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PubMed Central (PMC3 - NLM DTD) (2,742,912 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).

American Journal of Physiology - Gastrointestinal and Liver Physiology

Mostrando recursos 1 - 20 de 820

1. Cholecystokinin and pancreatic cancer: the chicken or the egg? - Smith, Jill P.; Solomon, Travis E.
The gastrointestinal peptide cholecystokinin (CCK) causes the release of pancreatic digestive enzymes and growth of the normal pancreas. Exogenous CCK administration has been used in animal models to study pancreatitis and also as a promoter of carcinogen-induced or Kras-driven pancreatic cancer. Defining CCK receptors in normal human pancreas has been problematic because of its retroperitoneal location, high concentrations of pancreatic proteases, and endogenous RNase. Most studies indicate that the predominant receptor in human pancreas is the CCK-B type, and CCK-A is the predominant form in rodent pancreas. In pancreatic cancer cells and tumors, the role of CCK is better established...

2. c-Fos mediates repression of the apical sodium-dependent bile acid transporter by fibroblast growth factor-19 in mice - Ghosh, Ayantika; Chen, Frank; Banerjee, Swati; Xu, Ming; Shneider, Benjamin L.
Fibroblast growth factor-19 (FGF-19), a bile acid-responsive enterokine, is secreted by the ileum and regulates a variety of metabolic processes. These studies examined the signal transduction pathways operant in FGF-19-mediated repression of the apical sodium-dependent bile acid transporter (ASBT). Responses to FGF-19 were assessed in Caco-2 and CT-26 cells and in mice where c-fos was conditionally silenced in the intestine by a cre-lox strategy. FGF-19 treatment of Caco-2 cells or wild-type mice led to a significant reduction in ASBT protein expression and enhanced phosphorylation of extracellular signaling kinase 1/2 (ERK1/2), c-Fos, and c-Jun. FGF-19 treatment of Caco-2 cells led to...

3. Translational repression of SLC26A3 by miR-494 in intestinal epithelial cells - Anbazhagan, Arivarasu N.; Priyamvada, Shubha; Kumar, Anoop; Maher, Daniel B.; Borthakur, Alip; Alrefai, Waddah A.; Malakooti, Jaleh; Kwon, John H.; Dudeja, Pradeep K.
SLC26A3 [downregulated in adenoma (DRA)] is a Cl−/HCO3− exchanger involved in electroneutral NaCl absorption in the mammalian intestine. Altered DRA expression levels are associated with infectious and inflammatory diarrheal diseases. Therefore, it is critical to understand the regulation of DRA expression. MicroRNAs (miRNAs) are endogenous, small RNAs that regulate protein expression via blocking the translation and/or promoting mRNA degradation. To investigate potential modulation of DRA expression by miRNA, five different in silico algorithms were used to predict the miRNAs that target DRA. Of these miRNAs, miR-494 was shown to have a highly conserved putative binding site in the DRA 3′-untranslated...

4. Endothelial nitric oxide synthase uncoupling and microvascular dysfunction in the mesentery of mice deficient in α-galactosidase A - Kang, Justin J.; Shu, Liming; Park, James L.; Shayman, James A.; Bodary, Peter F.
A defect in the gene for the lysosomal enzyme α-galactosidase A (Gla) results in globotriaosylceramide (Gb3) accumulation in Fabry disease and leads to premature death from cardiac and cerebrovascular events. However, gastrointestinal symptoms are often first observed during childhood in these patients and are not well understood. In this study, we demonstrate an age-dependent microvasculopathy of the mesenteric artery (MA) in a murine model of Fabry disease (Gla-knockout mice) resulting from dysregulation of the vascular homeostatic enzyme endothelial nitric oxide synthase (eNOS). The progressive accumulation of Gb3 in the MA was confirmed by thin-layer chromatographic analysis. A total absence of...

5. A novel RARα/CAR-mediated mechanism for regulation of human organic solute transporter-β gene expression - Xu, Shuhua; Sun, An-Qiang; Suchy, Frederick J.
The organic solute transporter-α/β (OSTα/β) is a heteromeric transporter that is essential for bile acid and sterol disposition and for the enterohepatic circulation. To better understand the mechanism underlying OST gene regulation, the effects of retinoic acid (RA) on OSTα/β gene expression were investigated. The results show a dose-dependent induction of OSTβ but not OSTα expression in both Huh7 and HepG2 cells by RA treatment. A novel functional RA receptor response element (RARE; so-called DR5) in the promoter of OSTβ gene was identified. The interaction of RARα/RXRα with the RARE was verified by electrophoretic mobility shift and chromatin immunoprecipitation assays...

6. Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets - Jensen, Michael L.; Thymann, Thomas; Cilieborg, Malene S.; Lykke, Mikkel; Mølbak, Lars; Jensen, Bent B.; Schmidt, Mette; Kelly, Denise; Mulder, Imke; Burrin, Douglas G.; Sangild, Per T.
Preterm birth, bacterial colonization, and formula feeding predispose to necrotizing enterocolitis (NEC). Antibiotics are commonly administered to prevent sepsis in preterm infants, but it is not known whether this affects intestinal immunity and NEC resistance. We hypothesized that broad-spectrum antibiotic treatment improves NEC resistance and intestinal structure, function, and immunity in neonates. Caesarean-delivered preterm pigs were fed 3 days of parenteral nutrition followed by 2 days of enteral formula. Immediately after birth, they were assigned to receive either antibiotics (oral and parenteral doses of gentamycin, ampicillin, and metronidazole, ANTI, n = 11) or saline in the control group (CON, n...

7. The role of receptor tyrosine kinase activation in cholangiocytes and pulmonary vascular endothelium in experimental hepatopulmonary syndrome - Yang, Wenli; Zhang, Junlan; Hu, Bingqian; Wu, Wei; Venter, Julie; Alpini, Gianfranco; Fallon, Michael B.
Pulmonary vascular dilation and angiogenesis underlie experimental hepatopulmonary syndrome (HPS) induced by common bile duct ligation (CBDL) and may respond to receptor tyrosine kinase (RTK) inhibition. Vascular endothelial growth factor-A (VEGF-A) expression occurs in proliferating cholangiocytes and pulmonary intravascular monocytes after CBDL, the latter contributing to angiogenesis. CBDL cholangiocytes also produce endothelin-1 (ET-1), which triggers lung vascular endothelin B receptor-mediated endothelial nitric oxide synthase (eNOS) activation and pulmonary intravascular monocyte accumulation. However, whether RTK pathway activation directly regulates cholangiocyte and pulmonary microvascular alterations in experimental HPS is not defined. We assessed RTK pathway activation in cholangiocytes and lung after CBDL...

8. Irritable bowel syndrome-diarrhea: characterization of genotype by exome sequencing, and phenotypes of bile acid synthesis and colonic transit - Camilleri, Michael; Klee, Eric W.; Shin, Andrea; Carlson, Paula; Li, Ying; Grover, Madhusudan; Zinsmeister, Alan R.
The study objectives were: to mine the complete exome to identify putative rare single nucleotide variants (SNVs) associated with irritable bowel syndrome (IBS)-diarrhea (IBS-D) phenotype, to assess genes that regulate bile acids in IBS-D, and to explore univariate associations of SNVs with symptom phenotype and quantitative traits in an independent IBS cohort. Using principal components analysis, we identified two groups of IBS-D (n = 16) with increased fecal bile acids: rapid colonic transit or high bile acids synthesis. DNA was sequenced in depth, analyzing SNVs in bile acid genes (ASBT, FXR, OSTα/β, FGF19, FGFR4, KLB, SHP, CYP7A1, LRH-1, and FABP6)....

9. Paeoniflorin abrogates DSS-induced colitis via a TLR4-dependent pathway - Zhang, Jingjing; Dou, Wei; Zhang, Eryun; Sun, Aning; Ding, Lili; Wei, Xiaohui; Chou, Guixin; Mani, Sridhar; Wang, Zhengtao
Paeonia lactiflora Pall is one of the most well-known herbs in China, Korea, and Japan for more than 1,200 years. Paeoniflorin, the major bioactive component of peony root, has recently been reported to have anticolitic activity. However, the underlying molecular mechanism is unclear. The present study was to explore the possible mechanism of paeoniflorin in attenuating dextran sulfate sodium (DSS)-induced colitis. Pre- and coadministration of paeoniflorin significantly reduced the severity of colitis and resulted in downregulation of several inflammatory parameters in the colon, including the activity of myeloperoxidase (MPO), the levels of TNF-α and IL-6, and the mRNA expression of...

