). However, the biological effects of myocardin and MRTF-A on HSC activation and liver fibrosis as well as the molecular mechanism under the process remain unclear. Here, we report that myocardin and MRTF-A's expression and nuclear accumulatio...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - January 13, 2020 Category: Physiology Authors: Shi Z, Ren M, Rockey DC Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Nanoformulated SOD1 Ameliorates the Combined NASH and Alcohol-Associated Liver Disease Partly via Regulating CYP2E1 Expression in Adipose Tissue and Liver.
Abstract Enhanced free fatty acid (FFA) flux from adipose tissue (AT) to liver plays an important role in the development of non-alcoholic steatohepatitis (NASH) and alcohol-associated liver disease (AALD). We determined the effectiveness of nanoformulated superoxide dismutase 1 (Nano) in attenuating liver injury in a mouse model exhibiting a combination of NASH and AALD. Male C57BL6/J mice were fed a chow diet (CD) or a high fat diet (HF) for 10 wk followed by pair-feeding the Lieber-DeCarli control (control) or ethanol (ET) diet for 4 wk. Nano was administered once every other day for the last 2 wk of ET feeding...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - January 13, 2020 Category: Physiology Authors: Gopal T, Kumar N, Perriotte-Olson C, Casey CA, Donohue TM, Harris EN, Talmon G, Kabanov AV, Saraswathi V Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Mechanisms underlying reduced weight gain in Intestinal Fatty Acid-Binding Protein (IFABP) null mice.
rch J Abstract Intestinal-fatty acid binding protein (IFABP; FABP2) is a 15 kDa intracellular protein abundantly present in the cytosol of the small intestinal (SI) enterocyte. High fat (HF) feeding of IFABP-/- mice resulted in reduced weight gain and fat mass relative to wild-type (WT) mice. Here, we examined intestinal properties that may underlie the observed lean phenotype of high fat-fed IFABP-/- mice. No alterations in fecal lipid content were found, suggesting that the IFABP-/- mice are not malabsorbing dietary fat. However, the total excreted fecal mass, normalized to food intake, was increased for the IFA...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - January 6, 2020 Category: Physiology Authors: Lackey AI, Chen T, Zhou YX, Bottasso Arias NM, Doran JM, Zacharisen SM, Gajda AM, Córsico B, Joseph LB, Storch J Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

TGR5 Signaling Mitigates Parenteral Nutrition Associated Liver Disease.
Abstract Bile acid receptors regulate the metabolic and immune functions of circulating enterohepatic bile acids. This process is disrupted by administration of parenteral nutrition (PN), which may induce progressive hepatic injury for unclear reasons, especially in the newborn, leading to PN-associated liver disease. To explore the role of bile acid signaling on neonatal hepatic function, we initially observed that TGR5-specific bile acids were negatively correlated with worsening clinical disease markers in the plasma of human newborns with prolonged PN exposure. To test our resulting hypothesis that TGR5 regula...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - January 6, 2020 Category: Physiology Authors: Willis KA, Gomes CK, Rao PK, Micic D, Moran ER, Stephenson EJ, Puchowicz MA, Al Abdallah Q, Mims TS, Gosain A, Yin D, Talati AJ, Chang EB, Han JC, Pierre JF Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Effects Of High Fat Diet And Intestinal Aryl Hydrocarbon Receptor Deletion On Colon Carcinogenesis.
Abstract Consumption of a high-fat diet has been associated with an increased risk of developing colorectal cancer (CRC). However, the effects of the interaction between dietary fat content and the aryl hydrocarbon receptor (AhR) on colorectal carcinogenesis remain unclear. Mainly known for its role in xenobiotic metabolism, AhR has been identified as an important regulator for maintaining intestinal epithelial homeostasis. Although previous research using whole-body AhR knockout mice has revealed an increased incidence of colon and cecal tumors, the unique role of AhR activity in intestinal epithelial cells (IECs...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - January 6, 2020 Category: Physiology Authors: Garcia-Villatoro EL, DeLuca JA, Callaway ES, Allred KF, Davidson LA, Hensel ME, Menon R, Ivanov I, Safe S, Jayaraman A, Chapkin RS, Allred CD Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

The role of microRNA-210-3p in hepatitis B virus-relatedhepatocellular carcinoma.
