植物中吡咯里西啶生物碱的检测与分析

吡咯里西啶生物碱广泛分布于植物界。很多吡咯里西啶生物碱对动物和人类有严重的毒性作用,包括肝脏毒性,肺脏毒性,致癌作用,致突变作用和神经毒性等。本文综述了植物中吡咯里西啶生物碱的分离,纯化,检测与分析。     

关于纳米二氧化硅毒性研究中实验方法问题的探讨

纳米二氧化硅在生产生活各个领域均有广泛的应用前景,人们暴露于纳米二氧化硅的机会越来越多,其毒性作用也受到了广泛关注。大量关于纳米二氧化硅毒性作用的研究已经开展,但目前依然没有国际公认的关于纳米材料毒性的评价标准,各个研究组因所用实验方法的不同导致研究结果相互不能比较、借鉴,甚至出现研究结论互相矛盾。本文就纳米二氧化硅毒性研究中实验方法的问题进行探讨,旨在为更科学、准确地评价纳米二氧化硅的毒性作用提供理论基础。     

纳米颗粒与生物大分子的相互作用及其生物毒性机制

纳米颗粒已得到广泛的应用,同时其潜在的毒性及生物学效应也引起了广泛的关注。许多文献证实纳米颗粒对生物体具有毒性作用,但在分子水平上对其毒性机制的研究较少。本文对近年来纳米颗粒与生物大分子相互作用的最新研究进行了综述,包括纳米颗粒与蛋白质、脂类、核酸等生物分子间的相互作用。     

2,4-二氯苯氧乙酸的研究进展

2,4-二氯苯氧乙酸经常作为除草剂和植物生长调节剂使用,在农林业中发挥了重大作用,尤其在水果(如柑橘)保鲜中应用广泛,但其毒性问题也受到广泛关注,因此了解2,4-D的生理作用、在生物及环境中的代谢降解、残留毒性和提取鉴定等的研究进展很有必要.     

氨磷汀在广泛期小细胞肺癌化疗中增效减毒作用的研究

目的观察氨磷汀在广泛期小细胞肺癌化疗中增效减毒的作用,以更好地指导临床用药。方法随机选取初治于大连医科大学附属第二医院肿瘤内科的广泛期小细胞肺癌患者69例,分为加氨磷汀组39例和不加氨磷汀组30例。统计入选的患者均用IP方案化疗,21d为1个周期。均有经CT扫描具有可测量肿瘤病灶。化疗4个周期后按照WHO制定的抗癌药物急性与亚急性不良反应分级标准,按RECIST方法进行疗效评估,研究氨磷汀在广泛期小细胞肺癌化疗中的增效减毒作用。结果化疗4个周期后,加氨磷汀组患者骨髓毒性、肝毒性、肾毒性、神经毒性明显低于不加氨磷汀组,两组比较差异有统计学意义(P0.05)。疗效、胃肠道反应、免疫系统方面加氨磷汀组患者与不加氨磷汀组比较差异无统计学意义(P0.05)。结论 (1)氨磷汀对广泛期小细胞肺癌患者IP方案化疗的近期疗效无影响。(2)氨磷汀能减少广泛期小细胞肺癌IP方案化疗的骨髓毒性、肝毒性、肾毒性、神经毒性等毒副作用,进一步提高化疗患者生活质量。     

毒性分子-抗毒性分子系统的生物学作用研究进展

毒性分子-抗毒性分子系统(toxin-antitoxin systems,TA systems)被发现广泛存在于细菌染色体、质粒以及古细菌基因组中。TA系统是由2个基因组成的操纵子,这2个基因分别编码稳定的毒性分子和不稳定的抗毒性分子。毒性分子总是蛋白质,抗毒性分子可能是蛋白质或RNA。因此,根据抗毒性分子的性质和作用方式的不同可将TA系统家族分为5种类型。Ⅰ型和Ⅲ型的抗毒性分子是RNA,能抑制毒性分子的合成或者与其隔离;II、IV和V型的抗毒性分子是蛋白质,能隔离、平衡毒性分子作用或抑制其合成。TA系统具有多种生物学功能。目前研究表明,TA系统可能在细菌应激应答、程序化细胞死亡、多重耐药的形成、防止DNA入侵、稳定大基因组片段等方面有重要的作用。     

