Hepatic Bile Formation: Bile acid transport and water flow in the canalicular conduit.
Abstract Advances in molecular biology that identified the many carrier-mediated organic anion transporters and advances in microscopy that have provided a more detailed anatomy of the canalicular conduit provide for an updating of the concept of osmotically determined canalicular flow. For the most part water flow is not trans-membrane but via specific pore proteins in both the hepatocyte and the tight junction. These pores independently regulate the rate at which water flows in response to and osmotic gradient and therefore are determinants of canalicular bile acid concentration. Review of the literature indicat...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 16, 2020 Category: Physiology Authors: Javitt NB Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Early life interaction between the microbiota and the Enteric Nervous System.
Abstract Recent studies on humans and their key experimental model, the mouse, have begun to uncover the importance of gastrointestinal (GI) microbiota and Enteric Nervous System (ENS) interactions during developmental windows spanning from conception to adolescence. Disruptions in GI microbiota and ENS during these windows by environmental factors particularly antibiotic exposure have been linked to increased susceptibility of the host to several diseases. Mouse models have provided new insights to potential signalling factors between the microbiota and ENS. We review very recent work on maturation of GI microbio...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 9, 2020 Category: Physiology Authors: Foong JPP, Hung LY, Poon S, Savidge TC, Bornstein JC Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Effects of Dietary Components on Intestinal Permeability in Health and Disease.
Abstract Altered intestinal permeability plays a role in many pathologic conditions. Intestinal permeability is a component of the intestinal barrier. This barrier is a dynamic interface between the body and the food and pathogens that enter the gastrointestinal tract. Therefore, dietary components can directly affect this interface, and many metabolites produced by the host enzymes or the gut microbiota can act as signaling molecules or exert direct effects on this barrier. Our aim was to examine the effects of diet components on the intestinal barrier in health and disease states. Herein, we conducted an in-dept...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 9, 2020 Category: Physiology Authors: Khoshbin K, Camilleri M Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Bile acids Metabolism and Circadian Rhythms.
Abstract Circadian rhythms are biological systems that synchronize cellular circadian oscillators with the organism's daily feeding-fasting or rest-activity cycles in mammals. Circadian rhythms regulate nutrient absorption and utilization at the cellular level, and are closely related to obesity and metabolic disorders. Bile acids are important modulators that facilitate nutrient absorption and regulate energy metabolism. Here, we provide an overview of the current connections and future perspectives between the circadian clock and bile acids metabolism as well as related metabolic diseases. Feeding and fasting cy...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 9, 2020 Category: Physiology Authors: Yang Y, Zhang J Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Involvement of capsaicin-sensitive nerves in the initiation of swallowing evoked by carbonated water in anesthetized rats.
Abstract Capsaicin powerfully evokes the swallowing reflex and is a known therapeutic agent for improving dysphagia and preventing aspiration pneumonia. However, the role of capsaicin-sensitive nerves in the initiation of swallowing evoked by various natural stimuli remains unclear. To explore this question, we blocked laryngeal capsaicin-sensitive nerves following the co-application of QX-314 and capsaicin (QX/Cap), and investigated the effects on swallowing evoked by mechanical and chemical stimulation in anesthetized rats. Swallows were evoked by capsaicin, carbonated water (CW), distilled water (DW), and punct...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 2, 2020 Category: Physiology Authors: Tsuji K, Tsujimura T, Sakai S, Suzuki T, Yoshihara M, Nagoya K, Magara J, Satoh Y, Inoue M Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Hsa_circRNA_001587 upregulates SLC4A4 expression to inhibit migration, invasion and angiogenesis of pancreatic cancer cells via binding to microRNA-223.
Abstract Pancreatic cancer (PC) is a malignant tumor that is difficult to diagnose and treat. Circular RNAs (circRNAs) are biomarkers that may be used to diagnose certain cancers or act as targets for cancer treatment. We aimed to explore the functions of human circular RNA 001587 (hsa_circRNA_001587) on the progression of PC and the underlying mechanism. The expression pattern of hsa_circRNA_001587 and microRNA-223 (miR-223) in PC tissues and cells was determined by RT-qPCR. Dual-luciferase reporter gene assay, RNA-pull down, Argonaute 2 (AGO2) immunoprecipitation assay, and Northern blot analysis were applied to...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - September 2, 2020 Category: Physiology Authors: Zhang X, Tan P, Zhuang Y, Du L Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

The role of a Reserve Stem Cell Subset of Enteroendocrine cells in intestinal stem cell dynamics and the Genesis of Small Intestinal Neuroendocrine Tumors.
