Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid

The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl) plays a role in tissue injury under inflammatory conditions. The present study tests the hypothesis that HOCl decreases nitric oxide (NO) bioavailability in the vasculature of Sprague-Dawley rats. Aortic ring segments were pretreated with HOCl (1-50 microM) followed by extensive washing. Endothelium-dependent relaxation was then assessed by cumulative addition of acetylcholine (ACh) or the calcium ionophore A23187. HOCl treatment significantly impaired both ACh- and A23187-mediated relaxation. In contrast, endothelium-independent relaxation induced by sodium nitroprusside was unaffected. The inhibitory effect of HOCl on ACh-induced relaxation was reversed by exposure of ring segments to L-arginine but not D-arginine. In cellular studies, HOCl did not alter endothelial NO synthase (NOS III) protein or activity, but inhibited formation of the NO metabolites nitrate (NO3(-) and nitrite (NO2(-). The reduction in total NO metabolite production in bovine aortic endothelial cells was also reversed by addition of L-arginine. These data suggest that HOCl induces endothelial dysfunction via modification of L-arginine.     

稻属三种植物叶片下表皮的形态比较

稻属有20多种,其中3种和其他物种明显不同.Oryza eichingeri被认为在亚洲和非洲间断分布;O. officinalis和O punctata被证明同时含有二倍体和四倍体.为了识别种内微形态差异,利用光镜和扫描电镜,对这3个物种的成熟叶片下表皮进行了观察.结果表明,O. eichingeri的叶脉长细胞乳突形状在种内是不一致的,除了斯里兰卡地理宗具有的瘤状乳突外,乌千达地理宗还具有长条状的乳突;同样,种内多样性也存在于O. officinalis和O.punctata内,特别存在于它们不同倍性的细胞型间.在D officinalis中,四倍体有粒状气孔器外围乳突和脉带表皮毛较少,二倍体细胞型具有三角形拱状排列的气孔器外围乳突和较密集的脉带表皮毛;而在O. punctata中,和四倍体相比,二倍体具有小的长细胞表面乳突和低密度分布的气孔.这些稳定的差异为3种植物的种内鉴定和分类修订提供了新的证据.     

Tryptase activates PKB in inflammatory reaction in ECV304 cells

Tryptase is involved in proteinase-activated receptor-2 (PAR-2) mediated up-regulation of IL-8 expression. The present report showed the effects of tryptase on gene expression and activation, including up-regulation IL-8 expression. The expression of mRNA for NF-kappaB first increased at 1 h after tryptase-treatment (1 ng/ml) and reached the plateau after 4 h. The NF-kappaB mRNA increased by 3-fold (n = 3, P < 0.05), AP-1 by 2-fold (n = 3, P < 0.05), and PKB by 10-fold (n = 3, P < 0.05). However, tryptase-treatment did not affect the expression of JNK and p38 MAPK when compared with control cells at mRNA level. Furthermore, in addition to increasing phosphorylation of p38 MAPK, tryptase-treatment also increased phosphorylation of PKB by 2-fold at 15 min following the treatment. The up-regulation and phosphorylation of PKB by tryptase could be abolished by either phosphoinositol-3-kinase (PI3K) inhibitor (LY294002) at 10 microM or antisense PKB cDNA transfection. The up-regulation of NF-kappaB expression could be inhibited by LY294002 and antisense PKB cDNA. These results indicate that tryptase can activate PI3K-PKB pathway and enhance IL-8 expression.     

Treatment of hypoxic-ischemic encephalopathy in mouse by transplantation of embryonic stem cell-derived cells

A 7-day-old hypoxic-ischemic encephalopathy (HIE) mouse model was used to study the effect of transplantation of embryonic stem (ES) cell-derived cells on the HIE. After the inducement in vitro, the ES cell-derived cells expressed Nestin and MAP-2, rather than GFAP mRNA. After transplantation, ES cell-derived cells can survive, migrate into the injury site, and specifically differentiate into neurons, showing improvement of the learning ability and memory of the HIE mouse at 8 months post-transplantation. The non-grafted HIE mouse brain showed typical pathological changes in the hippocampus and cerebral cortex, where the number of neurons was reduced, while in the cell graft group, number of the neurons increased in the same regions. Although further study is necessary to elucidate the precise mechanisms responsible for this functional recovery, we believe that ES cells have advantages for use as a donor source in HIE.     

Allelopathy of diterpenoids on three species of soil ciliates

Allelopathy of diterpenoids extracted from plants of the genus Robdosia on three common species of soil ciliates, Colpoda inflata, Colpoda cucullus and Euplotes muscicola, was studied by acute toxicity test, sub-lethal effect test and morphological observation. Acute toxicity test showed that there was remarkable toxicity of the diterpenoids on the individuals of the three soil ciliate species, and there was close correlation between toxicity and concentration of the diterpenoids. 12 h-LC₅₀ values of the diterpenoids on the individuals of C. inflata, C. cucullus and E. muscicola were 161.40 mg L^?1, 94.80 mg L^?1 and 83.70 mg L^?1 respectively, and 24 h-LC₅₀ values were 114.90 mg L^?1, 92.30 mg L^?1and 65.80 mg L^?1 separately. Sub-lethal effect test of soil ciliates suggested that there existed significant inhibition of the diterpenoids on population growth of the three ciliates with dose-dependant relationships, population density and growth rate of the test group was obviously lower than that of the control group. Morphological observation indicated that diterpenoids affected the body shapes of the three ciliates and made them shorter and thicker, and the higher the concentration of diterpenoids, the greater the affection. The results are of great significance for understanding the functions of ciliates and their relationships to other organisms, and for the application of allelopathy in biological pest control in the soil ecosystems.     

