Effect of atractylenolide Ⅲ on zearalenone-induced Snail1-mediated epithelial–mesenchymal transition in porcine intestinal epithelium

Background The intestinal epithelium performs essential physiological functions,such as nutrient absorption,and acts as a barrier to prevent the entry of harmful substances.Mycotoxins are prevalent contaminants found in ani-mal feed that exert harmful effects on the health of livestock.Zearalenone(ZEA)is produced by the Fusarium genus and induces gastrointestinal dysfunction and disrupts the health and immune system of animals.Here,we evaluated the molecular mechanisms that regulate the effects of ZEA on the porcine intestinal epithelium.Results Treatment of IPEC-J2 cells with ZEA decreased the expression of E-cadherin and increased the expression of Snai1 and Vimentin,which induced Snail1-mediated epithelial-to-mesenchymal transition(EMT).In addition,ZEA induces Snail-mediated EMT through the activation of TGF-βsignaling.The treatment of IPEC-J2 cells with atractyle-nolideⅢ,which were exposed to ZEA,alleviated EMT.Conclusions Our findings provide insights into the molecular mechanisms of ZEA toxicity in porcine intestinal epi-thelial cells and ways to mitigate it.

Establishment of a chicken intestinal organoid culture system to assess deoxynivalenol‑induced damage of the intestinal barrier function

Background Deoxynivalenol(DON)is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay,nutrient malabsorption,weight loss,emesis,and a reduction of feed intake in livestock.Since DON-contaminated feedstuff is absorbed in the gastrointestinal tract,we used chicken organoids to assess the DON-induced dysfunction of the small intestine.Results We established a culture system using chicken organoids and characterized the organoids at passages 1 and 10.We confirmed the mRNA expression levels of various cell markers in the organoids,such as KI67,leucine-rich repeat containing G protein-coupled receptor 5(Lgr5),mucin 2(MUC2),chromogranin A(CHGA),cytokeratin 19(CK19),lysozyme(LYZ),and microtubule-associated doublecortin-like kinase 1(DCLK1),and compared the results to those of the small intestine.Our results showed that the organoids displayed functional similarities in permeability compared to the small intestine.DON damaged the tight junctions of the organoids,which resulted in increased permeability.Conclusions Our organoid culture displayed topological,genetic,and functional similarities with the small intes-tine cells.Based on these similarities,we confirmed that DON causes small intestine dysfunction.Chicken organoids offer a practical model for the research of harmful substances.

Electrogastrography associated with symptomatic changes after prokinetic drug treatment for functional dyspepsia

AIM:To evaluate the effect of prokinetic drugs on electrogastrography(EGG) parameters according to symptomatic changes in patients with functional dyspepsia(FD).METHODS:Seventy-four patients with FD were prospectively enrolled in this study between December 2006 and December 2010.We surveyed the patients using a questionnaire on dyspeptic symptoms before and after an 8-wk course of prokinetic drug treatment.We also measured cutaneous pre-prandial and postprandial EGG recordings including percentage of gastric waves(normogastria,bradygastria,tachygastria),dominant frequency(DF),dominant power(DP),dominant frequency instability coefficient(DFIC),dominant power instability coefficient(DPIC),and the ratio of post-prandial to fasting in DP before and after the 8-wk course of prokinetic drug treatment.RESULTS:Fifty-two patients(70%) achieved symptomatic improvement after prokinetic drug treatment.Patients who had normal gastric slow waves showed symptom improvement group after treatment.Postprandial DF showed a downward trend in the symptom improvement group,especially in the itopride group.Post-prandial DP was increased regardless of symptom improvement,especially in the itopride group and mosapride group.Post-prandial DFIC and DPIC in the symptom improvement group were significantly increased after the treatment.The EGG power ratio was increased after treatment in the symptom improvement group(0.50 ± 0.70 vs 0.93 ± 1.77,P = 0.002),especially in the itopride and levosulpiride groups.CONCLUSION:Prokinetics could improve the symptoms of FD by regulating gastric myoelectrical activity,and EGG could be a useful tool in evaluating the effects of various prokinetics.

Endoscopic and clinicopathologic characteristics of early gastric cancer with high microsatellite instability

AIM： To investigate endoscopic and clinicopathologic characteristics of early gastric cancer （EGC） according to microsatellite instability phenotype. METHODS： Data were retrospectively collected from a single tertiary referral center. Of 981 EGC patients surgically treated between December 2003 and October 2007, 73 consecutive EGC patients with two or more microsatellite instability （MSI） mutation [high MSI （MSI-H）] and 146 consecutive EGC patients with one or no MSI mutation （non-MSI-H） were selected. The endoscopic and clinicopathologic features were compared between the MSI-H and non-MSI-H EGC groups.RESULTS： In terms of endoscopic characteristics, MSI-H EGCs more frequently presented with elevated pattern （OR 4.38, 95% Cl： 2.40-8.01, P 〈 0.001）, moderate- to-severe atrophy in the surrounding mucosa （OR 1.91, 95% CI： 1.05-3.47, P = 0.033）, antral location （OR 3.99, 95% CI： 2.12-7.52, P 〈 0.001） and synchronous le- sions, compared to non-MSI-H EGCs （OR 2.65, 95% CI： 1.16-6.07, P = 0.021）. Other significant clinicopatholog- ic characteristics of MSI-H EGC included predominance of female sex （OR 2.77, 95% CI： 1.53-4.99, P 〈 0.001）, older age （〉 70 years） （OR 3.30, 95% CI： 1.57-6.92, P = 0.002）, better histologic differentiation （OR 2.35, 95% Cl： 1.27-4.34, P = 0.007）, intestinal type by Lau- ren classification （OR 2.34, 95% CI： 1.15-4.76, P = 0.019）, absence of a signet ring cell component （OR 2.44, 95% CI： 1.02-5.86, P = 0.046）, presence of mu- cinous component （OR 5.06, 95% Cl： 1.27-20.17, P = 0.022）, moderate-to-severe lymphoid stromal reaction （OR 3.95, 95% CI： 1.59-9.80, P = 0.003）, and co-exist- ing underlying adenoma （OR 2.66, 95% CI： 1.43-4.95, P = 0.002）. CONCLUSION： MSI-H EGC is associated with unique endoscopic and clinicopathologic characteristics includ- ing frequent presentation in protruded type, co-exist- ing underlying adenoma, and synchronous lesions.