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Cellular and Molecular Gastroenterology and Hepatology

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https://www.readbyqxmd.com/read/28660242/bacterial-autophagy-offense-and-defense-at-the-host-pathogen-interface
#1
REVIEW
James E Casanova
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...
September 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28649594/specific-macronutrients-exert-unique-influences-on-the-adipose-liver-axis-to-promote-hepatic-steatosis-in-mice
#2
Caroline C Duwaerts, Amin M Amin, Kevin Siao, Chris Her, Mark Fitch, Carine Beysen, Scott M Turner, Amanda Goodsell, Jody L Baron, James P Grenert, Soo-Jin Cho, Jacquelyn J Maher
BACKGROUND & AIMS: 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. METHODS: Mice were fed 4 high-energy diets identical in calorie and nutrient content but different in nutrient composition for 3 weeks to 6 months...
September 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28649593/colonic-microbiota-encroachment-correlates-with-dysglycemia-in-humans
#3
Benoit Chassaing, Shreya M Raja, James D Lewis, Shanthi Srinivasan, Andrew T Gewirtz
BACKGROUND AND AIMS: 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...
September 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28593188/barrett-s-stem-cells-as-a-unique-and-targetable%C3%A2-entity
#4
Wa Xian, Frank McKeon
Although metaplasias have always attracted because of their strangeness, it is now clear they represent precursors for some of the most intractable human cancers. Despite this notoriety, they remain curiously understudied, and even their origins have been the subject of acrimonious debate stretching back to Virchow in the 19th century. Barrett's esophagus, with its high incidence, easy endoscopic access, and strong link to esophageal adenocarcinoma, would seem an ideal opportunity to address the origin problem...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28593187/the-esophageal-squamous-epithelial-cell-still-a-reasonable-candidate-for-the%C3%A2-barrett-s-esophagus-cell-of%C3%A2-origin
#5
David H Wang
Barrett's esophagus is the metaplastic change of the squamous epithelium lining the distal esophagus into an intestinalized columnar epithelium that predisposes to esophageal adenocarcinoma development. The cell that gives rise to Barrett's esophagus has not been identified definitively, although several sources for the Barrett's esophagus cell of origin have been postulated. One possible source is a fully differentiated squamous epithelial cell or a squamous epithelial progenitor or stem cell native to the esophagus that, through molecular reprogramming, either transdifferentiation or transcommitment, could give rise to an intestinalized columnar cell...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28593186/origin-of-barrett-s-epithelium-esophageal-submucosal-glands
#6
Katherine S Garman
The origin of the progenitor cell for Barrett's esophagus remains a major unsolved mystery. Understanding the source of this progenitor may improve strategies to prevent the development of esophageal adenocarcinoma. Esophageal submucosal glands (ESMGs) and ducts may serve as a potential source of progenitor cells that respond to esophageal injury. Through the use of human histologic and molecular analysis, ESMGs and ducts have been described in physical continuity with areas of columnar esophagus, and shared mutations have been described between ESMG ducts and Barrett's esophagus...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28593185/induction-of-colonic-regulatory-t-cells-by-mesalamine-by-activating-the-aryl-hydrocarbon-receptor
#7
Kyoko Oh-Oka, Yuko Kojima, Koichiro Uchida, Kimiko Yoda, Kayoko Ishimaru, Shotaro Nakajima, Jun Hemmi, Hiroshi Kano, Yoshiaki Fujii-Kuriyama, Ryohei Katoh, Hiroyuki Ito, Atsuhito Nakao
BACKGROUND & AIMS: Mesalamine is a first-line drug for treatment of inflammatory bowel diseases (IBD). However, its mechanisms are not fully understood. CD4(+) Foxp3(+) regulatory T cells (Tregs) play a potential role in suppressing IBD. This study determined whether the anti-inflammatory activity of mesalamine is related to Treg induction in the colon. METHODS: We examined the frequencies of Tregs in the colons of wild-type mice, mice deficient for aryl hydrocarbon receptor (AhR(-/-) mice), and bone marrow-chimeric mice lacking AhR in hematopoietic cells (BM-AhR(-/-) mice), following oral treatment with mesalamine...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28593184/epigenetics-and-liver-fibrosis
#8
REVIEW
Eva Moran-Salvador, Jelena Mann
Liver fibrosis arises because prolonged injury combined with excessive scar deposition within hepatic parenchyma arising from overactive wound healing response mediated by activated myofibroblasts. Fibrosis is the common end point for any type of chronic liver injury including alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis, and cholestatic liver diseases. Although genetic influences are important, it is epigenetic mechanisms that have been shown to orchestrate many aspects of fibrogenesis in the liver...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28593183/columnar-metaplasia-in-three-types-of-surgical-mouse-models-of-esophageal-reflux