硫化镉纳米粒子对原核生物的毒理作用

硫化镉纳米粒子（cadmium sulfide nanoparticles,CdS NPs）是一种重要的半导体,具有突出的光电特性、可调带隙和化学稳定性,在分析化学、生物医学、荧光成像和生物传感器等方面具有潜在应用价值。生物合成CdS NPs具有可控、低成本、环境友好等优势而被广泛研究。然而CdS NPs本身兼具纳米材料毒性及重金属硫化物毒性,其对原核微生物的毒性研究受到广泛关注。本文以大肠杆菌为例,对CdS NPs在原核生物细胞内的毒性机理研究进展进行了综述,包括CdS NPs的生物合成机制、CdS NPs对大肠杆菌的毒害作用以及大肠杆菌对该毒害作用的防御机制,着重论述了细菌在合成CdS NPs过程中Cd²⁺及CdS对合成细菌本身的毒理作用及该细菌所产生的相应应激机制。本文旨在更好、更全面地评估CdS NPs的毒性,促进抗CdS NPs的原核生物在相关领域的发展和应用。     

蜘蛛毒素的研究进展及其相关应用

蜘蛛毒素含有多种化学成分,除毒性作用外这些物质对机体产生多重影响并具有多种活性。近年来,大量新的毒性组分不断被分离纯化,其结构和功能性作用被广泛深入研究,蜘蛛毒素成为了生物毒素领域新的研究热点。本文对蜘蛛毒素在离子通道作用机制方面的最新研究进展进行了阐述,同时还探讨了蜘蛛毒素在医学实践中新的应用和发展。     

栀子提取物保肝利胆及其毒性作用的研究进展

栀子作为保肝利胆的中药已被广泛复方用于临床,栀子提取物在基础研究中也被发现有很突出的保肝利胆功效,但不可忽视的是栀子提取物具有保肝和肝毒性双重作用。本综述通过对栀子提取物的保肝、利胆以及其肝脏毒性作用的研究现状进行探讨,期待栀子相关新药能够及早研发、并合理应用,服务于临床。     

含镉量子点的毒性研究进展

含镉量子点是典型的量子点,近年来受到广泛研究。含镉量子点的潜在毒性是其在生物成像及生物医药方面应用和发展的关键制约因素,因此,对其毒性作用的研究具有重要意义。目前对含镉量子点的体外毒性研究主要集中在人肝癌细胞(HepG2)、神经分泌细胞(PC12)等细胞实验及斑马鱼胚胎体外培养实验。体内毒性研究包括小鼠等动物实验。这些研究证实,量子点对HepG2等细胞系和小鼠、贻贝等动物均具细胞毒性。研究者们普遍认为,量子点是通过释放其组成中的重金属,诱导生物体产生活性氧自由基,进而引发细胞凋亡或自噬,但对量子点的具体毒性作用机制并不完全清楚。该文对含镉量子点的体内和体外毒性研究工作进展进行了综述,包括含镉量子点对肝肾细胞、神经细胞、血液细胞及免疫细胞等体外毒性研究工作,对陆生及水生动物等的体内毒性研究工作,旨在更好、更全面地评估含镉量子点的毒性,为今后对量子点的毒性作用机制研究提供方向,促进含镉量子点在生物医学方面的发展和应用。     

柴胡属植物化学成分研究进展

从主要化学成分及药理作用方面,对柴胡属(BupleurumL.)植物近年来研究的主要进展和一些重要结果进行了概述。并指出,今后应该加强柴胡属的植物结构与其主要化学成分的关系以及综合利用的研究。     

Olfaction and the common chemical sense: some psychophysical contrasts.

Three experiments explored the olfactory and the common chemical attributes of sensations produced by various concentrations of n-butyl alcohol. These two attributes combine in an almost-linear fashion to produce the overall perceived intensity of the stimulus. Common chemical intensity makes only a small contribution to overall magnitude at low concentrations, but its proportional contribution increases with concentration. In like manner, speed of response (i.e., reciprocal of reaction time) to the common chemical attribute increases more rapidly than that to odor. Nevertheless, odor always makes its appearance sooner than the common chemical attribute, even when the two attributes are matched in perceived magnitude. Repeated inhalations cause odor intensity to decrease slightly but cause common chemical intensity to increase dramatically. The results obtained from the normal subjects studied here agree with those obtained from subjects with unilateral destruction of the trigeminal nerve.     

