American Journal of Physiology. Gastrointestinal and Liver Physiology

Dynamic liver function assessment by the 13 C-methacetin maximal liver function capacity (LiMAx) test reflects the overall hepatic CYP1A2 activity. One proven strategy for preoperative risk assessement in liver surgery includes the combined assessment of the dynamic liver function by the LiMAx test, the volumetric analysis of the liver and calculation of future liver remnant function. This so-called volume-function analysis assumes that the remaining CYP1A2 activity in any tumor lesion is zero. The here presented study aims to assess the remaining CYP1A2 activities in different hepatic tumor lesions and its consequences for the preoperative volume-function analysis in patients undergoing liver surgery...

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal malignancies worldwide. All-trans retinoic acide (ATRA) has been used as an anti-stromal agent in PDA, and its anti-tumour effect has also been reported in various kinds of cancer, including PDA. Inhibition of p21-activated kinases (PAKs) is associated with decreased tumour growth and increased gemcitabine sensitivity. The aim of this study was to evaluate the inhibitory effects of ATRA alone and in combination with gemcitabine on cell growth and migration of wild-type and gemcitabine-resistant PDA cells and the potential mechanism(s) involved...

To observe the effect and possible mechanism of TO901317 in vivo and in vitro to provide a new basis for the targeted therapy of Hepatocellular carcinoma (HCC). The expression of LXRα, Glut1, PCNA and MMP9 were analyzed from the HCC public database. The result showed that LXRα was down-regulated, whereas Glut1, PCNA and MMP9 were up-regulated in human HCC compared with normal liver. Furthermore, LXRα mRNA was negatively correlated with Glut1 mRNA. At the same time, HCC cells were cultivated in vitro and axillary injected into nude mice to establish xenograft model...

BACKGROUND & AIMS: Esophageal acid sensory signals are transmitted by both vagal and spinal pathways to the cerebral cortex. The influence and interplay of these pathways on the esophageal acid-related functional connectivity has been elusive. The aim is to evaluate the esophageal acid exposure-related effect on the anterior cingulate cortex (ACC) functional connectivity networks using functional MRI-guided functional connectivity MRI (fcMRI) analysis. METHODS: We studied 6 Sprague-Dawley rats for fcMRI experiments under dexmedetomidine hydrochloride anesthesia...

We investigated the migration of intestinal immune cells to the liver and their contribution to alcoholic liver disease. In mice fed ethanol, we found that an increased number of invariant natural killer T (iNKT) cells, which respond to antigen presented by CD1d, migrated from mesenteric lymph nodes to the liver. iNKT cells react to lipid antigens, so we studied their activities in mice with intestinal epithelial cell-specific deletion of Pparg (PpargΔIEC) as model for altering intestinal lipidomic profiles...

Hepatic steatosis is the beginning phase of non-alcoholic fatty liver disease, and hyperhomocysteinemia (HHcy) is a significant risk factor. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids, attenuating their cardiovascular protective effects. However, the involvement of sEH in HHcy-induced hepatic steatosis is unknown. The current study aimed to explore the role of sEH in HHcy-induced lipid disorder. We fed 6-week-old male mice a chow diet or 2% (wt/wt) high methione diet for 8 weeks to establish the HHcy model...

A large number of glucagon-like-peptide 1 (GLP-1) and peptide-YY (PYY) producing L-cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo, we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3...

Irritable bowel syndrome is one of the commonest gastrointestinal disorders. Although long-time considered a pure functional disorder, intense research in past years has rendered a very complex and varied array of observations indicating the presence of structural and molecular abnormalities underlying characteristic motor and sensitive changes and clinical manifestations. Analysis of gene and protein expression in the intestinal mucosa has shed light on the molecular mechanisms implicated in IBS physiopathology...

The intestinal microbiome plays an major role in the pathogenesis of liver disease, with a hallmark event being dysbiosis, or an imbalance of pathobionts and beneficial bacteria with the associated deleterious effects on its host. Reducing the number of intestinal bacteria with antibiotic treatment is generally advantageous in experimental liver diseases. Complete absence of intestinal microbiota as in germ-free rodents can be protective in autoimmune hepatitis, and hepatic tumors induced by chemicals; or it can exacerbate disease as in acute toxic liver injury and liver fibrosis/cirrhosis...

Ketosis is a metabolic adaptation to fasting, non-alcoholic fatty liver disease (NAFLD), and prolonged exercise. β-OH butyrate acts as a transcriptional regulator and at G-protein coupled receptors to modulate cellular signaling pathways in a hormone-like manner. While physiological ketosis is often adaptive, chronic hyperketonemia may contribute to the metabolic dysfunction of NAFLD. To understand how β-OH butyrate signaling affects hepatic metabolism we compared the hepatic fasting response in control and 3-hydroxy-3-methylglutaryl-CoA Synthase II (HMGCS2) knockdown mice that are unable to elevate β-OH butyrate production...

