Src kinases play a novel dual role in acute pancreatitis affecting severity but no role in stimulated enzyme secretion
In pancreatic acinar cells, the Src family of kinases (SFK) is involved in the activation of several signaling cascades that are implicated in mediating cellular processes (growth, cytoskeletal changes, apoptosis). However, the role of SFKs in various physiological responses such as enzyme secretion or in pathophysiological processes such as acute pancreatitis is either controversial, unknown, or incompletely understood. To address this, in this study, we investigated the role/mechanisms of SFKs in acute pancreatitis and enzyme release. Enzyme secretion was studied in rat dispersed pancreatic acini, in vitro acute-pancreat...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Nuche-Berenguer, B., Ramos-Alvarez, I., Jensen, R. T. Tags: PANCREATIC PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Effect of nasal noninvasive respiratory support methods on pharyngeal provocation-induced aerodigestive reflexes in infants
The pharynx is a locus of provocation among infants with aerodigestive morbidities manifesting as dysphagia, life-threatening events, aspiration-pneumonia, atelectasis, and reflux, and such infants often receive nasal respiratory support. We determined the impact of different oxygen delivery methods on pharyngeal stimulation-induced aerodigestive reflexes [room air (RA), nasal cannula (NC), and nasal continuous positive airway pressure (nCPAP)] while hypothesizing that the sensory motor characteristics of putative reflexes are distinct. Thirty eight infants (28.0 ± 0.7 wk gestation) underwent pharyngoesophageal mano...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Jadcherla, S. R., Hasenstab, K. A., Sitaram, S., Clouse, B. J., Slaughter, J. L., Shaker, R. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

p38 MAPK {alpha} and {beta} isoforms differentially regulate plasma membrane localization of MRP2
In hepatocytes, cAMP both activates p38 mitogen-activated protein kinase (MAPK) and increases the amount of multidrug resistance-associated protein-2 (MRP2) in the plasma membrane (PM-MRP2). Paradoxically, taurolithocholate (TLC) activates p38 MAPK but decreases PM-MRP2 in hepatocytes. These opposing effects of cAMP and TLC could be mediated via different p38 MAPK isoforms (α and β) that are activated differentially by upstream kinases (MKK3, MKK4, and MKK6). Thus we tested the hypothesis that p38α MAPK and p38β MAPK mediate increases and decreases in PM-MRP2 by cAMP and TLC, respectively. Studies wer...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Schonhoff, C. M., Park, S. W., Webster, C. R. L., Anwer, M. S. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Modulation of the microbiota-gut-brain axis by probiotics in a murine model of inflammatory bowel disease
Anxiety, depression, and altered memory are associated with intestinal diseases, including inflammatory bowel disease (IBD). Understanding the link between these behavioral changes and IBD is important clinically since concomitant mood disorders often increase a patient's risk of requiring surgery and developing secondary functional gastrointestinal diseases. Anxiety-like behavior (light/dark box test) and recognition memory (novel object recognition task) were determined at the peak and during resolution of inflammation in the dextran sodium sulfate (DSS) mouse model of acute colitis. DSS (5 days) was administered via dri...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Emge, J. R., Huynh, K., Miller, E. N., Kaur, M., Reardon, C., Barrett, K. E., Gareau, M. G. Tags: MICROBIOME AND HOST INTERACTIONS Source Type: research

Insights into the pathogenesis of ulcerative colitis from a murine model of stasis-induced dysbiosis, colonic metaplasia, and genetic susceptibility
Gut dysbiosis, host genetics, and environmental triggers are implicated as causative factors in inflammatory bowel disease (IBD), yet mechanistic insights are lacking. Longitudinal analysis of ulcerative colitis (UC) patients following total colectomy with ileal anal anastomosis (IPAA) where >50% develop pouchitis offers a unique setting to examine cause vs. effect. To recapitulate human IPAA, we employed a mouse model of surgically created blind self-filling (SFL) and self-emptying (SEL) ileal loops using wild-type (WT), IL-10 knockout (KO) (IL-10), TLR4 KO (T4), and IL-10/T4 double KO mice. After 5 wk, loop histology,...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Ward, M. A., Pierre, J. F., Leal, R. F., Huang, Y., Shogan, B., Dalal, S. R., Weber, C. R., Leone, V. A., Musch, M. W., An, G. C., Rao, M. C., Rubin, D. T., Raffals, L. E., Antonopoulos, D. A., Sogin, M. L., Hyman, N. H., Alverdy, J. C., Chang, E. B. Tags: MICROBIOME AND HOST INTERACTIONS Source Type: research

