Cellular and Molecular Gastroenterology and Hepatology

Editor picks for Cellular and Molecular Gastroenterology and Hepatology

Factors Associated With Missed and Cancelled Colonoscopy Appointments at Veterans Health Administration Facilities We examined individual and organizational factors associated with missed and cancelled colonoscopy appointments in Veteran Health Administration facilities.
Jan. 21, 2016

Proton Pump Inhibitors, Irritable Bowel Syndrome, and Small Intestinal Bacterial Overgrowth: Coincidence or Newton's Third Law Revisited?
Dec. 1, 2014

Spontaneous Control of Primary Hepatitis C Virus Infection and Immunity Against Persistent Reinfection
Oct. 27, 2014

Endoscopist-Directed Administration of Propofol: A Worldwide Safety Experience
Oct. 22, 2014

Activation of ?-Catenin and Yap1 in Human Hepatoblastoma and Induction of Hepatocarcinogenesis in Mice
Sept. 5, 2014

Cellular and Molecular Gastroenterology and Hepatology RSS

  • Demethylase JMJD6 as a new regulator of interferon signaling: effects of HCV and ethanol metabolism

    Demethylase JMJD6 expression is enhanced by acetaldehyde and HCV. It down-regulates STAT1 methylation in hepatocytes, thereby suppressing IFN-induced signaling via the JAK-STAT pathway and ISG activation. This leads to an increase in HCV RNA levels.
  • Colorectal cancer cells adhere to and migrate along the neurons of the enteric nervous system

    These findings reveal that colorectal cancer cells adhere to and migrate along enteric neurons partly via L1CAM and N-Cadherin. Thus, the dense network of local enteric neurons in the tumor microenvironment may serve as local route for colorectal cancer spreading.
  • Uncovering a predictive molecular signature for the onset of NASH-related fibrosis in a translational NASH mouse model

    This paper presents a predictive molecular signature which marks the early onset of fibrosis in a translational NASH mouse model. Overlap of genes and processes with human NASH and a list of top candidate biomarkers for early fibrosis are described.
  • Role of vasoactive intestinal peptide in promoting the pathogenesis of eosinophilic esophagitis (EoE)

  • Hypoxia in the Gut

    A continuous supply of molecular oxygen is essential for the maintenance of oxidative metabolism and thereby the function and survival of most cells of the human body. Over the course of evolution, we have developed the capacity, at the cellular level, to counteract the threat of developing hypoxia by eliciting an early warning adaptive response that is driven primarily by a transcription factor termed the hypoxia-inducible factor (HIF). In hypoxia, HIF becomes activated and drives the expression of a cohort of genes that promote adaptation to hypoxia including primary regulators of erythropoiesis (eg, erythropoietin), angiogenesis (eg, vascular endothelial growth factor), and metabolism (eg, glycolytic enzymes).
  • Location Matters in Defining T Cellmediated Immunity in Response to Salmonella Typhi Vaccination

    Infection with Salmonella enterica serovar Typhi results in nearly 250,000 deaths and more than 21 million illnesses worldwide. S Typhi is transmitted through the fecal-oral route through contaminated food or water and therefore is a major global health problem in regions that lack the infrastructure to provide safe water and ensure adequate sanitation. Of the 2 widely used S Typhi vaccines, Ty21a is an oral live-attenuated vaccine that confers moderate protection against infection for several years.
  • Lamin Deficiency in the Liver Sets the Stage for Nonalcoholic Steatohepatitis Development in Men

    Nuclear lamins are type V intermediate filament proteins that play important roles in maintaining nuclear shape and in transcriptional regulation. Moreover, they serve as signaling scaffolds at the inner nuclear membrane.1 Nuclear lamins fall into 2 separate classes, A-type and B-type, which are encoded by distinct genes. Mutations in their genes lead to tissue-selective disease phenotypes, termed laminopathies, which can affect muscle, adipose tissue, bone, liver, or multiple tissues depending on the site of the mutation.
  • Heterogeneity of Hepatitis C Virus Particles and Their Evolution During Infection

    Hepatitis C virus (HCV) was identified by molecular cloning of its RNA genome after conventional methods of virus identification failed. This failure was dueto both low levels of HCV particles in the blood of infected patients and particle heterogeneity. HCV is a highly variable virus. In addition to 6 genotypes and more than 60 subtypes, HCV mutants circulate in the blood as millions of quasispecies, many of which are able to escape host immune responses and even direct-acting antiviral (DAA) therapy.
  • ECM Bioscaffolds for Building Gastrointestinal Tissue

