知母皂苷抑制血小板聚集的活性成分筛选及构效关系分析

目的 筛选从知母中分离的甾体皂苷抑制血小板聚集的活性成分并对其进行构效关系分析.方法 雄性Wistar大鼠心脏取血,离心分离获得富血小板血浆,分别加入呋甾烷型或螺甾烷型甾体皂苷化合物孵育3min后,以二磷酸腺苷(ADP)诱导大鼠血小板聚集,采用比浊法检测血小板聚集情况,通过比较不同甾体皂苷化合物对ADP诱导血小板聚集的抑制作用分析化合物的构效关系.结果 8个呋甾烷型甾体皂苷均无抑制血小板聚集的活性;4个螺甾烷型甾体皂苷在不同程度上抑制了血小板聚集,其中知母皂苷AⅢ作用最强,随后依次是知母皂苷AⅠ、知母皂苷AⅢ异构体和知母皂苷Ⅲ,而萨尔萨皂苷元没有活性;在苷元结构C-3位连接不同类型糖基的甾体皂苷抑制血小板聚集的作用不同,其中C-3位糖基为葡萄糖(D-Glc)时能完全抑制血小板聚集,而连接其他糖基如半乳糖(D-Gal)、阿拉伯糖(D-Ara)、核糖(D-Rib)、鼠李糖(L-Rha)或甘露糖(D-Man)时,抑制活性有不同程度的减弱.结论 知母皂苷AⅢ是知母抑制血小板聚集的主要有效活性成分之一;甾体皂苷抑制血小板聚集的活性与其结构密切相关;第3、15、22位上的基团类型可影响甾体皂苷抑制血小板聚集的生物活性.     

SU11274衍生物的合成及受体酪氨酸激酶抑制活性评价

目的 合成SU11274衍生物并对其进行受体PTK抑制活性评价.方法 合成了用乙二胺、1,3-丙二胺、1,2-丙二胺、1,6-己二胺替代SU11274哌嗪基团的4个SU11274新衍生物,结构经1H-NMR和ESI-MS验证.采用ELISA方法对这4个化合物进行了受体PTK抑制活性评价.结果 合成的4个SU11274衍...     

人胎肝中两种抑瘤活性成分的分离和结构鉴定

胎肝细胞中存在低分子肿瘤抑制物。胎肝细胞悬液或裂解液用甲醇－丙酮提取后保留有大部分抑瘤活性。体外液体培养条件下以其对人急性粒系白血病细胞的抑制作用为指标，跟踪活性成分的分离过程。     

重组人proEMAPⅡ/p43体外抑制新生血管生成活性方法的建立

目的建立proEMAPⅡ/p43蛋白体外检测抑制新生血管生成活性的方法。方法利用内皮细胞增殖实验、细胞周期实验、细胞迁移实验、管腔形成实验、鸡胚绒毛尿囊膜实验等体外检测血管生成的模型,研究p43蛋白抑制血管生成的活性。结果 p43蛋白能明显抑制内皮细胞迁移和管腔形成,但对内皮细胞增殖和细胞周期没有明显的量效关系。结论最终选用细胞迁移实验和管腔形成实验作为主要活性检测方法,细胞迁移实验作为p43蛋白活性的定量检测方法,迁移抑制率作为活性高低的评价标准,管腔形成实验用于p43蛋白活性的定性研究。     

