Association Between Single-Nucleotide Polymorphism (SNP) in miR-146a, miR-196a2, and miR-499 and Risk of Ischemic Stroke: A Meta-Analysis.

BACKGROUND The association between 3 well known SNPs - miR-146a C/G (rs2910164), miR-196a2 T/C (rs11614913), and miR-499 A/G (rs3746444) - in pre-miRNA sequences and ischemic stroke (IS) are still conflicting and inconclusive. This meta-analysis aimed to pool previous studies get a more precise assessment of the association between these 3 SNPs and the risk of IS. MATERIAL AND METHODS Relevant studies were searched in online databases. The strength of the association between the SNPs and IS were estimated by pooling odds ratios (OR) and 95% confidence intervals (CI) using Review Manager (version 5.3). RESULTS Rs2910164 C allele was associated with lower IS risk. But this trend was only observed in Koreans under the allele model (OR=0.81, 95% CI=0.68-0.95, p=0.009), dominant model (OR=0.68, 95% CI=0.50-0.93, p=0.02), recessive model (OR=0.79, 95% CI=0.63-1.00, p=0.05), and homozygous model (OR=0.63, 95%CI=0.45-0.88, p=0.007). Rs11614913 T allele might be associated with higher IS risk under the dominant model (OR=1.45, 95% CI=1.19-1.78, p=0.0003), while rs3746444 A allele might be associated with decreased IS risk under the homozygous model (OR=0.48, 95% CI=0.23-0.98, p=0.04) only in Chinese, but not in Koreans. CONCLUSIONS Although the 3 SNPs might be associated with IS, the association varied significantly in different countries.

Topical use of platelet-rich plasma can improve the clinical outcomes after total knee arthroplasty: A systematic review and meta-analysis of 1316 patients.

OBJECTIVE: Platelet-rich plasma (PRP) is extracted by centrifuging whole blood and characterized with a high concentration of platelets. The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) and non-RCTs is to evaluate the efficacy and safety of platelet-rich plasma (PRP) versus placebo after total knee arthroplasty (TKA). METHODS: The Electronic databases of PubMed, Web of Science, Embase and Cochrane Database of Systematic Reviews were searched from inception to November 2016 and any studies involving PRP versus placebo for patients prepared for TKA were selected by two reviewers. The primary endpoint is the range of motion (ROM), which represents the function after TKA. The Western Ontario McMaster Universities Osteoarthritis Index Bellamy (WOMAC), pain at 24 h, 48 h and 7 day are also assessed the effect of PRP on the function and pain after TKA. The complications of infection is also compiled to assess the safety of PRP. Stata 12.0 was used to synthesis the final results. RESULTS: Eleven clinical trials with 1316 patients are included in the meta-analysis. The pooled results indicate that administration PRP significantly increase ROM on the third day (MD = 4.72, 95% CI 2.74, 6.69; P = 0.000) and 3 month postoperatively (MD = 7.55, 95% CI 5.91, 9.19; P = 0.000). There is no statistical difference between the two groups in terms of WOMAC questionnaire score in 3 months (MD = -4.88, 95% CI -12.12, 2.41; P = 0.190). There were no statistical significance between the two groups in pain intensity at 24 h, 48 h and 7 day. There is no statistically significant difference between the PRP versus placebo in terms of the occurrence of infection (RR = 0.64, 95%CI: 0.19-2.14, P = 0.464). CONCLUSION: Current meta-analysis indicates that PRP is associated with increasing the ROM after TKA in short term and long term. What's more, PRP can also decrease the WOMAC score and pain intensity without increasing the occurrence of infection.

MiR-34c-3p suppresses the proliferation and invasion of non-small cell lung cancer (NSCLC) by inhibiting PAC1/MAPK pathway.