孕鼠被动吸烟对子鼠学习记忆能力和海马LTP的影响

目的:探讨小鼠孕期被动吸烟对其子代小鼠学习记忆能力和神经机制长时程增强(LTP)效应的影响,及采用不同抗氧化剂的干预效应。方法:孕鼠给予被动吸烟染毒,并采用槲皮素和维生素E(VE)进行干预,待产子后研究子鼠水迷宫和LTP的变化。结果:被动吸烟使子鼠空间学习记忆能力下降。槲皮素组LTP与对照组相比增强显著(P<0.05);吸烟组LTP增强受到抑制(P<0.05);VE及与槲皮素协同干预组子鼠LTP较吸烟组增强显著(P<0.05)。结论:胚胎期被动吸烟使小鼠学习记忆功能下降,通过抗氧化剂干预可能得到改善。     

复方中药对大鼠力竭运动与恢复过程中端脑神经递质含量的影响

目的：探讨复方中药对运动大鼠中枢神经递质含量的影响,进一步认识中药提高运动能力和促进运动性疲劳恢复的作用机理。方法：选8周龄大鼠64只,随机分成服药组和对照组,服药组灌服中药煎剂8周。然后,每组再分成4个亚组分别于不同状态下断头处死,测其中枢递质含量。结果：服药组大鼠力竭运动时间极显著长于对照组（P〈0．01）;安静时,除谷氨酸（GLU）含量服药组极显著高于对照组（P〈0．01）外、其余各指标无组间显著性差异;定量负荷后,服药组5-羟色胺（5-HT）、5-羟吲哚乙酸（5-HIAA）、弘氨基丁酸（GABA）、多巴胺（DA）含量和5-HT／5-HIAA显著低于对照组,GLU、GLU／GABA和DA／5-HT明显高于对照组;力竭即刻,服药组5-HT、GABA含量和5-HT／5-mAA显著低于对照组（P〈0．05）,GLU含量、DA／5-HT和GLU／GABA显著高于对照组（P〈0．05）;恢复12h。服药组5-HT含量和5-HT／5-HIAA极显著低于对照组（P〈0．01）,GLU、DA、GABA含量和DA／5-HT明显高于对照组（P〈0．05）。结论：在大鼠运动至力竭性的过程中,复方中药制剂有明显抑制5-HT、5-HIAA、DA、GABA生成和促进GLU中枢递质合成的作用,其综合效应表现为兴奋性递质相对显著增多,使中枢神经兴奋性增强、明显延长大鼠运动时间和促进中枢疲劳的恢复。     

Dracorhodin perchlorate inhibits osteoclastogenesis through repressing RANKL-stimulated NFATc1 activity

Osteolytic skeletal disorders are caused by an imbalance in the osteoclast and osteoblast function. Suppressing the differentiation and resorptive function of osteoclast is a key strategy for treating osteolytic diseases. Dracorhodin perchlorate (D.P), an active component from dragon blood resin, has been used for facilitating wound healing and anti-cancer treatments. In this study, we determined the effect of D.P on osteoclast differentiation and function. We have found that D.P inhibited RANKL-induced osteoclast formation and resorbed pits of hydroxyapatite-coated plate in a dose-dependent manner. D.P also disrupted the formation of intact actin-rich podosome structures in mature osteoclasts and inhibited osteoclast-specific gene and protein expressions. Further, D.P was able to suppress RANKL-activated JNK, NF-κB and Ca²⁺ signalling pathways and reduces the expression level of NFATc1 as well as the nucleus translocation of NFATc1. Overall, these results indicated a potential therapeutic effect of D.P on osteoclast-related conditions.     

Coffee polyphenol caffeic acid but not chlorogenic acid increases 5'AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle

Chlorogenic acid is an ester of caffeic and quinic acids, and is one of the most widely consumed polyphenols because it is abundant in foods, especially coffee. We explored whether chlorogenic acid and its metabolite, caffeic acid, act directly on skeletal muscle to stimulate 5'-adenosine monophosphate-activated protein kinase (AMPK). Incubation of rat epitrochlearis muscles with Krebs buffer containing caffeic acid (≥0.1 mM, ≥30 min) but not chlorogenic acid increased the phosphorylation of AMPKα Thr(172), an essential step for kinase activation, and acetyl CoA carboxylase Ser(79), a downstream target of AMPK, in a dose- and time-dependent manner. Analysis of isoform-specific AMPK activity revealed that AMPKα2 activity increased significantly, whereas AMPKα1 activity did not change. This enzyme activation was associated with a reduction in phosphocreatine content and an increased rate of 3-O-methyl-d-glucose transport activity in the absence of insulin. These results suggest that caffeic acid but not chlorogenic acid acutely stimulates skeletal muscle AMPK activity and insulin-independent glucose transport with a reduction of the intracellular energy status.