背景信号抑制扩散加权成像对兔VX2肝移植瘤疗效评价的实验研究

目的探讨磁共振背景信号抑制扩散加权体部成像(MR DWIBS)在经肝动脉化疗栓塞术(TACE)联合静脉注射血管生成抑制剂内皮抑素(ES)治疗VX2肝移植瘤疗效评价中的作用。材料与方法荷瘤兔随机分为两组,每组8只。ES组经耳缘静脉注射ES0.7 mg.kg-1.d-1,连续应用12天;TACE+ES组经肝动脉给予超液化碘油0.2 ml/kg和阿霉素2 mg/kg,并经耳缘静脉注射内皮抑素0.7 mg.kg-1.d-1,连续应用12天。两组均于治疗前后行MR DWIBS检查,分别测量各组肿瘤组织在不同时间点的表观扩散系数(ADC),并评价DWIBS及DWIBS原始图经3D MIP重组及黑白翻转获得类PET图像的图像特征。结果 ADC值从治疗后第3天起即有变化,TACE+ES组ADC值在治疗后第3、7、13天均高于ES组并有统计学意义(P<0.05)。结论 DWIBS可以在治疗早期动态评价TACE术联合静脉注射血管生成抑制剂ES对VX2肝移植瘤的疗效。DWIBS结合ADC值的定量测量及类PET大范围成像,可以无创性活体评价药物抗肿瘤的治疗反应,为肿瘤的诊断、分期、疗效评价提供有价值的信息。     

非特异性酯酶α－NAE活性及抑制试验对急性白血病分型诊断的评价研究

本研究分别采用０，１．５，３．０，４．０，５．０，６．０，７．０，８．０，９．０，１０．０ｍｇ／ｍｌ共１０个不同浓度的ＮａＦ对２０６０份血液标本进行活性及抑制试验。结果表明：α－ＮＡＥ可存在于多种血细胞中，并且不能被以上任何浓度的ＮａＦ完全抑制，仅呈轻度或中度不完全抑制。这一结果为重新评价非特异性酯酶α－ＮＡＥ在急性白血病分型诊断中的价值和意义提供了新的理论依据     

芫花根醇提物弱极性组分化学成分及抗炎活性研究

目的 阐明芫花根醇提物弱极性组分化学成分及其对急性炎症的抑制活性。方法芫花根醇提物以硅胶柱层析,石油醚／丙酮梯度洗脱。以GC-MS分析弱极性组分的化学成分。以角叉菜胶致大鼠足肿胀和小鼠网状内皮系统对刚果红吞噬活性为模型,评价其对急性炎症的抑制活性。结果芫花根醇提物经硅胶柱层析得5个弱极性组分(F1～F5),GC-MS共检出98种化合物,其中脂肪族化合物48种,芳香族化合物24种,主要成分为苯甲酸酯衍生物。倍半萜1种,生物碱9种,三萜7种,其主要成分为齐墩果烷衍生物。甾族化合物9种。F1～F5对角又菜胶致大鼠足肿胀有显著的抑制作用,能显著提升小鼠网状内皮系统对刚果红的吞噬作用。结论芫花根醇提物弱极性组分中的苯甲酸酯衍生物、甾族化合物和齐墩果烷衍生物是其具有抗炎活性的物质基础。     

An evaluation of pre-exercise screening questionnaires used within the health and fitness industry in the United Kingdom

The Physical Activity Readiness Questionnaire (PARQ) and its successor the Revised Physical Activity Readiness Questionnaire (rPARQ) were designed to offer a safe pre-exercise screen for those wishing to undertake exercise. The rPARQ was created in order to reduce the number of people who were unnecessarily excluded from exercising by PARQ. This study compared the two questionnaires against each other and used the RISKO Coronary Heart Disease Risk Appraisal Form in order to ascertain the sensitivity of them both. In addition, the results were compared with those published in similar studies in North America. Fifty volunteers, from a South Wiltshire leisure centre, were screened using the PARQ, rPARQ and the RISKO. Having completed the three questionnaires, the subjects were then interviewed and finally had their blood pressure measured. The results showed that the number of subjects excluded by the PARQ was significantly (p<0.05) higher than the rPARQ. Comparisons between this study and North American studies revealed that both the PARQ and the rPARQ excluded significantly more subjects in the United Kingdom. This study highlighted flaws in the screening questionnaires when used with a United Kingdom population. These flaws, including high exclusion rates (compared with North American studies), could have serious implications given the projected growth in health and fitness participation in the United Kingdom.     

