Macrophage centripetal migration drives spontaneous healing process after spinal cord injury.

Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury

Bee products prevent VEGF-induced angiogenesis in human umbilical vein endothelial cells

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial growth factor (VEGF) is a key regulator of pathogenic angiogenesis in diseases such as cancer and diabetic retinopathy. Bee products [royal jelly (RJ), bee pollen, and Chinese red propolis] from the honeybee, <it>Apis mellifera</it>, have been used as traditional health foods for centuries. The aim of this study was to investigate the anti-angiogenic effects of bee products using human umbilical vein endothelial cells (HUVECs).</p> <p>Methods</p> <p>In an <it>in vitro </it>tube formation assay, HUVECs and fibroblast cells were incubated for 14 days with VEGF and various concentrations of bee products [RJ, ethanol extract of bee pollen, ethanol extract of Chinese red propolis and its constituent, caffeic acid phenethyl ester (CAPE)]. To clarify the mechanism of <it>in vitro </it>angiogenesis, HUVEC proliferation and migration were induced by VEGF with or without various concentrations of RJ, bee pollen, Chinese red propolis, and CAPE.</p> <p>Results</p> <p>RJ, bee pollen, Chinese red propolis, and CAPE significantly suppressed VEGF-induced <it>in vitro </it>tube formation in the descending order: CAPE > Chinese red propolis >> bee pollen > RJ. RJ and Chinese red propolis suppressed both VEGF-induced HUVEC proliferation and migration. In contrast, bee pollen and CAPE suppressed only the proliferation.</p> <p>Conclusion</p> <p>Among the bee products, Chinese red propolis and CAPE in particular showed strong suppressive effects against VEGF-induced angiogenesis. These findings indicate that Chinese red propolis and CAPE may have potential as preventive and therapeutic agents against angiogenesis-related human diseases.</p

An Inducer of VGF Protects Cells against ER Stress-Induced Cell Death and Prolongs Survival in the Mutant SOD1 Animal Models of Familial ALS

Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease, and recent evidence has suggested that endoplasmic reticulum (ER) stress signaling is involved in the pathogenesis of ALS. Here we identified a small molecule, SUN N8075, which has a marked protective effect on ER stress-induced cell death, in an in vitro cell-based screening, and its protective mechanism was mediated by an induction of VGF nerve growth factor inducible (VGF): VGF knockdown with siRNA completely abolished the protective effect of SUN N8075 against ER-induced cell death, and overexpression of VGF inhibited ER-stress-induced cell death. VGF level was lower in the spinal cords of sporadic ALS patients than in the control patients. Furthermore, SUN N8075 slowed disease progression and prolonged survival in mutant SOD1 transgenic mouse and rat models of ALS, preventing the decrease of VGF expression in the spinal cords of ALS mice. These data suggest that VGF plays a critical role in motor neuron survival and may be a potential new therapeutic target for ALS, and SUN N8075 may become a potential therapeutic candidate for treatment of ALS

ポリ塩化ビニルをマトリックスとした液膜型過塩素酸イオン選択性電極を用いる過塩素酸イオンのゼフィラミンによる沈殿電位差滴定

トリス(バソフェナントロリン)鉄(II)と過塩素酸イオンのイオン対を感応物質とするポリ塩化ビニル固化膜型過塩素酸イオン選択性電極を試作し,その電極特性を検討するとともに,同電極を指示電極に用い第四級アンモニウム塩のゼフィラミンを滴定剤として沈殿電位差滴定を行った. 作製した電極は10^〜10^Mの過塩素酸イオンにほぼNernst応答し,目的イオン濃度10^M溶液の電位はpH1〜13の範囲で一定であった.滴定においては,24.87〜74.60mgの過塩素酸イオンを0.6%以下の相対誤差と0.2%以下の相対標準偏差で簡便かつ迅速に定量が可能であった.実試料で過塩素酸イオンと共存することの多い硝酸イオンは正の誤差を与えるとともに,終点付近での電位飛躍を抑え,終点の判読を困難にしたが,酢酸酸性で粉末亜鉛を加え加熱し,硝酸イオンを選択的に還元することにより,その妨害を除去することが可能であった.本法を用いて実試料を分析した結果は,JIS法による分析結果と良い一致を示した.The construction of a perchlorate ion-selective electrode and its application to potentiometric titration of perchlorate ion in the explosives with Zephiramine was described. The PVC matrix membrane containing 7.7 (w/w)% of tris-(bathophenanthroline)iron (II) perchlorate ion-associate was used as an ion-sensing membrane. The disk membrane was affixed to a PVC tube (I.D. 7 mm) and silver-silver chloride electrode was used as the internal reference electrode. The composition of the cell including the present ion-selective electrode is as follows. Ag-AgCl electrode/reference solution, 50 mM NaClO4 in 50 mM NaCl/PVC ion-exchange membrane//sample solution/SCE The present ion-selective electrode exhibited a Nernstian response to perchlorate ion in the concentration range from 10^ to 10^ M. The potential of the electrode was constant over the pH range from 1 to 13. Selectivity coefficients were evaluated and the electrode exhibited a good selectivity with respect to most common anions, while it showed some interferences with respect to periodate, iodide, and thiocyanate ion. The present ion-selective electrode was successfully adopted to the potentiometric precipitation titration of perchlorate ion with Zephiramine. It was revealed that the presence of equal or excess amounts of nitrate ion in the sample solution lowered the potential break at the end-point. However, the interference can be eliminated by the reduction of nitrate ion by heating with acetic acid and zinc powder