藿香正气水中橙皮苷的超声提取工艺

目的:设计正交试验,对藿香正气水中橙皮苷的超声提取条件进行优化。方法:超声提取橙皮苷,用HPLC测定其含量。结果:在提取液为40%甲醇、温度为50℃、超声15min条件下,提取率高。橙皮苷在5～100μg·ml~(-1)(r=0.999 6,n=6)浓度范围具有良好线性关系,平均回收率为99.78%,RSD为1.38%。结论:方法简单、易操作,稳定可行,为藿香正气水的质量控制提供了方法。     

Stejnihagin, a novel snake metalloproteinase from Trimeresurus stejnegeri venom, inhibited L-type Ca channels

Snake venom metalloproteinases (SVMPs) mainly distribute in Crotalid and Viperid snake venom and are classified into the Reprolysin subfamily of the M12 family of metalloproteinases. Previous function investigations have suggested that SVMPs are the key toxins involved in a variety of snake venom-induced pathogenesis including systemic injury, local damage, hemorrhage, edema, hypotension, hypovolemia, inflammation and necrosis. However, up to now, there is no report on ion channels blocking activity about SVMPs. Here, from Trimeresurus stejnegeri venom we purified a component Stejnihagin containing a mixture of Stejnihagin-A and -B, with 86% sequences identity, both as members of SVMPs. In the study, whole-cell patch clamp and vessel tension measurement were employed to identify the effect of Stejnihagin on L-type Ca²⁺ channels and vessel contraction. The results show that Stejnihagin inhibited L-type Ca²⁺channels in A7r5 cells with an IC₅₀ about 37 nM and simultaneously blocked 60 mM K⁺-induced vessel contraction. Besides, the inhibitory effect of Stejnihagin on L-type Ca²⁺ channels was also independent of the enzymatic activity. This finding offers new insight into the snake venom metalloproteinase functions and provides a novel pathogenesis of T. stejnegeri venom. Furthermore, it may also provide a clue to study the structure-function relationship of animal toxins and voltage-gated Ca²⁺ channel.     

从肿瘤基因表达数据挖掘分类规则的研究

基于肿瘤基因表达数据,利用信息科学的方法和技术建立肿瘤预测分类模型,对肿瘤基因表达模式研究和肿瘤的诊断识别具有重要意义.本研究提出一种从肿瘤基因表达数据中直接挖掘分类规则建立肿瘤预测分类器的方法.该方法首先抽取实验样本集,分别找出标记肿瘤和正常组织样本的分类特征,由此生成可预测样本类别的分类规则,对每个未知类别样本,按照置信度最高原则,选择一个分类规则作为预测结构.本研究的实验数据来自Broad Institute的前列腺癌基因表达数据,实验结果显示该方法的预测精度在90%以上,且同时获得了大量结构透明的分类预测规则,表明本研究的方法是可行的和有效的.     

Altered expression of Aβ metabolism-associated molecules from d-galactose/AlCl3 induced mouse brain

Cerebral deposition of amyloid-β peptide (Aβ) is a critical feature of Alzheimer's disease (AD). Either aluminium trichloride (Al) or d-galactose (d-gal) induces Aβ overproduction in rat or mouse brain and has been used to produce models of aging and AD. Here it is shown that mice treated with Al plus d-gal represent a good model of AD with altered expression of Aβ metabolism-associated molecules. The work shows that Al/d-gal causes memory impairment and high Aβ levels in the cortex (Co) and hippocampus (Hi). Then, we found that beta-site APP cleavage enzyme 1 (BACE1) was increased in mouse Co and Hi. Al or Al plus d-gal suppressed mRNA of the low-density lipoprotein receptor-related protein 1(LRP1). d-gal also decreased the LRP expression in Hi, but not in Co. However, Al/d-gal did not affect the receptor for advanced glycation end products (RAGE) expression in mouse brains. Furthermore, Al/d-gal reduced the expression of neprilysin (NEP), but not the insulin degrading enzyme (IDE). This study indicates that Al/d-gal affects the expression of Aβ metabolism-associated molecules that are responsible for Aβ deposition during AD, suggesting that this mouse model can be a useful model for studying the mechanisms and biomarkers of AD and for drug screening.     

麻醉和手术对实验动物血浆药物半衰期的影响

目的：观察麻醉和手术对家兔血浆水杨酸钠半衰期的影响。方法：将动物分为：非手术组（时照组）和手术组（全身麻醉组与局部麻醉组）。经耳缘静脉注射10％的水杨酸钠溶液（1．5ml·kg^-1）10 min和40min后,分别采取各组的动脉血液和静脉血液,用721-1分光光度仪测量血浆水杨酸光密度值,计算其半衰期。结果：手术组的半衰期比对照组的明显延长（P〈0．05,t=3．56）;全身麻醉组的半衰期比局部麻醉组的明显延长（P〈0．05,t=2．3）;全身麻醉组或局部麻醉组动、静脉血液的半衰期相比无差异。结论：麻醉和手术能延长家免血浆水杨酸钠的半衰期,而动、静脉血液间无差异。     

Resistance to activation-induced cell death and elevated FLIPL expression of CD4+ T cells in a polyI:C-induced primary biliary cirrhosis mouse model