Abstract Small intestinal neuroendocrine tumors (SI-NET) are serotonin-secreting well-differentiated neuroendocrine tumors of putative enterochromaffin (EC) cell origin. Recent studies recognize a subset of EC cells that is label-retaining at the +4 position in the crypt and functions as a reserve intestinal stem cell (ISC). Importantly, this +4 reserve EC cell subset not only contributes to regeneration of the intestinal epithelium during injury and inflammation but also to basal crypt homeostasis at a constant rate. The latter function suggests that the +4 EC cell subset serves as an active reserve stem cell via a...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 26, 2020 Category: Physiology Authors: Sei Y, Feng J, Zhao X, Wank SA Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Exercise and Intestinal Permeability: Another Form of Exercise-Induced Hormesis?
Abstract Regular aerobic exercise has numerous benefits on human physiology, arguably by serving as a hormetic stressor resulting in positive adaptations over time. It has long been known that aerobic exercise at a variety of intensities and durations induces intestinal permeability, which is a feature of many pathologies of the gastrointestinal tract and metabolic diseases. Given the health benefits of exercise, it seems unlikely that intestinal permeability induced by exercise outweighs the positive adaptations. In fact, a growing body of evidence suggests adoption of exercise regimens lasting weeks to months im...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 26, 2020 Category: Physiology Authors: Keirns BH, Koemel NA, Sciarrillo CM, Anderson KL, Emerson SR Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Simulated Stool for Assessment of Anorectal Physiology.
Abstract Fecal continence is maintained by several mechanisms including anatomical factors, anorectal sensation, rectal compliance, stool consistency, anal muscle strength, mobility, and psychological factors. The homeostatic balance is easily disturbed, resulting in symptoms including fecal incontinence and constipation. Current technologies for assessment of anorectal function have limitations. Overlap exist between data obtained in different patient groups and there is lack of correlation between measurements and symptoms. This review describes a novel technology named Fecobionics for assessment of anorectal ph...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 12, 2020 Category: Physiology Authors: Chen SC, Futaba K, Leung WW, Wong C, Mak T, Ng S, Gregersen H Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Enlightening the Frontiers of Neurogastroenterology Through Optogenetics.
Abstract Neurogastroenterology refers to the study of the extrinsic and intrinsic nervous system circuits controlling the gastrointestinal (GI) tract. Over the past 5-10 years there has been an explosion in novel methodologies, technologies and approaches that offer great promise to advance our understanding of the basic mechanisms underlying GI function in health and disease. This review focuses on the use of optogenetics combined with electrophysiology in the field of neurogastroenterology. We discuss how these technologies and tools are currently being used to explore the brain-gut axis and debate the future re...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 5, 2020 Category: Physiology Authors: Johnson AC, Louwies T, Ligon CO, Greenwood-Van Meerveld B Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Sustained laryngeal transient receptor potential vanilloid 1 activation inhibits mechanically-induced swallowing in anesthetized rats.
Abstract A major component of gastric acid is hydrochloric acid (HCl), which can activate transient receptor potential vanilloid 1 (TRPV1). In the present study, we investigated how sustained laryngeal TRPV1 activation affects the frequency of the swallowing reflex. Experiments were carried out on 85 male Sprague-Dawley rats. The effects of short and sustained application of chemicals (3 µl of 0.1 N HCl or capsaicin) on the frequency of swallowing and of time-dependent changes in the occurrence of swallowing evoked by supralaryngeal nerve stimulation were determined. To evaluate vascular permeability of the ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 5, 2020 Category: Physiology Authors: Yoshihara M, Tsujimura T, Suzuki T, Nagoya K, Shiraishi N, Magara J, Terunuma M, Inoue M Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Acetaldehyde Suppresses HBV-MHC Class I Complex Presentation on Hepatocytes Via Induction of ER Stress and Golgi Fragmentation.
Abstract Alcohol consumption worsens HBV- infection pathogenesis. We have recently reported that acetaldehyde suppressed HBV-peptide-MHC class I complex display on hepatocytes, limiting recognition and subsequent removal of the infected hepatocytes by HBV-specific cytotoxic T lymphocytes (CTLs). This suppression was attributed to impaired processing of antigenic peptides by the proteasome. However, in addition to proteasome dysfunction, alcohol may induce endoplasmic reticulum (ER) stress and Golgi fragmentation in HBV-infected liver cells to reduce uploading of viral peptides to MHC class I and/or trafficking of ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 5, 2020 Category: Physiology Authors: Ganesan M, Mathews S, Makarov E, Petrosyan A, Kharbanda KK, Kidambi S, Poluektova LI, Casey CA, Osna NA Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Microbiota on Biotics: Probiotics, Prebiotics, and Synbiotics to Optimize Growth and Metabolism.
