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The combination of alteplase, a recombinant tissue plasminogen activator, and edaravone, an antioxidant, reportedly enhances recanalization after acute ischemic stroke. We examined the influence of edaravone on the thrombolytic efficacy of alteplase by measuring thrombolysis using a newly developed microchip-based flow-chamber assay. Rat models of embolic cerebral ischemia were treated with either alteplase or alteplase-edaravone combination therapy. The combination therapy significantly reduced the infarct volume and improved neurological deficits. Human blood samples from healthy volunteers were exposed to edaravone, alteplase, or a combination of alteplase and edaravone or hydrogen peroxide. Whole blood was perfused over a collagen- and thromboplastin-coated microchip; capillary occlusion was monitored with a video microscope and flow-pressure sensor. The area under the curve (extent of thrombogenesis or thrombolysis) at 30 minutes was 69.9% lower in the edaravone-alteplase- than alteplase-treated group. The thrombolytic effect of alteplase was significantly attenuated in the presence of hydrogen peroxide, suggesting that oxidative stress might hinder thrombolysis. D-dimers were measured to evaluate these effects in human platelet-poor plasma samples. Although hydrogen peroxide significantly decreased the elevation of D-dimers by alteplase, edaravone significantly inhibited the decrease. Edaravone enhances alteplase-mediated thrombolysis, likely by preventing oxidative stress, which inhibits fibrinolysis by alteplase in thrombi.

Objective: To compare the frequency of p16- and Ki-67-positive cells on immunohistostaining among women with progression, persistence, or regression of cervical intraepithelial neoplasia grade 2 (CIN2)., Methods: A retrospective study was conducted of women with CIN2 diagnosed by histology who were treated at a university hospital in Japan during 2004-2011. The immunostaining patterns for p16 and Ki-67 were analyzed and compared between patients with disease progression, persistence, or regression. Kaplan-Meier analysis was used to evaluate the progression rates stratified by immunostaining, and multivariate analysis of risk factors for progression was performed using the Cox proportional hazards model., Results: The analysis included 59 women with progression, 35 women with persistence, and 28 women with regression. Deep p16 expression (staining in more than half of the cervical intraepithelial compartment) and positive Ki-67 staining in more than 50% of cells were significantly more common among women with progression than among those with regression. The risk factors for progression of CIN2 were deep p16 expression (P<0.001) and a Ki-67 ratio of more than 50% (P<0.001)., Conclusion: Among women with CIN2, positive immunohistostaining for p16 and Ki-67 was strongly associated with disease progression., (Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Zebrafish have the ability for heart regeneration. However, another teleost animal model, the medaka, had not yet been investigated for this capacity., Results: Compared with zebrafish, the medaka heart responded differently to an injury: An excessive fibrotic response occurred in the medaka heart, and existing cardiomyocytes or cardiac progenitor cells remained dormant, resulting in no numerical difference between the uncut and injured heart with respect to the number of EdU-incorporated cardiomyocytes. The results obtained from the analysis of the medaka raldh2-GFP transgenic line showed a lack of raldh2 expression in the endocardium. Regarding periostin expression, the localization of medaka periostin-b, a marker of fibrillogenesis, in the medaka heart remained at the wound site at 30 dpa; whereas zebrafish periostin-b was no longer localized at the wound but was detected in the epicardium at that time., Conclusions: Compared with zebrafish heart regeneration, the medaka heart phenotypes suggest the possibility that the medaka could hardly regenerate its heart tissue or that these phenotypes for heart regeneration showed a delay., (Copyright © 2014 Wiley Periodicals, Inc.)

Cherry blossom flowers are familiar to the Japanese, and some species of the flowers soaked in salty vinegar are used as processed foods. The constituents of aqueous ethanol extract from cherry blossom (Prunus lannesiana) flowers (CBE) were examined and cinnamoyl and flavonol glucosides were isolated. To elucidate the pharmacological functions of CBE and its constituents, their effects on the production of advanced glycation end products (AGEs) and on AGE-induced fibroblast damage were examined. CBE and 1-O-(E)-caffeoyl-β-D-glucopyranoside (CaG), a principal compound in CBE, significantly suppressed the production of AGEs derived from glucose and albumin at 100 μg/mL. Among the flavonol glucosides, quercetin 3-O-β-D-glucopyranoside (QG) exhibited potent suppressive activity (IC50 : 30 μg/mL). CBE and CaG suppressed glyoxal-induced AGE production in fibroblasts at 10 μg/mL, but QG did not. In addition, CBE and CaG recovered collagen lattice formation consisting of collagen and glycated fibroblasts at 10 μg/mL. Moreover, CBE and its constituents, except kaempferol 3-O-(6″-malony)-β-D-glucopyranoside, significantly suppressed fibroblast apoptosis induced by carboxymethyl lysine-collagen at 10 μg/mL. These results show that cinnamoyl and flavonol glucosides of cherry blossom flowers suppress AGE production and AGE-induced fibroblast apoptosis. Cherry blossom flowers may be effective against skin AGE production and fibroblast damage by AGEs., (Copyright © 2011 John Wiley & Sons, Ltd.)