Gastric and pyloric sphincter muscle function and the developmental-dependent regulation of gastric content emptying in the rat
Feeding intolerance is a common issue in the care of preterm neonates. The condition manifests as delayed emptying of gastric contents and represents a therapeutic challenge, since the factors accounting for its manifestations are unknown. The main goal of this study was to comparatively investigate the age-related function of rat gastric and pyloric smooth muscle and their putative regulators. We hypothesized that a reduced gastric muscle contraction potential early in life contributes to the delayed gastric emptying of the newborn. Newborn and adult rat gastric (fundus) and pyloric sphincter tissues were comparatively st...
Source: AJP: Gastrointestinal and Liver Physiology - June 7, 2016 Category: Gastroenterology Authors: Sobchak, C., Fajardo, A. F., Shifrin, Y., Pan, J., Belik, J. Tags: TRANSLATIONAL HUMAN PATHOPHYSIOLOGY Source Type: research

Inhibition of SIRT2 suppresses hepatic fibrosis
In this study, we found that blocking the activity of sirtuin 2 (SIRT2) by using inhibitors or shRNAs significantly suppressed fibrogenic gene expression in HSCs. We further demonstrated that inhibition of SIRT2 results in the degradation of c-MYC, which is important for HSC activation. In addition, we discovered that inhibition of SIRT2 suppresses the phosphorylation of ERK, which is critical for the stabilization of c-MYC. Moreover, we found that Sirt2 deficiency attenuates the hepatic fibrosis induced by carbon tetrachloride (CCl4) and thioacetamide (TAA). Furthermore, we showed that SIRT2, p-ERK, and c-MYC proteins are...
Source: AJP: Gastrointestinal and Liver Physiology - June 7, 2016 Category: Gastroenterology Authors: Arteaga, M., Shang, N., Ding, X., Yong, S., Cotler, S. J., Denning, M. F., Shimamura, T., Breslin, P., Lüscher, B., Qiu, W. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Keratin 8 knockdown leads to loss of the chloride transporter DRA in the colon
Keratins (K) are intermediate filament proteins important in protection from stress. The roles of keratins in the intestine are not clear, but K8 knockout (K8–/–) mice develop a Th2-type colonic inflammation, epithelial hyperproliferation, and mild diarrhea caused by a keratin level-dependent decrease in short-circuit current and net sodium and chloride absorption in the distal colon. The lack of K8 leads to mistargeting or altered levels of membrane proteins in colonocytes; however, the main transporter responsible for the keratin-related ion transport defect is unknown. We here analyzed protein and mRNA level...
Source: AJP: Gastrointestinal and Liver Physiology - June 7, 2016 Category: Gastroenterology Authors: Asghar, M. N., Priyamvada, S., Nyström, J. H., Anbazhagan, A. N., Dudeja, P. K., Toivola, D. M. Tags: EPITHELIAL BIOLOGY AND SECRETION Source Type: research

The SCFA butyrate stimulates the epithelial production of retinoic acid via inhibition of epithelial HDAC
In the intestinal mucosa, retinoic acid (RA) is a critical signaling molecule. RA is derived from dietary vitamin A (retinol) through conversion by aldehyde dehydrogenases (aldh). Reduced levels of short-chain fatty acids (SCFAs) are associated with pathological microbial dysbiosis, inflammatory disease, and allergy. We hypothesized that SCFAs contribute to mucosal homeostasis by enhancing RA production in intestinal epithelia. With the use of human and mouse epithelial cell lines and primary enteroids, we studied the effect of SCFAs on the production of RA. Functional RA conversion was analyzed by Adlefluor activity assay...
Source: AJP: Gastrointestinal and Liver Physiology - June 7, 2016 Category: Gastroenterology Authors: Schilderink, R., Verseijden, C., Seppen, J., Muncan, V., van den Brink, G. R., Lambers, T. T., van Tol, E. A., de Jonge, W. J. Tags: RAPID REPORT Source Type: research

