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     

Human peripheral blood monuclear cells transfected with messenger RNA stimulate antigen-specific cytotoxic T-lymphocytes in vitro

The efficiency of test vaccines needs to be evaluated by quantification of the triggered cellular immune response. Usually, for these assays, autologous target cells expressing the vaccine antigen are required. In the context of messenger RNA (mRNA)-based vaccinations, the target cells used for the read-out are mRNA-transfected monocyte-derived dendritic cells (Mo-DCs). Their production typically requires samples of 100 ml blood from the patients, and limits the number of assays that can be performed. We show here that fresh peripheral blood mononuclear cells (PBMCs) can be transfected with mRNA by electroporation. Such cells are as efficient as mRNA-transfected Mo-DCs for their ability to activate memory T cells in vitro. Thus, mRNA-transfected PBMCs are a convenient replacement of mRNA-transfected Mo-DCs for the in vitro monitoring of natural or vaccine-induced immune responses.Received 17 February 2005; received after revision 1 May 2005; accepted 7 Juni 2005     

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development

Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.Received 30 November 2004; received after revision 24 January 2005; accepted 5 February 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     

Leptin receptor action and mechanisms of leptin resistance

The adipose tissue-derived hormone leptin regulates energy balance and neuroendocrine function. Resistance to the appetite-suppressing effects of leptin is associated with common forms of obesity. Here, we review the mechanisms by which leptin activates intracellular signals and the roles that these signals play in leptin action in vivo. Furthermore, we discuss potential mechanisms of leptin resistance, specifically focusing on data regarding the neuroanatomical locus of leptin resistance and potential mechanisms by which expression of the suppressor of cytokine signaling-3 may impair leptin action.Received 30 September 2004; received after revision 12 November 2004; accepted 23 November 2004     

Is chlamydial heat shock protein 60 a risk factor for oncogenesis?

Heat shock protein 60 (HSP60) plays an important role in the protein folding of prokaryotic and eukaryotic cells. Most of the papers published on chlamydial HSP60 concern its role in immune response during infection. In the last decade, exposure to Chlamydia trachomatis has been consistently associated with the development of cervical and ovarian cancer. Moreover, it has been suggested that chlamydial HSP60 may have an anti-apoptotic effect during persistent infection. We hypothesize that the accumulation of exogenous chlamydial HSP60 in the cytoplasm of actively replicating eukaryotic cells may interfere with the regulation of the apoptotic pathway. The concomitant expression of viral oncoproteins and/or the presence of mutations may lead to the ability to survive apoptotic stimuli, loss of replicative senescence, uncontrolled proliferation and, finally neoplastic transformation.Received 15 August 2004; received after revision 1 October 2004; accepted 7 October 2004     

低硫柴油直喷燃烧超细颗粒排放特性研究

对比研究了燃用普通柴油和低硫柴油其排气超细颗粒数量浓度分布及化学成分特征. 结果表明, 相对于燃用普通柴油, 燃用低硫柴油其排气总颗粒质量浓度略有降低, 而数量浓度显著降低, 且降幅随负荷和转速增大. 燃用普通柴油和低硫柴油其排气微粒数浓度粒径分布曲线形状基本相似, 同一测试工况下, 相对于燃用普通柴油, 燃用低硫柴油其排气积聚模态微粒数量浓度变化较小, 而核模态微粒排放显著降低. 发动机排气微粒主要由C, O, Cl, S, Si, Ca, Na, Al, K元素组成, 燃用普通柴油和低硫柴油其排气微粒元素组成基本相似, 但燃用低硫柴油排气微粒中没有发现S元素. 排气微粒中挥发性有机物(SOF)主要成分有饱和烷烃(碳原子数为C15~C26)、有机酸酯和多环芳烃等. 燃用低硫柴油时微粒采样中未发现多环芳烃.     

大气降水中低分子有机酸的季节变化及对酸雨形成的贡献(以贵阳市和尚重镇为例)

低分子有机酸是大气中普遍存在的一种化学成分, 对酸雨的形成有重要的贡献. 西南地区是酸雨污染重灾区, 2006年4月到2007年4月用离子色谱法测定了贵阳市和尚重镇大气降水中的7种低分子有机酸. 实验结果表明: 两地大气降水中, 甲酸、乙酸和草酸是最主要的有机酸, 贵阳市其雨量加权平均值分别为14.24, 9.35和2.79 μmol/L, 而尚重镇则分别为4.95, 1.35和2.31 μmol/L. 尚重镇大气降水中低分子有机酸生长季节浓度高于非生长季节浓度, 说明植物或土壤的释放可能是尚重镇大气有机酸的主要来源; 与之相反, 贵阳市大气降水中有机酸非生长季节浓度高于生长季节浓度, 可能与该地区冬季降水次数少, 每次雨量小以及降水同时易伴随颗粒物沉降有关. 贵阳市有机酸对自由酸贡献分别为: 甲酸?7.9%, 乙酸?4.7%, 草酸?6.1%, 3种主要有机酸贡献了18.7%的自由酸; 尚重镇分别为: 甲酸?25.1%, 乙酸?7.5%, 草酸?25.5%, 有机酸对自由酸贡献为58.1%. 贵阳市降水中有机酸根占阴离子总和的1.7%~19.2%, 平均值为6.6%. 尚重镇降水中有机酸根对总阴离子的贡献为0.5%~92.2%, 平均贡献为13.2%. 由此可见, 低分子有机酸, 尤其是边远地区, 对大气降水酸化的影响不可忽视.