Abstract Hepatitis B virus (HBV)-related hepatocarcinogenesis is not necessarily associated with the liver fibrotic stage and is occasionally seen at early fibrotic stages. MicroRNAs (miRNAs) are essentially 18- to 22-nucleotide-long endogenous noncoding RNAs. Aberrant miRNA expression is a common feature of various human cancers. The aberrant expression of specific miRNAs has been shown in hepatocellular carcinoma (HCC) tissue compared to nontumor tissue. We thus examined targetable miRNAs as a potential new biomarker related to the high risk of HBV-related hepatocarcinogenesis, toward the prevention of cancer-re...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - January 6, 2020 Category: Physiology Authors: Morishita A, Fujita K, Iwama H, Chiyo T, Fujihara S, Oura K, Tadokoro T, Mimura S, Nomura T, Tani J, Yoneyama H, Kobayashi K, Kamada H, Guan Y, Nishiyama A, Okano K, Suzuki Y, Himoto T, Shimotohno K, Masaki T Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Investigating fibrosis and inflammation in an ex vivo NASH murine model.
Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, characterized by excess fat accumulation (steatosis). Nonalcoholic steatohepatitis (NASH) develops in 15-20% of NAFLD patients, and frequently progresses to liver fibrosis and cirrhosis. We aimed to develop an ex vivo model of inflammation and fibrosis in steatotic murine precision-cut liver slices (PCLS). NASH was induced in C57Bl/6 mice using amylin and choline-deficient L-amino acid-defined (CDAA) diet. PCLS were prepared from steatohepatitic (sPCLS) and control (cPCLS) livers and cultured for 48h with LPS, TGFβ1 or elafibr...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - January 6, 2020 Category: Physiology Authors: Gore E, Bigaeva E, Oldenburger A, Jansen YJM, Schuppan D, Boersema M, Rippmann JF, Broermann A, Olinga P Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Addition of trans-fat and alcohol has divergent effects on atherogenic diet-induced liver injury in rodent models of steatohepatitis.
Conclusion The addition of trans-fat reduced the HFC-induced inflammation but augmented steatosis and dyslipidemia. Inclusion of alcohol induced a more inflammatory and fibrogenic phenotype. PMID: 31905026 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - January 6, 2020 Category: Physiology Authors: Daniels SJ, Leeming DJ, Detlefsen S, Bruun MF, Hjuler ST, Henriksen K, Hein P, Krag A, Karsdal MA, Nielsen MJ, Brockbank S, Cruwys S Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

RYK, a receptor of non-canonical Wnt ligand Wnt5a, is positively correlated with gastric cancer tumorigenesis and potential of liver metastasis.
Abstract Gastric cancer (GC) is a most prevalent human cancer around the globe. In GC, Wnt signaling is deregulated, and receptor-like tyrosine kinase (RYK) co-receptors have been identified to interact with non-canonical Wnt ligand Wnt5a. We therefore aimed to evaluate the role of RYK in GC development and metastasis. GC tumor samples were collected from 250 GC patients. Expressions of RYK, as well as markers for the epithelial-mesenchymal transition (EMT) such as N-cadherin and E-cadherin were subjected to correlation analysis with clinicopathological features. Endogenous RYK expression levels were compared in G...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - December 23, 2019 Category: Physiology Authors: Fu Y, Chen Y, Huang J, Cai Z, Wang Y Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Distal colonic transit is linked to gut microbiota diversity and microbial fermentation in humans with slow colonic transit.
This study suggests that the distal colon transit may affect not only microbiota diversity but also microbial metabolism. PMID: 31869241 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - December 23, 2019 Category: Physiology Authors: Müller M, Hermes GDA, Canfora EE, Smidt H, Masclee AAM, Zoetendal EG, Blaak EE Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Dobutamine reverses the cardio-suppressive effects of terlipressin without improving renal function in cirrhosis and ascites: a randomised controlled trial.
rag A Abstract AIM: Acute kidney injury and hepatorenal syndrome (HRS) are frequent complications in patients with cirrhosis and ascites. First-line treatment is terlipressin, which reverses HRS in approximately 40% of patients but also lowers cardiac output (CO). We aimed to investigate whether reversing the cardio-suppressive effect of terlipressin with the β-adrenoceptor agonist dobutamine would increase CO and thereby the glomerular filtration rate (GFR). METHODS: We randomised twenty-five patients with cirrhosis, ascites and impaired renal function (2:2:1): Group A received terlipressin followed by ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - December 16, 2019 Category: Physiology Authors: Israelsen M, Dahl EK, Madsen BS, Wiese S, Bendtsen F, Møller S, Fialla AD, Jensen BL, Krag A Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Mitochondria-targeted antioxidant mitoquinone attenuates liver inflammation and fibrosis in cirrhotic rats.