Abstract The early stages of the metagenomics era produced countless observational studies linking various human diseases to alterations in the gut microbiota. Only recently have we begun to decipher the causal roles that gut microbes play in many of these conditions. Despite an incomplete understanding of how gut microbes influence pathophysiology, clinical trials have tested empirically numerous microbiota-targeting therapies to prevent or treat disease. Unsurprisingly, these trials have yielded mixed results. Nonetheless, the consumer market for probiotics, prebiotics, and synbiotics continues to grow. This min...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 5, 2020 Category: Physiology Authors: Edwards PT, Kashyap PC, Preidis GA Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

The ALIOS diet in male and female rodents recapitulates the clinical and transcriptomic features of NAFLD and NASH.
CONCLUSIONS: The ALIOS diet in mice recapitulates many of the clinical features of NAFLD and therefore represents a robust and reproducible model for investigating the pathogenesis of NAFLD and its progression. PMID: 32755310 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 5, 2020 Category: Physiology Authors: Harris SE, Poolman TM, Arvaniti A, Cox RD, Gathercole LL, Tomlinson JW Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Relationship Between Distension-Contraction Waveforms during Esophageal Peristalsis: Effect of Bolus Volume, Viscosity and Posture.
CONCLUSION: We describe the characteristics of esophageal distension during peristalsis and the relationship between distension contraction in a relatively large cohort of normal subjects. These can be used to compare differences between normal subjects and patients with esophageal motility disorders in future studies. PMID: 32755311 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 5, 2020 Category: Physiology Authors: Mittal RK, Muta K, Ledgerwood-Lee M, Zifan A Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Extracellular vesicle-encapsulated microRNA-1228-3p from cancer-associated fibroblasts promotes the chemoresistance of hepatocellular carcinoma cells via PLAC8.
This study aimed to identify whether extracellular vesicles (EVs) could transfer miR-1228-3p into HCC cells and probe the mechanisms underlying its roles in tumorigenesis. Normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) were isolated from HCC patients, followed by isolation of EVs. The relationship between miR-1228-3p and placenta special gene 8 (PLAC8) was predicted by computer-based analysis and subsequently verified by dual-luciferase reporter gene assay. Cellular behaviors and drug resistance to Sorafenib were evaluated in the HCC cells in a co-culture system with NFs or CAFs containing aberrantly exp...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 5, 2020 Category: Physiology Authors: Zhang Y, Pan Q, Shao Z Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

An indisputable role of NHE8 in mucosal protection.
Abstract The loss of the intestinal Na+/H+ exchanger isoform 8 (NHE8) results in an ulcerative colitis-like condition with reduction of mucin production and dysbiosis, indicating that NHE8 plays an important role in intestinal mucosal protection. The aim of this study was to investigate the potential rebalance of the altered microbiota community of NHE8-deficient mice via fecal microbiota transplantation (FMT) and feeding probiotic VSL#3. We also aimed to stimulate mucin production by sodium butyrate administration via enema. Data from 16S rRNA sequencing showed that loss of NHE8 contributes to colonic microbial d...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - August 5, 2020 Category: Physiology Authors: Bernardazzi C, Xu H, Tong H, Laubitz D, Figliuolo da Paz V, Curiel L, Ghishan FK Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Post-transcriptional regulation of thiamin transporter-1 (THTR-1) expression by microRNA-200a-3p in pancreatic acinar cells.
Abstract The water-soluble vitamin B1 (thiamin) plays essential roles in normal metabolism and function of all human/mammalian cells, including the pancreatic acinar cells (PACs). Pancreatic acinar cells (PACs) obtain thiamin from their surrounding (circulation) via transport across the plasma membrane, a process that is mediated by THTR-1 and THTR-2. We have previously characterized different aspects of thiamin uptake by mouse and human primary PACs, but little is known about post-transcriptional regulation of the uptake event. We addressed this by focusing on the predominant thiamin transporter THTR-1 (encoded b...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - July 20, 2020 Category: Physiology Authors: Ramamoorthy K, Anandam KY, Yasujima T, Srinivasan P, Said HM Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

METTL3 promotes the progression of hepatocellular carcinoma through m6A-mediated up-regulation of microRNA-873-5p.
Abstract Increasing evidence have demonstrated that methyltransferase-like 3 (METTL3) plays an oncogenic role in the development of human hepatocellular carcinoma (HCC), however, the underlying mechanisms still remain largely unexplored. We investigated the effect of METTL3/microRNA-873-5p (miR-873-5p)/suppressor with the morphological effect on genitalia 1 (SMG1) axis on the progression of HCC. Bioinformatics databases were used to predict new HCC-related pathways. HCC cells were then selected for determining the expression of METTL3, miR-873-5p, and SMG1. Dual luciferase reporter gene assay, co-immunoprecipitati...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - July 20, 2020 Category: Physiology Authors: Zhao M, Jia M, Xiang Y, Zeng Y, Yu W, Xiao B, Dai R Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Knockout of Sulfatase 2 is associated with decreased steatohepatitis and fibrosis in a mouse model of nonalcoholic fatty liver disease.
