Increased mitochondrial palmitoylcarnitine/carnitine countertransport by flavone causes oxidative stress and apoptosis in colon cancer cells

Cancer cell metabolism is characterized by limited oxidative phosphorylation in order to minimize oxidative stress. We have previously shown that the flavonoid flavone in HT-29 colon cancer cells increases the uptake of pyruvate or lactate into mitochondria, which is followed by an increase in O₂^−.. production that finally leads to apoptosis. Similarly, a supply of palmitoylcarnitine in combination with carnitine induces apoptosis in HT-29 cells by increasing the mitochondrial respiration rate. Here we show that flavone-induced apoptosis is increased more than twofold in the presence of palmitoylcarnitine due to increased mitochondrial fatty acid transport and the subsequent metabolic generation of O₂^−. in mitochondria is the initiating factor for the execution of apoptosis. Received 12 August 2005; received after revision 12 October 2005; accepted 14 October 2005     

Marrow mesenchymal stem cells transduced with TPO/FL genes as support for ex vivo expansion of hematopoietic stem/progenitor cells

A new marrow-derived mesenchymal stem cell (hMSC) line that could support expansion of hematopoietic stem/progenitor cells (HSPCs) was developed. Primary hMSCs were infected with retrovirus containing Flt-3 ligand and thrombopoietin genes. CD34+ cells from cord blood were expanded with primary hMSCs or transduced hMSCs. The expansion of total nucleated cells, CD34+ cells and mixed colonies containing erythroid and myeloid cells and megakaryocytes for 2 weeks coculture with transduced hMSCs was remarkably increased. The outputs of long-term culture-initiating cells for 2 and 4 weeks coculture with transduced hMSCs were also largely increased. The expansion rates of HSPCs with transduced hMSCs were unchanged for 6 weeks. In contrast, the expansion rates of HSPCs with primary hMSCs declined drastically through 6 weeks. SCID-repopulating cell expansion with transduced hMSCs for 4 weeks was significantly higher than that of uncultured CD34+ cells and HSPCs expanded with primary hMSCs. Received 21 June 2005; received after revision 30 July 2005; accepted 24 August 2005     

Cellular responses to mild heat stress

Since its discovery in 1962 by Ritossa, the heat shock response has been extensively studied by a number of investigators to understand the molecular mechanism underlying the cellular response to heat stress. The most well characterized heat shock response is induction of the heat shock proteins that function as molecular chaperones and exert cell cycle regulatory and anti-apoptotic activities. While most investigators have focused their studies on the toxic effects of heat stress in organisms such as severe heat stress-induced cell cycle arrest and apoptosis, the cellular response to fever-ranged mild heat stress has been rather underestimated. However, the cellular response to mild heat stress is likely to be more important in a physiological sense than that to severe heat stress because the body temperature of homeothermic animals increases by only 1–2°C during febrile diseases. Here we provide information that mild heat stress does have some beneficial role in organisms via positively regulating cell proliferation and differentiation, and immune response in mammalian cells.Received 14 May 2004; received after revision 2 August 2004; accepted 16 August 2004     

A pathway profile-based method for drug repositioning

Finding new applications for existing pharmaceuticals,known as drug repositioning,is a validated strategy for resolving the problem of high expenditure but low productivity in drug discovery.Currently,the prevalent computational methods for drug repositioning are focused mainly on the similarity or relevance between known drugs based on their "features",including chemical structure,side effects,gene expression profile,and/or chemical-protein interactome.However,such drug-oriented methods may constrain the newly predicted functions to the pharmacological functional space of the existing drugs.Clinically,many drugs have been found to bind "off-target"(i.e.to receptors other than their primary targets),which can lead to undesirable effects.In this study,which integrates known drug target information,we propose a disease-oriented strategy for evaluating the relationship between drugs and disease based on their pathway profile.The basic hypothesis of this method is that drugs exerting a therapeutic effect may not only directly target the disease-related proteins but also modulate the pathways involved in the pathological process.Upon testing eight of the global best-selling drugs in 2010(each with more than three targets),the FDA(Food and Drug Administration,USA)-approved therapeutic function of each was included in the top 10 predicted indications.On average,60% of predicted results made using our method are proved by literature.This approach could be used to complement existing methods and may provide a new perspective in drug repositioning and side effect evaluation.     

