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

  • Systemic and terminal ileum mucosal immunity elicited by oral immunization with the Ty21a typhoid vaccine in humans

    This study examines mucosal immune responses to administration of the oral Ty21a-typhoid vaccine in humans. Local antigen-specific CD8+-TM responses were substantially different from those observed systemically. These data have broad implications human mucosal immune regulation as well as approaches to oral immunization.
  • HIF-1 deletion in the endothelium, but not in the epithelium, protects from radiation-induced enteritis

    This study examines the cell type-specific impact of HIF-1a activation in disease. The authors show that endothelial HIF-1a deletion confers resistance to radiation-induced enteritis, but similar deletion in intestinal epithelium does not. These results suggest new functions of endothelial HIF-1a-signaling pathways as mediators of mucosal inflammatory processes.
  • 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.
  • Esophageal submucosal gland culture model demonstrates capacity for proliferation and differentiation

    We describe a novel 3D culture model that reproduces ESMG proliferation in vivo associated with cancer and injury. ESMGs in culture form two different phenotypes of spheroids, one expressing markers of squamous epithelium and the other markers of columnar epithelium.
  • Hepatitis B Virus Activates Signal Transducer and Activator of Transcription 3 Supporting Hepatocyte Survival and Virus Replication

    The human hepatitis B virus (HBV) is a major cause of chronic hepatitis and hepatocellular carcinoma, but molecular mechanisms driving liver disease and carcinogenesis are largely unknown. We therefore studied cellular pathways altered by HBV infection.
  • Analysis of Hepatitis C Virus Particle Heterogeneity in Immunodeficient Human Liver Chimeric fah-/- Mice

    Hepatitis C virus (HCV) is a leading cause of chronic liver diseases and the most common indication for liver transplantation in the United States. HCV particles in the blood of infected patients are characterized by heterogeneous buoyant densities, likely owing to HCV association with lipoproteins. However, clinical isolates are not infectious invitro and the relative infectivity of the particles with respect to their buoyant density therefore cannot be determined, pointing to the need for better invivo model systems.
  • Neutrophils as Components of Mucosal Homeostasis

    Inflammatory responses in the intestinal mucosa inevitably result in the recruitment of neutrophils (polymorphonuclear leukocytes [PMNs]). Epithelial cells that line the mucosa play an integral role in the recruitment, maintenance, and clearance of PMNs at sites of inflammation. The consequences of such PMNepithelial interactions often determine tissue responses and, ultimately, organ function. For this reason, there is significant interest in understanding how PMNs function in the mucosa during inflammation.
  • 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.
  • Hepatocyte-Specific Deletion of Mouse Lamin A/C Leads to Male-Selective Steatohepatitis

    Lamins are nuclear intermediate filament proteins that comprise the major components of the nuclear lamina. Mutations in LMNA, which encodeslamins A/C, cause laminopathies, including lipodystrophy, cardiomyopathy, and premature aging syndromes. However, the role of lamins in the liver is unknown, and itis unclear whether laminopathy-associated liver disease iscaused by primary hepatocyte defects or systemic alterations.
  • 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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