Abstract Sulfatase 2 (SULF2) is a heparan sulfate editing enzyme that regulates the milieu of growth factors and cytokines involved in a variety of cellular processes. We used a murine model of diet-induced steatohepatitis to assess the effect of SULF2 down-regulation on the development of nonalcoholic steatohepatitis (NASH) and liver fibrosis. Wildtype B6;129 mice (WT) and Sulf2-knockout B6;129P2-SULF2Gt(PST111)Byg mice (Sulf2-KO) were fed a fast food diet (FFD) rich in saturated fats, cholesterol and fructose or a standard chow diet (SC) ad libitum for 9 months. WT mice on FFD showed a 3-fold increase in hepatic...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - July 20, 2020 Category: Physiology Authors: Kim TH, Banini BA, Asumda FZ, Campbell NA, Hu C, Moser CD, Shire AM, Han S, Ma C, Krishnan A, Mounajjed T, White TA, Gores GJ, LeBrasseur NK, Charlton MP, Roberts LR Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

The mechanism and treatment of gastrointestinal symptoms in patients with COVID-19.
Abstract In addition to the typical respiratory response, new coronavirus pneumonia (COVID-19) is also associated with very common gastrointestinal symptoms. Cases with gastrointestinal symptoms are more likely to be complicated by liver injury and acute respiratory distress syndrome (ARDS), and diarrhea can also lead to electrolyte disturbances, causing nausea and vomiting, headache, fatigue, etc. If not treated in time, coma and circulatory failure may ensue. As SARS-CoV-2 infects the human body through the combination of ACE2 in the gastrointestinal tract, the mechanism underlying the gastrointestinal symptoms ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - July 8, 2020 Category: Physiology Authors: Ye Q, Wang B, Zhang T, Xu J, Shang S Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

The reabsorption of bile acids regulated by FXR-OATP1A2 is the main factor for the formation of cholesterol gallstone.
In conclusion, the axis of FXR-OATP1A2 that physiologically regulated the reabsorption of bile acids might play an important role in the composition of bile acids and the development of gallstone. CYP8B1 gene was irrelevant to the altered composition of bile acids in patients with gallstone. PMID: 32597704 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - June 29, 2020 Category: Physiology Authors: Cai J, Wang Z, Chen G, Li D, Liu J, Hu H, Qin J Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Mitochondrial oxidative injury: A key player in nonalcoholic fatty liver disease.
Abstract Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide. NAFLD is tightly linked to the metabolic syndrome, insulin resistance and oxidative stress. Globally, its inflammatory form, nonalcoholic steatohepatitis (NASH), has become the main cause of liver related morbidity and mortality, mainly due to liver cirrhosis and primary liver cancer. One hallmark of NASH are changes in mitochondrial morphology and function that are accompanied by a blocked flow of electrons in the respiratory chain, which increases formation of mitochondrial reactive oxygen species in a self-p...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - June 29, 2020 Category: Physiology Authors: Dornas W, Schuppan D Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Ridinilazole, a narrow spectrum antibiotic for treatment of Clostridioides difficile infection, enhances preservation of microbiota-dependent bile acids.
This study uses a longitudinal study design to compare the effects of a narrow-spectrum (ridinilazole) or broad-spectrum antibiotic (vancomycin) on intestinal bile acid profiles and their associations with gut bacteria over the course of C. difficile infection treatment. At end-of-treatment (day 10), subjects receiving vancomycin showed a nearly 100-fold increase in the ratio of conjugated to secondary bile acids in their stool compared to baseline, whereas subjects receiving ridinilazole maintained this ratio near baseline levels. Correlation analysis detected significant positive associations between secondary bile acids...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - June 29, 2020 Category: Physiology Authors: Qian X, Yanagi K, Kane A, Alden N, Lei M, Snydman DR, Vickers RJ, Lee K, Thorpe CM Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Obeticholic acid improves fetal bile acid profile in a mouse model of gestational hypercholanemia.
In conclusion, OCA administration during gestation had no apparent detrimental impact on maternal or fetal morphometry and improved fetal hypercholanemia. As high serum bile acid concentrations in ICP are associated with increased rates of adverse fetal outcomes, further investigations into the potential use of OCA during cholestatic gestation are warranted. PMID: 32597707 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - June 29, 2020 Category: Physiology Authors: Pataia V, McIlvride S, Papacleovoulou G, Ovadia C, McDonald JAK, Wahlström A, Jansen E, Adorini L, Shapiro D, Marchesi JR, Marschall HU, Williamson C Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Early normalization of reduced urea synthesis capacity after direct-acting antiviral therapy in hepatitis C cirrhosis.