CONCLUSIONS: Mitochondria-targeted antioxidant mitoquinone improves liver inflammation and fibrosis in cirrhotic rats by reducing hepatic oxidative stress, preventing apoptosis and promoting removal of dysfunctional mitochondria. Therefore, it may represent a promising strategy for the prevention and treatment of liver cirrhosis. PMID: 31813234 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - December 9, 2019 Category: Physiology Authors: Turkseven S, Bolognesi M, Brocca A, Pesce P, Angeli P, Di Pascoli M Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

A myogenic motor pattern in mice lacking myenteric interstitial cells of Cajal explained by a second coupled oscillator network.
Abstract The interstitial cells of Cajal associated with the myenteric plexus (ICC-MP) are a network of coupled oscillators in the small intestine that generate rhythmic electrical phase waves leading to corresponding waves of contraction. Yet rhythmic action potentials and intercellular calcium waves have been recorded from c-kit mutant mice that lack the ICC-MP, suggesting that there may be a second pacemaker network. The gap junction blocker carbenoxolone induced a "pinstripe" motor pattern consisting of rhythmic "stripes" of contraction that appeared simultaneously across the intestine with...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - December 9, 2019 Category: Physiology Authors: Parsons SP, Huizinga JD Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Diversity of neurogenic smooth muscle electrical rhythmicity in mouse proximal colon.
DIVERSITY OF NEUROGENIC SMOOTH MUSCLE ELECTRICAL RHYTHMICITY IN MOUSE PROXIMAL COLON. Am J Physiol Gastrointest Liver Physiol. 2019 Dec 02;: Authors: Spencer NJ, Travis L, Wiklendt L, Hibberd TJ, Costa MC, Dinning P, Hu H Abstract The mechanisms underlying electrical rhythmicity in smooth muscle of the proximal colon are incompletely understood. Our aim was to identify patterns of electrical rhythmicity in smooth muscle of the proximal region of isolated whole mouse colon and characterize their mechanisms of origin. Two independent extracellular recording electrodes were used to record the patterns of...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - December 2, 2019 Category: Physiology Authors: Spencer NJ, Travis L, Wiklendt L, Hibberd TJ, Costa MC, Dinning P, Hu H Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

IFN- γ and IL-17A regulate intestinal crypt production of CXCL10 in the healthy and inflamed colon.
IFN-γ and IL-17A regulate intestinal crypt production of CXCL10 in the healthy and inflamed colon. Am J Physiol Gastrointest Liver Physiol. 2019 Dec 02;: Authors: Walrath T, Malizia RA, Zhu X, Sharp SP, DSouza SS, Lopez-Soler R, Parr B, Kartchner B, Lee EC, Stain SC, Iwakura Y, OConnor W Abstract During intestinal inflammation, immature cells within the intestinal crypt are called upon to replenish lost epithelial cell populations, promote tissue regeneration and restore barrier integrity. Inflammatory mediators including TH1/TH17-associated cytokines influence tissue health and regenerative pro...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - December 2, 2019 Category: Physiology Authors: Walrath T, Malizia RA, Zhu X, Sharp SP, DSouza SS, Lopez-Soler R, Parr B, Kartchner B, Lee EC, Stain SC, Iwakura Y, OConnor W Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Comparison of murine steatohepatitis models identifies a dietary intervention with robust fibrosis, ductular reaction and rapid progression to cirrhosis, cancer.
In conclusion, HF-CDAA feeding in C57Bl/6J mice was identified as an optimal model of steatohepatitis with robust fibrosis and ductular proliferations that progress to cirrhosis and HCC within 24 weeks. This model will aid the testing of interventions and drugs for severe NASH. PMID: 31630534 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - October 21, 2019 Category: Physiology Authors: Wei G, An P, Vaid K, Nasser I, Huang P, Tan L, Zhao S, Schuppan D, Popov Y Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Characterization of urea transport mechanisms in the intestinal tract of growing pigs.
