Mild Hypothermia Attenuates Intercellular Adhesion Molecule-1 Induction via Activation of Extracellular Signal-Regulated Kinase-1/2 in a Focal Cerebral Ischemia Model

Intercellular adhesion molecule-1 (ICAM-1) in cerebral vascular endothelium induced by ischemic insult triggers leukocyte infiltration and inflammatory reaction. We investigated the mechanism of hypothermic suppression of ICAM-1 in a model of focal cerebral ischemia. Rats underwent 2 hours of middle cerebral artery occlusion and were kept at 37°C or 33°C during occlusion and rewarmed to normal temperature immediately after reperfusion. Under hypothermic condition, robust activation of extracellular signal-regulated kinase-1/2 (ERK1/2) was observed in vascular endothelium of ischemic brain. Hypothermic suppression of ICAM-1 was reversed by ERK1/2 inhibition. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) in ischemic vessel was attenuated by hypothermia. STAT3 inhibitor suppressed ICAM-1 production induced by stroke. ERK1/2 inhibition enhanced phosphorylation and DNA binding activity of STAT3 in hypothermic condition. In this study, we demonstrated that hypothermic suppression of ICAM-1 induction is mediated by enhanced ERK1/2 activation and subsequent attenuation of STAT3 action

Composite Skyrme Model with Vector Mesons

We study the composite Skyrme model, proposed by Cheung and G\"{u}rsey, introducing vector mesons in a chiral Lagrangian. We calculate the static properties of baryons and compare with results obtained from models without vector mesons.Comment: LaTeX, 9 pages, 3 figures, to be published in Phys. Rev.

Regorafenib Regulates AD Pathology, Neuroinflammation, and Dendritic Spinogenesis in Cells and a Mouse Model of AD

The oral multi-target kinase inhibitor regorafenib, which targets the oncogenic receptor tyrosine kinase (RTK), is an effective therapeutic for patients with advanced gastrointestinal stromal tumors or metastatic colorectal cancer. However, whether regorafenib treatment has beneficial effects on neuroinflammation and Alzheimer's disease (AD) pathology has not been carefully addressed. Here, we report the regulatory function of regorafenib in neuroinflammatory responses and AD-related pathology in vitro and in vivo. Regorafenib affected AKT signaling to attenuate lipopolysaccharide (LPS)-mediated expression of proinflammatory cytokines in BV2 microglial cells and primary cultured microglia and astrocytes. In addition, regorafenib suppressed LPS-induced neuroinflammatory responses in LPS-injected wild-type mice. In 5x FAD mice (a mouse model of AD), regorafenib ameliorated AD pathology, as evidenced by increased dendritic spine density and decreased Aβ plaque levels, by modulating APP processing and APP processing-associated proteins. Furthermore, regorafenib-injected 5x FAD mice displayed significantly reduced tau phosphorylation at T212 and S214 (AT100) due to the downregulation of glycogen synthase kinase-3 beta (GSK3β) activity. Taken together, our results indicate that regorafenib has beneficial effects on neuroinflammation, AD pathology, and dendritic spine formation in vitro and in vivo.1

Pathological Involvement of Astrocyte-Derived Lipocalin-2 in the Demyelinating Optic Neuritis

PURPOSE. The current study was done to determine the role of lipocalin-2 (LCN2) in the pathogenesis of demyelinating optic neuritis using an experimental autoimmune optic neuritis (EAON) model. METHODS. The EAON was induced by subcutaneous immunization with an emulsified mixture of myelin oligodendrocyte glycoprotein ) peptide in mice. The LCN2 expression was examined in the optic nerve after MOG peptide injection. Degree of demyelination, inflammatory infiltration, glial activation, and expression profile of inflammatory mediators in the optic nerve were compared between LCN2 knockout (KO) animals and wild-type littermates by histological analysis and real-time PCR following EAON induction. Plasma levels of LCN2 in patients with optic neuritis were measured by ELISA. RESULTS. The expression of LCN2 was notably increased in the optic nerve after EAON induction. Expression of LCN2 was colocalized with reactive astrocytes. A significant reduction of demyelination, inflammatory infiltration, and gliosis was demonstrated in the optic nerve of LCN2 KO mice. The LCN2 KO mice also showed markedly reduced gene expression associated with the M1-polarized glia phenotype and toll-like receptor signaling in the optic nerve. The LCN2 levels in plasma were significantly higher in optic neuritis patients (71.6 6 10.6 ng/mL) compared to healthy controls (37.4 6 9.1 ng/mL, P ¼ 0.0284). CONCLUSIONS. In this study, we demonstrated a significant induction of LCN2 expression in astrocytes of the optic nerve following EAON induction. Our results imply that astrocytederived LCN2 may have a pivotal role in the development of demyelinating optic neuritis, and LCN2 can be a therapeutic target to alleviate immune and inflammatory damage in the optic nerve

Preparation and evaluation of activated carbon supported catalysts derived waste materials for hybrid type Na-air battery

Recently carbon supported catalysts (CSCs) have often been used to reduce the amount of noble metal catalyst required for improving the electrochemical performances of Na-air batteries (NABs). Herein, we successfully demonstrate a biomass-based CSC for hybrid-type NABs prepared via hydrothermal activation. The fabricated CSCs exhibited amorphous and disordered structure, and CSC-II based hybrid type NAB showed high specific discharge capacity of 799.85 mAh g ???1 , which is an equivalent to 95.5% of theoretical values. Furthermore, the N-doped CSC-II based battery exhibited improved performance related to carbon corrosion

Recent Progress of Electrochemical Energy Devices: Metal Oxide–Carbon Nanocomposites as Materials for Next-Generation Chemical Storage for Renewable Energy

With the importance of sustainable energy, resources, and environmental issues, interest in metal oxides increased significantly during the past several years owing to their high theoretical capacity and promising use as electrode materials for electrochemical energy devices. However, the low electrical conductivity of metal oxides and their structural instability during cycling can degrade the battery performance. To solve this problem, studies on carbon/metal-oxide composites were carried out. In this review, we comprehensively discuss the characteristics (chemical, physical, electrical, and structural properties) of such composites by categorizing the structure of carbon in different dimensions and discuss their application toward electrochemical energy devices. In particular, one-, two-, and three-dimensional (1D, 2D, and 3D) carbon bring about numerous advantages to a carbon/metal-oxide composite owing to the unique characteristics of each dimension