æk H Abstract BACKGROUND AND AIMS: Effects of direct-acting antiviral (DAA)-treatment of chronic hepatitis C (CHC) cirrhosis on metabolic liver function are unknown but important for prognosis. Ureagenesis is an essential metabolic liver function involved in whole-body nitrogen homeostasis. We aimed to investigate the ureagenesis capacity before and immediatelyafter DAA-therapy and relate the findings to hepatic inflammation and structural changes. METHODS: In an observational before-and-after intervention study, the ureagenesis capacity was quantified by functional hepatic nitrogen clearance (FHNC) in ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - June 29, 2020 Category: Physiology Authors: Laursen TL, Sandahl TD, Kazankov K, Eriksen PL, Kristensen LH, Holmboe CH, Laursen AL, Vilstrup H, Grønbæk H Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Broad spectrum antibiotics alter the microbiome, increase intestinal fxr, and decrease hepatic steatosis in zebrafish short bowel syndrome.
Abstract Short bowel syndrome (SBS) is associated with changes in the intestinal microbiome and marked local and systemic inflammation. There is also a late complication of SBS, intestinal failure associated liver disease (IFALD) in which hepatic steatosis progresses to cirrhosis. Most patients with SBS arrive at massive intestinal resection after a contaminating intraabdominal catastrophe and have a history of exposure to broad spectrum antibiotics. We therefore investigated whether the administration of broad spectrum antibiotics in conjunction with SBS in zebrafish (ZF) would replicate these systemic effects ob...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - June 29, 2020 Category: Physiology Authors: Maselli KM, Gee K, Isani M, Fode A, Schall KA, Grikscheit TC Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Grading TESI: Crypt and villus formation in tissue-engineered small intestine alters with stem/progenitor cell source.
Abstract The small intestine has a remarkable ability to enhance its absorptive and digestive surface area through the formation of villi, a process known as villification. We sought to learn if developing mouse and human tissue-engineered small intestine (TESI) followed known developmental biology routes to villification such as Shh/Ihh and BMP4/FoxF1 signaling in order to identify targets to enhance the development of TESI. After generating TESI from prenatal and postnatal stem cell sources, we evaluated the effect of cell source derivation on villification with a grading scheme to approximate developmental stag...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - June 29, 2020 Category: Physiology Authors: Gilliam EA, Schlieve CR, Fowler KL, Rea JN, Schall KA, Huang S, Spence JR, Grikscheit TC Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Transcriptomic identification of TMIGD1 and its relationship with the ileal epithelial cell differentiation in Crohn's disease.
; E, Mañosa M, Manye J Abstract BACKGROUND: Crohn's disease (CD) is a complex and multifactorial illness. There are still considerable gaps in our knowledge regarding its pathophysiology. A transcriptomic approach could shed some light on little-known biological alterations of the disease. We therefore aimed to explore the ileal transcriptome to gain knowledge about CD. METHODS: We performed whole transcriptome gene expression analysis on ileocecal resections from CD patients and inflammatory bowel disease-free controls, as well as on a CD-independent cohort to replicate selected results. Normalized da...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - June 8, 2020 Category: Physiology Authors: Zabana Y, Lorén V, Domènech E, Aterido A, Garcia-Jaraquemada A, Julià A, Vicario M, Pedrosa E, Ferreiro M, Troya J, Lozano JJ, Sarrias MR, Cabré E, Mañosa M, Manye J Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Xenometabolite signatures in the UC Davis Type 2 Diabetes Mellitus Rat model revealed using a metabolomics platform enriched with microbe-derived metabolites.
Abstract The gut microbiome has the potential to create or modify xenometabolites (i.e., non-host derived metabolites) through de novo synthesis or modification of exogenous and endogenous compounds. While there are isolated examples of xenometabolites influencing host health and disease, wide-scale characterization of these metabolites remain limited. We developed a metabolomics platform ("XenoScan") using liquid chromatography-mass spectrometry to characterize a range of known and suspected xenometabolites and their derivatives. This assay currently applies authentic standards for 189 molecules, enriched...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - June 8, 2020 Category: Physiology Authors: Mercer KE, Yeruva L, Pack L, Graham JL, Stanhope KL, Chintapalli SV, Wankhade UD, Shankar K, Havel PJ, Adams SH, Piccolo BD Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Hyperthermia induced changes in liver physiology and metabolism: A rationale for hyperthermic machine perfusion.
VE Abstract Liver transplantation is the standard treatment for end-stage liver disease. However, due to the ongoing disparity between supply and demand for optimal donor organs, there is increasing usage of extended criteria donor organs, including steatotic liver grafts. To mitigate the increased risks associated with extended criteria donor livers, ex-situ oxygenated machine perfusion (MP) has received increasing attention in recent years as an emerging platform for dynamic preservation, reconditioning and viability assessment to increase organ utilisation. MP can be applied at different temperatures. During h...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - June 8, 2020 Category: Physiology Authors: Thorne AM, Ubbink R, Brüggenwirth IMA, Nijsten MW, Porte RJ, de Meijer VE Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Acetylcholine Exerts Inhibitory and Excitatory Actions on Mouse Ileal Pacemaker Activity: The Role of Muscarinic versus Nicotinic Receptors.
