Breviscapine alleviates MPP+-induced damage and apoptosis of SH-SY5Y cells by activating Nrf2 pathway

Purpose: To investigate the role and mechanism of action of breviscapine (Brp) in 1-methyl-4- phenylpyridinium ion (MPP+)-induced cell injury in human neuroblastoma cell line, SH-SY5Y.Methods: The injury on SH-SY5Y cells was induced using MPP+. Cell viability and apoptotic ability were determined by CCK8 assay and Annexin V/PI staining, respectively. Protein expressions of nuclear factor E2-related factor 2 (Nrf2) and its related downstream proteins - hemeoxygenase 1(HO-1) and NAD(P)H-quinoneoxido reductase 1(NQO1), were determined using Western blotting.Results: Brp dose-dependently attenuated MPP+ induced reduction in the viability of SH SY5Y cells, but alleviated MPP+-induced oxidative stress (OS) and cell injury, as evidenced by the levels of reactive oxygen species (ROS), tyrosine hydroxylase (TH), lactic dehydrogenase (LDH), and dopaminetransporter (DAT) (p < 0.05). Brp decreased the amount of apoptotic cells induced by MPP+, as well as the protein levels of Bax and cleaved-caspase 3, and also induced the activation of Nrf2 signaling pathway (p < 0.05).Conclusion: Brp alleviates MPP+-induced cellular damage and cell apoptosis in SH-SY5Y cells by activating Nrf2 pathway. Thus, Brp is a potential therapeutic candidate for the treatment of PD

GPR48-Induced keratinocyte proliferation occurs through HB-EGF mediated EGFR transactivation

AbstractGPR48 can mediate keratinocyte proliferation and migration. Our investigations showed that AG1478, an inhibitor of EGFR tyrosine kinase, could block GPR48-mediated cellular processes. AG1478 treatment of Gpr48+/+ cells also decreased phosphorylation of EGFR, ERK and STAT3. Subsequent screening using conditioned media immunodepleted of EGFR ligands identified HB-EGF as the ligand responsible for phosphorylation of EGFR, ERK and STAT3. HB-EGF was reduced in Gpr48−/− cell culture medium, but its addition restored the phosphorylation of EGFR, ERK, STAT3, as well as cell proliferation. Confirmation that GPR48 mediates EGFR signaling pathway through HB-EGF was subsequently performed using an inhibitor of HB-EGF

Traffic Paradox Under Different Equilibrium Conditions Considering Elastic Demand

Traffic paradox is an important phenomenon which needs attention in transportation network design and traffic management. Previous studies on traffic paradox always examined user equilibrium (UE) or stochastic user equilibrium (SUE) conditions with a fixed traffic demand (FD) and set the travel costs of links as constants under the SUE condition. However, traffic demand is elastic, especially when there are new links added to the network that may induce new traffic demand, and the travel costs of links actually depend on the traffic flows on them. This paper comprehensively investigates the traffic paradox under different equilibrium conditions including the user equilibrium and the stochastic user equilibrium with a fixed and elastic traffic demand. Origin-destination (OD) mean unit travel cost (MUTC) has been chosen as the main index to characterize whether the traffic paradox occurs. The impacts of travelers’ perception errors and travel cost sensitivity on the occurrence of the traffic paradox are also analyzed. The conclusions show that the occurrence of the traffic paradox depends on the traffic demand and equilibrium conditions; higher perception errors of travelers may lead to a better network performance, and a higher travel cost sensitivity will create a reversed traffic paradox. Finally, several appropriate traffic management measures are proposed to avoid the traffic paradox and improve the network performance

Structural Interaction and Functional Regulation of Polycystin-2 by Filamin

Filamins are important actin cross-linking proteins implicated in scaffolding, membrane stabilization and signal transduction, through interaction with ion channels, receptors and signaling proteins. Here we report the physical and functional interaction between filamins and polycystin-2, a TRP-type cation channel mutated in 10–15% patients with autosomal dominant polycystic kidney disease. Yeast two-hybrid and GST pull-down experiments demonstrated that the C-termini of filamin isoforms A, B and C directly bind to both the intracellular N- and C-termini of polycystin-2. Reciprocal co-immunoprecipitation experiments showed that endogenous polycystin-2 and filamins are in the same complexes in renal epithelial cells and human melanoma A7 cells. We then examined the effect of filamin on polycystin-2 channel function by electrophysiology studies with a lipid bilayer reconstitution system and found that filamin-A substantially inhibits polycystin-2 channel activity. Our study indicates that filamins are important regulators of polycystin-2 channel function, and further links actin cytoskeletal dynamics to the regulation of this channel protein

Improving "color rendering" of LED lighting for the growth of lettuce

Light plays a vital role on the growth and development of plant. On the base of white light with high color rendering to the benefit of human survival and life, we proposed to improve “color rendering” of LED lighting for accelerating the growth of lettuce. Seven spectral LED lights were adopted to irradiate the lettuces under 150 μmol·m−2·s−1 for a 16 hd−1 photoperiod. The leaf area and number profiles, plant biomass, and photosynthetic rate under the as-prepared LED light treatments were investigated. We let the absorption spectrum of fresh leaf be the emission spectrum of ideal light and then evaluate the “color rendering” of as-prepared LED lights by the Pearson product-moment correlation coefficient and CIE chromaticity coordinates. Under the irradiation of red-yellow-blue light with high correlation coefficient of 0.587, the dry weights and leaf growth rate are 2-3 times as high as the sharp red-blue light. The optimized LED light for lettuce growth can be presumed to be limited to the angle (about 75°) between the vectors passed through the ideal light in the CIE chromaticity coordinates. These findings open up a new idea to assess and find the optimized LED light for plant growth