Long noncoding RNAs: novel links to inflammatory bowel disease?
(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Edgington-Mitchell, L. E. Tags: EDITORIAL FOCUS Source Type: research

Regulation and dysregulation of esophageal peristalsis by the integrated function of circular and longitudinal muscle layers in health and disease
Muscularis propria throughout the entire gastrointestinal tract including the esophagus is comprised of circular and longitudinal muscle layers. Based on the studies conducted in the colon and the small intestine, for more than a century, it has been debated whether the two muscle layers contract synchronously or reciprocally during the ascending contraction and descending relaxation of the peristaltic reflex. Recent studies in the esophagus and colon prove that the two muscle layers indeed contract and relax together in almost perfect synchrony during ascending contraction and descending relaxation of the peristaltic refl...
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Mittal, R. K. Tags: REVIEW Source Type: research

Intestinal brush-border Na+/H+ exchanger-3 drives H+-coupled iron absorption in the mouse
Divalent metal-ion transporter-1 (DMT1), the principal mechanism by which nonheme iron is taken up at the intestinal brush border, is energized by the H+-electrochemical potential gradient. The provenance of the H+ gradient in vivo is unknown, so we have explored a role for brush-border Na+/H+ exchanger (NHE) isoforms by examining iron homeostasis and intestinal iron handling in mice lacking NHE2 or NHE3. We observed modestly depleted liver iron stores in NHE2-null (NHE2–/–) mice stressed on a low-iron diet but no change in hematological or blood iron variables or the expression of genes associated with iron me...
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Shawki, A., Engevik, M. A., Kim, R. S., Knight, P. B., Baik, R. A., Anthony, S. R., Worrell, R. T., Shull, G. E., Mackenzie, B. Tags: NUTRIENT SENSING, NUTRITION, AND METABOLISM Source Type: research

PanIN-associated pericyte, glial, and islet remodeling in mice revealed by 3D pancreatic duct lesion histology
In this study we developed three-dimensional (3D) duct lesion histology to investigate PanIN and the associated pericyte, glial, and islet remodeling. Transparent mouse pancreata with a KrasG12D mutation were used to develop 3D duct lesion histology. Deep-tissue, tile-scanning microscopy was performed to generate panoramic views of the diseased pancreas for global examination of early stage and advanced duct lesion formation. Fluorescence signals of ductal and neurovascular networks were simultaneously detected to reveal associated remodeling. Significantly, in KrasG12D-mutant mice, when the low-grade PanINs emerge, duct l...
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Lin, P.-Y., Peng, S.-J., Shen, C.-N., Pasricha, P. J., Tang, S.-C. Tags: PANCREATIC PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Yes-associated protein impacts adherens junction assembly through regulating actin cytoskeleton organization
The Hippo pathway effector Yes-associated protein (YAP) regulates liver size by promoting cell proliferation and inhibiting apoptosis. However, recent in vivo studies suggest that YAP has important cellular functions other than controlling proliferation and apoptosis. Transgenic YAP expression in mouse hepatocytes results in severe jaundice. A possible explanation for the jaundice could be defects in adherens junctions that prevent bile from leaking into the blood stream. Indeed, immunostaining of E-cadherin and electron microscopic examination of bile canaliculi of Yap transgenic livers revealed abnormal adherens junction...
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Bai, H., Zhu, Q., Surcel, A., Luo, T., Ren, Y., Guan, B., Liu, Y., Wu, N., Joseph, N. E., Wang, T. -L., Zhang, N., Pan, D., Alpini, G., Robinson, D. N., Anders, R. A. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

A return to ad libitum feeding following caloric restriction promotes hepatic steatosis in hyperphagic OLETF rats
Hyperphagic Otsuka Long-Evans Tokushima fatty (OLETF) rats develop obesity, insulin resistance, and nonalcoholic fatty liver disease (NAFLD), but lifestyle modifications, such as caloric restriction (CR), can prevent these conditions. We sought to determine if prior CR had protective effects on metabolic health and NAFLD development following a 4-wk return to ad libitum (AL) feeding. Four-week-old male OLETF rats (n = 8–10/group) were fed AL for 16 wk (O-AL), CR for 16 wk (O-CR; ~70% kcal of O-AL), or CR for 12 wk followed by 4 wk of AL feeding (O-AL4wk). CR-induced benefit in prevention of NAFLD, including reduced h...
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Linden, M. A., Fletcher, J. A., Meers, G. M., Thyfault, J. P., Laughlin, M. H., Rector, R. S. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Autophagy confers resistance to lipopolysaccharide-induced mouse hepatocyte injury
During sepsis, bacterial products, particularly LPS, trigger injury in organs such as the liver. This common condition remains largely untreatable, in part due to a lack of understanding of how high concentrations of LPS cause cellular injury. In the liver, the lysosomal degradative pathway of autophagy performs essential hepatoprotective functions and is induced by LPS. We, therefore, examined whether hepatocyte autophagy protects against liver injury from septic levels of LPS. Mice with an inducible hepatocyte-specific knockout of the critical autophagy gene Atg7 were examined for their sensitivity to high-dose LPS. Incr...
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Lalazar, G., Ilyas, G., Malik, S. A., Liu, K., Zhao, E., Amir, M., Lin, Y., Tanaka, K. E., Czaja, M. J. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Pilot study of small bowel mucosal gene expression in patients with irritable bowel syndrome with diarrhea
In conclusion, altered transcriptome (and to lesser extent protein) expression of ion transport, barrier, immune, and mast cell mechanisms in small bowel may reflect different alterations in function and deserves further study in IBS-D. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Camilleri, M., Carlson, P., Valentin, N., Acosta, A., O'Neill, J., Eckert, D., Dyer, R., Na, J., Klee, E. W., Murray, J. A. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

