Circ_0016418 promotes melanoma development and glutamine catabolism by regulating the miR-605-5p/GLS axis.

BACKGROUND: Malignant melanoma is a skin cancer with a high rate of metastasis. Numerous circular RNAs (circRNAs) have been shown to play vital roles in melanoma. This research aimed to investigate the role and molecular basis of circ_0016418 in melanoma progression. METHODS: The abundanced of circ_0016418, miR-605-5p and glutaminase (GLS) were measured using quantitative real-time polymerase chain reaction or western blot analysis. Cell proliferation was evaluated using Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell migration and invasion were assessed by transwell assay. Cell cycle and apoptosis were monitored by flow cytometry. The levels of glutamine consumption and glutamate were examined using commercial kits. The interaction among circ_0016418, miR-605-5p and GLS was verified with the dual-luciferase reporter assay. A xenograft model was used to analyze tumor growth in vivo. RESULTS: Circ_0016418 and GLS were up-regulated, while miR-605-5p was down-regulated in melanoma tissues and cells. Circ_0016418 silencing hindered cell proliferation, metastasis, and glutamine catabolism and promoted cell cycle arrest and apoptosis in A375 and A875 cells. Circ_0016418 modulated melanoma progression and glutamine catabolism through sponging miR-605-5p. Also, miR-605-5p inhibited melanoma progression and glutamine catabolism by targeting GLS. Moreover, circ_0016418 depletion blocked tumor growth in vivo. CONCLUSION: Knockdown of circ_0016418 suppressed melanoma development and glutamine catabolism by modulating the miR-605-5p/GLS pathway.

Askin's tumor: 11 cases and a review of the literature.

Askin's tumor is a peripheral primitive neruoectodermal tumor within the thoracopulmonary region, which primarily occurs in children and young adults. In addition, Askin's tumor is commonly misdiagnosed, as it is rare and easily mistaken for other small round-cell tumors. The present study aimed to investigate the clinical characteristics, prognostic factors and treatment outcomes of patients diagnosed with Askin's tumor. Computed tomography (CT) scans, histopathology and immunohistochemical analysis were used for diagnosis. Patients were treated with combined (surgery-chemotherapy-radiotherapy) or mono-therapy (chemotherapy or radiotherapy) methods. A total of 11 consecutive patients with Askin's tumor (aged 8-22 years) were treated at the First Affiliated Hospital of Zhengzhou University between April 2010 and June 2013; nine patients underwent combined therapy and two patients were treated using mono-therapy. Chest lumps, swelling and pain were the most common presenting symptoms. Patients were followed up for ≤24 months post surgery and the results revealed that the median survival time of the combined and mono-therapy treatment groups were 15 and 7 months, respectively. Primary tumor size, metastasis, lactate dehydrogenase indicators and tumor stages were found to be important prognostic factors affecting patient outcome. In conclusion, the results of the present study demonstrated that the combination of surgery, chemotherapy and radiotherapy resulted in the optimal outcome for Askin's tumor patients.

The role of thrombospondin-1-mediated TGF-ß1 on collagen type III synthesis induced by high glucose.

Transforming growth factor-ß1 (TGF-ß1) has been thought to play a major role during cardiac fibrosis in the development of diabetic cardiomyopathy, and cardiac fibrosis mainly as a result of an increase of collagen type III occurs in the human hearts with diabetes. Thrombospondin-1 (TSP-1) has been reported to activate the latent complex of TGF-ß1. We examined the effects of TSP-1 on the expression of TGF-ß1 and collagen type III by rat cardiac fibroblasts in high ambient glucose. We demonstrated that high glucose induces the mRNA and protein expression of collagen type III, TGF-ß1, and TSP-1. Furthermore, the mRNA and protein expression of collagen type III induced by high glucose was downregulated after treatment with TGF-ß1 antibody, or TSP-1 siRNA. The expression of TGF-ß1 increased by high glucose was also reversed after treatment with TSP-1 siRNA. Our findings suggest that the TSP-1 participates in the upregulation of TGF-ß1, collagen type III by high glucose and may provide new therapeutic strategies for diabetic cardiomyopathy.

Effect of aspirin plus clopidogrel on inflammatory markers in patients with non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Aspirin can inhibit inflammatory reactions and platelet aggregation, but little is known about the effects of the combination of aspirin plus clopidogrel, a new antiplatelet agent, on inflammation. The purpose of this study was to determine whether aspirin plus clopidogrel can further suppress inflammation in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). METHODS: One hundred and fifteen patients with NSTEACS were randomized into two groups: group A (aspirin alone, n =58) and group B (aspirin plus clopidogrel, n =57). Patients in group A received a loading dose of 300 mg aspirin, then 100 mg per day. The patients in group B received a loading dose of 300 mg aspirin and 300 mg clopidogrel, then 100 mg aspirin and 75 mg clopidogrel per day. Serum high sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-alpha) were measured in all patients at baseline prior to any drug treatment after admission, and at 7 and 30 days after beginning drug treatment. Thirty healthy volunteers on no medications were enrolled as controls (group C). RESULTS: Baseline levels of hs-CRP and TNF-alpha in group A and group B were significantly higher than those in group C. Seven days after administration, the levels of hs-CRP in both group A and group B decreased significantly [Group A: (6.15 +/- 1.39) mg/L vs (9.18 +/- 1.62) mg/L, P <0.01; Group B:(4.99 +/- 1.62) mg/L vs (10.29 +/- 1.47) mg/L, P <0.01]. Similarly, levels of TNF- alpha in both groups decreased at 7 days compared to baseline [Group A: (90.99 +/- 28.91) pg/ml vs (117.20 +/- 37.13) pg/ml, P <0.01; Group B: (74.32 +/- 21.83) pg/ml vs (115.27 +/- 32.11) pg/ml, P <0.01]. Thirty days after administration, the levels of hs-CRP in both group A and group B decreased further to (3.49 +/- 1.53) mg/L, and (2.40 +/- 1.17) mg/L respectively (P <0.01 for both comparisons). Levels of TNF-alpha in groups A and B also decreased significantly between 7 and 30 days, to 63.28 +/- 29.01 pg/ml (group A) and (43.95 +/- 17.10) pg/ml (group B; P <0.01 for both comparisons). Significantly lower levels of hs-CRP and TNF-alpha were observed in group B compared to Group A at thirty days after initiating drug treatment (P <0.05). CONCLUSIONS: Aspirin plus clopidogrel treatment reduced levels of serum hs-CRP and TNF-alpha in patients with NSTEACS significantly more than aspirin alone. Because both aspirin and clopidogrel produce important anti-inflammatory effects, these results suggest the possibility that long-term treatment with aspirin plus clopidogrel may produce greater clinical benefits compared to treatment with aspirin alone.