Inhibition of cyclooxygenase-2 alleviates liver cirrhosis via improvement of the dysfunctional gut-liver axis in rats
This study was aimed to test the hypothesis that inhibition of COX-2 by celecoxib might alleviate liver cirrhosis via reduction of intestinal inflammatory transport in thiacetamide (TAA) rat model. COX-2/prostaglandin E2 (PGE2)/EP-2/p-ERK integrated signal pathways regulated the expressions of intestinal zonula occludens-1 (ZO-1) and E-cadherin, which maintain the function of intestinal epithelial barrier. Celecoxib not only decreased the intestinal permeability to a 4-kDa FITC-dextran but also significantly increased expressions of ZO-1 and E-cadherin. When celecoxib greatly decreased intestinal levels of LPS, TNF-α...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Gao, J.-H., Wen, S.-L., Tong, H., Wang, C.-H., Yang, W.-J., Tang, S.-H., Yan, Z.-P., Tai, Y., Ye, C., Liu, R., Huang, Z.-Y., Tang, Y.-M., Yang, J.-H., Tang, C.-W. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Changes in gluconeogenesis and intracellular lipid accumulation characterize uremic human hepatocytes ex vivo
It is well known that reduced glomerular filtration rate (GFR) leads to an increased risk of dyslipidemia, insulin resistance, and cardiovascular mortality. The liver is a central organ for metabolism, but its function in the uremic setting is still poorly characterized. We used human primary hepatocytes isolated from livers of nine donors with normal renal function to investigate perturbations in key metabolic pathways following exposure to uremic (n = 8) or healthy (n = 8) sera, and to serum-free control medium. Both uremic and healthy elicited consistent responses from hepatocytes from multiple donors and compared with ...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Li, M., Ellis, E., Johansson, H., Nowak, G., Isaksson, B., Gnocchi, D., Parini, P., Axelsson, J. Tags: TRANSLATIONAL HUMAN PATHOPHYSIOLOGY Source Type: research

Postnatal development of the myenteric glial network and its modulation by butyrate
The postnatal period is crucial for the development of gastrointestinal (GI) functions. The enteric nervous system is a key regulator of GI functions, and increasing evidences indicate that 1) postnatal maturation of enteric neurons affect the development of GI functions, and 2) microbiota-derived short-chain fatty acids can be involved in this maturation. Although enteric glial cells (EGC) are central regulators of GI functions, the postnatal evolution of their phenotype remains poorly defined. We thus characterized the postnatal evolution of EGC phenotype in the colon of rat pups and studied the effect of short-chain fat...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Cossais, F., Durand, T., Chevalier, J., Boudaud, M., Kermarrec, L., Aubert, P., Neveu, I., Naveilhan, P., Neunlist, M. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

Role of apoptotic hepatocytes in HCV dissemination: regulation by acetaldehyde
Alcohol consumption exacerbates hepatitis C virus (HCV) pathogenesis and promotes disease progression, although the mechanisms are not quite clear. We have previously observed that acetaldehyde (Ach) continuously produced by the acetaldehyde-generating system (AGS), temporarily enhanced HCV RNA levels, followed by a decrease to normal or lower levels, which corresponded to apoptosis induction. Here, we studied whether Ach-induced apoptosis caused depletion of HCV-infected cells and what role apoptotic bodies (AB) play in HCV-alcohol crosstalk. In liver cells exposed to AGS, we observed the induction of miR-122 and miR-34a....
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Ganesan, M., Natarajan, S. K., Zhang, J., Mott, J. L., Poluektova, L. I., McVicker, B. L., Kharbanda, K. K., Tuma, D. J., Osna, N. A. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Hydrocortisone-induced anti-inflammatory effects in immature human enterocytes depend on the timing of exposure
The immature human gut has a propensity to exaggerated inflammatory responses that are thought to play a role in the pathogenesis of necrotizing enterocolitis (NEC). Prenatal exposure to corticosteroids has been reported to reduce the risk of NEC, while postnatal dexamethasone treatment is associated with adverse neurodevelopmental outcomes in preterm infants. The aim of this study was to investigate the direct role of hydrocortisone in gene expression patterns and inflammatory responses in immature human enterocytes. Time-dependent hydrocortisone effects in nontransformed primary human fetal intestinal epithelial cell lin...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Rautava, S., Walker, W. A., Lu, L. Tags: EPITHELIAL BIOLOGY AND SECRETION Source Type: research

