肿瘤血管生成抑制剂的作用机制研究进展

肿瘤血管生成抑制剂批能破坏或抑制血管生成,有效地阻止肿瘤生长和转移的药物,可分为特异性和非特异性两大类。其作用机制主要有：（１）调控血管形成生长因子;（２）抑制基底膜降解;（３）影响信号转导通路;（４）调控细胞生长周期;（５）调控肿瘤机关基因。本文对其作用机制的进展作一综述。     

MD Simulations and first principles to evaluate the role of binary Fe–V alloys layer on the radiation resistance in the alpha-iron

Radiation damage in reactor materials caused by the collision of the fast neutrons has a great impact on the reliability and safety of nuclear reactors. The element vanadium has attracted interest in many fields due to its advantageous properties in alloys. Thus, molecular dynamics simulation (MD) and first-principles calculation have been executed here to explore the radiation-resistant properties of five materials adding a layer in the bulk (pure iron and four types of Fe–V alloys containing 10%-40% V). The following results were inferred from these simulations. Firstly, the number of Frenkel pairs (FPs) at the stable quenching stage in the bulk decreases when the Fe–V alloy is added as an anti-radiation layer to the bulk. These benefits are evident for the Fe₈₀V₂₀ and alloy layers with more vanadium. The main reason is that the Fe–V binding energy is greater than the Fe-Fe binding energy, which can make the Primary Knock-On atom (PKA) lose more energy at the Fe–V alloy layer. Secondly, the average value of point-defect, cluster and defect clustered fractions in the bulk of Fe–V alloy is smaller than that in the pure iron at the stable quenching stage, especially for the Fe₈₀V₂₀ alloy.     

Sucrose nonfermenting AMPK-related kinase (SNARK) regulates exercise-stimulated and ischemia-stimulated glucose transport in the heart

The signaling mechanisms mediating myocardial glucose transport are not fully understood. Sucrose nonfermenting AMP-activated protein kinase (AMPK)-related kinase (SNARK) is an AMPK-related protein kinase that is expressed in the heart and has been implicated in contraction-stimulated glucose transport in mouse skeletal muscle. We first determined if SNARK is phosphorylated on Thr²⁰⁸, a site critical for SNARK activity. Mice were treated with exercise, ischemia, submaximal insulin, or maximal insulin. Treadmill exercise slightly, but significantly increased SNARK Thr²⁰⁸ phosphorylation. Ischemia also increased SNARK Thr²⁰⁸ phosphorylation, but there was no effect of submaximal or maximal insulin. HL1 cardiomyocytes were used to overexpress wild-type (WT) SNARK and to knockdown endogenous SNARK. Overexpression of WT SNARK had no effect on ischemia-stimulated glucose transport; however, SNARK knockdown significantly decreased ischemia-stimulated glucose transport. SNARK overexpression or knockdown did not alter insulin-stimulated glucose transport or glycogen concentrations. To study SNARK function in vivo, SNARK heterozygous knockout mice (SNARK^+/−) and WT littermates performed treadmill exercise. Exercise-stimulated glucose transport was decreased by ~50% in hearts from SNARK^+/− mice. In summary, exercise and ischemia increase SNARK Thr²⁰⁸ phosphorylation in the heart and SNARK regulates exercise-stimulated and ischemia-stimulated glucose transport. SNARK is a novel mediator of insulin-independent glucose transport in the heart.     

Molecular cloning and expression analysis of RrNHX1 and RrVHA-c genes related to salt tolerance in wild Rosa rugosa

Salt stress is one important factor influencing the growth and development of plants, and salt tolerance of plants is a result of combined action of multiple genes and mechanisms. Rosa rugosa is not only an important ornamental plant, but also the natural aromatic plant of high value. Wild R. rugosa which is naturally distributed on the coast and islands of China has a good salt tolerance due to the special living environment. Here, the vacuolar Na⁺/H⁺ reverse transporter gene (NHX1) and the vacuolar H⁺-ATPase subunit C gene (VHA-c) closely related to plant salt tolerance were isolated from wild R. rugosa, and the expression patterns in R. rugosa leaves of the two genes under NaCl stress were determined by real-time quantitative fluorescence PCR. The results showed that the RrNHX1 protein is a constitutive Na⁺/H⁺ reverse transporter, the expression of the RrNHX1 gene first increased and then decreased with the increasing salt concentration, and had a time-controlled effect. The RrVHA-c gene is suggestive of the housekeeping feature, its expression pattern showed a similar variation trend with the RrNHX1 gene under the stress of different concentrations of NaCl, and its temporal expression level under 200 mM NaCl stress presented bimodal change. These findings indicated that RrNHX1 and RrVHA-c genes are closely associated with the salt tolerance trait of wild R. rugosa.     

