2017-12-06 22:18:21 UTC

Translating Basic Science Into Clinical Application

Dec. 7, 2017

The CMGH editors summarize five recently accepted studies in four sentences or less.

AGA’s basic science journal, Cellular and Molecular Gastroenterology and Hepatology (CMGH), is committed to accepting digestive biology research that use tissues or cells from patients or animal models to address important questions and make fundamental discoveries that can translate into human disease.

Below are five articles to note recently accepted to CMGH, as summarized by the CMGH board of editors.

A Different Approach to Treating EoE
Role of Vasoactive Intestinal Peptide in Promoting the Pathogenesis of Eosinophilic Esophagitis (EoE)
By Alok K. Verma and colleagues 
The authors have discovered a new signaling pathway by which the nervous system contributes to eosinophil recruitment in eosinophilic esophagitis. This research is noteworthy because nervous system involvement has not been previously described. These findings have important implications for patient care — drugs that interrupt these pathways are available and more can be developed.

Identification of Novel Cell Culture Platform
Formation of Human Colonic Crypt Array by Application of Chemical Gradients Across a Shaped Epithelial Monolayer
By Yuli Wang and colleagues
The investigators describe a novel cell culture platform that maintains a self-renewing monolayer of human intestinal epithelium with in-vivo intestinal architecture. Most significantly, it includes a polarized crypt with basally localized stem cells. These cell culture innovations not only advance our understanding of intestinal epithelial biology, but will serve as novel vehicles for drug testing and toxin screening, and improve intestinal tissue engineering approaches.

Improving Identification and Treatment for NASH
Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model
By Arianne van Koppen, Lars Verschuren and colleagues 
The authors of this paper used a systems biology approach to evaluate mRNA, protein and histological data in a mouse model of non-alcoholic steatohepatitis (NASH) that led to fibrosis, confirming their findings in human samples. They identified a “signature” of changes in metabolic and fibrosis genes that preceded the development of fibrosis. This is important because it may lead to the development of a blood test that allows identification (and treatment) of the patients with fatty liver disease who are most at risk of progressing to fibrosis and its complications. Additionally, the findings reported in this paper could lead to more efficient clinical trials in NASH and ultimately to the development of new therapies for NASH and fibrosis.

How Alcohol Enhances Liver Damage in HCV Patients
Demethylase JMJD6 as a New Regulator of Interferon Signaling: Effects of HCV and Ethanol Metabolism
By Murali Ganesan and colleagues
The authors of this manuscript identify one mechanism by which alcohol (specifically the alcohol metabolite acetaldehyde, acting via the demethylase JMJD6) impairs hepatocyte protection from hepatitis C viral (HCV) infection. This is one of several reasons mechanisms whereby alcohol consumption can enhance liver damage from HCV infection, and may have important implications for counseling patients.

Can Hydrogen Sulfide Treat Disorders of the Lower Esophageal Sphincter?
Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger
By Xiaopeng Bai and colleagues 
Hydrogen sulfide, a gas, is the “third gasotransmitter” joining nitric oxide and carbon monoxide as gaseous signaling molecules, although it is the least well studied of the trio. The authors of this manuscript study hydrogen sulfide in the esophagus, demonstrating that it maintains the tone of the lower esophageal sphincter, the muscle at the base of the esophagus that has a critical role in allowing food to pass into the stomach and also prevents stomach acid from refluxing backwards into the esophagus. This finding has potential clinical relevance because it suggests that inhibitors of hydrogen sulfide generation could be used to treat disorders of the lower esophageal sphincter, including achalasia.

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