#9
Fabio Terabe, Susumu Aikou, Junko Aida, Nobutake Yamamichi, Michio Kaminishi, Kaiyo Takubo, Yasuyuki Seto, Sachiyo Nomura
BACKGROUND AND AIMS: Esophageal adenocarcinoma develops in the setting of gastroesophageal reflux and columnar metaplasia in distal esophagus. Columnar metaplasia arising in gastroesophageal reflux models has developed in rat; however, gastroesophageal reflux models in mice have not been well-characterized. METHODS: One hundred thirty-five C57Bl/6J mice aged 8 weeks old were divided into the following operations: esophagogastrojejunostomy (side-to-side) (EGJ), esophageal separation and esophagojejunostomy (end-to-side) (EJ), and EJ and gastrectomy (end-to-side) (EJ/TG)...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28593182/the-circadian-clock-gene-bmal1-coordinates-intestinal%C3%A2-regeneration
#10
Kyle Stokes, Abrial Cooke, Hanna Chang, David R Weaver, David T Breault, Phillip Karpowicz
BACKGROUND & AIMS: The gastrointestinal syndrome is an illness of the intestine caused by high levels of radiation. It is characterized by extensive loss of epithelial tissue integrity, which initiates a regenerative response by intestinal stem and precursor cells. The intestine has 24-hour rhythms in many physiological functions that are believed to be outputs of the circadian clock: a molecular system that produces 24-hour rhythms in transcription/translation. Certain gastrointestinal illnesses are worsened when the circadian rhythms are disrupted, but the role of the circadian clock in gastrointestinal regeneration has not been studied...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28560293/isthmus-stem-cells-are-the-origins-of-metaplasia-in-the-gastric-corpus
#11
Yoku Hayakawa, James G Fox, Timothy C Wang
The acquisition of genetic/epigenetic mutations in long-lived gastrointestinal stem cells leads to the development of cancer, as well as precancerous lesions such as metaplasia and dysplasia. In the proximal stomach corpus, this model of progression from stem cells has been supported by studies in mice and human beings, showing abundant proliferation in the isthmus and clonal expansion of mutated cells from the stem cell region. An alternative theory proposes that gastric metaplasia arises from mature differentiated chief cells...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28560292/metaplasia-in-the-stomach-arises-from-gastric-chief-cells
#12
Jason C Mills, James R Goldenring
The development of intestinal-type gastric cancer is preceded by loss of parietal cells (oxyntic atrophy) and the induction of metaplastic cell lineages in the gastric mucosa. For example, mouse models have shown that spasmolytic polypeptide-expressing metaplasia can develop following oxyntic atrophy through transdifferentiation of zymogen-secreting chief cells. Evolution of spasmolytic polypeptide-expressing metaplasia from chief cells occurs via a coordinated dismantling of their secretory apparatus and reprogramming of their transcriptome...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28560291/gastrin-and-gastric-cancer
#13
REVIEW
Jill P Smith, Sandeep Nadella, Nick Osborne
Gastric cancer is the third leading cause of cancer-related mortality worldwide. Despite progress in understanding its development, challenges with treatment remain. Gastrin, a peptide hormone, is trophic for normal gastrointestinal epithelium. Gastrin also has been shown to play an important role in the stimulation of growth of several gastrointestinal cancers including gastric cancer. We sought to review the role of gastrin and its pathway in gastric cancer and its potential as a therapeutic target in the management of gastric cancer...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28560290/farnesoid-x-receptor-agonist-treatment-alters-bile-acid-metabolism-but%C3%A2-exacerbates-liver-damage-in-a-piglet-model-of-short-bowel%C3%A2-syndrome
#14
Prue M Pereira-Fantini, Susan Lapthorne, Cormac G M Gahan, Susan A Joyce, Jenny Charles, Peter J Fuller, Julie E Bines
BACKGROUND & AIMS: Options for the prevention of short-bowel syndrome-associated liver disease (SBS-ALDs) are limited and often ineffective. The farnesoid X receptor (FXR) is a newly emerging pharmaceutical target and FXR agonists have been shown to ameliorate cholestasis and metabolic disorders. The aim of this study was to assess the efficacy of obeticholic acid (OCA) treatment in preventing SBS-ALDs. METHODS: Piglets underwent 75% small-bowel resection (SBS) or sham surgery (sham) and were assigned to either a daily dose of OCA (2...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28560289/initiation-and-maintenance-of-gastric-cancer-a-focus-on-cd44-variant-isoforms-and-cancer-stem-cells
