基于核磁共振氢谱的组学技术在中药制药过程研究中的应用与展望

中药制药过程工艺复杂,过程控制水平与产品质量直接相关。进行制药过程质量评价与质量控制研究,提高制药过程理解,对保证中药制剂的安全性与有效性具有重要的意义。随着核磁共振技术的发展,核磁共振氢谱已在中药质量评价与代谢组学研究等领域得到广泛应用。本文主要介绍了氢核磁共振组学技术应用于中药炮制、提取等制药过程研究时,在辨识过程化学标志物、研究代谢物在过程中的转化转移规律等方面的应用进展,同时展望了基于氢核磁共振技术的过程组学研究在中药制药领域的应用前景。     

冠心宁片中水溶性组分的抗血栓活性研究

目的:使用转基因斑马鱼模型筛选冠心宁片中具有抗血栓活性的组分及药效物质,并探讨其作用机制。方法:将斑马鱼胚胎分为对照组、造模组、给药组及阳性药组,使用苯肼诱导血栓模型。通过荧光显微成像结合血红蛋白染色对冠心宁片各组分抗血栓作用进行定性和定量分析。进一步探寻活性组分中起抗血栓作用的主要成分。最后进行活性氧（ROS）检测及脂质氧化损伤丙二醛(Malondialdehyde,MDA)分析,探讨其抗血栓机制。结果:实验结果显示冠心宁片水溶性组分可显著减少外周血红细胞聚集(P<0.01),增加回心血量,且效果呈剂量依赖性。因多糖为冠心宁片水溶性成分中的主要物质,进一步实验发现丹参多糖和川芎多糖也具有抗血栓活性,且能显著降低斑马鱼的氧化应激水平,丹参多糖还具有下调胚胎脂质过氧化水平的作用。结论:丹参多糖和川芎多糖为冠心宁片水溶性组分中具有抗血栓作用的活性化合物,可能与其抑制氧化应激作用有关,具有开发为抗血栓治疗先导物的潜在应用前景。     

基于网络药理学探讨小青龙汤治疗慢性阻塞性肺疾病的作用机制

目的：利用网络药理学分析小青龙汤治疗慢性阻塞性肺疾病（COPD）的作用机制。方法：在中药系统药理学数据库与分析平台（TCMSP）检索小青龙汤药物活性成分和靶点,绘制中药-化合物-靶基因网络,筛选关键化合物;利用GeneCards和人类孟德尔遗传数据库（OMIM）搜索COPD疾病基因;绘制韦恩图并获取药物-疾病共同基因;利用小青龙汤-慢阻肺药物疾病共同基因绘制蛋白质-蛋白质相互作用（PPI）网络,根据网络关系选择核心基因;对核心基因分别进行基因本体（GO）功能注释和富集分析和京都基因和基因组百科全书（KEGG）通路富集分析。结果：挖掘得到小青龙汤中药活性成分137个,潜在作用靶点188个,慢性阻塞性肺疾病相关靶点6 949个,小青龙汤-COPD共同靶点160个,主要富集于92个生物过程和49条信号通路上。结论：小青龙汤中多个药物含有山柰酚、槲皮素、（+）-儿茶素、豆甾醇、β-谷固醇等成分,可作用于AKT1、IL6、MAPK1、PTGS2、TP53等核心基因,调控氧化应激反应、血小板α-颗粒等生物过程,参与HIF-1、PI3K-AKT信号通路的调节,干预氧化应激反应和炎症反应等过程,产生抑制炎症反应、抗氧化应激的作用,进而通过上述过程参与COPD的炎症反应与氧化应激过程。     

小腿截肢患者残端应力的三维有限元动态分析

目的:研究接受腔/残肢界面应力分布特征,为假肢优化设计提供基础。方法:基于核磁共振图像,获得小腿截肢患者残端和假肢几何特征,建立三维非线性有限元模型,通过比较站立状态和行走过程中的界面应力,研究动态载荷对界面压力的影响。结果:界面压力主要分布在髌韧带、胫骨内外侧和窝区,一个平地正常速度行走的步态周期内,残肢界面的最大平均正压力是单腿站立状态下的1.15倍,最大平均切应力是单腿站立状态的1.4倍。结论:动态载荷使残肢和接受腔之间的界面应力增大,行走过程的动态影响不宜忽略。     