Abstract The effect of acetylcholine (ACh) on pacemaking and spontaneous contractions in the gastrointestinal tract is not well-characterized. The current study aims to profile the effect of several muscarinic and nicotinic receptor agonists and antagonists on pacemaker potentials in the ICR mouse ileum. Pacemaker potentials of whole-thickness mouse ileal segments were recorded extracellularly using a 60-channel microelectrode array (MEA) platform. A spatiotemporal analysis integrated the frequency, amplitude and velocity measurements of pacemaker currents. Comparative data were obtained by recording spontaneous s...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - June 1, 2020 Category: Physiology Authors: Liu JYH, Du P, Rudd JA Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Inhibition of LXR Signaling by SULT2B1b Promotes Liver Regeneration After Partial Hepatectomy in Mouse Models of Nonalcoholic Fatty Liver Disease.
Abstract Hydroxysteroid sulfotransferase 2B1b (SULT2B1b) plays a critical role in hepatic energy homeostasis. Liver X receptors (LXRs) are implicated in multiple physiological functions, including the inhibition of hepatocyte proliferation and regulation of fatty acid and cholesterol metabolism. We have previously reported that SULT2B1b promotes hepatocyte proliferation by inactivating LXR signaling in vivo and in vitro, leading to our hypothesis that SULT2B1b promotes fatty liver regeneration. In the present study, female C57BL/6 and S129 mice were fed a high-fat diet for 8 weeks to establish a nonalcoholic fatty...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - June 1, 2020 Category: Physiology Authors: Zhang X, Xu Y, Bai Q, Li X, Han J, Hou Y, Ji Y, Zhang Z Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Corrigendum.
CORRIGENDUM. Am J Physiol Gastrointest Liver Physiol. 2020 Jun 01;318(6):G1054 Authors: PMID: 32463320 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - May 29, 2020 Category: Physiology Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

microRNA-382 suppresses the progression of pancreatic cancer through the PI3K/Akt signaling pathway by inhibition of Anxa3.
Abstract Pancreatic cancer (PC) is a lethal cancer in the digestive system. microRNAs (miRNAs) have been demonstrated to participate in PC progression. In this context, we thus aimed to explore the mechanism of miR-382 in epithelial mesenchymal transition (EMT) and lymph node metastasis in PC in relation to Anxa3 and the PI3K/Akt signaling pathway. Gene expression datasets GSE16515, GSE71989 and GSE32676 were screened out with the findings showed the significance of miR-382 and Anxa3 in PC. A total of 115 PC patients was selected for determination of miR-382 and Anxa3 expression with lowly expressed miR-382 and hi...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - May 28, 2020 Category: Physiology Authors: Wan X, Guo D, Zhu Q, Qu R Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Lipid droplets disrupt mechanosensing in human hepatocytes.
Abstract Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death in the world. Although most cases occur in stiff, cirrhotic livers, and stiffness is a significant risk factor, HCC can also arise in non-cirrhotic livers in the setting of non-alcoholic fatty liver disease (NAFLD). We hypothesized that lipid droplets in NAFLD might apply mechanical forces to the nucleus, functioning as mechanical stressors akin to stiffness. We investigated the effect of lipid droplets on cellular mechanosensing and found that primary human hepatocytes loaded with the fatty acids oleate and linoleate exhibited dec...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - May 28, 2020 Category: Physiology Authors: Chin L, Theise ND, Loneker AE, Janmey PA, Wells RG Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Alterations in Pancreatic Islet Cell Function in Response to Small Bowel Resection.
Conclusion Following massive SBR, there is significant hypertrophy of pancreatic islet cells with morphologically intact a- and b-cells. Significantly reduced pancreatic insulin release in both static and dynamic conditions demonstrate perturbed intrinsic b-cell function. GLP-1 is a key mediator of this amplification pathway. Decreased expression of serum GLP-1 and pancreatic GLP-1R in face of no change in insulin content offer a novel pathway for enteropancreatic glucose regulation following SBR. PMID: 32463335 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - May 28, 2020 Category: Physiology Authors: Courtney CM, Shyr ZA, Yan Z, Onufer EJ, Steinberger AE, Tecos ME, Barron LK, Guo J, Remedi MS, Warner BW Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Glucagon like peptide 1 and glucose-dependent insulinotropic polypeptide stimulate the release of substance P from TRPV1 and TRPA1 expressing sensory nerves.