化学肥料的土壤生态环境效应

目前我国的化肥生产和消费量均居世界第一.2006年全年化肥产量达5 304.8×10⁴ t,比2005年增长14.2％,化肥氮平均施用量超过220 kg·hm^-2,一季作物磷肥施用量超过102 kg·hm^-2（P₂O₅）.一些化肥中含有有毒重金属、无机酸和有机物等副成分,长期施用化肥导致污染物在土壤中累积,严重影响土壤的生态环境,使蔬菜、粮食、水果等农产品中的重金属、硝酸盐等有害物质严重超标,农产品质量受到严重威胁.本文分析了化肥污染土壤的原因、特点和后果及我国土壤环境现状,并提出了减轻化肥污染农业生态环境的技术和措施.     

Fluorescence correlation spectroscopy. II. An experimental realization

This paper describes the first experimental application of fluorescence correlation spectroscopy, a new method for determining chemical kinetic constants and diffusion coefficients. These quantities are measured by observing the time behaviour of the tiny concentration fluctuations which occur spontaneously in the reaction system even when it is in equilibrium. The equilibrium of the system is not disturbed during the experiment. The diffusion coefficients and chemical rate constants which determine the average time behaviour of these spontaneous fluctuations are the same as those sought by more conventional methods including temperature-jump or other perturbation techniques. The experiment consists essentially in measuring the variation with time of the number of molecules of specified reactants in a defined open volume of solution. The concentration of a reactant is measured by its fluorescence; the sample volume is defined by a focused laser beam which excites the fluorescence. The fluorescent emission fluctuates in proportion with the changes in the number of fluorescent molecules as they diffuse into and out of the sample volume and as they are created or eliminated by the chemical reactions. The number of these reactant molecules must be small to permit detection of the concentration fluctuations. Hence the sample volume is small (10^?8 ml) and the concentration of the solutes is low (～ 10^?9 M). We have applied this technique to the study of two prototype systems: the simple example of pure diffusion of a single fluorescent species, rhodamine 6G, and the more interesting but more challenging example of the reaction of macromolecular DNA with the drug ethidium bromide to form a fluorescent complex. The increase of the fluorescence of the ethidium bromide upon formation of the complex permits the observation of the decay of concentration fluctuations via the chemical reaction and consequently the determination of chemical rate constants.     

白兰花被片发育过程中香精油化学成分的GC-MS分析

用固相微萃取法萃取白兰(Michelia alba Dc.)花被片不同发育阶段的香精油,并用GC-MS对其化学成分进行鉴定,峰面积归一化法测定各成分的相对含量.结果表明,白兰花被片5个发育时期的香精油的化学成分不同,分别鉴定出30、29、28、30和27种化学成分.含量较多的是萜类化合物、烷烃类物质、酯类化合物、酸类化合物和醇类化合物.有16种化学成分在3个以上时期能检测到,其中14种萜类化合物,1种胺类化合物和1种芳香化合物.有7种成分是第Ⅳ期独有的.由此推测,白兰花发育的第Ⅳ时期是窨制花茶或提取香精油的最佳时期,但在不能及时窨制花茶或提取香精油或远距离运输的情况下,选择第Ⅲ时期采摘更为合适.     

Chemical biology of tetracycline antibiotics.

For more than half a century, tetracycline antibiotics have been used to treat infectious disease. However, what once used to be a commonly prescribed family of antibiotics has now decreased in effectiveness due to wide-spread bacterial resistance. The chemical scaffold of the tetracyclines is a versatile and modifiable structure that is able to interact with many cellular targets. The recent availability of detailed molecular interactions between tetracycline and its cellular targets, along with an understanding of the tetracycline biosynthetic pathway, has provided us with a unique opportunity to usher in a new era of rational drug design. Herein we discuss recent findings that have clarified the mode of action and the biosynthetic pathway of tetracyclines and that have shed light on the chemical biology of tetracycline antibiotics.     

Cyclic 3':5'-nucleotide phosphodiesterase. Ca2+ confers more helical conformation to the protein activator.