Globalization and the cultural safety of an immigrant Muslim community

AIM: This paper reports a study the aim of which was to further understanding of cultural safety by focusing on the social health of a small immigrant community of Muslims in a relatively homogeneous region of Canada following the terror attacks on 11 September 2001 (9/11). BACKGROUND: The aftermath of 9/11 negatively affected Muslims living in many centers of Western Europe and North America. Little is known about the social health of Muslims in smaller areas with little cultural diversity. Developed by Maori nurses, the cultural safety concept captures the negative health effects of inequities experienced by the indigenous people of New Zealand. Nurses in Canada have used the concept to understand the health of Aboriginal peoples. It has also been used to investigate the nursing care of immigrants in a Canadian metropolitan centre. Findings indicated, however, that the dichotomy between culturally safe and unsafe groups was blurred. METHOD: The methodology was qualitative, based on the constructivist paradigm. A purposive sample of 26 Muslims of Middle Eastern, Indian or Pakistani origin and residing in the province of New Brunswick, Canada were interviewed in 2002-2003. Findings. Participants experienced a sudden transition from cultural safety to cultural risk following 9/11. Their experience of cultural safety included a sense of social integration in the community and invisibility as a minority. Cultural risk stemmed from being in the spotlight of an international media and becoming a visible minority. CONCLUSION: Cultural risk is not necessarily rooted in historical events and may be generated by outside forces rather than by longstanding inequities in relationships between groups within the community. Nurses need to think about the cultural safety of their practices when caring for members of socially disadvantaged cultural minority groups as this may affect the health services delivered to them.     

Primary motor cortex long‐term plasticity in multiple system atrophy

In humans, intermittent and continuous theta‐burst stimulation (iTBS and cTBS) elicit long‐term changes in motor‐evoked potentials (MEPs) reflecting long‐term potentiation (LTP)‐ and depression (LTD)‐like plasticity in the primary motor cortex (M1). In this study, we used TBS to investigate M1 plasticity in patients with MSA. We also assessed whether responses to TBS reflect M1 excitability as tested by short‐interval intracortical inhibition (SICI), intracortical facilitation (ICF), short‐interval intracortical facilitation (SICF), and the input/output curves. We studied 20 patients with MSA and 20 healthy subjects (HS). Patients were clinically evaluated with the Unified Multiple System Atrophy Rating Scale. The left M1 was conditioned with TBS. Twenty MEPs were recorded from the right first dorsal interosseous muscle before TBS and 5, 15, and 30 minutes thereafter. In a subgroup of 10 patients, we also tested MEPs elicited by SICI, ICF, SICF, and input/output curves, before TBS. Between‐group analysis of variance showed that at all time points after iTBS MEPs increased, whereas after cTBS they decreased only in HS. In both subgroups tested, patients with predominant parkinsonian and cerebellar features, iTBS and cTBS left MEPs unchanged. MSA patients had reduced SICI, but normal ICF, SICF, and input/output curves. No correlation was found between patients' clinical features and responses to TBS and M1 excitability variables. These findings suggest impaired M1 plasticity in MSA. © 2013 International Parkinson and Movement Disorder Society     

Detoxification of oxidative stress in glioma stem cells: Mechanism,clinical relevance,and therapeutic development

Neural oncogenesis is currently incurable and invariably lethal. The development of innovative treatments for this devastating cancer will require a deeper molecular understanding of how cancer cells survive, proliferate, and escape from current therapies. In high‐grade gliomas (HGGs), glioma stem cells (GSCs) may causally contribute to tumor initiation and propagation, therapeutic resistance, and subsequent recurrence of tumors. Within a tumor mass, GSCs are enriched in a hypoxic niche in which the oxidative stress levels are substantially elevated. Paradoxically, however, recent studies suggest that GSCs appear to generate less reactive oxygen species (ROS), a chemical component responsible for elevation of oxidative stress levels. To date, molecular mechanisms for how GSCs reduce oxidative stress to allow preferential survival in hypoxic areas in tumors remains elusive. This review article summarizes recent studies on the role of ROS‐reducing enzymes, including peroxiredoxin 4, in detoxifying oxidative stress preferentially for GSCs in HGGs. In addition, the therapeutic potential of some of the recently identified antioxidant chemotherapeutic agents and avenues for future research in this area are discussed. © 2014 Wiley Periodicals, Inc.     

