Therapeutic Approaches to Vascular Protection in Ischemic Stroke

Reperfusion with recombinant tissue plasminogen activator (tPA) sometimes causes catastrophic hemorrhagic transformation (HT) in the ischemic brain. Consequently, the application of tPA has been strictly limited. Recent studies have indicated that matrix metalloproteinases (MMPs), especially MMP-9, play a critical role in blood brain barrier (BBB) disruption in the ischemic brain, leading to brain edema and HT. In the ischemic brain, free radicals and exogenous tPA itself can trigger MMP-9 activation through several signaling pathways containing LDL receptor-related protein (LRP) and proteinase-activated receptor 1 (PAR1). Therapeutic targeting of free radicals and MMP-9/t-PA related signaling pathways might be promising approaches to minimizing catastrophic HT in acute stroke patients. We provide an overview of the available scientific reports to improve our understanding of the mechanisms leading to HT, and highlight recent progress in the development of new therapeutic strategies for preventing HT in the post-stroke brain

Effect of edaravone on pregnant mice and their developing fetuses subjected to placental ischemia

Growing evidence indicates that reduced uterine perfusion pressure (RUPP) triggers the cascade of events leading to preeclampsia. Edaravone is a powerful free radical scavenger used for the treatment of ischemia/reperfusion diseases due to its anti-oxidative stress and anti-inflammatory properties. Here we investigate the effect of edaravone (3 mg/kg) on different maternal and fetal outcomes of RUPP-induced placental ischemia mice model. RUPP surgery was performed on gestation day (GD) 13 followed by edaravone injection from GD14 to GD18, sacrifice day. The results showed that edaravone injection significantly decreased the maternal blood pressure (113.2 +/- 2.3 mmHg) compared with RUPP group (131.5 +/- 1.9 mmHg). Edaravone increased fetal survival rate (75.4%) compared with RUPP group (54.4%), increased fetal length, weights, and feto-placental ratio (7.2 and 5.7 for RUPP and RUPP-Edaravone groups, respectively) compared with RUPP group. In addition, RUPP resulted in many fetal morphological abnormalities as well as severe delayed ossification, however edaravone decreased the morphological abnormalities and increased the ossification of the fetal endoskeleton. Edaravone improved the histopathological structure of the maternal kidney and heart as well as decreased the elevated blood urea and creatinine levels (31.5 +/- 0.15 mg/dl (RUPP), 25.6 +/- 0.1 mg/dl (RUPP+edaravone) for urea and 5.4 +/- 0.1 mg/dl (RUPP), 3.5 +/- 0.1 mg/dl (RUPP+edaravone) for creatinine) and decreased cleaved caspase-3 expression in the maternal kidney. In conclusion, this study demonstrated that our RUPP mice model recapitulated preeclampsia symptoms and edaravone injection ameliorated most of these abnormalities suggesting its effectiveness and potential application in preeclampsia treatment regimes

Peptide ligand screening of α-synuclein aggregation modulators by in silico panning

<p>Abstract</p> <p>Background</p> <p>α-Synuclein is a Parkinson's-disease-related protein. It forms aggregates <it>in vivo</it>, and these aggregates cause cell cytotoxicity. Aggregation inhibitors are expected to reduce α-synuclein cytotoxicity, and an aggregation accelerator has recently been reported to reduce α-synuclein cytotoxicity. Therefore, amyloid aggregation modulating ligands are expected to serve as therapeutic medicines.</p> <p>Results</p> <p>We screened peptide ligands against α-synuclein by <it>in silico </it>panning, a method which we have proposed previously. In this study, we selected as the target a very hydrophobic region known as the amyloid-core-forming region. Since this region cannot be dissolved in water, it is difficult to carry out the <it>in vitro </it>screening of its peptide ligand. We carried out 6 rounds of <it>in silico </it>panning using a genetic algorithm and a docking simulation. After the <it>in silico </it>panning, we evaluated the top peptides screened <it>in silico </it>by <it>in vitro </it>assay. These peptides were capable of binding to α-synuclein.</p> <p>Conclusion</p> <p>We demonstrated that it is possible to screen α-synuclein-binding peptides by <it>in silico </it>panning. The screened peptides bind to α-synuclein, thus affecting the aggregation of α-synuclein.</p

GOGOT: a method for the identification of differentially expressed fragments from cDNA-AFLP data

<p>Abstract</p> <p>Background</p> <p>One-dimensional (1-D) electrophoretic data obtained using the cDNA-AFLP method have attracted great interest for the identification of differentially expressed transcript-derived fragments (TDFs). However, high-throughput analysis of the cDNA-AFLP data is currently limited by the need for labor-intensive visual evaluation of multiple electropherograms. We would like to have high-throughput ways of identifying such TDFs.</p> <p>Results</p> <p>We describe a method, GOGOT, which automatically detects the differentially expressed TDFs in a set of time-course electropherograms. Analysis by GOGOT is conducted as follows: correction of fragment lengths of TDFs, alignment of identical TDFs across different electropherograms, normalization of peak heights, and identification of differentially expressed TDFs using a special statistic. The output of the analysis is a highly reduced list of differentially expressed TDFs. Visual evaluation confirmed that the peak alignment was performed perfectly for the TDFs by virtue of the correction of peak fragment lengths before alignment in step 1. The validity of the automated ranking of TDFs by the special statistic was confirmed by the visual evaluation of a third party.</p> <p>Conclusion</p> <p>GOGOT is useful for the automated detection of differentially expressed TDFs from cDNA-AFLP temporal electrophoretic data. The current algorithm may be applied to other electrophoretic data and temporal microarray data.</p

Preparation of Polyrotaxane Fibers. Part II: Tensile Properties of Polyrotaxane Fibers Treated with Two Cross-linking Reagents

Polyrotaxane fibers prepared with wet spinning of polyrotaxane consisting of poly(ethylene glycol) and cyclodextrins were cross-linked with two different cross-linking reagents, i.e., divinyl sulfone (DVS) and ethylene glycol diglycidyl ether (EGDE), to improve the tensile properties of the fibers. By cross-linking with DVS, the values for the tenacity at break and the initial modulus were increased with cross-linking time, while the elongation at break was improved only moderately. On the other hand, drastic improvements in elongation at break were observed after EGDE cross-linking, up to 645% of its original length, although the tenacity at break and the initial modulus showed only slight improvements. After cross-linking, only minor changes in the degree of crystallinity of the fibers were observed by wide-angle X-ray scattering measurements.ArticleTEXTILE RESEARCH JOURNAL. 80(12):1131-1137 (2010)journal articl