Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan,Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke

Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs.     

Surface morphological structures and electrochemical activity properties of iridium–niobium binary alloy electrodes

The electrochemical activities of Ir–Nb binary alloys were investigated as functions of the alloy compositions, crystal structures, and surface morphologies for a hydrogen peroxide and ascorbic acid redox reaction. High activities for the redox reaction of hydrogen peroxide were observed when pure Ir and an alloy with a composition of 77 at% Ir–23 at% Nb (Ir–23Nb) were used. Tests on eight electrodes—Ir, Ir–13Nb, Ir–17Nb, Ir–23Nb, Ir–30Nb, Ir–43Nb, Ir–62Nb, and Nb—showed that at a constant potential difference of 0.7 V vs. Ag/AgCl, the Ir–23Nb electrode had the best hydrogen peroxide oxidation capability: 9.2 μA/mm² for 2 mM hydrogen peroxide. Apart from Nb, Ir–23Nb gave the best performance in terms of preferential hydrogen peroxide oxidation against ascorbic acid. Subsequently, the Ir and Ir–23Nb electrodes were used for the fabrication of amperometric glucose sensors. We first coated the two electrodes with a γ-aminopropyltriethoxysilane membrane and then with a glucose oxidase membrane. Tests on the Ir and Ir–23Nb electrode glucose sensors showed that the latter had better glucose detection capability than the former: 0.226 μA/(mm² mM) for the Ir–23Nb sensor with 1.67 mM glucose. We investigated the relationship between the electrode responses to both hydrogen peroxide and ascorbic acid and the electrode surface structures.     

Levels of Lipid Peroxidation in Human Plasma and Erythrocytes: Comparison between Fatty Acids and Cholesterol

Lipid peroxidation has gained renewed attention with increasing evidence showing its biological role in producing toxic compounds and cellular signaling mediators. The assessment of lipid peroxidation levels in vivo is difficult partly because lipids are oxidized by different oxidants by different mechanisms to give versatile types of products, which may undergo metabolism and secondary reactions. In the present study, total hydroxyoctadecadienoic acids (tHODE) and 7α- and 7β-hydroxycholesterol (t7-OHCh) from 44 healthy human subjects were assessed as biomarkers after reduction with sodium borohydride followed by saponification with potassium hydroxide comparing with the prevailing standard 8-isoprostaglandin F_2α (t8-iso-PGF_2α). The average concentrations of tHODE, total 8-isoprostaglandin F_2α (t8-iso-PGF_2α), t7α-OHCh, and t7β-OHCh were 203, 0.727, 87.1, and 156 nmol/l plasma and 1,917, 12.8, 1,372, and 3,854 nmol/l packed erythrocytes, respectively. The ratios of tHODE and t7-OHCh to the parent substrates were 194 and 3,519 μmol tHODE/mol linoleates and 40.9 and 686 μmol t7-OHCh/mol cholesterol in plasma and erythrocytes, respectively. It was found that (1) t7-OHCh in blood was unexpectedly high, as high as or even higher than tHODE, (2) the amounts of tHODE was more than 100 fold higher than t8-iso-PGF_2α (3) the level of lipid oxidation products in erythrocytes was higher than that in plasma, and (4) lipid peroxidation products level tended to increase while antioxidant level decrease with age. These products may be used as potential biomarker for assessment of lipid peroxidation and oxidative stress in vivo.     

Encapsulation of hemoglobin in mesoporous silica (FSM)-enhanced thermal stability and resistance to denaturants

Hemoblogin (Hb), which is a typical oligomeric protein, was introduced into the pores of mesoporous silica (FSM: folded-sheet mesoporous material) that had a diameter of 7.5 nm. Soret CD spectra of Hb-FSM-7.5 conjugates showed a peak that was identical to that of free Hb. This suggests that Hb retained its highly ordered structure in the mesoporous silica. In addition, the UV-visible absorption spectrum showed that Hb had an increased resistance to heat denaturation in the silica. Even after heat treatment at 85 degrees C, Hb-FSM-7.5 retained its ligand-binding activity. The stability of Hb-FSM-7.5 was examined further by measuring its peroxidase-like activity. Encapsulation of Hb resulted in the retention of activity in the presence of high NaCl or Gdn-HCl levels. This suggests that encapsulation prevented dissociation and denaturing. Thus, it seems that the mesopores created a favorable environment for the oligomeric protein to perform its function, even under harsh conditions.     

