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The precise control for the micropatterning of nonparenchymal cells (endothelial cells; ECs and hepatic stellate cells; HSCs) is useful for regenerative medicine, artificial organs, and cell-based biodevice. The adhesion and alignment of nonparenchymal cells on a micro-patterned surface fabricated by two-step plasma polymerization process were investigated. The first functionalization step involves the deposition of a nitrogen-rich plasma-polymerized film to render the entire surface a cell-adherent region. Following this, a hydrophobic plasma-polymerized film is formed through a grid metal mask (hundred-micrometer-sized openings) to renders these areas cell repellent. Imaging ellipsometry showed that groove and ridge patterns 100 μm wide and steps with heights on the scale of tens of nanometers were obtained. EC and HSC culture experiments were conducted on the patterned surfaces. EC rapidly adhered and aligned along the cell-adherent groove of the patterned surface, while it did not adhere to the cell-repellent ridge. HSC patterning succeeded only when the height of the cell-repellent ridge was 20 nm, whereas the patterning failed when the ridge height was 10 nm. This indicates that EC patterning is possible with only a chemical effect, whereas HSC patterning required both a chemical effect and the topological constraints of the patterned surface.

Amyloid-β peptide (Aβ), which is generated by the β- and γ-secretase-mediated proteolysis of β-amyloid precursor protein (APP), plays an important role in the pathogenesis of Alzheimer's disease (AD). We recently reported that prostaglandin E(2) (PGE(2) ) stimulates the production of Aβ through both EP(2) and EP(4) receptors and that activation of the EP(4) receptor stimulates Aβ production through endocytosis and activation of γ-secretase. We here found that transgenic mice expressing mutant APP (APP23) mice showed a greater or lesser apparent cognitive deficit when they were crossed with mice lacking EP(2) or EP(4) receptors, respectively. Mice lacking the EP(4) receptor also displayed lower levels of Aβ plaque deposition and less neuronal and synaptic loss than control mice. Oral administration of a specific EP(4) receptor antagonist, AE3-208 to APP23 mice, improved their cognitive performance, as well as decreasing brain levels of Aβ and suppressing endocytosis and activation of γ-secretase. Taken together, these results suggest that inhibition of the EP(4) receptor improves the cognitive function of APP23 mice by suppressing Aβ production and reducing neuronal and synaptic loss. We therefore propose that EP(4) receptor antagonists, such as AE3-208, could be therapeutically beneficial for the prevention and treatment of AD.

Skin hyperpigmentation disorders as a result of abnormal melanin production induced by ultraviolet (UV) irradiation are both a clinical and a cosmetic problem. This melanin production is mediated by tyrosinase whose expression is positively regulated by microphthalmia-associated transcription factor (MITF). We recently found that expression of heat shock protein 70 (HSP70) inhibits melanin production. In this study, we searched for HSP70 inducers from Chinese herbs and selected an ethanol extract of Eupatorium lindleyanum (E. lindleyanum). Not only melanin production but also the activity and expression of tyrosinase were significantly suppressed in cells treated with E. lindleyanum extract as well as in HSP70-overexpressing cells. The expression of MITF was clearly suppressed in cells treated with E. lindleyanum extract but not in HSP70-overexpressing cells. These results suggest that E. lindleyanum extract suppresses the expression of tyrosinase and melanin production through both HSP70-dependent and HSP70-independent mechanisms.