氟暴露工人血浆抗热休克蛋白70抗体表达水平的研究

目的:检测氟暴露工人血浆抗热休克蛋白70(HSP70)抗体表达情况,探讨其与氟暴露应激反应的关系。方法:选择某铝厂氟暴露工人和非氟暴露工人各22人,用氟离子选择电极法测定血清氟、尿氟离子浓度,用Western-ELISA方法检测血浆抗HSP70抗体阳性率。结果:氟暴露组工人血清氟、尿氟离子浓度明显高于非暴露组(P<0.01);血浆HSP70抗体阳性率比较,氟暴露组抗HSP70抗体阳性率明显高于非暴露组(P<0.01)。结论:氟暴露环境下工人抗HSP70抗体阳性率明显增加,可能与氟暴露环境的应激保护反应有关。     

HSP70在经热应激预处理后减少大鼠肝脏缺血再灌注损伤过程中的作用

目的　探讨热应激预处理能够减少肝脏缺血再灌注损伤的机制,以期寻找减轻肝脏缺血再灌注损伤的有效措施。方法　建立大鼠肝脏缺血再灌注损伤模型。将42只大鼠随机分为6组:①正常对照组(N);②槲皮素组(Q):腹腔注射槲皮素(quercetin, 7mg·kg-1 );③肝脏缺血再灌注(ischemi areperfusion,I/R)组(I);④热应激预处理组(H+I):缺血再灌注前16h给予热应激预处理;⑤槲皮素+热应激预处理组(Q+H+I):缺血再灌注前16h先给予槲皮素腹腔注射(7mg·kg-1 )再给予热应激处理;⑥槲皮素+缺血组(Q+I):缺血再灌注前16h给予槲皮素腹腔注射(7mg·kg-1 )。观察以上各组大鼠在肝脏缺血再灌注6h后热休克蛋白70(Heatshockprotein70, HSP70 )的表达,血清谷丙转氨酶(ALT)、谷草转氨酶(AST)的活性及肝脏组织形态学改变。结果　大鼠肝脏HSP70表达由高到低依次为:H+I组、I组、Q+H+I组、I+Q组、Q组、N组;而检测血清ALT、AST含量由高到低依次为:Q+I组、I组、Q+H+I组、H+I组、Q组、N组;肝脏组织形态学的改变显示与上述血中ALT、AST含量变化相对应。结论　HSP70在经热应激预处理后减少肝脏缺血再灌注损伤的过程中起重要的作用。     

诱导分化联合热休克处理对K562细胞JWA和热休克蛋白70表达的影响

目的　研究不同诱导分化剂单独或与热休克联合作用下 ,K562细胞JWA蛋白表达的特点和规律 ,探讨JWA与热休克蛋白 70 (Hsp70 )表达的关系以及可能涉及的信号调节机制。方法　建立诱导K562细胞定向分化以及和热休克联合作用的实验模型 ,用Westernblot方法检测JWA、Hsp70、热休克转录因子 1(HSF1)、HSF2等蛋白表达。结果　 (1)佛波酯 (TPA ,10 0、2 0 0ng/ml)或阿霉素 (adri amycin ,4× 10 - 8mol/L)处理细胞 48h后 ,再热休克 (42℃ )处理 2h ,JWA和Hsp70蛋白表达均增加 ;而氯化高铁血红素 (hemin ,3× 10 - 5 mol/L ,48h)、阿糖胞苷 (Ara C ,80ng/ml,48h)和三氧化二砷 (As2 O3,1× 10 - 6 mol/L ,48h)处理后再热休克处理细胞 2h ,则JWA和Hsp70蛋白表达均下调 ;全反式维A酸(ATRA ,1× 10 - 6 mol/L ,48h)处理细胞后 ,再热休克处理 ,则JWA和Hsp70蛋白表达无明显变化。 (2 )不同诱导分化剂处理K562细胞后再热休克处理 ,HSF1和HSF2表达变化均不明显。结论　JWA不但参与K562细胞的诱导分化调节 ,也参与细胞对热应激的调节 ,JWA可能是多种化学诱导分化剂和热休克的共同靶基因。诱导K562细胞分化过程中 ,Hsp70的表达不需要热休克转录因子介导 ,JWA可能是一种与Hsp70信号通路平行的新的信号分子。我们的实验结果首     

复方丹参注射液联合西咪替丁治疗过敏性紫癜效果及安全性系统评价

【摘要】 目的 系统评价复方丹参注射液联合西咪替丁治疗过敏性紫癜的疗效及安全性。方法 检索各种中外文数据库、OA资源库、百度学术搜索引擎以及最新的纸质文献,追溯纳入研究的参考文献,全面收集有关复方丹参注射液联合西咪替丁治疗过敏性紫癜的临床随机对照试验。由两名评审员评估试验的质量并独立提取数据。使用RevMan53软件进行Meta分析。结果 共纳入15个随机对照试验,1005例患者,漏斗图呈不对称分布,提示可能存在发表偏倚或纳入文献方法学质量较低。Meta分析结果显示：在总有效率方面,复方丹参注射液联合西咪替丁组优于含有西咪替丁的常规治疗组和不含西咪替丁的常规治疗组,差异均有统计学意义（P＜005）;和对照组相比,复方丹参注射液联合西咪替治疗过敏性紫癜可以降低复发率和减少肾脏损害率（P＜005）,同时可以缩短皮疹、腹疼、消化道症状、关节疼痛等症状消失时间以及肾脏损害恢复时间（P＜005）;治疗期间均未见严重不良反应的报道。结论 复方丹参注射液联合西咪替丁治疗过敏性紫癜是一种相对安全、有效的治疗方案。但纳入研究的文献质量低,其疗效需要进一步高质量临床试验来验证。     