MicroRNAs have become recognized as key players in the development of malignancy. They are a family of small non-coding RNAs (22 nt~30 nt) that can negatively regulate the expression of cancer-related genes by sequence selective targeting of mRNAs, leading to either mRNA translational repression or degradation. Lung cancer is the leading cause of cancer-related death worldwide with a substantially low survival rate. In this study, we analyzed the expression profile of miR-34c-3p in non-small cell lung cancer (NSCLC) tissues and cell lines, as its participation in some other types of cancer has been shown by previous reports. We found that miR-34c-3p was downregulated both in NSCLC tissues and cell lines. Overexpression of miR-34c-3p suppressed cell proliferation and colony formation and also limited migration and invasion in A549 cells. Furthermore, our results also shown miR-34c-3p reduction was associated with increased PAC1 expression levels in which miR-34c-3p downregulated PAC1 expression by recognizing and binding to specific binding sites in PAC1 3'-UTR. Taken together, our study implicates important roles of miR-34c-3p in NSCLC pathogenesis and implicates its potential application in cancer therapy.

Expression of SATB1 and HER2 in breast cancer and the correlations with clinicopathologic characteristics.

BACKGROUND: Special AT-rich sequence binding protein 1 (SATB1) is found acting as a "genome organizer" that functions as a landing platform to regulate tissue-specific gene ex-pression. In breast cancer cell lines it has been proven that SATB1 could upregulate the expression of the HER2. In this paper, the relevance of SATB1 and HER2 expression was assessed in human breast cancer tissues, and their influence on tumor histological grade and patients' survival was explored. METHODS: Using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), 169 patients with breast cancer were assessed for SATB1 expression, HER2 amplification and hormone-receptor (HR) expression. The effects of SATB1 expression on HER2 and HR expression as well as their association with clinicopathologic characteristics were further analyzed by statistical evaluation. RESULTS: SATB1 expression was correlated with HER2 expression in breast cancer(r = 0.191; p = 0.013). SATB1, HER2 and SATB1/HER2 co-expression was negatively correlated with HR expression (r = -0.228, p = 0.003; r = -0.338, p = 0.000; r = -0.527, p = 0.000, respectively). SATB1 and HER2 single positive and their co-expression were all significantly correlated with higher histological grade (r = 0.239, p = 0.002; r = 0.160, p = 0.038; r = 0.306, p = 0.003, respectively). Multivariate cox regression analyses showed that SATB1 and HER2 were independent risk factors for breast cancer patients, while HR was a protective factor for patients' survival. Comparing to SATB1 or HER2 single positive expression, SATB1/HER2 co-expression tended to have even worse prognosis. CONCLUSIONS: SATB1 and HER2 performed a synergistic effect in breast cancer. Their expression correlated with poorly differentiated breast cancer and indicated an unfavorable prognosis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1400555050159723 .

Blockade of 11ß-hydroxysteroid dehydrogenase type 1 enzyme inhibits experimental collagenase-induced osteoarthritis.

Osteoarthritis (OA) is a common cause of functional deterioration in the joints of elderly adults and is a significant burden on the health of the aging population. 11ß­hydroxysteroid dehydrogenase type 1 enzyme (11ß­HSD1), which converts cortisone to cortisol, is known to contribute to a number of inflammatory diseases. However, the role of 11ß­HSD1 in human OA remains unclear. The aim of this study was to identify the effects of the selective 11ß­HSD1 inhibitor, BVT­2733, in murine collagenase­induced osteoarthritis (CIOA). CIOA mice were treated with BVT­2733 (100 mg/kg, orally) or control vehicle twice daily for five weeks. Cartilage and bone destruction were subsequently examined. The expression of bone markers and STAT3 phosphorylation in joint tissues were detected using western blot analysis. The concentrations of proinflammatory cytokines were determined by an enzyme­linked immunosorbent assay. Treatment with BVT­2733 attenuated cartilage and bone destruction, and reduced the expression of bone markers and p­STAT3 in the joints of CIOA mice. BVT­2733 also decreased the serum levels of interleukin (IL)­1ß, IL­6, IL­17 and vascular endothelial growth factor. In conclusion, the present study showed that BVT­2733 inhibits multiple inflammatory signaling pathways in the joints of CIOA mice, suggesting that 11ß­HSD1 inhibition may have therapeutic potential in human OA.