10. FXR silencing in human colon cancer by DNA methylation and KRAS signaling - Bailey, Ann M.; Zhan, Le; Maru, Dipen; Shureiqi, Imad; Pickering, Curtis R.; Kiriakova, Galina; Izzo, Julie; He, Nan; Wei, Caimiao; Baladandayuthapani, Veerabhadran; Liang, Han; Kopetz, Scott; Powis, Garth; Guo, Grace L.
Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas. This study investigates the regulation of FXR in the development of human colon cancer. We used immunohistochemistry of FXR in normal tissue (n = 238), polyps (n = 32), and adenocarcinomas, staged I–IV (n = 43, 39, 68, and 9), of the colon; RT-quantitative PCR, reverse-phase protein array, and Western blot analysis in 15 colon cancer cell lines; NR1H4 promoter methylation and mRNA expression in colon cancer samples from The Cancer Genome Atlas; DNA methyltransferase...

11. Acute ethanol preexposure promotes liver regeneration after partial hepatectomy in mice by activating ALDH2 - Ding, Xiang; Beier, Juliane I.; Baldauf, Keegan J.; Jokinen, Jenny D.; Zhong, Hai; Arteel, Gavin E.
It is known that chronic ethanol significantly impairs liver regeneration. However, the effect of acute ethanol exposure on liver regeneration remains largely unknown. To address this question, C57Bl6/J mice were exposed to acute ethanol (6 g/kg intragastrically) for 3 days, and partial hepatectomy (PHx) was performed 24 h after the last dose. Surprisingly, acute ethanol preexposure promoted liver regeneration. This effect of ethanol did not correlate with changes in expression of cell cycle regulatory genes (e.g., cyclin D1, p21, and p27) but did correlate with protection against the effect of PHx on indices of impaired lipid and carbohydrate metabolism. Ethanol...

12. Purinergic receptor X7 is a key modulator of metabolic oxidative stress-mediated autophagy and inflammation in experimental nonalcoholic steatohepatitis - Das, Suvarthi; Seth, Ratanesh Kumar; Kumar, Ashutosh; Kadiiska, Maria B.; Michelotti, Gregory; Diehl, Anna Mae; Chatterjee, Saurabh
Recent studies indicate that metabolic oxidative stress, autophagy, and inflammation are hallmarks of nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanisms that link these important events in NASH remain unclear. In this study, we investigated the mechanistic role of purinergic receptor X7 (P2X7) in modulating autophagy and resultant inflammation in NASH in response to metabolic oxidative stress. The study uses two rodent models of NASH. In one of them, a CYP2E1 substrate bromodichloromethane is used to induce metabolic oxidative stress and NASH. Methyl choline-deficient diet feeding is used for the other NASH model. CYP2E1 and P2X7 receptor gene-deleted mice are...

13. Evidence for and against epithelial-to-mesenchymal transition in the liver - Xie, Guanhua; Diehl, Anna Mae
The outcome of liver injury is determined by the success of repair. Liver repair involves replacement of damaged liver tissue with healthy liver epithelial cells (including both hepatocytes and cholangiocytes) and reconstruction of normal liver structure and function. Current dogma posits that replication of surviving mature hepatocytes and cholangiocytes drives the regeneration of liver epithelium after injury, whereas failure of liver repair commonly leads to fibrosis, a scarring condition in which hepatic stellate cells, the main liver-resident mesenchymal cells, play the major role. The present review discusses other mechanisms that might be responsible for the regeneration of new liver epithelial...

14. Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats - Zhong, Wei; Li, Qiong; Xie, Guoxiang; Sun, Xiuhua; Tan, Xiaobing; Sun, Xinguo; Jia, Wei; Zhou, Zhanxiang
Endotoxemia is a causal factor in the development of alcoholic liver injury. The present study aimed at determining the interactions of ethanol with different fat sources at the gut-liver axis. Male Sprague-Dawley rats were pair fed control or ethanol liquid diet for 8 wk. The liquid diets were based on a modified Lieber-DeCarli formula, with 30% total calories derived from corn oil (rich in polyunsaturated fatty acids). To test the effects of saturated fats, corn oil in the ethanol diet was replaced by either cocoa butter (CB, rich in long-chain saturated fatty acids) or medium-chain triglycerides (MCT, exclusively medium-chain saturated...

