American Journal of Physiology. Gastrointestinal and Liver Physiology

Prenatal inflammation may predispose to preterm birth and postnatal inflammatory disorders, such as necrotizing enterocolitis (NEC). Bioactive milk ingredients may help to support gut maturation in such neonates, but mother´s milk is often insufficient after preterm birth. We hypothesized that supplementation with bioactive ingredients from bovine milk (osteopontin, OPN; caseinoglycomacropeptide, CGMP; colostrum, COL) supports gut, immunity and NEC resistance in neonates born preterm after gram-negative infection before birth...

Endocytosis is a major mechanism through which cellular signaling by G protein-coupled receptors (GPCRs) is terminated. However, recent studies demonstrate that GPCRs are internalized in an active state and continue to signal from within endosomes, resulting in effects on cellular function that are distinct to those arising at the cell surface. Endocytosis inhibitors are commonly used to define the importance of GPCR internalization for physiological and pathophysiological processes. Here we provide the first detailed examination of the effects of these inhibitors on neurogenic contractions of gastrointestinal smooth muscle; a key preliminary step to evaluate the importance of GPCR endocytosis for gut function...

The pathophysiology of colonic diverticulosis has not been completely understood. The development of appropriate animal models is essential to study diverticular disease. To date, no large animal models are available for this disease condition. The objective of this study is to develop a swine model by damaging of colon wall, combined with or without low fiber diet to mimic the pathogenesis of diverticulosis. To create a weakness on the colon wall, collagenase was applied in vivo to degrade the collagen in the colon wall...

Reactive oxygen species, such as hydrogen peroxide (H2 O2 ), are believed to play a prominent role in the injury and loss of transport function that affects the intestinal epithelium in inflammatory conditions such as inflammatory bowel diseases (IBD). Defects in intestinal epithelial ion transport regulation contribute to dysbiosis and inflammatory phenotypes. We have previously shown that H2 O2 inhibits Ca2+ -dependent Cl- secretion across intestinal epithelial cells (IEC) via a phosphatidylinositol 3-kinase (PI3-K) and extracellular signal-regulated kinase (ERK) dependent mechanism that occurs, at least in part, through inhibition of the basolateral Na-K-2Cl co-transporter, NKCC1...

Inflammatory Bowel Disease (IBD) is characterized by epithelial barrier dysfunction with resultant inflammation as the mucosal immune system becomes exposed to luminal antigens. The hydroxylase inhibitor dimethyloxalylglycine (DMOG) reduces symptoms in experimental colitis through the upregulation of genes promoting barrier function and inhibition of epithelial cell apoptosis. The immunosuppressive drug cyclosporine reduces inflammation associated with IBD via suppression of immune cell activation. Given the distinct barrier protective effect of DMOG and the anti-inflammatory properties of cyclosporine, we hypothesised that combining these drugs may provide an enhanced protective effect by targeting both barrier dysfunction and inflammation simultaneously...

Perinatal high fat diet (pHFD) exposure increases the inhibition of dorsal motor nucleus of the vagus (DMV) neurons, potentially contributing to the dysregulation of gastric functions. The aim of this study was to test the hypothesis that pHFD increases the inhibition of DMV neurons by disrupting GABAA receptor subunit development. In vivo gastric recordings were made from adult anesthetized Sprague-Dawley rats fed a control or pHFD (14 or 60% kcal from fat, respectively) from embryonic day 13 (E13) to A a subunits, while mRNA and protein expression were measured via qPCR and western blotting, respectively...

The majority of Parkinson's disease (PD) patients experience gastrointestinal (GI) dysfunction. Recently, we described a nigro-vagal pathway, which uses dopaminergic (DA) inputs to dorsal motor nucleus of the vagus (DMV) and A2 area neurons to modulate gastric motility and tone. This pathway is disrupted in a rodent model of PD. The aim of the present study was to test the hypothesis that brainstem dopaminergic modulation of gastric tone and motility is altered in a rodent model of PD. Male Sprague Dawley rats received 3 weekly intraperitoneal injections of 10mg/kg paraquat (PQ) or saline (control)...

Hepatocellular carcinoma (HCC) is the second leading cause of the cancer-related mortality. Emerging evidence has demonstrated that some long non-coding RNAs (lncRNAs) are involved in the development and progression of HCC. Herein, the current study aimed to explore the potential mechanism of LINC01018 in regulating the progression of HCC. Initially, the expression of LINC01018, microRNA-182-5p (miR-182-5p), and forkhead box protein O1 (FOXO1) was quantified in 72 paired HCC and adjacent normal tissue samples, as well as HCC cells, followed by the identification of the interaction among them...

Cholestasis of pregnancy endangers fetal and neonatal survival, yet systematic knowledge of the cause and effect of disrupted bile acid (BA) homeostasis in pregnancy is limited. Here we show that gestation stage-associated BA dysregulation in swine correlated with fetal death resulting from compromised capacity for BA secretion and increased alternative systemic efflux. The balance of BA input and output in the developing uterus suggested little uptake and metabolism of maternal BA by the placenta-fetus unit, implying a protection role of placenta in preventing maternal BA transported into fetus...

Previous studies suggest that the renin-angiotensin system (RAS) is pathogenic factor for colitis. The goal of this study was to elucidate the molecular mechanism whereby angiotensin II (Ang II) promotes colonic inflammation. We found that renin was highly induced in colonic biopsies from patients with ulcerative colitis or Crohn's disease, and colonic renin and Ang II levels were markedly increased in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model, indicating that the colonic RAS is activated in colitis...