Necroptosis, a form of regulated necrosis, has been reported to be involved in numerous pathologies, including sepsis. However, a protective effect of the selective inhibitor of necroptosis, necrostatin-1 (Nec-1), against sepsis remains to be confirmed. Animals (rats and mice) were subjected to cecal ligation and puncture (CLP) to mimic clinical sepsis. Nec-1 or its vehicle (control) was administered 20 min before CLP. Survival time was observed up to 72 h after CLP. Specimens of liver tissue and serum were obtained in 6 h, 12 h and 18 h...

BACKGROUND: Inflammatory bowel diseases (IBD) are characterized by flares repetition and remission periods leading to chronic post-inflammatory sequels. Among them, one third of IBD patients are suffering from persisting functional symptoms or psychological comorbidities during remission. Our study aimed to assess functional and behavioral sequels of chronic colitis in rats with quiescent intestinal inflammation. METHODS: Chronic colitis was induced by a weekly intrarectal injection of TNBS for 3 weeks in 30 rats while control rats (n=24) received the vehicle...

Hepatic fibrosis is chronic liver damage with many causes that has a relatively high death rate. The current study showed that lncRNA GAS5, miR-23a and PTEN play important roles in the pathological process of hepatic fibrosis but have a relatively unclear regulatory mechanism. This study aimed to investigate the roles of lncRNA GAS5, miR-23a and PTEN in the pathological process of hepatic fibrosis and HSC activation. We used CCl4 intraperitoneal injections to establish a rat hepatic fibrosis model and exogenous TGF-β1 to establish a hepatic stellate cell (HSC) activation model...

Intestinal ischemia is an abdominal emergency with a mortality rate >50%, leading to epithelial barrier loss and subsequent sepsis. Epithelial renewal and repair after injury depend on intestinal epithelial stem cells (ISC) that reside within the crypts of Lieberkühn. Two ISC populations critical to epithelial repair have been described: 1) Active ISC (aISC; highly proliferative; Lgr5+, Sox9+) and 2) reserve ISC (rISC; less proliferative; Hopx+). 8-10 week-old Yorkshire-cross pigs were subjected to 1-4 hours of ischemia and an hour of reperfusion or recovery by reversible mesenteric vascular occlusion...

BACKGROUND: We are investigating the changes in hepatic lipid catabolism that contribute to alcohol-induced fatty liver. Following chronic ethanol exposure, abstinence from alcohol resolves steatosis. Here, we investigated the hepatocellular events that lead to this resolution by quantifying specific catabolic parameters that returned to control levels after EtOH was withdrawn. We hypothesized that after its chronic consumption ethanol withdrawal reactivates lipid catabolic processes that restore lipostasis...

Fatty liver is the earliest response of the liver to excessive ethanol consumption. Central in the development of alcoholic steatosis is increased mobilization of non-esterified free fatty acids (NEFA) to the liver from the adipose tissue. In this study, we hypothesized that ethanol-induced increase in ghrelin by impairing insulin secretion, could be responsible for the altered lipid metabolism observed in adipose and liver tissue. Male Wistar rats were fed for 5 to 8 weeks with control or ethanol Lieber-DeCarli diet, followed by biochemical analyses in serum and liver tissues...

Visceral pain is one of the principal complaints of patients with Irritable Bowel Syndrome (IBS), and this pain is reliably evoked by mechanical distension/stretch of distal colon and rectum (colorectum). This study focuses on the biomechanics of the colorectum that could play critical roles in mechanical neural encoding. We harvested the distal 30 mm of the colorectum from mice, divided evenly into three 10-mm-long segments (colonic, intermediate and rectal), and conducted biaxial mechanical stretch tests and opening-angle measurements for each tissue segment...

G Protein-Coupled Receptors (GPCRs) are essential for the neurogenic control of gastrointestinal (GI) function and are important and emerging therapeutic targets in the gut. Detailed knowledge of both the distribution and functional expression of GPCRs in the enteric nervous system (ENS) is critical to advance our understanding of how these receptors contribute to GI function during physiological and pathophysiological states. Equally important, but less well-defined, is the complex relationship between receptor expression, ligand binding, signaling and trafficking within enteric neurons...

INTRODUCTION: Each swallow induces a wave of inhibition followed by contraction in the esophagus. Unlike contraction that can easily be measured in humans using high resolution manometry (HRM), inhibition is difficult to measure. Luminal distension is a surrogate of the esophageal inhibition. AIMS: determine the effect of posture on the temporal and quantitative relationship between distension and contraction, along the entire length of the esophagus, in normal healthy subjects using concurrent HRM, impedance (HRMZ), and intraluminal ultrasound...

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of conditions ranging from simple steatosis (NAFL), over non-alcoholic steatohepatitis (NASH) with or without fibrosis, to cirrhosis with end-stage disease. The hepatic molecular events underlying the development of NAFLD and transition to NASH are poorly understood. The present study aimed to determine hepatic transcriptome dynamics in patients with NAFL or NASH compared to healthy normal-weight and obese individuals. RNA sequencing and quantitative histomorphometry of liver fat, inflammation and fibrosis was performed on liver biopsies obtained from healthy normal weight (n=14) and obese (n=12) individuals, NAFL (n=15) and NASH (n=16) patients...