LPC对缺血心肌起搏离子流的影响及ISO的效应

目的:观察在缺血条件下,溶血磷脂酰胆碱(LPC)对心肌起搏离子流(If)的影响以及能否被异丙肾上腺素(ISO)逆转.方法:采用双微电极电压钳制术,在各钳制电位测定并比较缺血心肌加入LPC和LPC加ISO的起搏离子流(If)幅值.结果:缺血降低If幅值,在模拟缺血液中加入LPC 2×10-5mol/L,If幅值在Ec -80～-120 mV水平进一步显著降低(n=5,P<0.05),加重了缺血对If离子流的抑制作用.在模拟缺血液中同时加入LPC 2×10-5mol/L和ISO 1×10-6mol/L,If幅值在Ec -90～-120 mV水平比模拟缺血时有显著增加(n=8,P<0.05),但未能达到缺血前基础水平.结论: 急性心肌缺血时,毒性代谢产物 LPC 加重起搏离子流的受抑程度,即使局部儿茶酚胺大量释放和积聚,也不能完全逆转上述抑制效应.     

PaP3噬菌体57kD蛋白编码基因的确定

分离鉴定了PaP3噬菌体57 kD蛋白的编码基因并对其功能进行了初步探讨。用PEG沉淀结合CsCl梯度密度离心分离、纯化噬菌体颗粒,通过SDSPAGE分析该噬菌体的衣壳蛋白,转印PVDF膜后,对57 kD蛋白用Edman降解法进行N端氨基酸测序,进而从PaP3全基因组的256个ORFs中确认该蛋白质的编码基因及其对应的氨基酸序列。结果显示噬菌体PaP3有9种结构蛋白分子,其中57 kD蛋白是由ORF34793编码的。57kD蛋白编码基因全长1542bp,G+C百分含量为49.16%,编码514个氨基酸。该蛋白分子量为57.4kD,等电点为5.879。实验表明该蛋白是一种结构性蛋白,很可能是噬菌体衣壳蛋白中的一种壳微粒。     

The Ca2+ homeostasis defects in a pgm2Delta strain of Saccharomyces cerevisiae are caused by excessive vacuolar Ca2+ uptake mediated by the Ca2+-ATPase Pmc1p

Loss of the major isoform of phosphoglucomutase (PGM) causes an accumulation of glucose 1-phosphate when yeast cells are grown with galactose as the carbon and energy source. Remarkably, the pgm2Delta strain also exhibits a severe imbalance in intracellular Ca(2+) homeostasis when grown under these conditions. In the present study, we examined how the pgm2Delta mutation alters yeast Ca(2+) homeostasis in greater detail. We found that a shift from glucose to galactose as the carbon source resulted in a 2-fold increase in the rate of cellular Ca(2+) uptake in wild-type cells, whereas Ca(2+) uptake increased 8-fold in the pgm2Delta mutant. Disruption of the PMC1 gene, which encodes the vacuolar Ca(2+)-ATPase Pmc1p, suppressed the Ca(2+)-related phenotypes observed in the pgm2Delta strain. This suggests that excessive vacuolar Ca(2+) uptake is tightly coupled to these defects in Ca(2+) homeostasis. An in vitro assay designed to measure Ca(2+) sequestration into intracellular compartments confirmed that the pgm2Delta mutant contained a higher level of Pmc1p-dependent Ca(2+) transport activity than the wild-type strain. We found that this increased rate of vacuolar Ca(2+) uptake also coincided with a large induction of the unfolded protein response in the pgm2Delta mutant, suggesting that Ca(2+) uptake into the endoplasmic reticulum compartment was reduced. These results indicate that the excessive Ca(2+) uptake and accumulation previously shown to be associated with the pgm2Delta mutation are due to a severe imbalance in the distribution of cellular Ca(2+) into different intracellular compartments.     

延胡索分类的化学证据

东阳产延胡索与大连产齿瓣延胡索经成分分离和TLC、HPLC对比,发现延胡索以啊扑啡类生物碱如glaucine为主,而齿瓣延胡索则含corynoline类生物碱。根据生物碱的类型及含量比较,二者有明显差异,结合延胡索的植物形态和植化分类特征判断,将延胡索作为与齿瓣延胡索近缘的独立种处理较为合理,即为Corydalis yanhusuo W. T. Wang ex Z.Y. Su et C. Y. Wu     

Synthesis,biological evaluation, 3D-QSAR studies of novel aryl-2H-pyrazole derivatives as telomerase inhibitors

A series of novel aryl-2H-pyrazole derivatives bearing 1,4-benzodioxan or 1,3-benzodioxole moiety were designed as potential telomerase inhibitors to enhance the ability of aryl-2H-pyrazole derivatives to inhibit telomerase, a target of anticancer. The telomerase inhibition tests showed that compound 16A displayed the most potent inhibitory activity with IC₅₀ value of 0.9 μM for telomerase. The antiproliferative tests showed that compound 16A exhibited high activity against human gastric cancer cell SGC-7901 and human melanoma cell B16-F10 with IC₅₀ values of 18.07 and 5.34 μM, respectively. Docking simulation showed that compound 16A could bind well with the telomerase active site and act as telomerase inhibitor. 3D-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent telomerase inhibitory activity.     

