Icariin ameliorates memory deficits through regulating brain insulin signaling and glucose transporters in 3×Tg-AD mice

Icariin,a major prenylated flavonoid found in Epimedium spp.,is a bioactive constituent of Herba Epimedii and has been shown to exert neuroprotective effects in experimental models of Alzheimer’s disease.In this study,we investigated the neuroprotective mechanism of icariin in an APP/PS1/Tau triple-transgenic mouse model of Alzheimer’s disease.We performed behavioral tests,pathological examination,and western blot assay,and found that memory deficits of the model mice were obviously improved,neuronal and synaptic damage in the cerebral cortex was substantially mitigated,and amyloid-βaccumulation and tau hyperphosphorylation were considerably reduced after 5 months of intragastric administration of icariin at a dose of 60 mg/kg body weight per day.Furthermore,deficits of proteins in the insulin signaling pathway and their phosphorylation levels were significantly reversed,including the insulin receptor,insulin receptor substrate 1,phosphatidylinositol-3-kinase,protein kinase B,and glycogen synthase kinase 3β,and the levels of glucose transporter 1 and 3 were markedly increased.These findings suggest that icariin can improve learning and memory impairments in the mouse model of Alzheimer’s disease by regulating brain insulin signaling and glucose transporters,which lays the foundation for potential clinical application of icariin in the prevention and treatment of Alzheimer’s disease.

Sea level change under IPCC-A2 scenario in Bohai, Yellow, and East China Seas

Because of the environmental and socioeconomic impacts of anthropogenic sea level rise （SLR）, it is very important to understand the processes leading to past and present SLRs towards more reliable future SLR projections. A regional ocean general circulation model （ROGCM）, with a grid refinement in the Bohai, Yellow, and East China Seas （BYECSs）, was set up to project SLR induced by the ocean dynamic change in the 21st century. The model does not consider the contributions from ice sheets and glacier melting. Data of all forcing terms required in the model came from the simulation of the Community Climate System Model version 3.0 （CCSM3） under the International Panel on Climate Change （IPCC）-A2 scenario. Simulation results show that at the end of the 21st century, the sea level in the BYECSs will rise about 0.12 to 0.20 m. The SLR in the BYECSs during the 21st century is mainly caused by the ocean mass redistribution due to the ocean dynamic change of the Pacific Ocean, which means that water in the Pacific Ocean tends to move to the continental shelves of the BYECSs, although the local steric sea level change is another factor.

Sea level variability in East China Sea and its response to ENSO

Sea level variability in the East China Sea （ECS） was examined based primarily on the analysis of TOPEX/Poseidon altimetry data and tide gauge data as well as numerical simulation with the Princeton ocean model （POM）. It is concluded that the inter-annual sea level variation in the ECS is negatively correlated with the ENSO index, and that the impact is more apparent in the southern area than in the northern area. Both data analysis and numerical model results also show that the sea level was lower during the typical E1 Niflo period of 1997 to 1998. E1 Nifio also causes the decrease of the annual sea level variation range in the ECS. This phenomenon is especially evident in the southern ECS. The impacts of wind stress and ocean circulation on the sea level variation in the ECS are also discussed in this paper. It is found that the wind stress most strongly affecting the sea level was in the directions of 70° and 20° south of east,, respectively, over the northern and southern areas of the ECS. The northwest wind is particularly strong when E1 Nifio occurs, and sea water is transported southeastward, which lowers the sea level in the southern ECS. The sea level variation in the southern ECS is also significantly affected by the strengthening of the Kuroshio. During the strengthening period of the Kuroshio, the sea level in the ECS usually drops, while the sea level rises when the Kuroshio weakens.

Seasonal and interannual variabilities of mean velocity of Kuroshio based on satellite data

Combining sea level anomalies with the mean dynamic topography derived from the geoid of the EGM08 global gravity field model and the CLS01 mean sea surface height, this study examined the characteristics of global geostrophic surface currents and the seasonal and interannual variabilities of the mean velocity of the Kuroshio （the Kuroshio source and Kuroshio extension）. The patterns of global geostrophic surface currents we derived and the actual ocean circulation are basically the same. The mean velocity of the Kuroshio source is high in winter and low in fall, and its seasonal variability accounts for 18% of its total change. The mean velocity of the Kuroshio extension is high in summer and low in winter, and its seasonal variability accounts for 25% of its total change. The interannual variabilities of the mean velocity of the Kuroshio source and Kuroshio extension are significant. The mean velocity of the Kuroshio source and ENSO index are inversely correlated. However, the relationship between the mean velocity of the Kuroshio extension and the ENSO index is not clear. Overall, the velocity of the Kuroshio increases when La Nina occurs and decreases when E1 Nino occurs.

Glycogen Synthase Kinase 3β Inhibitor (2'Z,3'E)-6-Bromo-indirubin-3'-Oxime Enhances Drug Resistance to 5-Fluorouracil Chemotherapy in Colon Cancer Cells

Objective： To explore the effects and mechanism of glycogen synthase kinase 3β （GSK-313） inhibitor （2＇Z,3＇E）-6-bromo-indirubin-3＇-oxime （BIO） on drug resistance in colon cancer cells. Methods： The colon cancer SW480 and SW620 cells were treated with BIO, 5-fluorouracil （5-FU） and BIO/5-FU, separately. Cell cycle distribution, apoptosis level and efflux ability of rhodamine 123 （Rh123） were detected by flow cytometry. The protein expressions of P-glycoprotein （P-gp）, multidrug resistance protein 2 （MRP2）, thymidylate synthase （TS）, β-catenin, E2F-1 and βcl-2 were detected by Western blot. β-catenin and P-gp were stained with double immunofluorescence and observed under a confocal microscope. Results： BIO up-regulated β-catenin, P-gp, MRP2 and TS, enhanced the efflux ability of Rh123, decreased Bcl-2 protein and gave the opposite effect to E2F-1 protein in SW480 and SW620 ceils. Furthermore, BIO significantly inhibited cell apoptosis, increased S and G2/M phase cells, and reduced the cell apoptosis induced by 5-FU in SW480 cells, whereas the effects were slight or not obvious in SW620 cells. Conclusion： GSK-3β was involved in drug resistance regulation, and activation of β-catenin and inhibition of E2F-1 may be the most responsible for the enhancement of 5-FU chemotherapy resistance induced by GSK-β inhibitor β10 in colon cancer.