This study aimed to investigate whether inhibition of glycogen synthase kinase-3? (GSK-3?) could promote chondrocytes proliferation. The expression pattern of GSK-3? was firstly determined by immunohistochemistry (IHC) in normal mouse. Tibias were then isolated and cultured for 6 days. The tibias were treated with dimethylsulfoxide (control) or GSK-3 inhibitor SB415286 (SB86). Length of tibias was measured until 6 days after treatment. These bones were either stained with alcian blue/alizarin red or analyzed by IHC. In addition, GSK-3? and ?-catenin were analyzed by Western blot. Finally, cartilage-specific GSK-3? deletion mice (KO) were generated. Efficiency of GSK-3? deletion was determined through Western blot and IHC. After treated by inhibitor SB86, the overall length of growth plate was not changed. However, growth of tibia in SB86 group was increased by 31 %, the length of resting and proliferating was increased 13 % (P < 0.01), whereas the length of hypertrophic was decreased by 57 % (P < 0.01). Besides, the mineralized length was found to be significant longer than the control group (P < 0.05). In KO mice, growth plate and calvaria tissue both exhibit significant reduction of GSK-3? (P < 0.05) whereas the lengths of tibias in KO were almost same compared with control mice. Finally, an increase amount of ?-catenin protein was observed in SB86 (P < 0.05). In addition, significantly increased ?-catenin was also found in the growth plate of KO mice (P < 0.05). Inhibition of GSK-3 could promote longitudinal growth of bone through increasing bone formation. Besides, the inactivation of GSK-3? could lead to enhancing ?-catenin, therefore promote chondrocytes proliferation.
There has been more and more evidence to confirm the essential role of inflammatory processes in the development of coronary artery disease (CAD). Interleukin-21 (IL-21), the most recently discovered CD132-dependent cytokine, plays a key role in regulating inflammation. The aim of the study was to understand the effect of peripheral IL-21 on the pathogenesis and progression of CAD. Serum level of IL-21 in 92 CAD patients and 73 controls was measured by the enzyme-linked immunosorbent assay. Data showed that IL-21 expression was significantly increased in CAD than in controls (p < 0.001). Interestingly, when comparing IL-21 level with different genders, male subjects revealed higher IL-21 than female subjects (p = 0.024). Also, we observed that patients with hypertension had upregulated level of serum IL-21 (p = 0.002). Moreover, serum level of IL-21 was positively correlated with total cholesterol level (p = 0.015) or low-density lipoprotein cholesterol (p = 0.0009) of CAD cases. In addition, we analyzed IL-21 level with the severity of CAD, and identified that cases with 3-vessel affected had significantly elevated level of IL-21 than those with 1-vessel or 2-vessel affected. These data suggested that serum level of IL-21 may be closely associated with the development and progression of CAD.
Inflammation plays important roles in the development of atherosclerosis and coronary artery disease (CAD). Interleukin-2 (IL-2) is a proinflammatory cytokine and induces proliferation of T cells. The aim of the study was to understand the effect of IL-2 on the development of CAD from genetic polymorphism perspective and serum level perspective. IL-2 -330T/G and +114T/G polymorphisms were tested in 692 CAD cases and 723 healthy controls. IL-2 expression of these two polymorphisms was compared. Serum level of IL-2 in CAD patients and controls was analyzed. Data showed that prevalence of IL-2 -330GG genotype was significantly increased in CAD than in controls (p = 5.1 × 10(-6)). Function analysis revealed that subjects carrying IL-2 -330GG genotype had higher serum level of IL-2 than those with TG or TT genotypes (p < 0.01). Serum level of IL-2 in the study subjects was further analyzed, and results showed that CAD patients had significantly increased IL-2 level than healthy controls (p < 0.01). Also, cases with three vessels affected were observed to have higher IL-2 level than cases with one vessel affected (p < 0.05). These data suggested IL-2 polymorphism could affect the susceptibility to CAD by elevating protein expression, and serum level of IL-2 may be closed correlated with the development and progression of this disease.
Despite the knowledge of many genetic alterations present in Ewings sarcoma (ES), the complexity of this disease precludes placing its biology into a simple conceptual framework. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) can decrease T-cell activation and attenuate antitumor responses. Polymorphisms in the CTLA-4 gene have been shown to be associated with different diseases. Here, we investigated the association of four CTLA-4 gene polymorphisms, -1661A/G (rs4553808), -318C/T (rs5742909), +49G/A (rs231775), and CT60A/G (rs3087243), with ES in the Chinese population. A total of 308 ES cases and 362 healthy controls were recruited and CTLA-4 polymorphisms were tested by polymerase chain reaction-restriction fragment length polymorphism. Results showed that frequencies of the CTLA-4 gene +49AA genotype, +49A allele, and GTAG haplotype were significantly increased in ES patients compared to healthy controls (odds ratio [OR]=2.42, 95% confidence interval [CI] 1.43-4.09, p<0.001; OR 1.38, 95% CI 1.11-1.73, p=0.005, and OR=1.46, 95% CI 1.06-2.02, p=0.020, respectively). We further compared CTLA-4 polymorphisms in ES patients based on different clinical parameters and data revealed that ES patients with metastasis had higher numbers of the +49AA genotype than those without metastasis (p=0.004). These results indicated that the CTLA-4 polymorphism could be a risk factor for ES and suggested a potential role of CTLA-4 in the metastasis of this malignancy.
To study the clinical outcomes of Numelock II polyaxial system in treatment of type C fractures of the distal radius.
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