American Journal of Physiology. Gastrointestinal and Liver Physiology

Our aim was to investigate the feasibility of measuring antral contractions and duodenal bolus propagation (DBP) during dynamic antral contraction scintigraphy (DACS) as an assessment of antro-pyloro-duodenal coordination (APDC). METHODS: GES with DACS was performed with Tc-99m sulfur colloid (SC) using increasing doses of 74 MBq (2 mCi) for 10 subjects, 185 MBq (5 mCi) for 11, and 370 MBq (10 mCi) for 11. DACS was performed for 10 min after static images at 0, 30, 60, 120, 180, 240 min in anterior and right anterior oblique (RAO) projections...

Presently, there are no studies examining the neuromodulatory effects of brain-derived neurotropic factor (BDNF) on the basal internal anal sphincter (IAS) tone and non-adrenergic, non-cholinergic (NANC) relaxation. To examine this, we determined the neuromuscular effects of BDNF on basal IAS-smooth muscle tone and the smooth muscle cells (SMCs), and NANC nerve stimulation, before and after high-affinity receptor tyrosine kinase B (TrkB) antagonist K252a. We also investigated the mechanisms underlying BDNF-augmented increase in the IAS tone and NANC relaxation...

Detection of nutritional and noxious food components in the gut is a crucial component of gastrointestinal function. Contents in the gut lumen interact with enteroendocrine cells dispersed throughout the gut epithelium. Enteroendocrine cells release many different hormones, neuropeptides and neurotransmitters that communicate either directly or indirectly with the central nervous system and the enteric nervous system, a network of neurons and glia located within the gut wall. Several populations of enteric neurons extend processes that innervate the gastrointestinal lamina propria, however, how these processes develop and begin to transmit information from the mucosa is not fully understood...

Gastrointestinal comorbidities are common in individuals with mood and behavioral dysfunction. Similarly, patients with gastrointestinal problems more commonly suffer from co-morbid psychiatric diagnoses. Though the central and enteric nervous systems (CNS and ENS, respectively) have largely been studied separately, there is emerging interest in factors that may contribute to disease states involving both systems. There is strong evidence to suggest that serotonin may be an important contributor to these brain-gut conditions...

The gut microbiome is the natural intestinal inhabitant that has been recognized recently as a major player in the maintenance of human health and the pathophysiology of many diseases. Those commensals produce metabolites that have various effects on host biologic functions. Therefore, alterations in the normal composition or diversity of microbiome have been implicated in various diseases, including liver cirrhosis and nonalcoholic fatty liver disease. Moreover, accumulating evidence suggests that progression of dysbiosis can be associated with worsening of liver disease...

Progressive fibrosis, liver failure and cancer are central liver-related outcomes of nonalcoholic steatohepatitis (NASH), but notoriously difficult to achieve in mouse models. We performed a direct, quantitative comparison of hepatic fibrosis progression in well-defined methionine- and choline-deficient (MCD) and choline-deficient, amino-acid defined (CDAA) diets with increasing fat content (10-60% by calories) in C57Bl/6J and BALB/cAnNCrl mice.In C57Bl/6J mice, MCD feeding resulted in moderate fibrosis at week 8 (2-fold increase in hepatic collagen content) and progressive weight loss, irrespective of fat content...

Intestinal functions, including motility and secretion, are locally controlled by enteric neural networks housed within the wall of the gut. The fidelity of these functions depends on the precision of intercellular signaling amongst cellular elements, including enteric neurons, epithelial cells, immune cells, and glia, all of which are vulnerable to disruptive influences during inflammatory events. This review article describes current knowledge regarding inflammation-induced neuroplasticity along key elements of enteric neural circuits, what is known about the causes of these changes, and possible therapeutic targets for protecting and/or repairing the integrity of intrinsic enteric neurotransmission...

BACKGROUND AND AIMS: Hepatitis B virus (HBV) exploits multiple strategies to evade host immune surveillance. Programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling plays a critical role in regulating T cell homeostasis. However, it remains largely unknown as to how HBV infection elevates PD-L1 expression in hepatocytes. METHODS: A mouse model of HBV infection was established by hydrodynamic injection with a vector containing 1.3-fold over-length HBV genome (pHBV1...

Infants receiving long-term parenteral nutrition (PN) develop PN associated liver disease (PNALD). We previously showed that PN containing soy-based lipid supplemented with vitamin E (α-tocopherol) prevents the development of PNALD. We hypothesize that this occurs via vitamin E-activation of pregnane X receptor (PXR) mediated pathways involved in bile acid metabolism. Neonatal piglets received PN for 14 d containing Intralipid (IL, soy-based lipid emulsion), IL supplemented with 12.6 mg/kg*d-1 vitamin E (VITE), or IL with 10 mg/kg*d-1 Rifadin IV (RIF) a PXR agonist...

Perforations, anastomotic leak and subsequent intraabdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiologic healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation...