The ultraviolet spectrum of a protein activator of cyclic nucleotide phosphodiesterase and adenylate cyclase purified to homogeneity from bovine brain displayed absorption peaks at 252, 259, 265, 269, and 277 nm. The activator contained no phosphate and did not serve as a substrate for cyclic adenosine 3':5'-monophosphate- or cyclic guanosine 3':5'-monophosphate-dependent protein kinases. The activator binds Ca2+, and the active form appears to be a Ca2+ activator complex (Lin, Y.M., Liu, Y.P., and Cheung, W.Y. (1974) J. Biol. Chem. 249, 4943-4954). Optical rotatory dispersion measurement showed that the Ca2+-free activator exhibited a reduced mean residue rotation ([m']231) of -5700, corresponding to 39% of helical content. In the presence of Ca2+, the [m']231 was increased to -7500, corresponding to 57% of helical content. The Ca2+ -induced conformational change was corroborated by a chemical method. In the presence of Ca2+, the activator was more resistant to trypsin inactivation, presumably because proteins with more helical structures are more resistant to tryptic attack. The activator is rich in aspartate and glutamate. Chemical block of some of the carboxyl groups with glycine ethyl ester or methoxyamine diminished the [m']231 of the activator and its activity, suggesting that blockade of some of the carboxyl groups in the activator unfolded the molecule, leading to a loss of activity. We conclude that Ca2+, which confers more helical structure to the activator, converts the inactive, less helical structure to the active, more helical structure, and that chemical modification of the activator leading to unfolding of the molecule abolishes its biological activity.     

Decomposition of Toxic Chemical Substance Management in Three U.S. Manufacturing Sectors from 1991 to 2008

This study analyzes toxic chemical substance management in three U.S. manufacturing sectors from 1991 to 2008. Decomposition analysis applying the logarithmic mean Divisia index is used to analyze changes in toxic chemical substance emissions by the following five factors: cleaner production, end‐of‐pipe treatment, transfer for further management, mixing of intermediate materials, and production scale. Based on our results, the chemical manufacturing sector reduced toxic chemical substance emissions mainly via end‐of‐pipe treatment. In the meantime, transfer for further management contributed to the reduction of toxic chemical substance emissions in the metal fabrication industry. This occurred because the environmental business market expanded in the 1990s, and the infrastructure for the recycling of metal and other wastes became more efficient. Cleaner production is the main contributor to toxic chemical reduction in the electrical product industry. This implies that the electrical product industry is successful in developing a more environmentally friendly product design and production process.     

Activity of penicillin acylase from E. coli in the reversed-micelle system AOT--H2O--octane

The behavior of a penicillin acylase from E. coli was studied in the reversed-micelle system AOT--H2O--octane. Kinetic studies of the enzymatic hydrolysis of the m-carboxy-p-nitroanilide of phenylacetic acid, titration of the penicillin acylase active site with an irreversible specific inhibitor (phenylmethylsulfonyl fluoride), sedimentation analysis at different hydration degrees, and chemical modification showed that the enzyme loses no more than 20% of its initial activity during 3-4 h in the reversed-micelle systems of different hydration degrees and retains its catalytically active structure.     

Engineering the prion protein using chemical synthesis.

In recent years, the technology of solid-phase peptide synthesis (SPPS) has improved to the extent that chemical synthesis of small proteins may be a viable complementary strategy to recombinant expression. We have prepared several modified and wild-type prion protein (PrP) polypeptides, of up to 112 residues, that demonstrate the flexibility of a chemical approach to protein synthesis. The principal event in prion disease is the conformational change of the normal, alpha-helical cellular protein (PrPc) into a beta-sheet-rich pathogenic isoform (PrP(Sc)). The ability to form PrP(Sc) in transgenic mice is retained by a 106 residue 'mini-prion' (PrP106), with the deletions 23-88 and 141-176. Synthetic PrP106 (sPrP106) and a His-tagged analog (sPrP106HT) have been prepared successfully using a highly optimized Fmoc chemical methodology involving DCC/HOBt activation and an efficient capping procedure with N-(2-chlorobenzyloxycarbonyloxy) succinimide. A single reversed-phase purification step gave homogeneous protein, in excellent yield. With respect to its conformational and aggregational properties and its response to proteinase digestion, sPrP106 was indistinguishable from its recombinant analog (rPrP106). Certain sequences that proved to be more difficult to synthesize using the Fmoc approach, such as bovine (Bo) PrP(90-200), were successfully prepared using a combination of the highly activated coupling reagent HATU and t-Boc chemistry. To mimic the glycosylphosphatidyl inositol (GPI) anchor and target sPrP to cholesterol-rich domains on the cell surface, where the conversion of PrPc is believed to occur, a lipophilic group or biotin, was added to an orthogonally side-chain-protected Lys residue at the C-terminus of sPrP sequences. These groups enabled sPrP to be immobilized on either the cell surface or a streptavidin-coated ELISA plate, respectively, in an orientation analogous to that of membrane-bound, GPI-anchored PrPc. The chemical manipulation of such biologically relevant forms of PrP by the introduction of point mutations or groups that mimic post-translational modifications should enhance our understanding of the processes that cause prion diseases and may lead to the chemical synthesis of an infectious agent.