The objective of this study was to characterize the presence and relative contribution of known urea transporters to urea flux in the growing pig. Intestinal tissue samples (duodenum, jejunum, ileum, cecum, and colon) were obtained from 9 barrows (50.8 ± 0.9 kg) and analyzed for mRNA abundance of UT-B and AQP-3, 7, and 10. Immediately after tissue collection, samples from the jejunum and cecum were placed in Ussing chambers for analysis of the serosal-to-mucosal urea flux (Jsm-urea) with no inhibition or when incubated in the presence of phloretin to inhibit UT-B-mediated transport, NiCl2 to inhibit AQP-mediated tra...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - October 11, 2019 Category: Physiology Authors: Krone JE, Agyekum AK, Ter Borgh M, Hamonic K, Penner GB, Columbus DA Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Intermittent restraint-induced sympathetic activation attenuates hepatic steatosis and inflammation in a high fat-diet fed-mouse model.
Abstract NAFLD is very prevalent worldwide, and is associated with insulin resistance and metabolic syndrome. Stress is physiological and biological response to maintain homeostasis of body against stressors while severe stress response is an important contributor to various illnesses including metabolic syndrome and brain disorders. We have evaluated the effects of intermittent restraint stress on NAFLD in a HFD-fed mouse model. C57/BL6 mice had free access to a 60% HFD for 8 weeks, with or without intermittent restraint stress (3 h) conducted 3 times a week. HFD administration increased fat accumulation in liver...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - October 11, 2019 Category: Physiology Authors: Lee SB, Kim HG, Lee JS, Kim WY, Lee MM, Kim YH, Lee JO, Kim HS, Son CG Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Cell-Specific Regulatory Effects of CXCR2 on Cholestatic Liver Injury.
In conclusion, neutrophil CXCR2 guides the cell to the site of injury, while CXCR2 on liver cells affects liver damage independent of neutrophil accumulation. CXCR2 appears to be a viable therapeutic target for cholestatic liver injury. PMID: 31604030 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - October 11, 2019 Category: Physiology Authors: Konishi T, Schuster RM, Goetzman HS, Caldwell CC, Lentsch AB Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets.
Abstract Perforations, anastomotic leak and subsequent intraabdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiologic healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - October 11, 2019 Category: Physiology Authors: Jacobson RA, Wienholts K, Williamson AJ, Gaines S, Hyoju S, van Goor H, Zaborin A, Shogan BD, Zaborina O, Alverdy JC Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Rifampicin, Not Vitamin E, Suppresses Parenteral Nutrition Associated Liver Disease Development through Pregnane X Receptor Pathway in Piglets.
Abstract Infants receiving long-term parenteral nutrition (PN) develop PN associated liver disease (PNALD). We previously showed that PN containing soy-based lipid supplemented with vitamin E (α-tocopherol) prevents the development of PNALD. We hypothesize that this occurs via vitamin E-activation of pregnane X receptor (PXR) mediated pathways involved in bile acid metabolism. Neonatal piglets received PN for 14 d containing Intralipid (IL, soy-based lipid emulsion), IL supplemented with 12.6 mg/kg*d-1 vitamin E (VITE), or IL with 10 mg/kg*d-1 Rifadin IV (RIF) a PXR agonist. Pigs treated with IL and VITE, bu...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - October 11, 2019 Category: Physiology Authors: Guthrie G, Stoll B, Chacko S, Lauridsen C, Plat J, Burrin DG Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Hepatitis B virus-triggered PTEN/ β-catenin/c-Myc signaling enhances PD-L1 expression to promote immune evasion.
CONCLUSION: Our findings suggest that HBV-triggered PTEN/β-catenin/c-Myc signaling via HBx and HBp enhances PD-L1 expression, leading to inhibition of T cell response, and promotes HBV immune evasion. PMID: 31604033 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - October 11, 2019 Category: Physiology Authors: Sun Y, Yu M, Qu M, Ma Y, Zheng D, Yue Y, Guo S, Tang L, Li G, Zheng W, Wang M, Guo D, Li C Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Enteric neuroplasticity and dysmotility in inflammatory disease: key players and possible therapeutic targets.
Abstract Intestinal functions, including motility and secretion, are locally controlled by enteric neural networks housed within the wall of the gut. The fidelity of these functions depends on the precision of intercellular signaling amongst cellular elements, including enteric neurons, epithelial cells, immune cells, and glia, all of which are vulnerable to disruptive influences during inflammatory events. This review article describes current knowledge regarding inflammation-induced neuroplasticity along key elements of enteric neural circuits, what is known about the causes of these changes, and possible therap...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - October 11, 2019 Category: Physiology Authors: Spear ET, Mawe GM Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Botox Injection into the Lower Esophageal Sphincter Induces Hiatal Paralysis and Gastroesophageal Reflux.