鳀鱼蛋白酶水解物的营养成分分析及评价

目的 测定鳀鱼蛋白酶水解物的一般成分、氨基酸、脂肪酸、7种微量元素的含量,评价其化学成分,为进一步的功能研究提供参考.方法 采用化学分析,氨基酸、脂肪酸组成分析,微量元素分析等方法.结果 鳀鱼蛋白酶水解物粗蛋白含量为71.2%,粗脂肪含量为0.1%,总糖含量为1.5%,并含有17种氨基酸、5种脂肪酸及7种微量元素.结论 鳀鱼蛋白酶水解物氨基酸、微量元素含量丰富,是值得进一步研究的海洋生物制品.     

In vitro evaluation of the astatinated chimeric monoclonal antibody U36, a potential candidate for treatment of head and neck squamous cell carcinoma

Purpose The purpose of this study was to analyse the properties of the astatinated chimeric MAb (cMAb) U36 as a conjugate to selectively target and eradicate head and neck squamous cell carcinoma (HNSCC).Methods cMAb U36 was labelled with ²¹¹At via the linker N-succinimidyl 4-(trimethylstannyl)benzoate (SPMB). The quality of the conjugate was extensively evaluated for binding and internalisation capacity, and compared with ¹²⁵I-SPMB-cMAb U36. The cellular toxicity of the astatinated conjugate was assessed in two types of in vitro growth assay and compared with ¹³¹I-labelled cMAb U36 (directly labelled).Results Comparisons between ²¹¹At-cMAb U36 and ¹²⁵I-cMAb U36 demonstrated an optimal functional capacity of the labelled products. Immunoreactivity and affinity assays showed high immunoreactive fractions (>93%), and an affinity in good agreement between the astatinated and iodinated antibodies. For both conjugates, specific binding to HNSCC cells could be demonstrated, as well as some internalisation. Retention of the astatinated conjugate was just slightly lower than for the iodinated conjugate and still reasonable for therapeutic use (31±2% vs 42.6±1.0% at 22 h), demonstrating no adverse effects from astatination of the antibody. Studies on cellular toxicity demonstrated a dose-dependent and antigen-specific cellular toxicity for ²¹¹At-cMAb U36, with about 10% cell survival at 50 decays per cell. The ¹³¹I-labelled conjugate was not as efficient, with a surviving cell fraction of about 50% at 55 decays per cell.Conclusion These results indicate that ²¹¹At-cMAb U36 might be a promising future candidate for eradicating HNSCC micrometastases in vivo.     

Assessment of the transfer,persistence, prevalence and recovery of DNA traces from clothing: An inter-laboratory study on worn upper garments

Among the various items recovered from crime scenes or persons involved in a crime event, clothing items are commonly encountered and submitted for forensic DNA sampling. Depending on the case circumstances and the activity-of-interest, sampling of the garment may concentrate on collecting DNA from the wearer, or from one or more offenders who have allegedly contacted the item and/or wearer. Relative to the targeted DNA, background DNA already residing on the item from previous contacts, or transferred during or after the crime event, may also be collected during sampling and observed in the resultant DNA profile. Given our limited understanding of how, and from where, background DNA is derived on clothing, research on the transfer, persistence, prevalence, and recovery (TPPR) of DNA traces from upper garments was conducted by four laboratories. Samples were collected from several areas of two garments, each worn on separate working or non-working days and individually owned by four individuals from each of the four laboratories, and processed from DNA extraction through to profiling. Questionnaires documented activities relating to the garment prior to and during wearing, and reference profiles were obtained from the wearer and their close associates identified in the questionnaire. Among the 448 profiles generated, variation in the DNA quantity, composition of the profiles, and inclusion/exclusion of the wearer and their close associates was observed among the collaborating laboratories, participants, garments worn on different occasions, and garment areas sampled.     