Transcriptomic and CRISPR/Cas9 technologies reveal FOXA2 as a tumor suppressor gene in pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with low survival rates and limited therapeutic options. Thus elucidation of signaling pathways involved in PDAC pathogenesis is essential for identifying novel potential therapeutic gene targets. Here, we used a systems approach to elucidate those pathways by integrating gene and microRNA profiling analyses together with CRISPR/Cas9 technology to identify novel transcription factors involved in PDAC pathogenesis. FOXA2 transcription factor was found to be significantly downregulated in PDAC relative to control pancreatic tissues. Functional experiments reveal...
Source: AJP: Gastrointestinal and Liver Physiology - June 7, 2016 Category: Gastroenterology Authors: Vorvis, C., Hatziapostolou, M., Mahurkar-Joshi, S., Koutsioumpa, M., Williams, J., Donahue, T. R., Poultsides, G. A., Eibl, G., Iliopoulos, D. Tags: CALL FOR PAPERS Source Type: research

The glial cell-line derived neurotrophic factor: a novel regulator of intestinal barrier function in health and disease
Regulation of the intestinal epithelial barrier is a differentiated process, which is profoundly deranged in inflammatory bowel diseases. Recent data provide evidence that the glial cell line-derived neurotrophic factor (GDNF) is critically involved in intestinal epithelial wound healing and barrier maturation and exerts antiapoptotic effects under certain conditions. Furthermore, not only the enteric nervous system, but also enterocytes synthesize GDNF in significant amounts, which points to a potential para- or autocrine signaling loop between enterocytes. Apart from direct effects of GDNF on enterocytes, an immunomodula...
Source: AJP: Gastrointestinal and Liver Physiology - June 7, 2016 Category: Gastroenterology Authors: Meir, M., Flemming, S., Burkard, N., Wagner, J., Germer, C.-T., Schlegel, N. Tags: MINIREVIEW Source Type: research

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance
The compounds of sphingomyelin-ceramide-glycosphingolipid pathways have been studied as potential secondary messenger molecules in various systems, along with liver function and insulin resistance. Secondary messenger molecules act directly or indirectly to affect cell organelles and intercellular interactions. Their potential role in the pathogenesis of steatohepatitis and diabetes has been suggested. Data samples collected from patients with Gaucher's disease, who had high levels of glucocerebroside, support a role for compounds from these pathways as a messenger molecules in the pathogenesis of fatty liver disease and d...
Source: AJP: Gastrointestinal and Liver Physiology - June 7, 2016 Category: Gastroenterology Authors: Ilan, Y. Tags: REVIEWS Source Type: research

Periodontal dysbiosis linked to periodontitis is associated with cardiometabolic adaptation to high-fat diet in mice
We report that the severity of glucose intolerance is related to the severity of periodontitis and cardiac disorders. In detail, alveolar bone loss was more accentuated in DS than Inter, DR, and normal chow-fed mice. Molecular markers of periodontal inflammation, such as TNF-α and plasminogen activator inhibitor-1 mRNA levels, correlated positively with both alveolar bone loss and glycemic index. Furthermore, the periodontal microbiota of DR mice was dominated by the Streptococcaceae family of the phylum Firmicutes, whereas the periodontal microbiota of DS mice was characterized by increased Porphyromonadaceae and Pr...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Branchereau, M., Reichardt, F., Loubieres, P., Marck, P., Waget, A., Azalbert, V., Colom, A., Padmanabhan, R., Iacovoni, J. S., Giry, A., Terce, F., Heymes, C., Burcelin, R., Serino, M., Blasco-Baque, V. Tags: MICROBIOME AND HOST INTERACTIONS Source Type: research

Importance of the alternative NF-{kappa}B activation pathway in inflammation-associated gastrointestinal carcinogenesis
Chronic inflammation is a common factor in the development of many gastrointestinal malignancies. Examples include inflammatory bowel disease predisposing to colorectal cancer, Barrett's esophagus as a precursor of esophageal adenocarcinoma, and Helicobacter pylori-induced gastric cancer. The classical activation pathway of NF-B signaling has been identified as regulating several sporadic and inflammation-associated gastrointestinal tract malignancies. Emerging evidence suggests that the alternative NF-B signaling pathway also exerts a distinct influence on these processes. This review brings together current knowledge of ...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Merga, Y. J., O'Hara, A., Burkitt, M. D., Duckworth, C. A., Probert, C. S., Campbell, B. J., Pritchard, D. M. Tags: REVIEWS Source Type: research