CONCLUSION: ISIB, in addition to decreasing LES pressure, paralyzes the esophageal hiatus (crural diaphragm) and induces GER. PMID: 31589467 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - October 7, 2019 Category: Physiology Authors: Kumar D, Zifan A, Mittal RK Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Use of organoids to study regenerative responses to intestinal damage.
Abstract Intestinal organoid cultures provide an in vitro model system for studying pathways and mechanisms involved in epithelial damage and repair. Derived from either embryonic or induced pluripotent stem cells or adult intestinal stem cells or tissues, these self-organizing multi-cellular structures contain polarized mature cells that recapitulate both the physiology and heterogeneity of the intestinal epithelium. These cultures provide a cutting-edge technology for defining regenerative pathways that are induced following radiation or chemical damage, which directly target the cycling intestinal stem cell, or...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - October 7, 2019 Category: Physiology Authors: Blutt SE, Klein OD, Donowitz M, Shroyer NF, Guha C, Estes MK Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

A computational fluid dynamics simulation of liquid swallowing by impaired pharyngeal motion: bolus pathway and pharyngeal residue.
Abstract Common practices to improve the ability to swallow include modifying physical properties of foods and changing the posture of patients. Here, we quantified effects of the viscosity of liquid bolus and the patient posture on the bolus pathway and pharyngeal residue using a computational fluid dynamics simulation. We developed a computational model of an impaired pharyngeal motion with a low pharyngeal pressure and no pharyngeal adaptation. We varied viscosities from 0.002 to 1 Pa·s and postures from -15 degree to 30 degree (from nearly vertical to forward leaning). Because of no pharyngeal adaptatio...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 30, 2019 Category: Physiology Authors: Ohta J, Ishida S, Kawase T, Katori Y, Imai Y Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Proteomics analysis of the matrisome from MC38 experimental mouse liver metastases.
Conclusions: In conclusion, our study provides a comprehensive ECM characterization of MC38 experimental liver metastases and proposes Annexin A1 as a putative target for this disease. PMID: 31545917 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 23, 2019 Category: Physiology Authors: Yuzhalin AE, Lim SY, Gordon-Weeks AN, Fischer R, Kessler BM, Yu D, Muschel RJ Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

NSAID-induced injury of gastric epithelial cells is reversible. Roles of mitochondria, AMP kinase, NGF and PGE2.
CONCLUSIONS: DFN and INDO induce extensive mitochondrial injury and GEPC death, which can be significantly reversed by NGF, dmPGE2 and AICAR. PMID: 31545918 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 23, 2019 Category: Physiology Authors: Ahluwalia A, Hoa N, Jones MK, Tarnawski AS Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Emerging Role of Extracellular Vesicles in Liver Diseases.
Abstract Extracellular vesicles (EVs) are membrane-defined nanoparticles released by most cell types. The EVs released by cells may differ quantitatively and qualitatively from physiological states to disease states. There are several unique properties of EVs including their proteins, lipids and nucleic acids cargoes, stability in circulation, and presence in biofluids which make them a critical vector for cell-to-cell communication and impart utility as a biomarker. EVs may also serve as a vehicle for selective cargo secretion. Similarly, EV cargo may be selectively manipulated for targeted therapeutic delivery. ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 23, 2019 Category: Physiology Authors: Malhi H Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

The IBD associated long non-coding RNA IFNG-AS1 regulates the balance between inflammatory and anti-inflammatory cytokine production after T-cell stimulation.
This study focuses on non-coding RNA transcripts as potential mediators of IBD pathophysiology. One particular gene, interferon gamma-antisense 1 (IFNG-AS1), has been consistently observed to be elevated in the intestinal mucosa of actively inflamed IBD patients versus healthy controls. This study builds on these observations demonstrating that the second splice variant is specifically altered and this alteration even stratifies within inflamed patients. Using a CRISPR-based over-expression system, IFNG-AS1 was selectively overexpressed directly from its genomic loci in T-cells. An unbiased mRNA array on these cells identi...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 23, 2019 Category: Physiology Authors: Rankin CR, Shao L, Elliott J, Rowe L, Patel A, Videlock EJ, Benhammou JN, Sauk JS, Ather N, Corson M, Alipour O, Gulati A, Pothoulakis C, Padua DM Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

MiR-21 in Substance P-induced exosomes promotes cell proliferation and migration in human colonic epithelial cells.