15. Modulation of NF-κB and Nrf2 control of inflammatory responses in FHs 74 Int cell line is tocopherol isoform-specific - Elisia, Ingrid; Kitts, David D.
The present study investigates the relative ability of α-, γ-, and δ-tocopherol (Toc) to modulate cell signaling events that are associated with inflammatory responses in fetal-derived intestinal (FHs 74 Int) cells. Secretion of the proinflammatory cytokine IL-8 in FHs 74 Int cells was stimulated in the following order: α-Toc < γ-Toc < δ-Toc. A similar proinflammatory response was observed when inflammation was induced in FHs 74 Int cells. Modulation of IL-8 expression by Toc corresponded to an isoform-specific modulation of NF-κB and nuclear factor-erythroid 2-related factor 2 (Nrf2) cell signaling pathways involved in expression of proinflammatory cytokines and antioxidant enzymes,...

16. Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1−/− mice impair the peristaltic reflex and propulsion - Mahavadi, Sunila; Bhattacharya, Sayak; Kumar, Divya P.; Clay, Chereena; Ross, Gracious; Akbarali, Hamid I.; Grider, John R.; Murthy, Karnam S.
Caveolae are specialized regions of the plasma membrane that concentrate receptors and associated signaling molecules critical in regulation of cellular response to transmitters and hormones. We have determined the effects of caveolin-1 (Cav-1) deletion, caveolin-1 siRNA, and caveolar disruption in mice on the signaling pathways that mediate contraction and relaxation in colonic smooth muscle and on the components of the peristaltic reflex in isolated tissue and propulsion in intact colonic segments. In Cav-1−/− mice, both relaxation and contraction were decreased in smooth muscle cells and muscle strips, as well as during both phases of the peristaltic reflex and colonic propulsion....

17. Increased plasma corticosterone contributes to the development of alcoholic fatty liver in mice - Sun, Xiuhua; Luo, Weijun; Tan, Xiaobing; Li, Qiong; Zhao, Yantao; Zhong, Wei; Sun, Xinguo; Brouwer, Cory; Zhou, Zhanxiang
Ethanol ingestion increases endogenous glucocorticoid levels in both humans and rodents. The present study aimed to define a mechanistic link between the increased glucocorticoids and alcoholic fatty liver in mice. Plasma corticosterone levels were not affected in mice on a 2-wk ethanol diet regimen but significantly increased upon 4 wk of ethanol ingestion. Accordingly, hepatic triglyceride levels were not altered after 2 wk of ethanol ingestion but were elevated at 4 wk. Based on the observation that 2 wk of ethanol ingestion did not significantly increase endogenous corticosterone levels, we administered exogenous glucocorticoids along with the 2-wk ethanol treatment to...

18. Reduced funding and sequestration impact young biomedical researchers - Carulli, Alexis J.

19. Strain-specific suppression of microRNA-320 by carcinogenic Helicobacter pylori promotes expression of the antiapoptotic protein Mcl-1 - Noto, Jennifer M.; Piazuelo, M. Blanca; Chaturvedi, Rupesh; Bartel, Courtney A.; Thatcher, Elizabeth J.; Delgado, Alberto; Romero-Gallo, Judith; Wilson, Keith T.; Correa, Pelayo; Patton, James G.; Peek, Richard M.
Helicobacter pylori is the strongest risk factor for gastric cancer, and strains harboring the cag pathogenicity island, which translocates the oncoprotein CagA into host cells, further augment cancer risk. We previously reported that in vivo adaptation of a noncarcinogenic H. pylori strain (B128) generated a derivative strain (7.13) with the ability to induce adenocarcinoma, providing a unique opportunity to define mechanisms that mediate gastric carcinogenesis. MicroRNAs (miRNAs) are small noncoding RNAs that regulate expression of oncogenes or tumor suppressors and are frequently dysregulated in carcinogenesis. To identify miRNAs and their targets involved in H. pylori-mediated carcinogenesis, miRNA microarrays were performed...

20. Intravenous fish oil lipid emulsion promotes a shift toward anti-inflammatory proresolving lipid mediators - Kalish, Brian T.; Le, Hau D.; Fitzgerald, Jonathan M.; Wang, Samantha; Seamon, Kyle; Gura, Kathleen M.; Gronert, Karsten; Puder, Mark
Parenteral nutrition (PN)-associated liver disease (PNALD) is a life-threatening complication of the administration of PN. The development of PNALD may be partly due to the composition of the lipid emulsion administered with PN: soybean oil-based lipid emulsions (SOLE) are associated with liver disease, while fish oil-based lipid emulsions (FOLE) are associated with prevention and improvement of liver disease. The objective of this study was to determine how the choice of lipid emulsion modified the production of bioactive lipid mediators (LMs). We utilized a mouse model of steatosis to study the differential effect of FOLE and SOLE. We subsequently validated these...

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