Microsomal prostaglandin E synthase-1 protects against Fas-induced liver injury
In this study, we developed transgenic (Tg) mice with targeted expression of mPGES-1 in the liver to assess Fas-induced hepatocyte apoptosis and acute liver injury. Compared with wild-type (WT) mice, the mPGES-1 Tg mice showed less liver hemorrhage, lower serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, less hepatic necrosis/apoptosis, and lower level of caspase cascade activation after intraperitoneal injection of the anti-Fas antibody Jo2. Western blotting analysis revealed increased expression and activation of the serine/threonine kinase Akt and associated antiapoptotic molecules in the liver t...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Yao, L., Chen, W., Han, C., Wu, T. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

General control nonderepressible 2 deletion predisposes to asparaginase-associated pancreatitis in mice
Treatment with the antileukemic agent asparaginase can induce acute pancreatitis, but the pathophysiology remains obscure. In the liver of mice, eukaryotic initiation factor 2 (eIF2) kinase general control nonderepressible 2 (GCN2) is essential for mitigating metabolic stress caused by asparaginase. We determined the consequences of asparaginase treatment on the pancreata of wild-type (WT, GCN2-intact) and GCN2-deleted (Gcn2) mice. Mean pancreas weights in Gcn2 mice treated with asparaginase for 8 days were increased (P < 0.05) above all other groups. Histological examination revealed acinar cell swelling and altered st...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Phillipson-Weiner, L., Mirek, E. T., Wang, Y., McAuliffe, W. G., Wek, R. C., Anthony, T. G. Tags: PANCREATIC PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Role of muscarinic-3 receptor antibody in systemic sclerosis: correlation with disease duration and effects of IVIG
Gastrointestinal dysmotility in systemic sclerosis (SSc) is associated with autoantibodies against muscarinic-3 receptor (M3-R). We investigated the temporal course of the site of action of these autoantibodies at the myenteric neurons (MN) vs. the smooth muscle (SM) M3-R in relation to disease duration, and determined the role of intravenous immunoglobulin (IVIG) in reversing these changes. Immunoglobulins purified from SSc patients (SScIgG) were used to assess their differential binding to MN and SM (from rat colon) employing immunohistochemistry (IHC). Effect of SScIgG on neural and direct muscle contraction was determi...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Kumar, S., Singh, J., Kedika, R., Mendoza, F., Jimenez, S. A., Blomain, E. S., DiMarino, A. J., Cohen, S., Rattan, S. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

microRNA-192 suppresses the expression of the farnesoid X receptor
In this study, we investigated the extent to which FXR is regulated by miR-192. Two in silico-predicted binding sites for miR-192-3p within the NR1H4-3' untranslated region (UTR) were examined in vitro by luciferase reporter assays. Wild-type and mutated forms of the NR1H4-3'UTR were subcloned into a pmirGLO vector and cotransfected into Huh-7 cells with miR-192-3p. To study the effects of miR-192 on the expression of FXR, FXR target genes and cell proliferation, Huh-7 and Caco-2 cells were transfected with miR-192-5p and -3p mimics or antagomirs. In addition, the correlation between FXR and miR-192 expression was studied ...
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Krattinger, R., Boström, A., Schiöth, H. B., Thasler, W. E., Mwinyi, J., Kullak-Ublick, G. A. Tags: HORMONES, NEUROTRANSMITTERS, GROWTH FACTORS, RECEPTORS, AND SIGNALING Source Type: research

Effects of laryngeal restriction on pharyngeal peristalsis and biomechanics: Clinical implications
In conclusion, repeated swallows against a resistive load induced by restricting the anterosuperior excursion of the larynx safely induces fatigue in pharyngeal peristalsis and thus has the potential to strengthen the pharyngeal contractile function. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Shaker, R., Sanvanson, P., Balasubramanian, G., Kern, M., Wuerl, A., Hyngstrom, A. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

Transcriptional modulation of SLC26A3 (DRA) by sphingosine-1-phosphate
In conclusion, transcriptional modulation of DRA expression and function in response to S1P through a PI3/Akt pathway represents a novel role of S1P as a potential proabsorptive agent. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - May 31, 2016 Category: Gastroenterology Authors: Anbazhagan, A. N., Priyamvada, S., Alakkam, A., Kumar, A., Borthakur, A., Saksena, S., Gill, R. K., Alrefai, W. A., Dudeja, P. K. Tags: EPITHELIAL BIOLOGY AND SECRETION Source Type: research