CONCLUSIONS: Our results demonstrate that SP/NK-1R signaling regulates exosome biogenesis and induces their miR-21 cargo sorting. Moreover, exosomal miR-21 promotes proliferation and migration of target cells. PMID: 31545921 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 23, 2019 Category: Physiology Authors: Bakirtzi K, Law IKM, Fang K, Iliopoulos D, Pothoulakis C Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Metformin Alters the Duodenal Microbiome and Decreases the Incidence of Pancreatic Ductal Adenocarcinoma Promoted by Diet-induced Obesity.
CONCLUSION: Administration of metformin eliminated PDAC formation in KC mice. This change was associated with significant microbial changes in both the mucosal and luminal microbiome of the duodenum. This suggests that the microbiome may be a potential mediator of the chemo-preventive effects of metformin. PMID: 31545922 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 23, 2019 Category: Physiology Authors: Dong TS, Chang HH, Hauer M, Lagishetty V, Katzka W, Rozengurt E, Jacobs JP, Eibl G Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Enteric neuron density correlates with clinical features of severe gut dysmotility.
This study was designed to identify an objective morphometric method for paraffin-embedded tissue samples to assess the myenteric inter-ganglionic distance, i.e. the micrometer between two adjacent clusters of myenteric neurons immunoreactive for neuron specific enolase, as well as the number of myenteric and submucosal neuronal cell bodies / ganglion in jejunal specimens of patients with severe GI dysmotility. Jejunal full-thickness biopsies were collected from 32 patients (22 females; 16-77 years) with well-characterized severe dysmotility and 8 controls (4 females; 47-73 years). A symptom questionnaire was filled prior ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 23, 2019 Category: Physiology Authors: Boschetti E, Malagelada C, Accarino A, Malagelada JR, Cogliandro RF, Gori A, Bonora E, Giancola F, Bianco F, Tugnoli V, Clavenzani P, Azpiroz F, Stanghellini V, Sternini C, De Giorgio R Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Rifaximin prevents ethanol-induced liver injury in obese KK-Ay mice through modulation of small intestinal microbiota signature.
In conclusion, RFX prevents AH through modulation of small intestinal microbiota/innate immune responses in obese KK-Ay mice. PMID: 31509430 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 11, 2019 Category: Physiology Authors: Kitagawa R, Kon K, Uchiyama A, Arai K, Yamashina S, Kuwahara-Arai K, Kirikae T, Ueno T, Ikejima K Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Human pancreatic afferent and efferent nerves: mapping and 3-D illustration of exocrine, endocrine, and adipose innervation.
Abstract The pancreas consists of both the exocrine (acini and ducts) and endocrine (islets) compartments to participate in and regulate the body's digestive and metabolic activities. These activities are subjected to neural modulation, but characterization of the human pancreatic afferent and efferent nerves remains difficult due to the lack of 3-D image data. Here we prepare transparent human donor pancreases for 3-D histology to reveal the pancreatic microstructure, vasculature, and innervation in a global and integrated fashion. The pancreatic neural network consists of the substance P (SP) -positive sensory (...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 11, 2019 Category: Physiology Authors: Chien HJ, Chiang TC, Peng SJ, Chung MH, Chou YH, Lee CY, Jeng YM, Tien YW, Tang SC Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Dietary Bovine Milk Exosomes Elicit Changes in Bacterial Communities in C57BL/6 Mice.
Abstract Exosomes and exosome-like vesicles participate in cell-to-cell communication in animals, plant and bacteria. Dietary exosomes in bovine milk are bioavailable in non-bovine species, but a fraction of milk exosomes reaches the large intestine. We hypothesized that milk exosomes alter the composition of the gut microbiome in mice. C57BL/6 mice were fed AIN-93G diets, defined by their content of bovine milk exosomes and RNA cargos: exosome/RNA-depleted (ERD) versus exosome/RNA-sufficient (ERS) diets. Feeding was initiated at age three weeks and cecum content was collected at ages 7, 15 and 47 weeks. Microbial...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 11, 2019 Category: Physiology Authors: Zhou F, Paz HA, Sadri M, Cui J, Kachman SD, Fernando SC, Zempleni J Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Dysbiosis: from fiction to function.
Abstract Advances in data collection technologies reveal that an imbalance (dysbiosis) in the composition of host-associated microbial communities (microbiota) is linked to many human illnesses. This association makes dysbiosis a central concept for understanding how the human microbiota contributes to health and disease. However, it remains problematic to define the term dysbiosis by cataloguing microbial species names. Here we discuss how incorporating the germ-organ concept, ecological assumptions and immunological principles into a theoretical framework for microbiota research provides a functional definition ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 11, 2019 Category: Physiology Authors: Tiffany CR, Baumler AJ Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Possible application of melatonin treatment in human diseases of the biliary tract.
