6‐Dehydrogingerdione,an active constituent of dietary ginger,induces cell cycle arrest and apoptosis through reactive oxygen species/c‐Jun N‐terminal kinase pathways in human breast cancer cells

This study is the first to investigate the anticancer effect of 6‐dehydrogingerdione (DGE), an active constituent of dietary ginger, in human breast cancer MDA‐MB‐231 and MCF‐7 cells. DGE exhibited effective cell growth inhibition by inducing cancer cells to undergo G2/M phase arrest and apoptosis. Blockade of cell cycle was associated with increased levels of p21, and reduced amounts of cyclin B1, cyclin A, Cdc2 and Cdc25C. DGE also enhanced the levels of inactivated phosphorylated Cdc2 and Cdc25C. DGE triggered the mitochondrial apoptotic pathway indicated by a change in Bax/Bcl‐2 ratios, resulting in caspase‐9 activation. We also found the generation of reactive oxygen species is a critical mediator in DGE‐induced cell growth inhibition. DGE clearly increased the activation of apoptosis signal‐regulating kinase 1 and c‐Jun N‐terminal kinase (JNK), but not extracellular signal‐regulated kinase 1/2 (ERK1/2) and p38. In addition, antioxidants vitamin C and catalase significantly decreased DGE‐mediated JNK activation and apoptosis. Moreover, blocking JNK by specific inhibitors suppressed DGE‐triggered mitochondrial apoptotic pathway. Taken together, these findings suggest that a critical role for reactive oxygen species and JNK in DGE‐mediated apoptosis of human breast cancer.     

一种铅冷快堆主要构件的辐照损伤计算

为满足公众对更安全、更经济和环境更友好的核能系统的需求,提出一种铅铋合金冷却的铅冷快堆(Breeding Lead-based Economical Safe System–Demonstration,BLESS-D)。BLESS-D反应堆采用池式结构,热功率300 MW。金属材料受中子辐照时将造成材料的晶格缺陷,导致材料的宏观性能变化,改变其物理和机械性能。BLESS-D反应堆中有许多在反应堆寿期内不可更换的关键部件和设备,这些构件在反应堆运行期间如受到中子辐照损伤,将影响构件材料的性能,进而导致设备的使用寿命,限制了反应堆的寿命。本文通过计算BLESS-D反应堆主要部件和设备的原子离位数(Displacement Per Atom,DPA),评估结构材料的辐照损伤程度。利用SPECTER程序和MCNP程序进行燃料包壳、内部容器、主泵泵壳、蒸汽发生器壳和反应堆容器的DPA模拟计算,计算结果与发生材料辐照效应的DPA限值进行比较,发现内部容器的累积DPA在20年寿期内超过了材料辐照效应限值,需要进一步分析并优化设计,确保其寿期内的安全性。     

Glabridin,an isoflavan from licorice root,inhibits migration,invasion and angiogenesis of MDA‐MB‐231 human breast adenocarcinoma cells by inhibiting focal adhesion kinase/Rho signaling pathway

Scope: In this study we first report the antimigration, antiinvasive effect of glabridin, a flavonoid obtained from licorice, in MDA‐MB‐231 human breast adenocarcinoma cells. Methods and results: Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of MDA‐MB‐231 cells. In addition, glabridin also blocked human umbilical vein endothelial cells (HUVEC) migration and decreased MDA‐MB‐231‐mediated angiogenesis. Further investigation revealed that the inhibition of cancer angiogenesis by glabridin was also evident in a nude mice model. Blockade of MDA‐MB‐231 cells and HUVEC migration was associated with an increase of αγβ3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src (Tyr 416), decreasing the interaction of FAK and Src. Inhibition of the FAK/Src complex by glabridin also blocked AKT and ERK1/2 activation, resulting in reduced activation of RhoA as well as myosin light chain phosphorylation. Conclusion: This study demonstrates that glabridin may be a novel anticancer agent for the treatment of breast cancer in three different ways: inhibition of migration, invasion and angiogenesis.     

