Telmisartan mitigates hyperglycemia-induced vascular inflammation by increasing GSK3ß-Ser9 phosphorylation in endothelial cells and mouse aortas.

Telmisartan, an angiotensin II type 1 receptor blocker (ARB), attenuates hyperglycemia-aggravated vascular inflammation by decreasing IκB kinase ß (IKKß) expression in endothelial cells. Because glycogen synthase 3ß (GSK3ß) is involved in inflammatory process by regulating nuclear factor-κB (NF-κB) activity, we investigated whether GSK3ß mediates telmisartan-ameliorated vascular inflammation in hyperglycemia-treated endothelial cells and high-fat diet (HFD)-fed mice. Telmisartan remarkably induced GSK3ß-Ser9 phosphorylation in hyperglycemia-treated endothelial cells that accompanied a decrease in hyperglycemia-induced NF-κB p65-Ser536 phosphorylation, vascular cell adhesion molecule-1 (VCAM-1) expression, and THP-1 monocyte adhesion. Ectopic expression of GSK3ß-S9A, a constitutively active mutant of GSK3ß, significantly restored complete telmisartan-inhibited NF-κB p65-Ser536 phosphorylation, VCAM-1 expression, and THP-1 monocyte adhesion. In addition, it reversed telmisartan-repressed IKKß expression. Among the ARB, including losartan and fimasartan, only telmisartan increased GSK3ß-Ser9 phosphorylation, and telmisartan-induced GSK3ß-Ser9 phosphorylation remained unchanged by pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor γ (PPARγ) antagonist. Finally, in the aortas of HFD-fed mice, telmisartan treatment significantly attenuated HFD-induced upregulation of NF-κB p65-Ser536 phosphorylation, VCAM-1 expression, and IKKß expression and downregulation of GSK3ß-Ser9 phosphorylation. Taken together, our findings demonstrated that telmisartan ameliorates hyperglycemia-exacerbated vascular inflammation, at least in part, by inducing GSK3ß-Ser9 phosphorylation, which consequently inhibits IKKß expression, NF-κB p65-Ser536 phosphorylation, and VCAM-1 expression in a PPARγ-independent manner.

A superhydrophobic layer formed by fluoro-derivative-treated gold sheets on grown-up zinc oxide nanoparticles for a spherical DNA hydrogel.

A facile deposition process was developed for the fabrication of a new superhydrophobic layer composed of an underlying zinc oxide nanoparticle support and a gold top layer doped with the hydrophobic chemical, heptadecafluoro-1-decanethiol (HDFT). The resulting microscaled and spherical DNA-based hydrogels could serve as a platform for pseudo-nucleus mimics.

A gene-networked gel matrix-supported lipid bilayer as a synthetic nucleus system.

A spheroidal transgene-networked gel matrix was designed as a synthetic nucleus system. It was spheroidically manufactured using both advanced lithography and DNA nanotechnology. Stable Aqueorea coerulescens green fluorescent protein (AcGFP)-encoding gene cross-networks have been optimized in various parameters: the number of gene-networked gel (G-net-gel) spheroids, the concentration of a AcGFP plasmid in the scaffold, and the molar ratio between the X-DNA building blocks and the gene. It was then assessed that 800 units of the gene networked gel matrix at a 4000:1 molar ratio of X-DNA blocks and AcGFP gene components accomplished 20-fold enhanced in vitro protein expression efficiency for 36 h. Furthermore, once with lipid capping, it reproduced the natural nucleus system, demonstrating the 2-fold increased levels of messenger RNAs (mRNAs) relative to solution phase vectors.

Budding dynamics of the lipid membrane.

Liposomes are widely used in industrial engineering systems including cosmetics and pharmaceutical and biotechnological applications. A fundamental understanding of the dynamics of lipid bud formation is required to efficiently produce various high-technological liposomes with well-controlled sizes and shapes. In this study, a novel patterning method of controlling the uniformity of the sizes and shapes of liposome buds nucleated from a flat lipid film casted on a flat substrate is reported. The dried-out lipid components had been swelling during aqueous hydration, and they pinched away in approximately one hour. The sizes and spacing of the liposome buds were monitored during hydration. It was observed that the average size of the buds slowly increased, but their spacing did not significantly change. Moreover, the bud size distribution was a very narrow Gaussian, which implies the formation of buds with uniform sizes. The analytical calculation of the equilibrium state was theoretically developed and compared with the experiments. It is envisioned that this study will provide insights on a sustained-release drug vehicle.