Abstract Melatonin was discovered in 1958 by Aaron Lerner; its name comes from the ability of melatonin to change the shape of amphibian melanophores from stellate to roundish. Starting from the 80s, the role of melatonin in the regulation of mammalian circadian and seasonal clocks has been elucidated. Presently, several other effects have been identified in different organs. For example, he beneficial effects of melatonin in models of liver damage have been described. This review gives first a general background on experimental and clinical data on the use of melatonin in liver damage. The second part of the revi...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 11, 2019 Category: Physiology Authors: Baiocchi L, Zhou T, Liangpunsakul S, Ilaria L, Milana M, Meng F, Kennedy L, Kusumanchi P, Yang Z, Ceci L, Glaser S, Francis H, Alpini GD Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Ursodeoxycholic acid: A promising therapeutic target for inflammatory bowel diseases?
Abstract The secondary bile acid, ursodeoxycholic acid (UDCA), has long been known to have medicinal properties. As the therapeutically active component of bear bile, it has been used for centuries in traditional Chinese Medicine to treat a range of conditions, while manufactured UDCA has been used for decades in Western medicine to treat cholestatic liver diseases. The beneficial qualities of UDCA are thought to be due to its well-established cytoprotective and anti-inflammatory actions. In addition to its established role in treating liver disease(s), UDCA is now under investigation for numerous conditions assoc...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 11, 2019 Category: Physiology Authors: Keely SJ, Steer CJ, Lajczak-McGinley NK Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Nod2 deficiency functionally impairs adaptation to short bowel syndrome via alterations of the epithelial barrier function.
t G Abstract Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) gene mutations are a risk factor for Crohn´s disease and also associated with worse outcome in short bowel syndrome (SBS) patients, independent of the underlying disease. The aim of the study was to analyze the effect of Nod2 deficiency on barrier function and stool microbiome after extensive ileocecal resection in mice. Male C57BL6/J wild-type and Nod2 knock-out mice underwent 40% ileocecal resection. Sham control mice received simple transection of the ileum. Clinical outcome was monitored daily. Barrier function was measure...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 11, 2019 Category: Physiology Authors: Berlin P, Reiner J, Witte M, Wobar J, Lindemann S, Barrantes I, Kreikemeyer B, Bastian M, Schäffler H, Bannert K, Jaster R, Lamprecht G Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

OATP1B3-1B7 a novel Organic Anion Transporting Polypeptide is modulated by FXR ligands and transports bile acids.
In this study we not only showed that SLCO1B3 and the mRNA encoding for OATP1B3-1B7 share the 5' untranslated region, but also that silencing of an initial SLCO1B3 exon lowered the amount of SLCO1B3 and of SLCO1B7 mRNA in Huh-7 cells. To validate the assumption that both transcripts are regulated by the same promoter we tested the influence of the bile acid sensor farnesoid X receptor (FXR) on their transcription. Treatment of Huh-7 and HepaRG cells with activators of this known regulator of OATP1B3 not only increased SLCO1B3, but also OATP1B3-1B7 mRNA transcription. Applying a heterologous expression system we showed that...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 11, 2019 Category: Physiology Authors: Malagnino V, Hussner J, Issa A, Midzic A, Meyer Zu Schwabedissen HE Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Lactobacillus reuteri DSM 17938 feeding of healthy newborn mice regulates immune responses while modulating gut microbiota and boosting beneficial metabolites.
In conclusion, early oral administration of LR to healthy breastfed mice led to microbial and metabolic changes which could be beneficial to general health. PMID: 31482733 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 4, 2019 Category: Physiology Authors: Liu Y, Tian X, He B, Hoang TK, Taylor CM, Blanchard E, Freeborn J, Park S, Luo M, Couturier J, Tran DQ, Roos S, Wu G, Rhoads JM Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Proteomics in gastroparesis: Unique and overlapping protein signatures in diabetic and idiopathic gastroparesis.
cal Research Consortium GpCRC N Abstract BACKGROUND: Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in diabetic mice. Loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages has been reported in full thickness gastric biopsies from gastroparesis patients. AIM: We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein e...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 4, 2019 Category: Physiology Authors: Grover M, Dasari S, Bernard CE, Chikkamenahalli LL, Yates KP, Pasricha PJ, Sarosiek I, McCallum RW, Koch KL, Abell TL, Kuo B, Shulman RJ, Gibbons SJ, McKenzie TJ, Kellogg TA, Kendrick ML, Tonascia J, Hamilton FA, Parkman HP, Farrugia G, Gastroparesis Clin Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Letter to Editor: Chronic alcohol exposure alters circulating insulin and ghrelin levels in hepatic steatosis: a translational research perspective.
