MiR-877-5p targets PDK-1 to promote aspirin-induced apoptosis in gastric mucosal cells.

This study aimed to investigate the role of miR-877-5p in aspirin-induced gastric mucosal injury. MiRNA microarray analysis was performed using paired gastric mucosal samples to find differentially expressed miRNAs. miR-877-5p was selected for subsequent analyses. Used as a model system, gastric epithelial cells (GES-1) were transfected with miR-877-5p mimic/inhibitor, then treated with aspirin. The expression of miR-877-5p in GES-1 cells was examined using quantitative real-time PCR (qRT-PCR). Flow cytometry analysis was used to detect cell apoptosis. Western blot assay was used to measure the protein levels of PDK1. The interaction between miR-877-5p and PDK1 was determined by luciferase reporter assay. The expression of miR-877-5p in gastric mucosal injury samples was higher than that in normal samples. Also, depletion of miR-877-5p reduced the apoptosis of GES-1 cells. Luciferase reporting assay confirmed that PDK1 was a target gene of miR-877-5p. PDK1 inhibited the apoptosis of GES-1 cells treated by aspirin. Moreover, this inhibitory effect was abrogated after PDK1 knockdown. Downregulation of miR-877-5p reduced the apoptosis by targeting PDK1 in GES-1 cells treated by aspirin, indicating that miR-877-5p may be a potential therapeutic target for gastric mucosal injury caused by aspirin.

The mechanism of miR-363-3p/DUSP10 signaling pathway involved in the gastric mucosal injury induced by clopidogrel.

Clopidogrel-induced gastric injury is an important clinical problem. However, the exact mechanism is still unclarified. Increasing evidence indicates that miRNAs may be involved in the pathogenesis of gastric mucosal injury. In this study, the aim was to investigate the role of miR-363-3p in the gastric mucosal injury caused by clopidogrel. MiRNA microarray analysis was performed using paired gastric mucosal in order to find differential expression of miRNAs. The levels of miR-363-3p were examined in gastric mucosal injury caused by clopidogrel. The GES-1 cells were used as a model system, miR-363-3p mimic/inhibitor was transfected into GES-1 cells, then GES-1 cells were treated with clopidogrel. The levels of miR-363-3p and DUSP10 were examined in GES-1 cells using quantitative real-time PCR (qRT-PCR). CCK-8 assay and flow cytometry analysis were used to detect cell proliferation and apoptosis, respectively. Western blot assay was used to measure the protein levels of DUSP10. The interaction between miR-363-3p and DUSP10 was determined by luciferase reporter assay. MiR-363-3p was selected as a differentially expressed miRNA. The expression of miR-363-3p in gastric mucosal injury caused by clopidogrel was higher than that in normal samples. Also, depletion of miR-363-3p increased the proliferation of GES-1 cells and reduced the apoptosis. Luciferase-reporting assay results confirmed that DUSP10 was one of the target genes of miR-363-3p. DUSP10 inhibited apoptosis in GES-1 cells treated by clopidogrel. Moreover, DUSP10 knockdown abrogated the inhibitory effects on apoptosis in GES-1 cells mediated by miR-363-3p inhibitor. Knockdown of miR-363-3p increased the proliferation and reduced the apoptosis by targeting DUSP10 in GES-1 cells treated by clopidogrel, indicating that miR-363-3p may be a potential therapeutic target for gastric mucosal injury caused by clopidogrel.

Method for the detection of submucosal tumors of the esophagus in submucosal tunnel under the preoperative identification / 中国内镜杂志

Objective To investigate the preoperative identification of esophageal submucosal tumor by endoscope. Methods 40 patients of esophageal submucosal tumors with lesions range from 1.0 to 2.0 cm from March 2012 to August 2016 were randomly divided into A, B groups. Patients in group A underwent submucosal tunneling endoscopic resection (STER) 3.0 cm from the lesions, while patients in group B first underwent submucosal injection of saline to mark the lesions, then perform STER in the same way. Then record the time of checking. Results The average time of group A was (420.0 ± 25.0) s, the average time of B group was (300.0 ± 25.0) s, there was statistical differences between the two groups. Conclusion Preoperative identification of the lesions before STER holds more advantages.