#15
REVIEW
Yana Zavros
Gastric cancer is the third most common cause of cancer-related death. Although the incidence of gastric cancer in the United States is relatively low, it remains significantly higher in some countries, including Japan and Korea. Interactions between cancer stem cells and the tumor microenvironment can have a substantial impact on tumor characteristics and contribute to heterogeneity. The mechanisms responsible for maintaining malignant cancer stem cells within the tumor microenvironment in human gastric cancer are largely unknown...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28560288/regulation-of-gastric-carcinogenesis-by-inflammatory%C3%A2-cytokines
#16
REVIEW
Kevin A Bockerstett, Richard J DiPaolo
Chronic inflammation caused by infection with Helicobacter pylori and autoimmune gastritis increases an individual's risk of developing gastric cancer. More than 90% of gastric cancers are adenocarcinomas, which originate from epithelial cells in the chronically inflamed gastric mucosa. However, only a small subset of chronic gastritis patients develops gastric cancer, implying a role for genetic and environmental factors in cancer development. A number of DNA polymorphisms that increase gastric cancer risk have mapped to genes encoding cytokines...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28560287/mend-your-fences-the-epithelial-barrier-and-its-relationship-with-mucosal-immunity-in-inflammatory-bowel-disease
#17
REVIEW
Eva Martini, Susanne M Krug, Britta Siegmund, Markus F Neurath, Christoph Becker
The intestinal epithelium can be easily disrupted during gut inflammation as seen in inflammatory bowel disease (IBD), such as ulcerative colitis or Crohn's disease. For a long time, research into the pathophysiology of IBD has been focused on immune cell-mediated mechanisms. Recent evidence, however, suggests that the intestinal epithelium might play a major role in the development and perpetuation of IBD. It is now clear that IBD can be triggered by disturbances in epithelial barrier integrity via dysfunctions in intestinal epithelial cell-intrinsic molecular circuits that control the homeostasis, renewal, and repair of intestinal epithelial cells...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28560286/uncovering-pathogenic-mechanisms-of-inflammatory-bowel-disease-using-mouse-models-of-crohn-s-disease-like-ileitis-what-is-the-right-model
#18
REVIEW
Fabio Cominelli, Kristen O Arseneau, Alexander Rodriguez-Palacios, Theresa T Pizarro
Crohn's disease and ulcerative colitis, together known as inflammatory bowel disease, are debilitating chronic disorders of unknown cause and cure. Our evolving understanding of these pathologies is enhanced greatly by the use of animal models of intestinal inflammation that allow in vivo mechanistic studies, preclinical evaluation of new therapies, and investigation into the causative factors that underlie disease pathogenesis. Several animal models, most commonly generated in mice, exist for the study of colitis...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28508029/a-b-cell-gene-signature-correlates-with-the-extent-of-gluten-induced-intestinal-injury-in-celiac-disease
#19
Mitchell E Garber, Alok Saldanha, Joel S Parker, Wendell D Jones, Katri Kaukinen, Kaija Laurila, Marja-Leena Lähdeaho, Purvesh Khatri, Chaitan Khosla, Daniel C Adelman, Markku Mäki
BACKGROUND & AIMS: Celiac disease (CeD) provides an opportunity to study autoimmunity and the transition in immune cells as dietary gluten induces small intestinal lesions. METHODS: Seventy-three celiac disease patients on a long-term, gluten-free diet ingested a known amount of gluten daily for 6 weeks. A peripheral blood sample and intestinal biopsy specimens were taken before and 6 weeks after initiating the gluten challenge. Biopsy results were reported on a continuous numeric scale that measured the villus-height-to-crypt-depth ratio to quantify gluten-induced intestinal injury...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28462386/association-of-variants-of-arginine-vasopressin-and-arginine%C3%A2-vasopressin-receptor-1a-with-severe-acetaminophen%C3%A2-liver-injury
#20
Matthew Randesi, Orna Levran, Joel Correa da Rosa, Julia Hankins, Jody Rule, Mary Jeanne Kreek, William M Lee
BACKGROUND & AIMS: Acetaminophen-related acute liver injury and liver failure (ALF) result from ingestion of supratherapeutic quantities of this analgesic, frequently in association with other forms of substance abuse including alcohol, opioids, and cocaine. Thus, overdosing represents a unique high-risk behavior associated with other forms of drug use disorder. METHODS: We examined a series of 21 single nucleotide polymorphisms (SNPs) in 9 genes related to impulsivity and/or stress responsivity that may modify response to stress...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
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