Cooperative therapeutic action of retinoic acid receptor and retinoid x receptor agonists in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative process involving amyloid-ß (Aß) peptide deposition, neuroinflammation, and progressive memory loss. Here, we evaluated whether oral administration of retinoic acid receptor (RAR)α,ß agonist Am80 (tamibarotene) or specific retinoid X receptor (RXR) pan agonist HX630 or their combination could improve deficits in an AD model, 8.5-month-old amyloid-ß protein precursor 23 (AßPP23) mice. Co-administration of Am80 (0.5 mg/kg) and HX630 (5 mg/kg) for 17 days significantly improved memory deficits (Morris water maze) in AßPP23 mice, whereas administration of either agent alone produced no effect. Only co-administration significantly reduced the level of insoluble Aß peptide in the brain. These results thus indicate that effective memory improvement via reduction of insoluble Aß peptide in 8.5-month-old AßPP23 mice requires co-activation of RARα,ß and RXRs. RARα-positive microglia accumulated Aß plaques in the AßPP23 mice. Rat primary microglia co-treated with Am80/HX630 showed increased degradation activity towards 125I-labeled oligomeric Aß1-42 peptide in an insulin-degrading enzyme (IDE)-dependent manner. The co-administration increased mRNA for IDE and membrane-associated IDE protein in vivo, suggesting that IDE contributes to Aß clearance in Am80/HX630-treated AßPP23 mice. Am80/HX630 also increased IL-4Rα expression in microglial MG5 cells. The improvement in memory of Am80/HX630-treated AßPP23 mice was correlated with the levels and signaling of hippocampal interleukin-4 (IL-4). Therefore, Am80/HX630 may promote differentiation of IL-4-responsive M2-like microglia and increase their activity for clearance of oligomeric Aß peptides by restoring impaired IL-4 signaling in AßPP23 mice. Combination treatment with RAR and RXR agonists may be an effective approach for AD therapy.

Magnetic field-induced off-resonance third-order optical nonlinearity of iron oxide nanoparticles incorporated mesoporous silica thin films during heat treatment.

Highly dispersed and uniform Fe(2)O(3) nanoparticles (NPs) have been incorporated into the pore channels of SBA-15 mesoporous silica thin films (MSTFs). And such Fe(2)O(3) NPs incorporated MSTFs did not show detectable nonlinear optical (NLO) signals at off-resonance wavelength 1064 nm by Z-scan technique. However after a vacuum heat treatment at 800 degrees C for 1 h under 6 T magnetic field, the Fe(2)O(3) NPs incorporated MSTFs with very low Fe content (0.8 approximately 1.5 at.%) presented distinctive NLO signals with chi(3) value in an order of 10(-10) esu. We proposed the physical reason for the NLO property generation to be the magnetic domain orientation of the iron oxide NPs incorporated within the pore channels of the MSTFs by the magnetic field heat treatment.

Oral administration of synthetic retinoid Am80 (Tamibarotene) decreases brain beta-amyloid peptides in APP23 mice.

The purpose of this study is to investigate whether a synthetic retinoid Am80 (tamibarotene) exhibits any improving effects on amyloid precursor protein (APP)23 mice, a model of Alzheimer's disease. Am80 was orally administered in feed to 20-week (5-month)-old APP23 mice at a dose of 0 (control) or 0.5 mg/kg/d for 14 weeks. The Am80 treatment reduced significantly the insoluble Abeta levels in brain, in particular Abeta(42), while it gave no apparent effects on the soluble Abeta levels. The results suggest that oral administration of Am80 may have potency to reduce the extracellular Abeta(42) of insoluble and possibly oligomeric or protofibril forms, which are related to the cause and/or progression of Alzheimer's disease. The Am80 treatment showed no significant effect on spatial learning and memory of APP23 mice by Morris water maze analysis. The main reason for the absence of significance seems based on the large deviation and some mice both in the treated and the non-treated groups would neither swim nor make efforts to reach the platform.

Structural control of Fe-based alloys through diffusional solid/solid phase transformations in a high magnetic field.

A magnetic field has a remarkable influence on solid/solid phase transformations and it can be used to control the structure and function of materials during phase transformations. The effects of magnetic fields on diffusional solid/solid phase transformations, mainly from austenite to ferrite, in Fe-based alloys are reviewed. The effects of magnetic fields on the transformation temperature and phase diagram are explained thermodynamically, and the transformation behavior and transformed structures in magnetic fields are discussed.