Protective effects and its mechanism of rebamipide on aspirin-induced injury in human gastric mucosal epithelium cells / 中华消化杂志

Objective To investigate the protective effects and its mechanism of rebamipide on aspirin-induced injury in human gastric mucosal epithelium cells (GES-1).Methods GES-1 cells monolayer culture model was established in vitro.Then the cells were divided into negative control group,aspirin injured group and combination of rebamipide at different concentration (0.2,0.5,1.0 mrnol/L) and aspirin groups.The cell proliferation,the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) of each group were detected.The ultrastructural changes of each group were observed by transmission electron microscopy (TEM).The expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) at protein level in the cells of each group were detected by Western blot.Nrf2 interfering suppression test was performed and then the influence of Nrf2 small interfering RNA (siRNA) on the expression of HO-1 protein was observed.One-way analysis of variance was performed for comparison among multi-groups and t-test was used for comparison between the two groups.Results The cell viability of aspirin injured group and combination of rebamipide at different concentration (0.2,0.5,1.0 mmol/L) and aspirin groups were (49.56±3.88)％,(59.34±4.36) ％,(70.79 ± 5.96) ％ and (86.07 ± 5.20) ％,respectively,and the difference was statistically significant (F=30.634,P＜ 0.01).Compared with aspirin injured group,the content of MDA significantly lowered in combination of rebamipide at different concentration (0.2,0.5,1.0 mmol/L) and aspirin groups ((2.26±0.25) nrnol/rng vs (1.85±0.13) nmol/mg vs (1.62±0.11) nmol/mg vs (1.13±0.15) nmol/mg),and the difference was statistically significant (F=23.821,P＜0.05).Compared with aspirin injured group,the activity of SOD significantly increased in combination of rebamipide at 0.5 and 1.0 mmol/L and aspirin groups ((8.49±0.89) U/rng vs (11.50±1.03) U/mg vs (13.74±0.76) U/mg),the difference was statistically significant (F=25.666,P＜0.05).Under TEM,the cell ultrastrucmral was obviously inured in aspirin treated,while rebamipide could relieve the injury.The differences of relative expression quantity of Nrf2 and HO-1 at protein level among combination of rebamipide at 0.2,0.5 and 1.0 mmol/L and aspirin groups and aspirin injured group were statistically significant (0.35±0.04 vs 0.46± 0.05 vs 0.84±0.08 vs 0.15±0.02,0.72±0.09 vs 0.93±0.11 vs 1.29±0.14 vs 0.39±0.07,F=92.550and 38.235,both P＜0.05).After transfected with Nrf2 siRNA,the expression of HO-1 was 0.38±0.04 in aspirin injured group and 0.62±0.08 in combination of rebamipide and aspirin group,which was lower than that before transfection (0.61 ± 0.05,1.33± 0.09),respectively.The differences were statistically significant (t =6.276 and 10.444,both P＜0.05).Conclusion Rebamipide may activate Nrf2/HO-1 pathway and relieve aspiriwinduced oxidative stress in GF1 ceils.

Diagnostic value of dilated intercellular space for non-erosive reflux disease / 中华消化内镜杂志

Objective To explore the diagnostic value of dilated intercellular space detected by light microscope for non-erosive reflux disease (NERD) and erosive esophagitis (RE). Methods A total of 104 subjects were divided into normal control group (n = 20), NERD group (n = 30) and RE group (n = 54).Biopsies were taken at 2-3 cm above the dentate line and were examined by light microscope to calculate the intercellular space and compared between different groups. Results The mean values of intercellular space in RE ( 1.40 ±0. 17 μm) and NERD ( 1.11 ± 0. 14 μm) were significantly higher than that in control group (0.66±0. 18 μm, x2 = 154. 170, P =0.000). But no significant difference was noted between RE and NERD groups ( t = 0. 044, P = 0. 834). The cut-off value of mean intercellular space with light microscope was 0. 89 μm, with sensitivity and specificity at 95.2% and 95.0%, respectively. Conclusion Dilated intercellular space under light microscope can be a sensitive, specific and objective indicator of NERD.

The study on the mechanim of clopidogrel in human gastric epithelial GES-1 cell line injury / 中华消化杂志

ObjectiveTo explore the mechanism of clopidogrel in human gastric epithelial cell line (GES-1) injury.MethodsSet up GES-1 cells monolayer culture model.Then the GES-1 cells were divided into negative control group,U0126 intervented group,clopidogrel intervented group and combined intervented group (U0t26 treated firstly then clopidogrel intervented).The cell proliferation and apoptosis in each group was examined by methyl thiazolyl tetrazolium (MTT) assay and Flow cytometry.TheexpressionofphosphorylatedERK1/2ineachgroupwasdetectedby immunocytochemistry method,and the expression quantity of phosphorylated ERK1/2 in each group was measured by western blot.ResultsThe result of MTT assay showed that compared with negative control group,the proliferation of GES-1 cells was inhibited in U0126 group,clopidogrel group and combined intervented group,and the inhibition percentage was 21.8％ ±2.7％,46.3％ ± 3.4％ and 82.9 ％ ± 0.8 ％ respectively ( F=615.556,P =0.000 ).The result of immunocytochemistry indicated that the expression of p-ERK in U0126 group,Clopidogrel group and combined intervented group decreased compared with negative control group,which was 10.80±1.64,7.20± 1.64,4.40±0.89and 1.40±0.55 respecitively (F=49.426,P=0.000).The result of western blot and immunocytochemistry was of the same trend.Conclusion In GES-1 cell model,clopidogrel may injureGES-1 cells through MAPK/EPK signal transduction pathway.