Asymmetric desymmetrization of meso-diols by C(2)-symmetric chiral 4-pyrrolidinopyridines.

In this work we developed C(2)-symmetric chiral nucleophilic catalysts which possess a pyrrolidinopyridine framework as a catalytic site. Some of these organocatalysts effectively promoted asymmetric desymmetrization of meso-diols via enantioselective acylation

Phosphodiesterase-III Inhibitor Prevents Hemorrhagic Transformation Induced by Focal Cerebral Ischemia in Mice Treated with tPA

The purpose of the present study was to investigate whether cilostazol, a phosphodiesterase-III inhibitor and antiplatelet drug, would prevent tPA-associated hemorrhagic transformation. Mice subjected to 6-h middle cerebral artery occlusion were treated with delayed tPA alone at 6 h, with combined tPA plus cilostazol at 6 h, or with vehicle at 6 h. We used multiple imaging (electron microscopy, spectroscopy), histological and neurobehavioral measures to assess the effects of the treatment at 18 h and 7 days after the reperfusion. To further investigate the mechanism of cilostazol to beneficial effect, we also performed an in vitro study with tPA and a phosphodiesterase-III inhibitor in human brain microvascular endothelial cells, pericytes, and astrocytes. Combination therapy with tPA plus cilostazol prevented development of hemorrhagic transformation, reduced brain edema, prevented endothelial injury via reduction MMP-9 activity, and prevented the blood-brain barrier opening by inhibiting decreased claudin-5 expression. These changes significantly reduced the morbidity and mortality at 18 h and 7 days after the reperfusion. Also, the administration of both drugs prevented injury to brain human endothelial cells and human brain pericytes. The present study indicates that a phosphodiesterase-III inhibitor prevents the hemorrhagic transformation induced by focal cerebral ischemia in mice treated with tPA

Super water-repellent treatment of various cloths by deposition of catalytic-CVD polytetrafluoroethylene films

Polytetrafluoroethylene (PTFE), commercial name “Teflon,” films prepared by catalytic chemical vapor deposition (Cat-CVD), often called “hot-wire CVD,” are deposited on various cloths of cotton, cotton denim, nylon, and polyester. After deposition on such cloths, they show super water-repellent property without impairing breathability. The whole surface of fibers of these cloths is completely covered with PTFE layers which form reticulated sharp convex–concave network structures with a size of a few micrometers or less in pitch. The super water-repellent property can be seen even at the back side of the cloths when PTFE films are deposited only at the front side

Regioselective Diversification of a Cardiac Glycoside, Lanatoside C, by Organocatalysis

Acylation of lanatoside C in the presence of organocatalyst <b>5</b> gave the C(4′′′′)-<i>O</i>-acylate in up to 90% regioselectivity (catalyst-controlled regioselectivity). Various functionalized acyl groups can be introduced at the C(4′′′′)-OH by a mixed anhydride method in the presence of <b>5</b> or the related organocatalyst. On the other hand, DMAP-catalyzed acylation of lanatoside C gave the C(3′′′′)-<i>O</i>-acylate in up to 97% regioselectivity (substrate-controlled regioselectivity). Thus, diverse regioselective introduction of acyl groups among eight free hydroxy groups of lanatoside C was achieved

Diabetes Mellitus Aggravates Hemorrhagic Transformation after Ischemic Stroke via Mitochondrial Defects Leading to Endothelial Apoptosis

<div><p>Diabetes is a crucial risk factor for stroke and is associated with increased frequency and poor prognosis. Although endothelial dysfunction is a known contributor of stroke, the underlying mechanisms have not been elucidated. The aim of this study was to elucidate the mechanism by which chronic hyperglycemia may contribute to the worsened prognosis following stroke, especially focusing on mitochondrial alterations. We examined the effect of hyperglycemia on hemorrhagic transformation at 24 hours after middle cerebral artery occlusion (MCAO) in streptozotocin (STZ) -induced diabetic mice. We also examined the effects of high-glucose exposure for 6 days on cell death, mitochondrial functions and morphology in human brain microvascular endothelial cells (HBMVECs) or human endothelial cells derived from induced pluripotent stem cells (iCell endothelial cells). Hyperglycemia aggravated hemorrhagic transformation, but not infarction following stroke. High-glucose exposure increased apoptosis, capase-3 activity, and release of apoptosis inducing factor (AIF) and cytochrome c in HBMVECs as well as affected mitochondrial functions (decreased cell proliferation, ATP contents, mitochondrial membrane potential, and increased matrix metalloproteinase (MMP)-9 activity, but not reactive oxygen species production). Furthermore, morphological aberration of mitochondria was observed in diabetic cells (a great deal of fragmentation, vacuolation, and cristae disruption). A similar phenomena were seen also in iCell endothelial cells. In conclusion, chronic hyperglycemia aggravated hemorrhagic transformation after stroke through mitochondrial dysfunction and morphological alteration, partially via MMP-9 activation, leading to caspase-dependent apoptosis of endothelial cells of diabetic mice. Mitochondria-targeting therapy may be a clinically innovative therapeutic strategy for diabetic complications in the future.</p></div

Effects of chronic high-glucose exposure on apoptotic cell death in HBMVECs.

<p>A: Experimental protocol <i>in vitro</i>. B: Nuclear staining for Hoechst 33342. The number of cells exhibiting nuclear stain was counted (n = 10). The scale bar indicates 50 µm. C: Number of TUNEL-positive cells (n = 4). The scale bar indicates 100 µm. D: Caspase-3/7 activities (n = 10). E: Immunoblotting for Active Caspase-3. F: Immunoblotting for Caspase-7. G: Release of apoptosis inducing factor (AIF) and cytochrome <i>c</i> (Cyto <i>c</i>) into cytosol, and transit into the nucleus (n = 3). All data are expressed as mean ± SEM (shown as ratio to 5.5 mM). *P<0.05, **P<0.01 vs. 5.5 mM (Dunnet's test). HBMVECs, human brain microvascular endothelial cells.</p

Effects of cilostazol on the tPA-stimulated human brain microvascular endothelial cells, pericytes, and astrocytes.

<p>Cell damage after 300-µg/ml tPA treatment was assessed by measuring LDH release into the culture medium in endothelial cells (A), pericytes (B), and astrocytes (C). The LDH level was increased by 300-µg/ml tPA treatment, and the increase was reduced by cilostazol at 30 and 100 µM in endothelial cells, and by cilostazol at 100 µM in pericytes. In addition, db-cAMP at 300 and 1000 µM significantly prevented cell damage induced by tPA in endothelial cells. ^##P<0.05 vs. no treatment, *P<0.05, **p<0.01 vs. 300-µg/ml tPA alone (Dunnett's test, n = 4–8). Data are expressed as means ± SEM.</p

Diagram illustrating the postulated mechanism through which hyperglycemia aggravates hemorrhagic transformation after ischemic stroke.

<p>Hyperglycemia increases the activity of MMP-9 in an ROS-independent manner, which promotes the opening of mitochondrial permeability transition pores (mitochondrial depolarization; Δ<b>ψ</b>_m ↓↓). The mitochondria that have lost normal function can no longer produce ATP, and emit various pro-apoptotic factors, such as AIF and cytochrome c into the cytosol. These factors subsequently activate caspase-3 and induce apoptotic cell death in HBMVECs. On the other hand, functional failure leads to morphological alteration of mitochondria, (fragmentation, vacuolation, cristae disruption). Eventually, both of these functional and morphological disturbances result in the aggravation of hemorrhagic transformation after ischemic stroke.</p