Xenin-25 is a neurotensin-like peptide that is secreted by enteroendocrine cells in the small intestine. Xenin-8 is reported to augment duodenal anion secretion by activating afferent neural pathways. The intrinsic neuronal circuits mediating the Xenin-25-induced anion secretion were characterized using Ussing chambered mucosa-submucosa preparation from the rat ileum. Serosal application of Xenin-25 increased the short-circuit current ( Isc) in a concentration-dependent manner. The responses were abolished by the combination of Cl- -free and HCO3 - -free solutions...

Maintenance of gut integrity has long been recognized as crucial for survival in sepsis but alterations in protein metabolism have not previously been documented. Therefore in the present study, we measured in a Pseudomonas aeruginosa induced porcine sepsis model, fractional protein synthesis (FSR) and breakdown rates (FBR) in jejunal mucosa in a fasted conscious state. METHODS: FSR was measured by the incorporation rate of stable tracer amino acid (L-[ring-13C6]-phenylalanine) into tissue protein...

Intra-acinar trypsinogen activation occurs in the earliest stages of pancreatitis and is believed to play important roles in pancreatitis pathogenesis. However, the exact role of intra-acinar trypsin activity in pancreatitis remains elusive. Here, we aimed to examine the specific effects of intra-acinar trypsin activity on the development of pancreatitis using a transgenic mouse model. This transgenic mouse model allowed for the conditional expression of a mutant trypsinogen that can be activated specifically inside pancreatic acinar cells...

Invasion and metastasis are responsible for the majority of deaths in gastric cancer (GC). microRNA-33a (miR-33a)might function as a tumor suppressor in multiple cancers. Here, we describe the regulation and function of miR-33a in GC and mechanisms involved in epithelial-mesenchymal transition (EMT) and metastasis. Firstly, GC tissues and adjacent normal tissues were collected. miR-33a up-regulation or SNAI2 depletion on GC cells were introduced in order to assess the detailed regulatory mechanism of them. We assessed the expression of miR-33a, SNAI2, Snail/Slug signaling pathway-related genes and EMT-related markers in GC tissues and cells...

Trypsin is the major serine protease responsible for intestinal protein digestion. An inhibitor, camostat (CS), reduced weight gain, hyperglycemia and dyslipidemia in obese rats; however, the mechanisms for this are largely unknown. We reasoned that CS creates an apparent dietary protein restriction, which is known to increase hepatic fibroblast growth factor 21 (FGF21). Therefore, metabolic responses to CS and a gut-restricted CS metabolite, FOY-251, were measured in mice. Food intake, body weight, blood glucose, branched chain amino acids (LC/MS), hormone levels (ELISA), liver pathology (histology) and transcriptional changes (qRT-PCR) were measured in ob/ob mice, lean or Diet-Induced Obese (DIO) C57BL/6 mice...

BACKGROUND: Tumor-associated angiogenesis plays a critical role in the pathogenesis of cholangiocarcinoma (CCA). In this study, we examined the biological effects and molecular mechanisms of transcription factor 21 (TCF21) on CCA-associated angiogenesis. METHODS: TCF21 expression was compared between 15 pairs of para-tumor normal tissues and CCA tissues, and also between normal bile duct epithelial cells and two CCA cell lines, QBC-939 and TFK-1 using real-time PCR and Western blot...

Enteroendocrine L cells and GLP-2 secretion are activated in the intestinal adaptation process following bowel resection in short bowel patients. Our aim was to assess whether enteral activation of Takeda G-protein-coupled receptor 5 (TGR5) expressed in enteroendocrine L cells could augment endogenous GLP-2 secretion and the intestinal adaptation response in a piglet model. In study 1, parenterally-fed, neonatal pigs (n=6/group) were gavaged with vehicle, olive extract (OE) at 10 or 50 mg/kg, or ursolic acid (UA) 10 mg/kg and plasma GLP-2 were measured for 6 hr...

Mortality associated with liver disease was observed in patients with short bowel syndrome (SBS); however, its mechanism remains unclear. Bile acid (BA) dysmetabolism may be one of the putative mechanisms, and farnesoid X receptor (FXR) is the key regulator of BA synthesis. Here, we showed that in a rat model of small bowel resection associated with liver disease (SBR-ALD), BA composition of hepatic tissues reflected a larger proportion of primary and secondary unconjugated BAs, and those of colon contents and serum showed an increased ratio of secondary unconjugated BAs...

BACKGROUND: Electroacupuncture (EA) has been reported for treating constipation in clinical studies. However, little is known on possible mechanisms involved in the prokinetic effect of EA. AIMS: To investigate the effects and underlying autonomic mechanisms of EA via chronically implanted electrodes for constipation rat induced by Loperamide (Lop). METHODS: Lop was given to regular rats to induce constipation. EA was performed via a pair of electrodes chronically implanted at bilateral acupoint ST36...

Thiamin (vitamin B1) is essential for normal cellular metabolism and function. Pancreatic acinar cells (PACs) obtain thiamin from circulation, via a specific carrier-mediated process that involves the plasma membrane thiamin transporters -1 and -2 (THTR-1 and THTR-2; products of SLC19A2 and SLC19A3 genes, respectively). There is nothing known about the effect of bacterial products/toxins on thiamin uptake by PACs. We addressed this issue in the current investigation by examining the effect of the bacterial flagellin on physiological and molecular parameters of the thiamin uptake by PACs...