Abstract Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from enteroendocrine cells (EEC) in response to nutrient ingestion and lowers blood glucose levels by stimulation of insulin secretion, and thus are defined as incretins. GLP-1 receptor (GLP-1R) expression has been identified on enteric neurons that include intrinsic afferent neurons, extrinsic spinal and vagal sensory afferents, but has not been shown to have an incretin effect through these nerves. GLP-1 and GIP enter the mesenteric lymphatic fluid (MLF) after a meal via the interstitial fluid (IF) from l...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - May 18, 2020 Category: Physiology Authors: Mayer F, Gunawan AL, Tso P, Aponte GW Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Cellular maps of gastrointestinal organs: getting the most from tissue clearing.
We present a brief overview of the chemical concepts that underpin tissue clearing, what sorts of questions whole-mount imaging can answer, how to choose a clearing agent, an example of how to clear and image alimentary tissue, and what to do after obtaining the image. This short review will encourage other gastrointestinal researchers to consider how utilizing tissue clearing and creating 3d "maps" of tissue might deepen the impact of their studies. PMID: 32421359 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - May 18, 2020 Category: Physiology Authors: Liu CY, Polk DB Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Microbial Metabolite Indole-3-Propionic Acid Supplementation Does Not Protect Mice from the Cardiometabolic Consequences of a Western Diet.
In conclusion, supplementation with IPA did not improve cardiometabolic outcomes in WD-fed mice and may have worsened some parameters in SD-fed mice, suggesting that IPA is not a critical signal mediating WD-induced cardiometabolic dysfunction downstream of the gut microbiota. PMID: 32421360 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - May 18, 2020 Category: Physiology Authors: Lee DM, Ecton KE, Trikha SRJ, Wrigley SD, Thomas KN, Battson ML, Wei Y, Johnson SA, Weir TL, Gentile CL Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Lipopolysaccharides (LPS) transport during fat absorption in rodent small intestine.
Abstract Lipopolysaccharides (LPS) are potent pro-inflammatory molecules that enter the systemic circulation from the intestinal lumen by uncertain mechanisms. We investigated these mechanisms and the effect of exogenous glucagon-like peptide-2 (GLP-2) on LPS transport in rodent small intestine. Transmucosal LPS transport was measured in Ussing-chambered rat jejunal mucosa. In anesthetized rats, the appearance of FITC-LPS into the portal vein (PV) and the mesenteric lymph was simultaneously monitored after intraduodenal perfusion of FITC-LPS with oleic acid and taurocholate (OA/TCA). In vitro, luminally-applied LP...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - May 11, 2020 Category: Physiology Authors: Akiba Y, Maruta K, Takajo T, Narimatsu K, Said H, Kato I, Kuwahara A, Kaunitz JD Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Antibiotic exposure post weaning disrupts the neurochemistry and function of enteric neurons mediating colonic motor activity.
Abstract The period during and immediately after weaning is an important developmental window when marked shifts in gut microbiota can regulate the maturation of the enteric nervous system (ENS). Because microbiota-derived signals that modulate ENS development are poorly understood, we examined the physiological impact of the broad spectrum antibiotic, vancomycin administered post weaning on colonic motility, neurochemistry of enteric neurons and neuronal excitability. The functional impact of vancomycin on enteric neurons was investigated by Ca2+ imaging in Wnt1-Cre;R26R-GCaMP3 reporter mice to characterize alter...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - May 11, 2020 Category: Physiology Authors: Hung LY, Parathan P, Boonma P, Wu Q, Wang Y, Haag A, Luna RA, Bornstein JC, Savidge T, Foong JPP Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Corrigendum.
CORRIGENDUM. Am J Physiol Gastrointest Liver Physiol. 2020 May 01;318(5):G988 Authors: PMID: 32374216 [PubMed - in process] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - May 1, 2020 Category: Physiology Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

HDAC6-dependent ciliophagy is involved in ciliary loss and cholangiocarcinoma growth in human cells and murine models.
Abstract Reduced ciliary expression is reported in several tumors, including cholangiocarcinoma (CCA). We previously showed primary cilia have tumor suppressor characteristics and HDAC6 is involved in ciliary loss. However, mechanisms of ciliary disassembly are unknown. Herein, we tested the hypothesis that HDAC6-dependent autophagy of primary cilia, i.e. ciliophagy, is the main mechanism driving ciliary disassembly in CCA. Utilizing the cancer genome atlas database, human CCA cells, and a rat orthotopic CCA model, we assessed basal and HDAC6-regulated autophagy levels. The effects of RNA-silencing or pharmacologi...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - April 27, 2020 Category: Physiology Authors: Peixoto E, Jin S, Thelen K, Biswas A, Richard S, Morleo M, Mansini A, Holtorf S, Carbone F, Pastore N, Ballabio A, Franco B, Gradilone SA Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Human intestinal enteroids as a model of Clostridioides difficile-induced enteritis.