Delayed and stage specific phosphorylation of H2AX during preimplantation development of gamma-irradiated mouse embryos

Within minutes of the induction of DNA double-strand breaks in somatic cells, histone H2AX becomes phosphorylated in the serine 139 residue at the damage site. The phosphorylated H2AX, designated as gamma-H2AX, is visible as nuclear foci in the irradiated cells which are thought to serve as a platform for the assembly of proteins involved in checkpoint response and DNA repair. It is known that early stage mammalian embryos are highly sensitive to radiation but the mechanism of radiosensitivity is not well understood. Thus, we investigated the damage response of the preimplantation stage development by analyzing focus formation of gamma-H2AX in mouse embryos gamma-irradiated in utero. Our analysis revealed that although H2AX is present in early preimplantation embryos, its phosphorylation after 3 Gy gamma-irradiation is hindered up to the two cell stage of development. When left in utero for another 24-64 h, however, these irradiated embryos showed delayed phosphorylation of H2AX. In contrast, phosphorylation of H2AX was readily induced by radiation in post-compaction stage embryos. It is possible that phosphorylation of H2AX is inefficient in early stage embryos. It is also possible that the phosphorylated H2AX exists in the dispersed chromatin structure of early stage embryonic pronuclei, so that it cannot readily be detected by conventional immunostaining method. In either case, this phenomenon is likely to correlate with the lack of cell cycle arrest, apoptosis and high radiosensitivity of these developmental stages.     

Architecture of colloidal crystals constructed by silica hybrid nanoparticles

Silica (SiO₂)‐crosslinked polystyrene (PS) particles possessing photofunctional N,N‐diethyldithiocarbamate (DC) groups on their surface were prepared by the free‐radical emulsion copolymerization of a mixture of SiO₂ (diameter D_n = 192 nm), styrene, divinyl benzene, 4‐vinylbenzyl N,N‐diethyldithiocarbamate (VBDC), and 2‐hydroxyethyl methacrylate with a radical initiator under UV irradiation. In this copolymerization, the inimer VBDC had the formation of a hyperbranched structure by a living radical mechanism. These particles had DC groups on their surface. Subsequently, poly(methyl methacrylate) brushes encapsulated SiO₂ particles were synthesized by the grafting from a photoinduced atom transfer radical polymerization (ATRP) approach of methyl methacrylate initiated by SiO₂‐crosslinked PS particles as a macroinitiator. We constructed the colloidal crystals using these photofunctional particles. Moreover, the SiO₂ particle array of colloidal crystals was locked by radical photopolymerization with vinyl monomer as a matrix. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Higher coverage of carboxylic acid groups on oxidized single crystal diamond (001)

The effects of crystal orientation to the surface chemistry of single crystal diamond (001) and (111) were investigated after wet chemical oxidation. Direct carboxylation has been successfully achieved via wet chemical oxidation on native diamond (001) and (111) surface with distinguished portions of carboxylic acid groups (-COOH). High resolution X-ray photoelectron spectroscopy (XPS) analysis revealed that various kinds of chemical groups including both single and double oxygen-related components were covalently functionalized onto the single crystal diamond. The percentages of -COOH are approximately 9.2% and 4.7% on (001) and (111) surface respectively, showing evidently that the density of -COOH groups on (001) surface is surprisingly higher than that of (111) surface. Comprehensive comparison revealed that oxygen-related groups is higher on (001) compared with that of (111) surface. The conversion mechanism was supposed to explain the evolution from hydrogenated to oxygenated functionalizations on diamond with differently oriented crystal facets, and the crystal orientation was the significant factor in controlling the surface reactivity and hence the oxidization process.     

Orientation-selective removal of upright Ag nanoplates from a TiO₂ film

Upright Ag nanoplates on a nanoparticulate TiO(2) film are oriented on the basis of plasmon-induced charge separation. Polarized visible light removes nanoplates oriented perpendicularly to polarization via excitation of in-plane transverse mode. Polarized near-infrared light removes nanoplates in parallel geometry via excitation of in-plane longitudinal mode.     

Numerical analysis of field-effect surface passivation for solar cells

In order to investigate the influence of surface potential on the electric characteristics of solar cells, the characteristics of conventional cells and back-contact type high-efficiency silicon cells were analyzed using 2-dimensional numerical simulation, varying the surface electrical potential. The locations where surface electrical potential is controlled are the rear side in conventional cells and the front side in back-contact cells. As a result of the calculations, it was found that field-effect surface passivation yields cell characteristics equivalent to those of a cell with effective surface recombination velocity of 0 cm/s, even if the cell has a poor interface (i.e., D_it > 1.0 × 10¹¹cm⁻²eV⁻¹). It was also found that both the use of a higher resistivity wafer and — especially in p-type substrates — the formation of inversion layers causes the field-effect surface passivation to work the fullest effect. In addition, a computer simulation based on physical-parameter measurements taken from actual materials forecasts that a back-contact cell would realistically be able to exceed 25% efficiency under AM1.5 global, one-sun illumination.