    Regenerative medicine is a rapidly advancing field that uses principles of tissue engineering, developmental biology, stem cell biology, immunology, and bioengineering to reconstruct diseased or damaged tissues. Biologic scaffolds composed of extracellular matrix have shown great promise as an inductive substrate to facilitate the constructive remodeling of gastrointestinal (GI) tissue damaged by neoplasia, inflammatory bowel disease, and congenital or acquired defects. The present review summarizes the preparation and use of extracellular matrix scaffolds for bioengineering of the GI tract, identifies significant advances made in regenerative medicine for the reconstruction of functional GI tissue, and describes an emerging therapeutic approach.
  • Indian Hedgehog Suppresses a Stromal CellDriven Intestinal Immune Response

    Upon intestinal epithelial damage a complex wound healing response is initiated to restore epithelial integrity and defend against pathogenic invasion. Epithelium-derived Indian Hedgehog (Ihh) functions as a critical sensor in this process. Signaling occurs in a paracrine manner because the receptor for Ihh is expressed only in the mesenchyme, but the exact Hedgehog target cell has remained elusive. The aim of this study was to elucidate further the nature of this target cell in the context of intestinal inflammation.
  • Setting up a Lab: The Early Years

    This months Paths and Places column was written by Aida Habtezion, an Associate Professor of Medicine (Gastroenterology and Hepatology) at Stanford University. Dr Habtezion, who studies leukocyte trafficking and the immune response in the gut, provides advice on successfully navigating the early years of an independent career as a physician-scientist. Dr. Habtezion has received multiple awards and was recently promoted to Associate Professor with tenure, making her an ideal role model for early career success.
  • HIF-1 Deletion in the Endothelium, but Not in the Epithelium, Protects From Radiation-Induced Enteritis

    Radiation therapy in the pelvic area is associated with side effects that impact the quality of life of cancer survivors. Interestingly, the gastrointestinal tract is able to adapt to significant changes in oxygen availability, suggesting that mechanisms related to hypoxia sensing help preserve tissue integrity in this organ. However, hypoxia-inducible factor (HIF)-dependent responses to radiation-induced gut toxicity are unknown. Radiation-induced intestinal toxicity is a complex process involving multiple cellular compartments.
  • Early Diagnosis of Gastroesophageal Cancers and the Cytosponge: A Work in Progress

    In the Perspective article in the March issue of Cellular and Molecular Gastroenterology and Hepatology,1 the Cytosponge erroneously was cited during the publication process as a Medtronic device (Medtronic, Minneapolis, MN). We would like to clarify that all published studies on Cytosponge to date have been performed using a research design patented by the Medical Research Council UK and made by local manufacturers and performed under permission from the Medical Health Regulatory Agency of the United Kingdom.
  • All Hands on Deck: Commensals, Th17 Cells, and Neutrophils Provide Short-term Compensation of Constitutive Permeability Defects Against Acute Infection

    Although ample evidence has been generated that increased intestinal permeability contributes to many inflammatory and disease phenotypes, both in the intestines and in extra-intestinal sites such as the liver, it also has been shown in several model systems that a barrier defect alone generally is insufficient to induce chronic inflammatory conditions such as ulcerative colitis and Crohns disease. This is reflected in clinical data showing that a subset of healthy first-degree relatives of Crohns disease patients show increased intestinal permeability but do not go on to develop full-blown disease, even though increased permeability can serve as a predictor of disease relapse.
  • The Quest for Relevant Hepatocellular Carcinoma Biomarkers

    Interest in the field of -omics within the past decade has led to further advancement in the understanding of numerous biochemical pathways as well as their dysregulation in pathology. The technologies allow characterization and quantification at various molecular levels (genes, transcription factors, proteins, and metabolites), enabling the study of key genetic and epigenetic pathways. Importantly, by phenotyping organisms at various molecular levels, -omics applications can be translated into molecular diagnostics and therapeutics in a clinical setting.
  • 2017 AGA Council Section Research Mentor Awardees

    Each year, Digestive Disease Week brings together the best clinical, translational, and basic science in the field.It is also an opportunity for many trainees and young investigators to present their work, receive advice from senior investigators, and build their professional networks. At Digestive Disease Week 2017, the AGA Institute recognized 1 member from each of the 13 Council sections who have committed themselves to training these young investigators and have shown a track record of outstanding research mentorship.
  • In NAFLD, You Are What You Eat, Not Simply How Much You Eat

    On May 20, 2016, the Food and Drug Administration (FDA) published a set of new regulations.1 These new labeling requirements were the result of FDA review of new scientific data on the associations between nutrients and chronic diseases, health-related conditions, physiological endpoints, and/or maintaining a healthy dietary pattern. The proposal drew over 500 public comments, the majority of which were related to classifications of fats and carbohydrates, signifying that (1) there is great public interest in the topic of nutrition, (2) there exists great confusion regarding how one categorizes nutrients, and (3) more science is needed to determine definitively which nutrients and what quantity of these nutrients promote health or disease.
  • Bacterial Encroachment in Metabolic Syndrome: TooMuchTogetherness?