当归挥发油质量评价及透皮吸收研究

目的:考察不同方法提取的当归挥发油质量,并考察其透皮性能,为筛选当归挥发油提取方法及制剂研发提供依据。方法:采用水蒸气蒸馏法、超临界萃取法和溶剂萃取法提取当归挥发油,高效液相色谱法测定当归挥发油中主要成分藁本内酯,用改良的Franz扩散池进行体外透皮实验。结果:溶剂萃取法提取的当归挥发油中藁本内酯含量高,0.5%、1.0%、2.0%当归挥发油经皮渗透12 h,藁苯内酯单位面积累积渗透量分别为(1 102±40.31)μg/cm2、(1 812±43.81)μg/cm2、(2 408±76.83)μg/cm2。结论:当归挥发油透皮性能良好,为进一步开发外用制剂奠定良好基础。     

The Arm Posture Score for assessing arm swing during gait: An evaluation of adding rotational components and the effect of different gait speeds

In 3D gait analysis, quantification of leg movements is well established, whereas a measure of arm swing has been lacking. Recently, the Arm Posture Score (APS) was introduced to characterize arm movements in children with cerebral palsy, including information from four variables (APS₄) in the sagittal and frontal planes. A potential limitation of the APS is that it does not include rotational movements and has not yet been evaluated with regard to gait speed. The aims of this study were (i) to investigate the effect on APS of adding two components of arm rotation (APS₆) and (ii) to determine the influence of gait speed on the APS measures, when applied to non-disabled adults. Forty-two subjects walked 10 m at a self-selected speed (1.34 m/s), and in addition a subgroup of 28 subjects walked at a slow speed (0.66 m/s) set by a metronome. Data were collected from markers in a whole-body set up and by eight optoelectronic cameras. The results demonstrated significantly higher APS₆ than APS₄ values for both arms, irrespective of gait speed. Speed condition, whether self-selected or slow, had a significant effect on both APS measures. The two additional arm components are suggested to provide relevant information about arm swing during walking. However, APS₆ needs to be implemented in gait analysis of individuals with gait arm pathologies in order to further examine its utility. We recommend that gait speed should to be taken into account when using APS measures to quantify arm swing during gait.     

Development and inter-laboratory evaluation of the VISAGE Enhanced Tool for Appearance and Ancestry inference from DNA

Responding to the growing scientific and practical interest in forensic DNA phenotyping, the VISible Attributes through GEnomics (VISAGE) Consortium was founded in 2017 with the main goal of developing and validating new and reliable molecular and statistical tools to predict appearance, ancestry and age from DNA. Here, we describe the development and inter-laboratory evaluation and validation of the VISAGE Enhanced Tool for Appearance and Ancestry inference from DNA. The VISAGE Enhanced Tool for Appearance and Ancestry is the first forensic-driven genetic laboratory tool that comprises well-established markers for eye, hair and skin color with more recently discovered DNA markers for eyebrow color, freckling, hair shape and male pattern baldness and bio-geographic ancestry informative DNA markers. The bio-geographic ancestry markers include autosomal SNPs (bi- and tri-allelic SNPs), X-SNPs, Y-SNPs and autosomal Microhaplotypes. In total, primers targeting 524 SNPs (representing a 97.6% assay conversion rate) were successfully designed using AmpliSeq into a single primer pool (i.e., one multiplex assay) and sequenced with the Ion S5. In a collaborative framework, five VISAGE laboratories tested the VISAGE Enhanced Tool for Appearance and Ancestry on reproducibility, sensitivity, genotyping concordance, mixtures, species specificity and performance in relevant forensic conditions, including inhibitor-spiked, mock casework and artificially degraded samples. Based on our results, the VISAGE Enhanced Tool for Appearance and Ancestry is a robust, reproducible, and – for the large SNP number - fairly sensitive MPS assay with high concordance rates. With the VISAGE Enhanced Tool for Appearance and Ancestry introduced here, the VISAGE Consortium delivers the first single DNA-test for combined appearance prediction based on seven traits together with bio-geographic ancestry inference based on major continental regions for separated bi-parental and paternal ancestry, which represents the most comprehensive validated laboratory tool currently available for Forensic DNA Phenotyping.