三羟异黄酮对HER-2/neu高表达乳腺癌细胞血管生成相关因子表达的影响

三羟异黄酮(genistein)是大豆中的一种非营养成分,其结构与黄酮化合物类似,能竞争性地与雌激素受体结合,故称之为植物雌激素(phytoestrogen)。它具有广泛的生物学作用,如抗肿瘤、抗病毒、抗真菌、抗氧化、抗突变、抗高血压、抗增生等,其中genistein抑制肿瘤的血管生成是当前研究的热点之一。肿瘤的血管生成是肿瘤进一步生长转移的基础,该过程受肿瘤细胞和血管内皮细胞分泌的血管生成相关因     

Pulmonary artery pressure and cardiac function in children and adolescents after rapid ascent to 3,450 m

High-altitude destinations are visited by increasing numbers of children and adolescents. High-altitude hypoxia triggers pulmonary hypertension that in turn may have adverse effects on cardiac function and may induce life-threatening high-altitude pulmonary edema (HAPE), but there are limited data in this young population. We, therefore, assessed in 118 nonacclimatized healthy children and adolescents (mean ± SD; age: 11 ± 2 yr) the effects of rapid ascent to high altitude on pulmonary artery pressure and right and left ventricular function by echocardiography. Pulmonary artery pressure was estimated by measuring the systolic right ventricular to right atrial pressure gradient. The echocardiography was performed at low altitude and 40 h after rapid ascent to 3,450 m. Pulmonary artery pressure was more than twofold higher at high than at low altitude (35 ± 11 vs. 16 ± 3 mmHg; P < 0.0001), and there existed a wide variability of pulmonary artery pressure at high altitude with an estimated upper 95% limit of 52 mmHg. Moreover, pulmonary artery pressure and its altitude-induced increase were inversely related to age, resulting in an almost twofold larger increase in the 6- to 9- than in the 14- to 16-yr-old participants (24 ± 12 vs. 13 ± 8 mmHg; P = 0.004). Even in children with the most severe altitude-induced pulmonary hypertension, right ventricular systolic function did not decrease, but increased, and none of the children developed HAPE. HAPE appears to be a rare event in this young population after rapid ascent to this altitude at which major tourist destinations are located.     

Tumor necrosis factor-α impairs oligodendroglial differentiation through a mitochondria-dependent process

Mitochondrial defects, affecting parameters such as mitochondrial number and shape, levels of respiratory chain complex components and markers of oxidative stress, have been associated with the appearance and progression of multiple sclerosis. Nevertheless, mitochondrial physiology has never been monitored during oligodendrocyte progenitor cell (OPC) differentiation, especially in OPCs challenged with proinflammatory cytokines. Here, we show that tumor necrosis factor alpha (TNF-α) inhibits OPC differentiation, accompanied by altered mitochondrial calcium uptake, mitochondrial membrane potential, and respiratory complex I activity as well as increased reactive oxygen species production. Treatment with a mitochondrial uncoupler (FCCP) to mimic mitochondrial impairment also causes cells to accumulate at the progenitor stage. Interestingly, AMP-activated protein kinase (AMPK) levels increase during TNF-α exposure and inhibit OPC differentiation. Overall, our data indicate that TNF-α induces metabolic changes, driven by mitochondrial impairment and AMPK activation, leading to the inhibition of OPC differentiation.Multiple sclerosis (MS) is a neurological disorder of the central nervous system that is characterized by demyelination and neurodegeneration. Although the pathogenesis of MS is not completely understood, various findings suggest that immune-mediated loss of myelin and different types of mitochondrial dysfunction are associated with this disease.¹ Mitochondria are often described as cellular powerhouses that utilize oxygen to produce adenosine triphosphate (ATP), a molecule that is critical for most cellular functions.² In addition, mitochondria are the major sites of the intracellular production of highly reactive free radicals that, if not neutralized, alter cellular metabolism and damage cellular components.³In several studies, mitochondrial dysfunction has been reported to be frequently associated with demyelination, whereas proper function is required for correct oligodendrocyte differentiation and myelination.^{4, 5} Furthermore, there is in vitro evidence that cytokine-induced oligodendrocyte injury involves mitochondrial dysfunction.⁶ One cytokine that is of particular interest in MS is tumor necrosis factor alpha (TNF-α). Evidence implicating TNF-α in the underlying pathology of MS includes: (i) reports that MS patients have elevated TNF-α levels at the sites of active MS lesions at autopsy,⁷ (ii) reports that TNF-α levels are elevated in the cerebrospinal fluid and serum of individuals with MS compared with unaffected individuals and that these TNF-α levels correlate with the severity of the lesions.^{8, 9}Moreover, it has been widely reported that TNF-α is able to impair oligodendrocyte differentiation and that in leukemia cell lines, TNF-α-induced cell death requires impairments in the activity of mitochondrial respiratory chain complex I. Complex I is strategically important for regulating ATP synthesis and is one of the most important sources of reactive oxygen species (ROS) within cells.¹⁰ Despite this evidence, the relationships between mitochondrial physiology, TNF-α, and oligodendrocyte differentiation have not yet been examined. This study addressed the hypothesis that the impairment of oligodendrocyte differentiation caused by TNF-α exposure is causally linked to altered mitochondrial physiology.     

