Overexpression of microRNA-495 improves the intestinal mucosal barrier function by targeting STAT3 via inhibition of the JAK/STAT3 signaling pathway in a mouse model of ulcerative colitis.

We aim to investigate the role of microRNA-495 (miR-495) in the intestinal mucosal barrier by indirectly targeting signal transducer and activator of transcription 3 (STAT3) through the Janus kinase-signal transducer and activator of transcription (JAK)/STAT3 signaling pathway in a mouse model of ulcerative colitis (UC). BALB/c mice were selected for establishing mice model of UC, and intestinal tissues of normal and UC mice were collected. ELISA was conducted for detecting levels of TNF-α, IL-6, IFN-γ and IL-10. The levels of SOD, MPO, MDA and NO were tested in the intestinal tissues. Dual luciferase reporter gene assay was applied to determine whether miR-495 directly targets STAT3. Cells were cultured, transfected and assigned into: normal group, blank group, NC group, miR-495 mimic group, miR-495 inhibitor group, siRNA-STAT3 group and miR-495 inhibitor+siRNA-STAT3 group. MTT was used for testing cell proliferation, flow cytometry for cell cycle and apoptosis. Northern blotting and Western blotting were performed to detect miR-495 expression and expressions of STAT3, JAK and Claudin-1. Results show that the UC group had higher expression levels of TNF-α, IL-6, IFN-γ, MPO, MDA, NO, STAT3 and JAK and lower expression levels of IL-10, SOD, miR-495 and Claudin-1, compared to the normal group. Dual luciferase reporter gene assay confirmed that STAT3 was the target gene of miR-495. The miR-495 mimic and siRNA-STAT3 groups had higher expressions of Claudin-1, higher cell proliferation and increased amount of cells in S phase, but lower expressions of STAT3 and JAK, decreased amount of cells in G0/G1 phase and cell apoptotic rate compared with the blank, NC groups. We also found that the miR-495 inhibitor+siRNA-STAT3 group had reduced miR-495 expression. No significant differences were found in mRNA and protein expressions of STAT3, JAK and Claudin-1, cell proliferation, apoptosis and cycle amongst the miR-495 inhibitor+siRNA-STAT3 groups. Our study provides evidence that miR-495 improves the intestinal mucosal barrier function by targeting STAT3 through inhibiting the JAK/STAT3 signaling pathway in UC mice.

Correlations of MMP-2 and TIMP-2 gene polymorphisms with the risk and prognosis of gastric cancer.

AIM: To investigate the correlations of MMP-2 and TIMP-2 polymorphisms with the risk and prognosis of gastric cancer (GC). METHODS: With an incorporation of 254 GC patients in the case group and 250 healthy subjects enrolled as the control group, this experiment was conducted. Denaturing high performance liquid chromatography method was adopted to detect all genotypes under partial denaturation, haloptype analysis was completed with the Shesis software. Serum MMP-2 and TIMP-2 levels were determined by the immunohistochemical semi-quantitative analysis. The follow-up examination was conducted after the patients had completed systemic therapy and discharged. RESULTS: The distribution frequencies of MMP-2-735C/T locus genotypes between groups were compared (P > 0.05). However, the distributions of alleles and genotype frequencies of MMP-2-1306C/T, TIMP-2-303G/A and -418G/C all exhibited statistical difference (all P < 0.05). The gene polymorphism of MMP-2-1306C/T was statistically correlated with the expression of MMP-2 protein (P < 0.05); the same result was also found regarding TIMP-2-303G/A (P < 0.05). The haplotype analysis revealed that the CGC frequency of the case group was apparently higher than that of the control group (P < 0.05), the positive survival rate of CGC was apparently lower than the negative one. CONCLUSION: MMP-2-1306C/T, TIMP-2-303G/A and -418G/C variants might be correlated with GC susceptibility. Serum MMP-2 and TIMP-2 protein levels might be associated with GC susceptibility; Additionally, CGC haplotype might be the risk factor of GC.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): a new strategy to increase resectability in liver surgery.

BACKGROUND: Partial hepatectomy with clear surgical margins is the main curative treatment for hepatic malignancies. The safety of liver resection, to a great extent, depends on the volume of future liver remnant. This manuscript reviews some important strategies that have been developed to increase resectability for patients with borderline volume of future liver remnant, particularly associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). METHODS: To identify potentially relevant articles, we searched Medline and PubMed from January 2010 to December 2013 using the keywords "Associating liver partition and portal vein ligation for staged hepatectomy", "ALPPS", "portal vein embolization", "future liver remnant", "liver hypertrophy", and "liver failure". A number of references from the key articles were also cited. There were no exclusion criteria for published information to the topics. RESULTS: Portal vein ligation (PVL) or embolization (PVE) are traditional approaches to induce liver hypertrophy of the future liver remnant (FLR) prior to hepatectomy in primarily non-resectable liver tumors. However, about 14 percent of patients fail to this approach. Adequate hypertrophy of the FLR using PVL or PVE generally takes more than four weeks. ALPPS can induce rapid growth of the FLR, which is more effective than by portal vein embolization or occlusion alone. Reportedly, the hypertrophy extent of FLR was 40%-80% within 6-9 days in contrast to approximately 8%-27% within 2-60 days by PVL/PVE. However, ALPPS was reported to have high operative morbidity (16%-64% of patients), mortality (12%-23% of patients) and bile leakage rates. Bile leakage and sepsis remain a major cause of morbidity, and the main cause of mortality includes hepatic insufficiency. CONCLUSION: ALPPS has emerged as a new strategy to increase resectability of hepatic malignancies. Due to high morbidity and mortality rates of ALPPS procedure, the surgical candidates should be selected carefully. Moreover, there are very limited available evidence for its technical feasibility, safety and oncological outcome which are needed for further evaluation in larger scale of studies.