Attention Deficits and Divorce

Objective:

Building on previous work on the role of attention deficits associated with the regulation of executive control in psychiatric disorders, we examine whether these attention deficits are related to an interpersonal disturbance, the experience of divorce.

Method:

Attentional capacities of 95 randomly selected couples from the general population were measured with a well-established task, the Attentional Network Task, which assesses the efficiency of 3 attention networks (that is, alerting, orienting, and executive control). Among the 190 participants, 32 had experienced a divorce in the past. ANCOVAs were used to compare divorced people in marital or cohabiting unions with people in first unions in their performance on this purely cognitive task.

Results:

Our findings indicate that divorced people who are currently living in a cohabiting relationship show significantly lower executive control than other adults living as couples, after controlling for sex, age, income, and education. This subgroup of divorced people not only exhibit greater difficulty in responding to some stimuli while ignoring irrelevant ones but also manifest cognitive deficits in conflict resolution.

Conclusions:

This study highlights the links between attention and the long-term maintenance of intimate relationships. Our results may have important implications for the identification of people at risk for divorce.     

Early life arsenic exposure and brain dopaminergic alterations in rats

Recently, we found that early life exposure to arsenic at low doses resulted to cause brain cholinergic deficits and exhibited a trend of recovery on withdrawal of arsenic exposure. In continuation to this, the present study has been carried out to assess the impact of low level arsenic exposure on brain dopaminergic system and associated behavior in developing rats and investigate if neurobehavioral changes are recovered or persistent. Early life exposure (PD22–PD59) to arsenic (2 or 4 mg/kg body weight, p.o.) in rats resulted to increase the motor activity on PD60, compared to controls. The hyperactivity in arsenic exposed rats was found to be linked with increase in the binding of DA-D2 receptors (38%, 56%), mRNA expression of DAR-D2 receptor gene (68%, 97%) and expression of tyrosine hydroxylase protein (1.93, 2.73-fold) in the corpus striatum as compared to controls on PD60. Exposure to arsenic enhanced generation of ROS (47%, 84%) and was associated with decrease in the mitochondrial membrane potential (13.3%, 15.33%), activity of mitochondrial complexes and increased oxidative stress. Disruption in the expression of pro-apoptotic, anti-apoptotic and stress marker proteins was also distinct in the corpus striatum of arsenic exposed rats. The severity of changes in the behavioral and neurochemical endpoints were found to persist in rats exposed to arsenic at high dose and exhibited a trend of recovery at low dose on withdrawal of arsenic exposure on PD90. Early life arsenic exposure appears to be critical and vulnerable as development of dopamine receptors continues during this period.     

Effects of prenatal chronic mild stress exposure on hippocampal cell proliferation,expression of GSK-3α, β and NR2B in adult offspring during fear extinction in rats

Stress during pregnancy has been implicated as a risk factor for the development of many mental disorders; however, the influence of prenatal stress on the fear or anxiety-related behaviors, especially the fear extinction in adult offspring has been little investigated. In order to investigate how prenatal stress affects fear extinction, which is regarded as a form of new learning that counteracts the expression of Pavlovian's conditioned fear, a rat model of prenatal chronic mild stress (PNS) was used to evaluate the effects of PNS on fear extinction in adult offspring. The expression of hippocampal glycogen synthase kinase-3s (GSK-3α, β), N-methyl-d-aspartic acid receptors (NMDARs)-2B and the hippocampal cell proliferation in dentate gyrus in the adult offspring during fear extinction were studied. Our results showed that PNS significantly reduced body weight of pups, indicating PNS might induce growth retardation in offspring. Moreover, PNS significantly enhanced the freezing behavior of offspring at the phase of extinction, suggesting PNS impaired the abilities of fear extinction learning. In addition, PNS significantly increased the levels of GSK-3α, β and NR2B, but reduced hippocampal cell proliferation during fear extinction. Taken together, our findings suggest that maternal stress during pregnancy can impair the fear extinction of adult offspring, probably by affecting the neural plasticity of brain.