High-fat diets rich in saturated fat protect against azoxymethane/dextran sulfate sodium-induced colon cancer
We examined the effects of three HFDs differing in the percentage of total calories from saturated fat (SF) (6, 12, and 24% of total caloric intake), but identical in total fat (40%), and a commercially available Western diet (26 and 41% saturated and total fat, respectively) on colon cancer development using the azoxymethane (AOM)/dextran sulfate sodium (DSS) murine model. A second dose-response experiment was performed using diets supplemented with the saturated-fatty-acid (SFA)-rich coconut oil. In experiment 1, we found an inverse association between SF content and tumor burden. Furthermore, increased SF content was as...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Enos, R. T., Velazquez, K. T., McClellan, J. L., Cranford, T. L., Nagarkatti, M., Nagarkatti, P. S., Davis, J. M., Murphy, E. A. Tags: CALL FOR PAPERS Source Type: research

TAM receptor tyrosine kinase function and the immunopathology of liver disease
Tyro3, Axl, MERTK (TAM) receptor tyrosine kinases are implicated in the regulation of the innate immune response through clearance of apoptotic cellular debris and control of cytokine signaling cascades. As a result they are pivotal in regulating the inflammatory response to tissue injury. Within the liver, immune regulatory signaling is employed to prevent the overactivation of innate immunity in response to continual antigenic challenge from the gastrointestinal tract. In this review we appraise current understanding of the role of TAM receptor function in the regulation of both innate and adaptive immunity, with a focus...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Mukherjee, S. K., Wilhelm, A., Antoniades, C. G. Tags: REVIEWS Source Type: research

Intestinal SGLT1 in metabolic health and disease
The Na+-glucose cotransporter 1 (SGLT1/SLC5A1) is predominantly expressed in the small intestine. It transports glucose and galactose across the apical membrane in a process driven by a Na+ gradient created by Na+-K+-ATPase. SGLT2 is the major form found in the kidney, and SGLT2-selective inhibitors are a new class of treatment for type 2 diabetes mellitus (T2DM). Recent data from patients treated with dual SGLT1/2 inhibitors or SGLT2-selective drugs such as canagliflozin (SGLT1 IC50 = 663 nM) warrant evaluation of SGLT1 inhibition for T2DM. SGLT1 activity is highly dynamic, with modulation by multiple mechanisms to ensure...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Lehmann, A., Hornby, P. J. Tags: REVIEWS Source Type: research

Young Investigator Perspectives. Rethinking the biomedical postdoc: but first let's get the data
(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Pierre, J. F. Tags: EDITORIAL Source Type: research

Inhibition of pancreatic acinar mitochondrial thiamin pyrophosphate uptake by the cigarette smoke component 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
We examined the effect of long-term/chronic exposure of PAC in vitro (pancreatic acinar 266-6 cells) and in vivo (wild-type or transgenic mice carrying the SLC25A19 promoter) of the cigarette smoke toxin, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), on the MTPP uptake process. Our in vitro and in vivo findings demonstrate that NNK negatively affects MTPP uptake and reduced expression of MTPPT protein, MTPPT mRNA, and heterogenous nuclear RNA, as well as SLC25A19 promoter activity. The effect of NNK on Slc25a19 transcription was neither mediated by changes in expression of transcriptional factor NFY-1 (known to dri...
Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: Srinivasan, P., Thrower, E. C., Gorelick, F. S., Said, H. M. Tags: PANCREATIC PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research