肾缺血增强大鼠延髓腹外侧头端区神经元电话动和Fos蛋白表达

在67只切断两侧缓冲神经的麻醉Sprague-Dawley大鼠,应用细胞外记录的电生理方法和免疫组织化学技术,分别观察肾缺血对延髓腹外侧头端区巨细胞旁外侧核神经元自发放电活动和Fos蛋白表达的影响.所得结果如下(1)左肾动脉阻断后,28个单位的放电频率由11.40±1.08增至21.1±1.74spikes/s(P<0.001),血压和心率无明显变化(P>0.05);(2)在17个放电单位中,应用腺苷受体拮抗剂8-苯茶碱(8-phenyltheophylline,10mg/kg)可明显抑制肾缺血的兴奋效应(P<0.05);(3)肾缺血后,延髓腹外侧头端区的Fos蛋白样免疫反应神经元显著增加(P<0.01);(4)预先应用8-苯茶碱可明显减弱肾缺血所激活的Fos蛋白表达反应(P<0.05).以上结果提示肾缺血增强延髓腹外侧头端区神经元的放电活动和Fos蛋白表达,而此作用可能与肾脏缺血所产生的腺苷激活肾内感受器有关.     

单面针的生物碱研究

自芸香科(Rutaceae)花椒属植物单面针(Zanthoxylum nitidum var. fastuosum How ex Huang)的根皮中分得五种已知生物碱:乙氧基白屈菜红碱(ethoxychelerythrine)(Ⅰ);氯化光花椒碱(nitidine chloride)(Ⅱ);去甲基白屈菜红碱(des-N-methychelerythrine)(Ⅲ);α—别隐品碱(α-allocryptopine)(Ⅳ);鹅掌揪宁(liriodenine)(Ⅴ).     

Infestation and Related Ecology of Chigger Mites on the Asian House Rat (Rattus tanezumi) in Yunnan Province,Southwest China

This paper is to illustrate the infestation and related ecological characteristics of chigger mites on the Asian house rat (Rattus tanezumi). A total of 17,221 chigger mites were collected from 2,761 R. tanezumi rats, and then identified as 131 species and 19 genera in 2 families. Leptotrombidium deliense, the most powerful vector of scrub typhus in China, was the first major dominant species on R. tanezumi. All the dominant mite species were of an aggregated distribution among different individuals of R. tanezumi. The species composition and infestations of chiggers on R. tanezumi varied along different geographical regions, habitats and altitudes. The species-abundance distribution of the chigger mite community was successfully fitted and the theoretical curve equation was Ŝ (R)=37e^−(0.28R)². The total chigger species on R. tanezumi were estimated to be 199 species or 234 species, and this further suggested that R. tanezumi has a great potential to harbor abundant species of chigger mites. The results of the species-plot relationship indicated that the chigger mite community on R. tanezumi in Yunnan was an uneven community with very high heterogeneity. Wide geographical regions with large host samples are recommended in the investigations of chigger mites.     

Bone phenotype of P2X4 receptor knockout mice: implication of a P2X7 receptor mutation?

Transgenic and knockout animal models are widely used to investigate the role of receptors, signaling pathways, and other peptides and proteins. Varying results are often published on the same model from different groups, and much effort has been put into understanding the underlying causes of these sometimes conflicting results. Recently, it has been shown that a P2X4R knockout model carries a so-called passenger mutation in the P2X7R gene, potentially affecting the interpretation of results from studies using this animal model. We therefore report this case to raise awareness about the potential pitfalls using genetically modified animal models, especially within P2 receptor research. Although purinergic signaling has been recognized as an important contributor to the regulation of bone remodeling, the process that maintains the bone quality during life, little is known about the role of the P2X4 receptor (P2X4R) in regulation of bone remodeling in health and disease. To address this, we analyzed the bone phenotype of P2rx4tm1Rass (C57BL/6J) knockout mice and corresponding wildtype using microCT and biomechanical testing. Overall, we found that the P2X4R knockout mice displayed improved bone microstructure and stronger bones in an age- and gender-dependent manner. While cortical BMD, trabecular BMD, and bone volume were higher in the 6-month-old females and 3-month-old males, this was not the case for the 3-month-old females and the 6-month-old males. Bone strength was only affected in the females. Moreover, we found that P2X4R KO mice carried the P2X7 receptor 451P wildtype allele, whereas the wildtype mice carried the 451L mutant allele. In conclusion, this study suggests that P2X4R could play a role in bone remodeling, but more importantly, it underlines the potential pitfalls when using knockout models and highlights the importance of interpreting results with great caution. Further studies are needed to verify any specific effects of P2X4R on bone metabolism.

     

大麦G－带变动性以及与染色粒的一致性分析

以大麦为材料,进行了Ｇ－带带纹变动性分析以及Ｇ－带与减数分裂粗线期染色粒的比较。有丝分裂早中期至中期两个不同时期Ｇ－带带纹总数减少３６％,染色体组的绝对长度缩短２５％,带数减少的幅度大于染色体长度缩短的幅度。染色体组中每条染色体之间带纹减少的比例不尽相同,变幅在０．２９－０．５０之间。不同染色体绝对长度减少的幅度在０．２７－３．７０μ之间。从早中期至中期,每单位染色体绝对长度带数具相对减少的趋势。选择第６染色体进行的比较显示,减数分裂的染色粒与有丝分裂的Ｇ－带带纹之间具有很好的对应关系,Ｇ－带带纹和染色粒间的数目、位置和着色程度上都具一致性。对Ｇ－带性质和植物中Ｇ－带的应用等问题进行了讨论。