HEAT SHOCK PROTEIN72 PROTECTS HIPPOCAMPAL NEURONS FROM APOPTOSIS INDUCED BY CHRONIC PSYCHOLOGICAL STRESS

When exposed to nonlethal heat stress (i.e., heat shock preconditioning), HSP72 expression increased in the mammalian brain. HSP72 enhance the viability of neurons and decrease TUNEL-positive neurons under several kinds of stress (e.g., ischemic). Chronic psychological stress is a kind of stress that could cause hippocampal neuron apoptosis. But whether overexpression of HSP72 can decrease TUNEL-positive hippocampal neurons caused by chronic psychological stress is unclear. To investigate the possible protective role of HSP72 in decreasing chronic psychological stress–induced hippocampal neuron apoptosis, this study analyzed HSP72 expression, apoptotic neurons in the hippocampus of mice. Adult mice were divided into four groups unstressed group; chronic psychological stress group; heat shock stress group; heat shock preconditioning plus psychological stress group; receiving no experimental stress, chronic psychological stress, heat shock stress, heat shock preconditioning plus psychological stress separately. Mice were killed after one month, two months, or three months of stress. A three-way ANOVA (psychological stress × heat shock stress × time) revealed a significant effect of heat shock stress in increasing HSP72 expression, decreasing neuronal apoptosis in hippocampus CA3 region caused by chronic psychological stress, and showed that HSP72 protected hippocampus CA3 neurons from chronic psychological stress.     

Activation of natural killer cells by heat shock protein 70

Intracellular heat shock proteins (HSP) function as molecular chaperones, they support folding and transport mechanisms of other proteins under physiological conditions and following physical or chemical stress. More recently, extracellular localized HSP have been found to play key roles in the induction of a cellular immune response. Either they act as carrier molecules for immunogenic peptides that are presented on Antigen Presenting Cells (APC) to cytotoxic T-cells or they themselves act as activatory molecules for the innate immune system. Binding of uncomplexed HSP to HSP-receptors on APC has been found to induce the secretion of inflammatory cytokines. Furthermore, an unusual tumor-selective membrane-localization of non-conserved regions of the 72000Da HSP (Hsp70) has been found to act as a recognition structure for natural killer (NK) cells. In this review the interaction of NK cells with Hsp70 or peptides derived thereof will be eluciated in more detail.     

Fixation of distal femoral osteotomies with self-reinforced poly(L/DL)lactide 70 : 30 and self-reinforced poly(L/DL)lactide 70 : 30/bioactive glass composite rods. An experimental study on rabbits

Two self-reinforced poly(L/DL)lactide 70 : 30 or self-reinforced poly(L/DL)lactide 70 : 30/bioactive glass (SR-P(L/DL)LA/bioactive glass) composite rods (2 mm × 40 mm) were implanted into the dorsal subcutaneous tissue and osteotomies of the distal femur were fixed with these rods (2 mm × 26 mm) in 36 rabbits. The follow-up times varied from 3 to 100 weeks. After the animals were killed, three-point bending and shear tests and molecular weight measurements were performed for subcutaneously placed rods. Radiological, histological, histomorphometrical, microradiographic and oxytetracycline-fluorescence studies of the osteotomized and intact control femora were performed. After 12 weeks the SR-P(L/DL)LA rods had fragmented into pieces and the mechanical properties could not be measured. The SR-P(L/DL)LA/bioactive glass rods lost their mechanical properties slower, and at 24 weeks the bending strength had decreased by 39% and the shear strength by 50%. After that the mechanical properties of the SR-P(L/DL)LA/bioactive glass rods could not be measured. All osteotomies healed well, and no gross signs of inflammatory reactions were observed. One slight displacement was seen in the three-week follow-up group with SR-P(L/DL)LA rods. Signs of resorption of the implants were seen after 48 weeks in the SR-P(L/DL)LA group and after 24 weeks in the SR-P(L/DL)LA/bioactive glass group. The SR-P(L/DL)LA/bioactive glass rods were almost totally resorbed from the bone at 100 weeks. The present investigation showed that the mechanical strength and fixation properties of the SR-P(L/DL)LA and the SR-P(L/DL)LA/bioactive glass composite rods are suitable for fixation of cancellous bone osteotomies in rabbits.     

Intracellular antigens as targets for antibody based immunotherapy of malignant diseases

This review discusses the potential use of intracellular tumor antigens as targets of antibody‐based immunotherapy for the treatment of solid tumors. In addition, it describes the characteristics of the intracellular tumor antigens targeted with antibodies which have been described in the literature and have been identified in the authors'' laboratory. Finally, the mechanism underlying the trafficking of the intracellular tumor antigens to the plasma membrane of tumor cells are reviewed.     

Tanespimycin: the opportunities and challenges of targeting heat shock protein 90

Background: Heat shock protein 90 (HSP90) is the core of a multi-chaperone complex critical for the folding, trafficking, and stabilization of many client proteins that are involved in tumor cell proliferation, survival, and angiogenesis. Targeting HSP90 results in degradation of these client proteins. Objective: Data supporting the development of tanespimycin, which targets HSP90, are reviewed. Methods: Clinical data available for tanespimycin development are presented. Results: Tanespimycin can be given safely at biologically active doses with mild toxicity such as nausea, vomiting, diarrhea, and fatigue. Although single-agent studies have shown limited activity, combinations of tanespimycin with bortezomib or trastuzumab have suggested promising avenues of further evaluation in multiple myeloma and breast cancer, respectively. Conclusions: Further development of HSP90-targeted strategies include testing of novel chemical structures having better solubility and stability and the potential for oral administration. Targeting of HSP90 in combination with other heat shock proteins, such as HSP70 or HSP27, may be an alternative strategy that warrants further exploration.