Nicotinic Autoreceptors Mediating Enhancement of Acetylcholine Release Become Operative in Conditions of "Impaired" Cholinergic Presynaptic Function

Abstract: The existence in the mammalian CNS of release-inhibiting muscarinic autoreceptors is well established. In contrast, few reports have focused on nicotinic autoreceptors mediating enhancement of acetylcholine (ACh) release. Moreover, it is unclear under what conditions the function of one type of autoreceptor prevails over that of the other. Rat cerebrocortex slices, prelabeled with [³H]choline, were stimulated electrically at 3 or 0.1 Hz. The release of [³H]ACh evoked at both frequencies was inhibited by oxotremorine, a muscarinic receptor agonist, and stimulated by atropine, a muscarinic antagonist. Nicotine, ineffective at 3 Hz, enhanced [³H]ACh release at 0.1 Hz; mecamylamine, a nicotinic antagonist, had no effect at 3 Hz but inhibited [³H]ACh release at 0.1 Hz. The cholinesterase inhibitor neostigmine decreased [³H]ACh release at 3 Hz but not at 0.1 Hz; in the presence of atropine, neostigmine potentiated [³H]ACh release, an effect blocked by mecamylamine. In synaptosomes depolarized with 15 mM KCI, ACh inhibited [³H]ACh release; this inhibition was reversed to an enhancement when the external [Ca²⁺] was lowered. The same occurred when, at 1.2 mM Ca²⁺, external [K⁺] was decreased. Oxotremorine still inhibited [³H]ACh release at 0.1 mM Ca²⁺. When muscarinic receptors were inactivated with atropine, the K⁺ (15 mM)-evoked release of [³H]ACh (at 0.1 mM Ca²⁺) was potently enhanced by ACh acting at nicotinic receptors (EC₅₀? 0.6 µM). In conclusion, synaptic ACh concentration does not seem to determine whether muscarinic or nicotinic autoreceptors are activated. Although muscarinic autoreceptors prevail under normal conditions, nicotinic autoreceptors appear to become responsive to endogenous ACh and to exogenous nicotinic agents under conditions mimicking impairment of ACh release. Our data may explain in part the reported efficacy of cholinesterase inhibitors (and nicotinic agonists) in Alzheimer's disease.     

药用真菌子实体多糖SEC-HPLC图谱的相似度定量评价研究

目的:对灵芝属Ganoderma下4个种共7个菌株及灰树花Grifola frondosa和云芝Trametes versicolor共9种子实体粗多糖进行了体积排阻HPLC色谱(SEC-HPLC),并分析了相似度.方法:各样品水提物的HPLC图谱用平方欧氏距离法计算了相似度,用离差平方和法进行聚类分析.结果:灵芝属内各样品聚类距离为8,灰树花与云芝的聚类距离为16,它们与灵芝属的距离为25,说明同一灵芝属内的不同种及同种不同菌株所产生的多糖分子量分布近似度远高于来自树花菌属的灰树花或栓菌属的云芝.结论:此方法可量化描述不同多糖间SEC-HPLC的相似关系,有作为真菌多糖样品质量控制手段的潜在能力.