Separation of hematopoietic stem and progenitor cells from human peripheral blood through polyurethane foaming membranes modified with several amino acids

The separation of hematopoietic stem and progenitor cells (CD34⁺ cells) from peripheral blood was investigated using foamed polyurethane (PU) membranes modified with several amino acids. CD34⁺ cells were collected by first allowing the blood to permeate through the membranes, and then passing the recovered solution through the membranes. Optimal conditions for the separation of CD34⁺ cells were investigated. The highest recovery ratio of CD34⁺ cells was obtained using three sheets of PU membranes having carboxylic acid groups (PU? COOH) modified with glycine, the membranes having been pretreated by immersion in phosphate buffer solution prior to permeation of blood. A high recovery ratio of CD34⁺ cells was achieved in a recovery process using 0.5 wt % human serum albumin (HSA) or 20% dextran solution passed through PU? COOH membranes. The recovery ratios of CD34⁺ cells using platelet‐poor plasma and platelet‐rich plasma were approximately 20% and 30%, respectively, significantly less than the ratio found using 0.5 wt % HSA solution. Surface‐modified membranes having carboxylic acid groups showed a higher recovery ratio of CD34⁺ cells than membranes having zwitterionic groups. The effect of carboxylic acid groups on the surface‐modified PU membranes was to generate weak interactions by electrostatic repulsion between CD34⁺ cells and the membranes because of the negatively charged surfaces of the cells, allowing them to be detached from the membranes and collected in the recovered solution. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Electric measurement of the electroporation efficiency of mash from wine grapes

The degree of cell opening after electroporation can be derived from an electric impedance measurement in a frequency range between 500 Hz and 10 MHz. For a simple detection in a continuously flowing medium a measurement at a discrete frequency evaluating the phase shift between a measurement voltage across an electrode system and a current flowing through the sample volume has been investigated. The paper describes impedance measurements of the mash of wine grapes. For different grape varieties the frequency dependency of the phase shift has been measured. The data showed that the frequency of maximum phase shift differs with the grape variety. For the mash of wine grapes the measurement results based on the measurement of the complex impedance have been compared to the degree of extraction of color from the peel tissue of red wine grapes as a conventional method to determine the degree of denaturation. The measurements showed a correspondence between the color intensity of the must and the electric measurements.     

Effects of nanosecond pulsed electric field exposure on arabidopsis thaliana

Seven days old seedlings of Arabidopsis thaliana, suspended in a 0.4 S/m buffer solution were exposed to nanosecond pulsed electric fields (nsPEF) with a duration of 10 ns, 25 ns and 100 ns. The electric field was varied from 5 kV/cm up to 50 kV/cm. The specific treatment energy ranged between 100 J/kg and 10 kJ/kg. Due to electroporation of the plasmamembrane of the plant cells, the seedlings completely died off, when 100 ns pulses and high electric field pulses were applied. But even at the highest specific treatment energies, 10 ns pulses had no lethal effect on the seedlings. An evaluation of the leaf area 5 and 7 days after pulsed electric field treatment revealed values twice the area of sham treated seedlings up to a specific treatment energy of 4 kJ/kg, when the applied field amplitude was low or the pulse duration 10 ns. A growth stimulating effect after short pulse exposition clearly could be detected. Contrary to the growth inhibiting effect of plasmamembrane electroporation on the seedlings, a growth stimulation by nsPEF treatment does not scale with the treatment energy within the applied parameter range.     

Quantification of the Raf-C1 interaction with solid-supported bilayers

By use of the quartz crystal microbalance technique, the interaction of the Raf-Ras binding domain (RafRBD) and the cysteine-rich domain Raf-C1 with lipids was quantified by using solid-supported bilayers immobilized on gold electrodes deposited on 5 MHz quartz plates. Solid-supported lipid bilayers were composed of an initial octanethiol monolayer chemisorbed on gold and a physisorbed phospholipid monolayer varying in its lipid composition as the outermost layer. The integrity of bilayer preparation was monitored by impedance spectroscopy. For binding experiments, a protein construct comprising the RafRBD and Raf-C1 linked to the maltose binding protein and a His tag, termed MBP-Raf-C1, was used. Dissociation constants and rate constants of the association and dissociation were obtained for various 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/1,2-dimyristoyl-sn-glycero-3-phosphoserine (DMPS) lipid mixtures. Independently of the phosphatidylserine (PS) content, the dissociation constants were in the order of 5x10(-7) M, while the on-rate constants were in the range of 2x10(3) (M s)(-1) and the off-rate constants in the range of 1x10(-3) s(-1). The maximum frequency shift increased significantly with increasing amounts of DMPS; this indicates that this negatively charged lipid is the primary binding site for MBP-Raf-C1. Exchange of DMPS for 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) did not alter the thermodynamics and kinetics of protein binding, which implies that the protein interaction is mainly electrostatically driven. Scanning force microscopy (SFM) was employed to render protein adsorption visible and to confirm the assumption of a protein monolayer on the lipid layer. SFM images clearly revealed that the protein binds preferentially, but not solely, to negatively charged phosphatidylserine headgroups. We hypothesize that PS-enriched domains are initial binding sites with high affinity for Raf-C1, but that lateral interactions may account for protein domain growth.