    As our understanding of the intestinal microbiotas structure, function, regulation, and wide-ranging influence on human health grows, several important roadblocks to therapeutic targeting remain. First is the descriptive nature of most studies to date, which in many cases have documented steady-state phenotypes without investigating causeeffect relationships. Substantive progress is underway in this direction, with a number of investigators beginning to mechanistically address causal relationships using mouse models and direct manipulation or transfer of microbial populations.
  • The Microbiome Activates CD4 T-cellmediated Immunity toCompensate for Increased Intestinal Permeability

    Despite a prominent association, chronic intestinal barrier loss is insufficient to induce disease in human subjects or experimental animals. We hypothesized that compensatory mucosal immune activation might protect individuals with increased intestinal permeability from disease. We used a model in which intestinal barrier loss is triggered by intestinal epithelial-specific expression of constitutively active myosin light chain kinase (CA-MLCK). Here we asked whether constitutive tight junction barrier loss impacts susceptibility to enteric pathogens.
  • Do Animal Models of Acute Pancreatitis Reproduce HumanDisease?

    Acute pancreatitis is currently the most common cause of hospital admission among all nonmalignant gastrointestinal diseases. To understand the pathophysiology of the disease and as a potential step toward developing targeted therapies, attempts to induce the disease experimentally began more than 100 years ago. Recent decades have seen progress in developing new experimental pancreatitis models as well as elucidating many underlying cell biological and pathophysiological disease mechanisms. Some models have been developed to reflect specific causes of acute pancreatitis in human beings.
  • Maintaining a Vibrant and Productive Laboratory as a Senior Investigator

    This issues columnist for Paths and Places is Dr James Boyer, the Ensign Professor of Medicine at Yale, former president of the American Association for the Study of Liver Diseases, as well as the International Association for the Study of the Liver, and a senior investigator who runs a vigorous and impactful research program funded by a grant currently in its 40th year. We asked Dr Boyer to discuss his decision to maintain a research program (as opposed to switching his focus to teaching or administration) at this stage of his career.
  • Acinar-to-Ductal Metaplasia Induced by Transforming Growth Factor Beta Facilitates KRASG12D-driven Pancreatic Tumorigenesis

    Transforming growth factor beta (TGF) acts either as a tumor suppressor or as an oncogene, depending on the cellular context and time of activation. TGF activates the canonical SMAD pathway through itsinteraction with the serine/threonine kinase type I and II heterotetrameric receptors. Previous studies investigating TGF-mediated signaling in the pancreas relied eitheronloss-of-function approaches or on ligand overexpression, and its effects on acinar cells have so far remained elusive.
  • Identification of the Consistently Altered Metabolic Targets in Human Hepatocellular Carcinoma

    Cancer cells rely on metabolic alterations to enhance proliferation and survival. Metabolicgene alterations that repeatedly occur in liver cancer arelargely unknown. We aimed to identify metabolic genesthat are consistently deregulated, and are of potential clinical significance in human hepatocellular carcinoma (HCC).
  • Bacterial Autophagy: Offense and Defense at the HostPathogen Interface

    Autophagy is a fundamental cellular process used for the turnover and recycling of cytosolic components and damaged organelles. Originally characterized as a response to cellular stress, it now is well established that autophagy also is used as a defensive mechanism to combat the infection of host cells by intracellular pathogens. However, although this defensive strategy does limit the proliferation of most pathogens within their host cells, successful pathogens have evolved countermeasures that subvert or circumvent the autophagic response.
  • Specific Macronutrients Exert Unique Influences on the Adipose-Liver Axis to Promote Hepatic Steatosis in Mice

    The factors that distinguish metabolically healthy obesity from metabolically unhealthy obesity are not well understood. Diet has been implicated as a determinant of the unhealthy obesity phenotype, but which aspects of the diet induce dysmetabolism are unknown. The goal of this study was to investigate whether specific macronutrients or macronutrient combinations provoke dysmetabolism in the context of isocaloric, high-energy diets.
  • Colonic Microbiota Encroachment Correlates With Dysglycemia in Humans

    Mucoid structures that coat the epithelium play an essential role in keeping the intestinal microbiota at a safe distance from host cells. Encroachment of bacteria into the normally almost-sterile inner mucus layer has been observed in inflammatory bowel disease and in mouse models of colitis. Moreover, such microbiota encroachment has also been observed in mouse models of metabolic syndrome, which are associated low-grade intestinal inflammation. Hence, we investigated if microbiota encroachment might correlate with indices of metabolic syndrome in humans.
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