Abstract Clostridioides difficile is an important nosocomial pathogen that produces toxins to cause life-threatening diarrhea and colitis. Toxins bind to epithelial receptors and promote the collapse of the actin cytoskeleton. C. difficile toxin activity is commonly studied in cancer-derived and immortalized cell lines. However, the biological relevance of these models are limited. Moreover, no model is available for examining C. difficile-induced enteritis, an understudied health problem. We hypothesized human intestinal enteroids (HIEs) express toxin receptors and provide a new model to dissect C. difficile cyto...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - March 30, 2020 Category: Physiology Authors: Engevik MA, Danhof HA, Chang-Graham AL, Spinler JK, Engevik KA, Hermann B, Endres BT, Garey KW, Hyser JM, Britton RA, Versalovic J Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Fermentable Fibers Induce Rapid Macro and Micronutrient Depletion in Toll-like Receptor 5 Deficient Mice.
Abstract Functional fermentable fibers are considered essential for a healthy diet. Recently, we demonstrated that gut microbiota dysbiotic mice fed an inulin-containing diet (ICD) developed hepatocellular carcinoma (HCC) within 6 months. In particular, a subset of toll-like receptor 5-deficient (T5KO) mice prone to HCC exhibited rapid onset of hyperbilirubinemia (HB) and cholemia; these symptoms provide rationale that ICD induces cholestasis. Our objective in the current study was to determine whether inulin-fed T5KO-HB mice exhibit other known consequences of cholestasis, including essential fatty acid and fat-s...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - March 23, 2020 Category: Physiology Authors: Golonka RM, Yeoh BS, Li Y, Saha P, Abokor A, Cheng X, Xiao X, Chandrashekar DS, Varambally S, Gonzalez DJ, Ross AC, Vijay-Kumar M Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Glucagon receptor signaling is not required for L-carbamoyl glutamate and L-citrulline induced ureagenesis in mice.
J, Holst JJ Abstract Glucagon regulates hepatic amino acid metabolism and increases ureagenesis. Ureagenesis is activated by N-acetylglutamate (NAG), formed via activation of N-acetylglutamate synthase (NAGS). Aiming to identify the steps whereby glucagon both acutely and chronically regulates ureagenesis, we investigated whether glucagon receptor mediated activation of ureagenesis is required in a situation where NAGS activity and/or NAG levels are sufficient to activate the first step of the urea cycle in vivo. Female C57Bl/6JRj mice, treated with a glucagon receptor antagonist (GRA), glucagon receptor knockout ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - March 16, 2020 Category: Physiology Authors: Galsgaard KD, Pedersen J, Kjeldsen SAS, Winther-Sørensen M, Stojanovska E, Vilstrup H, Ørskov C, Wewer Albrechtsen NJ, Holst JJ Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

MiR-524-5p inhibits angiogenesis through targeting WNK1 in colon cancer cells.
Abstract There is increasing evidence that microRNA (miRNA) abnormity is involved in the occurrence and the development of various malignancies, including colon cancer. MiRNA-524-5p has been reported to possess anti-cancer activity in various tumors, which function is seldom investigated in colon cancer cells. The aim of this study was to explore the effect of miRNA-524-5p/with-nolysine kinases 1 (WNK1) system on angiogenesis in colon cancer cell line (HT-29 and COLO205 cells) and further investigate the potential mechanisms. We found miRNA-524-5p expression was relatively high in COLO205 cells and relatively low ...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - March 16, 2020 Category: Physiology Authors: Li X, Li Z, Zhu Y, Li Z, Yao L, Zhang L, Yuan L, Shang Y, Liu J, Li C Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

When physiology meets technology: redefining colonic mass movements.
PMID: 32174133 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Gastrointestinal and Liver Physiology)
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - March 16, 2020 Category: Physiology Authors: Bassotti G Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research

Helicobacter pylori infection impairs chaperone-assisted maturation of Na,K-ATPase in gastric epithelium.
Abstract Helicobacter pylori infection always induces gastritis, which may progress to ulcer disease or cancer. The mechanisms underlying mucosal injury by the bacteria are incompletely understood. Here we identify a novel pathway for H. pylori-induced gastric injury, the impairment of maturation of the essential transport enzyme and cell adhesion molecule, Na,K-ATPase. The Na,K-ATPase is comprised of α and β subunits that assemble in the ER prior to trafficking to the plasma membrane. Attachment of H. pylori to gastric epithelial cells increased Na,K-ATPase ubiquitylation, decreased its surface and tot...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - March 16, 2020 Category: Physiology Authors: Marcus EA, Tokhtaeva E, Jimenez JL, Wen Y, Naini BV, Heard AN, Kim S, Capri J, Cohn W, Whitelegge JP, Vagin O Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research