Effect of nitrate supplementation on hepatic blood flow and glucose homeostasis: a double-blind, placebo-controlled, randomized control trial
Nitric oxide alters gastric blood flow, improves vascular function, and mediates glucose uptake within the intestines and skeletal muscle. Dietary nitrate, acting as a source of nitric oxide, appears to be a potential low-cost therapy that may help maintain glucose homeostasis. In a randomized, double-blind, placebo-controlled crossover study, 31 young and older adult participants had a standardized breakfast, supplemented with either nitrate-rich beetroot juice (11.91 mmol nitrate) or nitrate-depleted beetroot juice as placebo (0.01 mmol nitrate). MRI was used to assess apparent diffusion coefficient (ADC), portal vein fl...
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Shepherd, A. I., Wilkerson, D. P., Fulford, J., Winyard, P. G., Benjamin, N., Shore, A. C., Gilchrist, M. Tags: NUTRIENT SENSING, NUTRITION, AND METABOLISM Source Type: research

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis
Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be revi...
Source: AJP: Gastrointestinal and Liver Physiology - August 31, 2016 Category: Gastroenterology Authors: Zhan, X., Wang, F., Bi, Y., Ji, B. Tags: INFLAMMATION, IMMUNITY, AND INFECTION Source Type: research

Ursodeoxycholic acid inhibits TNF{alpha}-induced IL-8 release from monocytes
Monocytes are critical to the pathogenesis of inflammatory bowel disease (IBD) as they infiltrate the mucosa and release cytokines that drive the inflammatory response. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid with anti-inflammatory actions, has been proposed as a potential new therapy for IBD. However, its effects on monocyte function are not yet known. Primary monocytes from healthy volunteers or cultured U937 monocytes were treated with either the proinflammatory cytokine, TNFα (5 ng/ml) or the bacterial endotoxin, lipopolysaccharide (LPS; 1 μg/ml) for 24 h, in the absence or presence of UDC...
Source: AJP: Gastrointestinal and Liver Physiology - August 8, 2016 Category: Gastroenterology Authors: O'Dwyer, A. M., Lajczak, N. K., Keyes, J. A., Ward, J. B., Greene, C. M., Keely, S. J. Tags: INFLAMMATION, IMMUNITY, AND INFECTION Source Type: research

Milk diets influence doxorubicin-induced intestinal toxicity in piglets
Chemotherapy-induced gastrointestinal (GI) toxicity is a common adverse effect of cancer treatment. We used preweaned piglets as models to test our hypothesis that the immunomodulatory and GI trophic effects of bovine colostrum would reduce the severity of GI complications associated with doxorubicin (DOX) treatment. Five-day-old pigs were administered DOX (1 x 100 mg/m2) or an equivalent volume of saline (SAL) and either fed formula (DOX-Form, n = 9, or SAL-Form, n = 7) or bovine colostrum (DOX-Colos, n = 9, or SAL-Colos, n = 7). Pigs were euthanized 5 days after initiation of chemotherapy to assess markers of small intes...
Source: AJP: Gastrointestinal and Liver Physiology - August 8, 2016 Category: Gastroenterology Authors: Shen, R. L., Pontoppidan, P. E. L., Rathe, M., Jiang, P., Hansen, C. F., Buddington, R. K., Heegaard, P. M. H., Müller, K., Sangild, P. T. Tags: NUTRIENT SENSING, NUTRITION, AND METABOLISM Source Type: research

Ablation of interaction between IL-33 and ST2+ regulatory T cells increases immune cell-mediated hepatitis and activated NK cell liver infiltration
In conclusion, IL-33 acts as a potent immune modulator protecting the liver through activation of ST2+ Treg cells and control of NK cells. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - August 8, 2016 Category: Gastroenterology Authors: Noel, G., Arshad, M. I., Filliol, A., Genet, V., Rauch, M., Lucas-Clerc, C., Lehuen, A., Girard, J.-P., Piquet-Pellorce, C., Samson, M. Tags: INFLAMMATION, IMMUNITY, AND INFECTION Source Type: research

GGsTop, a novel and specific {gamma}-glutamyl transpeptidase inhibitor, protects hepatic ischemia-reperfusion injury in rats
In conclusion, treatment with GGsTop increased glutathione levels and prevented formation of free radicals in the hepatic tissue that led to decreased IR-induced liver injury. GGsTop could be used as a pharmacological agent to prevent IR-induced liver injury and the related adverse events. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - August 8, 2016 Category: Gastroenterology Authors: Tamura, K., Hayashi, N., George, J., Toshikuni, N., Arisawa, T., Hiratake, J., Tsuchishima, M., Tsutsumi, M. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice
The metabolic benefits induced by gastric bypass, currently the most effective treatment for morbid obesity, are associated with bile acid (BA) delivery to the distal intestine. However, mechanistic insights into BA signaling in the mediation of metabolic benefits remain an area of study. The bile diversion () mouse model, in which the gallbladder is anastomosed to the distal jejunum, was used to test the specific role of BA in the regulation of glucose and lipid homeostasis. Metabolic phenotype, including body weight and composition, glucose tolerance, energy expenditure, thermogenesis genes, total BA and BA composition i...
Source: AJP: Gastrointestinal and Liver Physiology - July 31, 2016 Category: Gastroenterology Authors: Pierre, J. F., Martinez, K. B., Ye, H., Nadimpalli, A., Morton, T. C., Yang, J., Wang, Q., Patno, N., Chang, E. B., Yin, D. P. Tags: NUTRIENT SENSING, NUTRITION, AND METABOLISM Source Type: research