植物脂肪酸及其衍生物防御信号研究进展

植物由于不能移动而发展了复杂而精密的抗病系统.近年来,人们发现作为细胞膜组分的脂肪酸在植物的各种抗病机制中发挥着举足轻重的作用.脂肪酸及其衍生物不仅参与植物基础免疫和系统免疫,还参与经典抗病基因(R基因)介导的抗病过程.目前,已发现许多与脂肪酸(尤其是16碳和18碳脂肪酸及其衍生物)代谢相关的突变体,对这些突变体抗病性改变的分子机制研究成为植物抗病领域研究热点之一.本文综述了脂肪酸及其衍生物在植物防御信号转导中的最新研究进展,旨在为植物抗病遗传育种研究提供新的参考.     

Metabolomics: Concept, methods and potential prospect in marine biology

The term "omics" refers to the comprehensive analysis of a specific biological system.With the development of omics,a number of omics subdisciplines have emerged,which play an important role in system biology.As a subdiscipline of omics,metabolomics provides a comprehensive analysis of the metabolome and has been widely applied to various fields of biology.In this paper,we introduce the concept,approaches,applications,and promising prospects of metabolomics.     

2-KGA混菌发酵过程的结构模型及实验验证

探讨了古龙酸混菌发酵过程中普通生酮古龙酸菌(Ketogulonicigenium vulgare)和巨大芽孢杆菌(Bacillus megaterium)的交互作用机制.分析了K. vulgare以L 山梨糖为碳源时的代谢途径,建立了K. vulgare的宏观动力学模型,引入了一阶闭环调节器模型来描述糖酵解等酶系的建立过程.该模型描述了K. vulgare中物质流和能量流的平衡关系,据此可解得比碳源消耗速率、比生长速率、比乙酰辅酶A生成速率、比氧消耗速率等关键反应速率.结合生物反应器模型可获得操纵变量与状态变量之间的关系.实验验证了上述模型的有效性.     

运用绿色荧光蛋白探讨肉葡萄球菌双精氨酸分泌途径

根据肉葡萄球菌(Staphylococcus carnosus)TM300的基因组序列设计引物,经PCR扩增得到其tufA基因的启动子Peftu片段与大肠杆菌–葡萄球菌穿梭载体pBT2-Tat-GFP连接,构建了穿梭质粒pBT2-ETG.结果表明,穿梭质粒pBT2-ETG成功地转入大肠杆菌与肉葡萄球菌宿主中稳定表达具有活性的绿色荧光蛋白GFP,并被转运到肉葡萄球菌宿主的细胞壁,为进一步研究肉葡萄球菌双精氨酸(Tat)转运系统正确分泌其他外源蛋白奠定了实验基础.     

Necroptosis——一种新型程序性死亡机制的研究进展

坏死在众多生理和病理进程中都扮演着重要的作用.最近,一种新型的被称为"necroptosis"的细胞坏死程序受到了人们的普遍关注.从形态学上来讲,necroptosis表现出和坏死相同的特征;然而,它却有自己独特的信号通路,这种通路需要受体相互作用蛋白激酶RIP1和RIP3的参与,形成诱导死亡信号复合体,从而促进细胞程序性坏死,但可以被necrostatins特异性地抑制.Necroptosis有助于免疫系统的调节,癌症的治疗以及多种压力下细胞的应答.本篇综述中我们将总结这种特殊的程序性死亡的信号通路、生物学效应和病理学意义.     

基于逻辑框架法的农业科技项目效益实现路径分析

借鉴逻辑框架模型,深入分析农业科技项目效益产生的机理和路径,实证研究表明:农业科技投入与科技成果、科技推广和农业经济有正相关关系,农业科技投入虽然对农业经济有一定的直接影响作用,但主要是通过科技成果和科技推广间接作用于农业经济,且具有较强的影响作用。因此,在进行农业科技项目效益评价时,不能以简单的输入/输出方法来进行评估,应该采用"理论驱动"法对农业科技项目预期的关系链进行全面分析和评估,促进农业科技项目和科技推广项目有机结合,提高农业科技项目的效益。