Primary biliary cirrhosis (PBC) is a type of organ-specific autoimmune disease in which immune tolerance is impaired by an unknown mechanism. We established a PBC animal model by injecting C57BL/6 mice with polyI:C to study activation-induced cell death (AICD) in CD4+ T lymphocytes and changes of apoptosis-associated molecules as a first step to understand the immune tolerance of PBC mice. Obvious inflammatory cell infiltration was observed in the portal area of the liver tissues in model mice and antimitochondrial antibodies (AMA) positive rate was 80%. The AICD level in both splenic and hepatic CD4+ T cells in the model group were all lower than those in controls, and in the model group the level for hepatic CD4+ T cells were significantly lower than that for splenic CD4+ T cells. Quantitative PCR revealed that FasL mRNA and TRAIL expression in CD4+ T cells in the model group decreased significantly compared with that in the control group. Western blots revealed that the expression of the anti-apoptotic protein FLIP_L in the model group increased significantly with the FLIP_L expression in hepatic CD4+ T cells significantly higher than that in splenic CD4+ T cells. There was a positive linear correlation between the number of infiltrated portal areas and relative expression of FLIP_L in splenic CD4+ T cells in model group. There were no obvious changes for caspase-8 in either group. These results show that the anti-apoptotic ability of CD4+ T lymphocytes play an important role in immune tolerance in the PBC mouse model, and elevated FLIP_L expression may enhance this ability. The inhibition of FasL and TRAIL expression may also help enhance this anti-apoptotic ability in CD4+ T lymphocytes and contribute to the aggravation of portal area inflammation.     

肘前、外侧两种手术入路治疗桡骨头骨折的比较

目的探讨显露桡骨头骨折的有效手术入路。方法采用肘前侧手术入路显露桡骨头并结合微型空心螺钉固定治疗桡骨头骨折12例,其中2例MasonⅢ型骨折的骨折块于前臂完全旋后时位于桡骨头的前侧。采用传统的肘外侧手术入路10例,显露桡骨头骨折并用微型空心螺钉埋头固定。结果前侧手术入路显露骨折时间平均为20．7分,外侧入路显露骨折时间平均为11．6分。按照Broberg和Morrey肘关节评分标准评定手术疗效：前侧入路组优良率为92％,外侧入路组优良率为90％,两组间无明显差异。结论肘前侧入路可有效显露并固定桡骨头骨折,降低桡神经深支损伤的可能性,尤其适用于治疗前臂完全旋后时桡骨头前侧骨折这一特殊类型骨折。两种入路可视具体情况加以选用。     

Alu序列甲基化水平与两种乳腺癌细胞系转移能力高度相关

目的 探讨Alu序列甲基化与乳腺癌转移潜能的关系.方法 用亚硫酸氢盐修饰联合限制性内切酶分析法(combined bisulfite restriction analysis,COBRA)、亚硫酸氢盐修饰结合直接测序法(bisulfite sequencing,BSP)检测两株转移能力不同的乳腺癌细胞系MCF7和MDA-MB-435S中Alu甲基化状态,每个样品挑取10个克隆测序.结果 MCF7和MDA-MB-435S中Alu甲基化水平均明显低于报道的正常人体细胞Alu甲基化水平,但MCF7中Alu的甲基化水平明显高于MDA-MB-435S.同时,Alu甲基化位点在基因组中分布不均匀.结论 乳腺癌的转移潜能可能与Alu序列的去甲基化以及去甲基化位点的分布相关,值得进一步探讨.     

Bio-inspired design of dental multilayers: Experiments and model

This paper combines experiments, simulations and analytical modeling that are inspired by the stress reductions associated with the functionally graded structures of the dentin–enamel-junctions (DEJs) in natural teeth. Unlike conventional crown structures in which ceramic crowns are bonded to the bottom layer with an adhesive layer, real teeth do not have a distinct “adhesive layer” between the enamel and the dentin layers. Instead, there is a graded transition from enamel to dentin within a 10 to 100 μm thick regime that is called the Dentin Enamel Junction (DEJ). In this paper, a micro-scale, bio-inspired functionally graded structure is used to bond the top ceramic layer (zirconia) to a dentin-like ceramic-filled polymer substrate. The bio-inspired functionally graded material (FGM) is shown to exhibit higher critical loads over a wide range of loading rates. The measured critical loads are predicted using a rate dependent slow crack growth (RDEASCG) model. The implications of the results are then discussed for the design of bio-inspired dental multilayers.     

Akt2 is required for macrophage chemotaxis

Tumor‐associated macrophages play an important role in tumorigenesis and metastasis. Trafficking of macrophages to the proximity of tumors is mediated by CSF‐1, a growth factor. In this study, we investigated the role of PKB/Akt in CSF‐1‐induced macrophage migration. Disruption of Akt2 expression by small interference RNA impaired chemotaxis of both THP‐1 cells and mouse peritoneal macrophages. Phosphorylation of PKCζ, an essential component in chemotaxis signaling pathway, was reduced. LIMK/Cofilin, downstream of PKCζ, regulated cytoskeleton rearrangement during cell migration. Disruption of Akt2 expression inhibited CSF‐1‐induced LIMK/Cofilin phosphorylation, which contributed to defects in actin polymerization and chemotaxis. Furthermore, MCP‐1, a chemokine, ‐induced macrophage chemotaxis was also impaired. Taken together, our results demonstrated that Akt2 plays an essential role in both CSF‐1‐ and chemokine‐induced chemotaxis of macrophages.