PMID: 31461304 [PubMed - in process] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 29, 2019 Category: Physiology Authors: Pandey S Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Reply to "Letter to Editor: Chronic alcohol exposure alters circulating insulin and ghrelin levels in hepatic steatosis: a translational research perspective".
Reply to "Letter to Editor: Chronic alcohol exposure alters circulating insulin and ghrelin levels in hepatic steatosis: a translational research perspective". Am J Physiol Gastrointest Liver Physiol. 2019 Sep 01;317(3):G361-G362 Authors: Rasineni K, Casey CA, Kharbanda KK PMID: 31461305 [PubMed - in process] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 29, 2019 Category: Physiology Authors: Rasineni K, Casey CA, Kharbanda KK Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Liraglutide improves hepatic steatosis and metabolic dysfunctions in a 3-week dietary mouse model of non-alcoholic steatohepatitis.
CONCLUSION: This study provides a novel 3-week dietary model of mice that rapidly develop NASH features, and this model will be suitable for evaluating the therapeutic efficacy of compounds in preclinical drug development for NASH. PMID: 31460789 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 28, 2019 Category: Physiology Authors: Duparc T, Briand F, Trenteseaux C, Mérian J, Combes G, Najib S, Sulpice T, Martinez LO Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Post-Traumatic Stress Disorder is Associated with Altered Gut Microbiota that Modulates Cognitive Performance in Veterans with Cirrhosis.
Abstract Post-traumatic stress disorder(PTSD) is associated with cirrhosis in Veterans and therapeutic results are suboptimal. An altered gut-liver-brain axis exists in cirrhosis due to hepatic encephalopathy(HE), but the added impact of PTSD is unclear. Aim: Define linkages between gut microbiota and cognition in cirrhosis with/without PTSD. Cirrhotic Veterans (with/without prior HE) underwent cognitive testing (PHES, inhibitory control test,ICT and block design BDT), serum lipopolysaccharide-binding protein(LBP) and stool collection for 16SrRNA microbiota composition and predicted function analysis(PiCRUST). PTS...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 28, 2019 Category: Physiology Authors: Bajaj JS, Sikaroodi M, Fagan A, Heuman DM, Gilles HC, Gavis EA, Fuchs M, Gonzalez-Maeso J, Nizam S, Gillevet PM, Wade JB Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Roles of the noradrenergic nucleus locus coeruleus and dopaminergic nucleus A11 region as supraspinal defecation centers in rats.
Abstract We previously demonstrated that administration of norepinephrine, dopamine and serotonin into the lumbosacral defecation center caused propulsive contractions of the colorectum. It is known that the monoamines in the spinal cord are mainly released from descending neurons in the brainstem. In fact, stimulation of the medullary raphe nuclei, the origin of descending serotonergic neurons, enhances colorectal motility via the lumbosacral defecation center. Therefore, the purpose of this study was to examine the roles ofthe noradrenergic nucleus locus coeruleus (LC) and dopaminergic nucleus A11 region in the ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 28, 2019 Category: Physiology Authors: Nakamori H, Naitou K, Horii Y, Shimaoka H, Horii K, Sakai H, Yamada A, Furue H, Shiina T, Shimizu Y Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Effect of different bariatric surgeries on dietary protein bioavailability in rats.
This study aims at evaluating dietary protein bioavailability after different bariatric surgeries in rats. Diet-induced, obese Wistar rats were operated for vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB). The control group was composed of pair-fed, sham-operated rats (Sham). Two weeks after surgery, rats were fed a 15N protein meal. Protein bioavailability was assessed by determination of 15N recovery in the gastrointestinal tract and organs 6 h after the meal. Fractional protein synthesis rate (FSR) was assessed using a flooding dose of 13C valine. Weight loss was the highest in RYGB and the lowest in ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 28, 2019 Category: Physiology Authors: Tessier R, Ribeiro-Parenti L, Bruneau O, Khodorova NV, Cavin JB, Bado A, Azzout-Marniche D, Calvez J, Le Gall M, Gaudichon C Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research