Starkgotfredsen8477

Osteoarthritis (OA) is a degenerative disease characterized by cartilage destruction. Previous research has demonstrated that long non-coding RNAs serve a role in OA progression. The current study aimed to determine the function and mechanism of taurine upregulated gene (TUG) 1 in OA. The results of reverse transcription quantitative PCR revealed that TUG1 was elevated in OA cartilage tissues and interleukin (IL)-1β-induced chondrocytes. Cell Counting kit-8 and flow cytometry analysis revealed that TUG1 knockdown promoted cell viability and inhibited cell apoptosis. Furthermore, matrix metalloprotein (MMP) 13, collagen II and aggrecan expression was determined by western blotting, of which the results demonstrated that TUG1 knockdown significantly decreased MMP13 expression and increased collagen II and aggrecan expression in IL-1β-stimulated chondrocytes, indicating that extracellular matrix (ECM) damage was inhibited. Additionally, using bioinformatics analysis, dual-luciferase reporter and RNA immunoprecipitation assays, TUG1 was revealed to upregulate fucosyltransferase (FUT) 1 by targeting miR-17-5p. Furthermore, miR-17-5p was downregulated and FUT1 upregulated in OA cartilage tissues and IL-1β-induced chondrocytes. MPI-0479605 cell line TUG1 overexpression reversed the aforementioned effects on cell viability, cell apoptosis and ECM degradation mediated by miR-17-5p in IL-1β-activated chondrocytes. Additionally, the effects of FUT1 knockdown on cell viability, apoptosis and ECM degradation mediated by FUT1 knockdown were reversed by miR-17-5p inhibition. In conclusion, TUG1 knockdown inhibited OA progression by downregulating FUT1 via miR-17-5p.Intravenous (i.v.) glucocorticoid is recommended for active moderate-to-severe thyroid-associated ophthalmopathy (TAO). However, the details of the treatment schedule are still debatable. The present prospective randomized trial was performed to compare clinical outcomes and serum cytokines between the two regimens. A cohort of 90 patients with active moderate-to-severe TAO was randomized to receive i.v. methyl prednisolone on a weekly protocol or daily scheme. The response rate was evaluated at the 12-week follow-up visit. Serum interleukin (IL)-2, IL-6 and IL-17 levels were measured in 160 patients with TAO, 60 patients with isolated Graves' disease (GD) and 60 normal control (NC) at baseline, as well as patients with active moderate-to-severe TAO at the 12th week after treatment. The daily scheme had a higher response rate than the weekly protocol without a significant difference (77.8 vs. 63.6%, P>0.05). No major adverse events were recorded under either regimen. Overall, minor events were more common on the daily scheme (11.36 vs. 4.35%, P less then 0.05)than on the weekly protocol, whereas the deterioration of eye symptoms (two patients) was only reported on the weekly protocol. At baseline, the IL-17 level in the TAO group was higher than that in the isolated GD and NC groups (P less then 0.05). In addition, the IL-17 level in the active TAO group was higher than that in the inactive TAO group (P less then 0.05). Furthermore, the IL-17 level had significantly decreased under the two regimens at the 12-week visit (P less then 0.05). In conclusion, for patients with active moderate-to-severe TAO, daily i.v. glucocorticoid therapy has a relative higher response rate than the weekly protocol with a few more minor adverse events. These two regimens have their own merits with regard to adverse effects. IL-17 has the potential to be a biomarker for evaluating TAO activity and treatment effects.Hypophosphatasia (HPP) is a rare hereditary systemic disease that is characterized by defective bone and/or dental mineralization, and is caused by mutations in the alkaline phosphatase gene (ALPL). The present study investigated the ALPL mutation in a Chinese Han family with HPP and studied the pathogenesis of the mutations of the ALPL gene. DNA was extracted from peripheral venous blood of the family members. Sanger sequencing was used to screen the mutations. Associations between pathogenesis for both mutations were analyzed by bioinformatics, subcellular localization, measurement of enzyme activity and western blotting. Sanger sequencing revealed the compound heterozygous mutations c.203C>T (p.T68M) and c.571G>A (p.E191K). The mutations were located at exon 4 and 6 of the ALPL gene and were predicted by Polyphen-2 analysis to be harmful. Protein analysis indicated a decrease in mature protein production and lower enzyme activity in 293T cells transfected with plasmids carrying the mutations. The ALPL gene was cloned into the pcDNA3.1(+) vector and mutant plasmids ALPL-pT68M and ALPL-pE191K were constructed. Immunofluorescence observed in cells transfected with the ALPL-pE191K mutant plasmid was mainly located in the cell membrane. However, staining in the cytoplasm was increased compared with the wild type, and almost no fluorescence was identified in 293T cells transfected with the ALPL-pT68M mutant plasmid. The present findings demonstrated that the compound heterozygous c.571G>A and c.203C>T mutations may contribute to childhood HPP by resulting in mislocalization, decreased protein expression and loss of enzyme activity in a Han Chinese family. The results of the current study may provide insights into the potential molecular mechanism of HPP.Metastatic renal cell carcinoma (RCC) is associated with poor prognosis. Ras protein activator like 2 (RASAL2) protein has been previously demonstrated to serves as a tumor suppressor in a variety of malignancies. Therefore, the aim of the present study was to investigate the role of RASAL2 in RCC. Reverse transcription-quantitative PCR, western blot analysis and immunohistochemistry were performed to measure mRNA and protein expression in RCC tissues, whilst immunofluorescence and western blotting were performed to evaluate protein expression in RCC cells. A Cell Counting Kit-8 and 5-bromo-2'-deoxyuridine staining were applied to determine cell viability, and Transwell assays were conducted to measure RCC cell invasion and migration. RASAL2 expression was identified to be downregulated in RCC tissues, which associate negatively with RCC pathological grade. Sox2 expression, in addition to ERK1/2 and p38 MAPK phosphorylation, were demonstrated to be increased in RCC tissues. In RCC cells, RASAL2 overexpression decreased the expression of Sox2 and the activation of ERK1/2 and p38 MAPK.