Upregulation of SATB1 Is Associated with Prostate Cancer Aggressiveness and Disease Progression

Disease aggressiveness remains a critical factor to the progression of prostate cancer. Transformation of epithelial cells to mesenchymal lineage, associated with the loss of E-cadherin, offers significant invasive potential and migration capability. Recently, Special AT-rich binding protein (SATB1) has been linked to tumor progression. SATB1 is a cell-type restricted nuclear protein, which functions as a tissue-specific organizer of DNA sequences during cellular differentiation. Our results demonstrate that SATB1 plays significant role in prostate tumor invasion and migration and its nuclear localization correlates with disease aggressiveness. Clinical specimen analysis showed that SATB1 was predominantly expressed in the nucleus of high-grade tumors compared to low-grade tumor and benign tissue. A progressive increase in the nuclear levels of SATB1 was observed in cancer tissues compared to benign specimens. Similarly, SATB1 protein levels were higher in a number of prostate cancer cells viz. HPV-CA-10, DU145, DUPro, PC-3, PC-3M, LNCaP and C4-2B, compared to non-tumorigenic PZ-HPV-7 cells. Nuclear expression of SATB1 was higher in biologically aggressive subclones of prostate cancer cells with their respective parental cell lines. Furthermore, ectopic SATB1 transfection conferred increased cell motility and invasiveness in immortalized human prostate epithelial PZ-HPV-7 cells which correlated with the loss of E-cadherin expression. Consequently, knockdown of SATB1 in highly aggressive human prostate cancer PC-3M cells inhibited invasiveness and tumor growth in vivo along with increase in E-cadherin protein expression. Our findings demonstrate that SATB1 has ability to promote prostate cancer aggressiveness through epithelial-mesenchymal transition.     

CpG-Oligodeoxynucleotide Treatment Protects against Ionizing Radiation-Induced Intestine Injury

Background

the bone marrow and the intestine are the major sites of ionizing radiation (IR)-induced injury. Our previous study demonstrated that CpG-oligodeoxynucleotide (ODN) treatment mitigated IR-induced bone marrow injury, but its effect on the intestine is not known. In this study, we sought to determine if CpG-ODN have protective effect on IR-induced intestine injury, and if so, to determine the mechanism of its effect.

Methods and Findings

Mice were treated with CpG-ODN after IR. The body weight and survival were daily monitored for 30 days consecutively after exposure. The number of surviving intestinal crypt was assessed by the microcolony survival assay. The number and the distribution of proliferating cell in crypt were evaluated by TUNEL assay and BrdU assay. The expression of Bcl-2, Bax and caspase-3 in crypt were analyzed by Immunohistochemistry assay. The findings showed that the treatment for irradiated mice with CpG-ODN diminished body weight loss, improved 30 days survival, enhanced intestinal crypts survival and maintained proliferating cell population and regeneration in crypt. The reason might involve that CpG-ODN up-regulated the expression of Bcl-2 protein and down-regulated the expression of Bax protein and caspase-3 protein.

Conclusion

CpG-ODN was effective in protection of IR-induced intestine injury by enhancing intestinal crypts survival and maintaining proliferating cell population and regeneration in crypt. The mechanism might be that CpG-ODN inhibits proliferating cell apoptosis through regulating the expression of apoptosis-related protein, such as Bax, Bcl-2 and caspase-3.     

HCV-specific interleukin-21+CD4+ T cells responses associated with viral control through the modulation of HCV-specific CD8+ T cells function in chronic hepatitis C patients

Interleukin-21 (IL-21)+CD4+ T cells are involved in the immune response against hepatitis B virus (HBV) by secreting IL-21. However, the role of IL-21+CD4+ T cells in the immune response against chronic hepatitis C (CHC) virus infection is poorly understood. This study aimed to investigate the role of IL-21+CD4+ T cells in CHC patients and the potential mechanisms. The study subjects included nineteen CHC patients who were grouped by viral load (low, < 10⁶ RNA copies/ml, n = 8; high, > 10⁶ RNA copies/ml, n = 11). The peripheral frequency of HCV-specific IL-21+CD4+ T cells was higher in the low viral load group and was negatively correlated with the serum HCV RNA viral load in all CHC patients. Meanwhile, IL-21+ cells accumulated in the liver in the low viral load group. In vitro, IL-21 treatment increased the expression of proliferation markers and cytolytic molecules on HCV-specific CD8+ T cells. In summary, these findings suggest that HCV-specific IL-21+CD4+ T cells might contribute to HCV control by rescuing HCV-specific CD8+ T cells in CHC patients.     

我国转基因水稻商品化应用的潜在环境生物安全问题

转基因水稻的研发和商品化应用将为提高我国水稻的生产力提供新的机遇,并缓解我国的粮食安全问题.转基凶水稻的人规模环境释放和商品化生产可能会带来一定的环境生物安全问题,处理不好会影响转基因水稻的进一步研究和发展.通常所指的环境生物安全问题主要包括以下几个方面:(1)抗生物胁迫转基因对非靶标生物的影响及效应;(2)外源基因向非转基因作物和野生近缘种逃逸及其可能带来的生态后果;(3)转基因作物对农业生态系统、土壤微生物以及生物多样性的潜在影响;(4)抗生物胁迫转基因的长期使用导致靶标生物对转基因产生抗性等.为了安全有效和持续利用转基因生物技术及其产品,有必要对转基因水稻的环境生物安全性进行科学评价.基于风险评价的原则,本文对转基因水稻在我国商品化生产和大规模种植可能带来的环境生物安全问题进行了理性分析,希望为我国转基因水稻商品化应用的决策和生物安全评价提供科学依据.