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Background and Aim: Circular ubiquitin‐like, containing PHD and ring finger domains 1 (circUHRF1) is aberrantly upregulated in human hepatocellular carcinoma (HCC) tissues. However, the underlying molecular mechanisms remain obscure. The present study aimed at elucidating the interactive function of circUHRF1–G9a–ubiquitin‐like, containing PHD and ring finger domains 1 (UHRF1) mRNA–eukaryotic translation initiation factor 4A3 (EIF4A3)–PDZ and LIM domain 1 (PDLIM1) network in HCC. Methods: Expression of circUHRF1, mRNAs of G9a, UHRF1, PDLIM1, epithelial–mesenchymal transition (EMT)‐related proteins, and Hippo–Yap pathway components was determined by quantitative polymerase chain reaction (Q‐PCR), immunofluorescence, or Western blot analysis. Tumorigenic and metastatic capacities of HCC cells were examined by cellular assays including Cell Counting Kit‐8, colony formation, wound healing, and transwell assays. Molecular interactions between EIF4A3 and UHRF1 mRNA were detected by RNA pull‐down experiment. Complex formation between UHRF1 and PDLIM1 promoter was detected by chromatin immunoprecipitation assay. Co‐immunoprecipitation was performed to examine the binding between UHRF1 and G9a. Results: Circular ubiquitin‐like, containing PHD and ring finger domains 1, G9a, and UHRF1 were upregulated, while PDLIM1 was downregulated in HCC tissue samples and cell lines. Cellular silencing of circUHRF1 repressed HCC proliferation, invasion, migration, and EMT. G9a formed a complex with UHRF1 and inhibited PDLIM1 transcription. Conclusion: Eukaryotic translation initiation factor 4A3 regulated circUHRF1 expression by binding to UHRF1 mRNA promoter. circUHRF1 increased the stability of G9a and UHRF1 mRNAs through recruiting EIF4A3. Overexpression of circUHRF1 aggravated HCC progression through Hippo–Yap pathway and PDLIM1 inhibition. By elucidating the molecular function of circUHRF1–G9a–UHRF1 mRNA–EIF4A3–PDLIM1 network, our data shed light on the HCC pathogenesis and suggest a novel therapeutic strategy for future HCC treatment. [ABSTRACT FROM AUTHOR]

On June 7-9, 2017, The Canadian College of Neuropsychopharmacology (CCNP) held its 40th Annual Meeting in Kingston, Ontario. At the core of the scientific program were 6 symposia, where clinical [...]

The temperature field, the equivalent plastic strain field, the highest temperature and the cooling problem of INCONEL718 superalloy in radial forging were studied with Forge simulation software. In the first pass, temperature rising is focused on the surface to the half radial distance area. After the second pass, the billet core is the highest temperature area, and the temperature becomes more uniform than before, even if 45℃ higher than the initial. The highest temperature of the billet during radial forging rises firstly and then falls slightly. Thermal radiation is the main cooling mode in all of the cooling methods. The simulation result of equivalent plastic strain indicates that the billet has been forged through after the second pass. At last, a comparison with sample observations shows that the simulation results are reliable.

Background: Recently, extract of Ginkgo biloba leaves (GbE) have become widely known phytomedicines and have shown various pharmacological activities, including improvement of blood circulation, protection of oxidative cell damage, prevention of Alzheimer's disease, treatment of cardiovascular disease and diabetes complications. This study was designed to investigate the effects of an ethanolic GbE on renal fibrosis in diabetic nephropathy (DN) and to clarify the possible mechanism by which GbE prevents renal fibrosis. Study design: We investigated the protective effects of GbE on renal fibrosis in STZ-induced diabetic rats. Rats were randomized into six groups termed normal control, diabetes mellitus, low dose of GbE (50 mg/kg/d), intermediate dose of GbE (100 mg/kg/d), high dose of GbE (200 mg/kg/d) and rapamycin (1 mg/kg/d). Methods: After 12 weeks, the rats were sacrificed and then fasting blood glucose (FBG), creatinine (Cr), blood urea nitrogen (BUN), urine protein, relative kidney weight, glycogen and collagen accumulation, and collagen IV and laminin expression were measured by different methods. The amounts of E-cadherin, a-SMA and snail, as well as the phosphorylation of Akt, mTOR and p70S6K in the renal cortex of rats, were examined by western blotting. Results: Compared with diabetic rats, the levels of Cr, BUN, urine protein, relative kidney weight, accumulation of glycogen and collagen, and expression of collagen IV and laminin in the renal cortex were all decreased in GbE treated rats. In addition, GbE reduced the expression of E-cadherin, α-SMA, snail and the phosphorylation of Akt, mTOR and p70S6K in diabetic renal cortex. Conclusion: GbE can prevent renal fibrosis in rats with diabetic nephropathy, which is most likely to be associated with its abilities to inhibit the Akt/mTOR signaling pathway. Keywords: Diabetic nephropathy Renal fibrosis Akt mTOR Ethanolic ginkgo biloba extract, Introduction According to the estimate released by the World Health Organization, the number of diabetic people has reached to approximately 347 million worldwide in 2008, accounting for 9.5% of the [...]