CXC chemokine receptor 2 (CXCR2) is critical for neutrophil recruitment and hepatocellular viability, but has not been studied in the context of cholestatic liver injury following bile duct ligation (BDL). The present study sought to elucidate the cell-specific roles of CXCR2 on acute liver injury after BDL. Wild-type and CXCR2 -/- mice were subjected BDL. CXCR2 chimeric mice were created to assess cell specific role of CXCR2 on liver injury after BDL. SB225002, a selective CXCR2 antagonist, was administrated intraperitoneally after BDL to investigate the potential of pharmacological inhibitor...

NAFLD is very prevalent worldwide, and is associated with insulin resistance and metabolic syndrome. Stress is physiological and biological response to maintain homeostasis of body against stressors while severe stress response is an important contributor to various illnesses including metabolic syndrome and brain disorders. We have evaluated the effects of intermittent restraint stress on NAFLD in a HFD-fed mouse model. C57/BL6 mice had free access to a 60% HFD for 8 weeks, with or without intermittent restraint stress (3 h) conducted 3 times a week...

Pigs are capable of nitrogen salvage via urea recycling, which involves the movement of urea into the gastrointestinal tract. Aquaporins (AQP) and urea transporter B (UT-B) are involved in urea-recycling in ruminants; however, their contribution to urea flux in the intestinal tract of the pig is not known. The objective of this study was to characterize the presence and relative contribution of known urea transporters to urea flux in the growing pig. Intestinal tissue samples (duodenum, jejunum, ileum, cecum, and colon) were obtained from 9 barrows (50...

Intestinal organoid cultures provide an in vitro model system for studying pathways and mechanisms involved in epithelial damage and repair. Derived from either embryonic or induced pluripotent stem cells or adult intestinal stem cells or tissues, these self-organizing multi-cellular structures contain polarized mature cells that recapitulate both the physiology and heterogeneity of the intestinal epithelium. These cultures provide a cutting-edge technology for defining regenerative pathways that are induced following radiation or chemical damage, which directly target the cycling intestinal stem cell, or damage resulting from viral, bacterial, or parasitic infection of the epithelium...

BACKGROUND: Endoscopic intrasphincteric injection of botox (ISIB) is used routinely for the treatment of achalasia esophagus and other spastic motor disorders. Studies show that botox reduces the smooth muscle lower esophageal sphincter (LES) pressure. The esophageal hiatus, formed by the right crus of diaphragm surrounds the cranial half of the LES, it works like an external LES. AIM: We studied the effects of ISIB on the LES and hiatal contraction and reflux (GER)...

Common practices to improve the ability to swallow include modifying physical properties of foods and changing the posture of patients. Here, we quantified effects of the viscosity of liquid bolus and the patient posture on the bolus pathway and pharyngeal residue using a computational fluid dynamics simulation. We developed a computational model of an impaired pharyngeal motion with a low pharyngeal pressure and no pharyngeal adaptation. We varied viscosities from 0.002 to 1 Pa·s and postures from -15 degree to 30 degree (from nearly vertical to forward leaning)...

Gastrointestinal (GI) symptoms can originate from severe dysmotility due to enteric neuropathies. Current methods used to demonstrate enteric neuropathies are mainly based on classic qualitative histopathological / immunohistochemical evaluation. This study was designed to identify an objective morphometric method for paraffin-embedded tissue samples to assess the myenteric inter-ganglionic distance, i.e. the micrometer between two adjacent clusters of myenteric neurons immunoreactive for neuron specific enolase, as well as the number of myenteric and submucosal neuronal cell bodies / ganglion in jejunal specimens of patients with severe GI dysmotility...

BACKGROUND: Pancreatic ductal adenocarcinoma's (PDAC) growing incidence has been linked to the rise in obesity and type 2 diabetes mellitus. In previous work we have shown that metformin can prevent the increased incidence of PDAC in a KrasG12D mouse model subjected to a diet high in fat and calories (HFCD). One potential way that metformin can affect the host is through alterations in the gut microbiome. Therefore, we investigated microbial associations with PDAC development and metformin use in the same mouse model...

BACKGROUND & AIMS: Exosomes are cellular vesicles involved in intercellular communication via their specialized molecular cargo such as miRNAs. Substance P (SP), a neuropeptide / hormone and its high affinity receptor, NK-1R, are highly expressed during colonic inflammation. Our previous studies show that SP/NK-1R signaling stimulates differential miRNA expression and promotes colonic epithelial cell proliferation. In this study, we examined whether SP/NK-1R signaling regulates exosome biogenesis and differentiates exosome-miRNA cargo sorting...

The inflammatory bowel diseases (IBD) are a complex set of chronic gastrointestinal inflammatory conditions arising from the interplay of genetic and environmental factors. This study focuses on non-coding RNA transcripts as potential mediators of IBD pathophysiology. One particular gene, interferon gamma-antisense 1 (IFNG-AS1), has been consistently observed to be elevated in the intestinal mucosa of actively inflamed IBD patients versus healthy controls. This study builds on these observations demonstrating that the second splice variant is specifically altered and this alteration even stratifies within inflamed patients...