基于网络药理学预测当归贝母苦参丸治疗前列腺癌作用靶点及细胞内信号转导通路

目的:通过网络药理学方法预测分析当归贝母苦参丸治疗前列腺癌的潜在机制。方法:通过TCMSP数据库检索中药的化学成分和作用靶点,并于UniProtKB网络平台获取每种靶蛋白的基因名。借助CTD等数据库查询疾病靶点。在STRING数据库中构建蛋白-蛋白互作网络（PPI）,于Cytoscape中进行网络可视化分析。通过DAVID数据平台对关键靶蛋白进行分析。结果:从TCMSP数据库中共筛选得到26个药物有效成分。PPI网络包括135个药物疾病交集靶基因,关键蛋白为34个。基因本体论（GO）分析这些靶基因涉及生物功能条目最多,共290个。京都基因与基因组百科全书（KEGG）通路主要涉及肿瘤信号通路等。结论:当归贝母苦参丸治疗前列腺癌是多靶点、多通路协同作用的结果,能够通过抑制细胞增殖,促进细胞凋亡,抑制迁移以及抑制肿瘤血管生成等多方面发挥其抗肿瘤作用。     

利用流式分选技术富集空载质粒转染特定巨噬细胞的方法及条件优化

目的：建立BD FACSAria II流式细胞分选仪富集PX458空载质粒转染J774A.1细胞的方法并进行技术优化,确立用于筛选J774A.1细胞的最佳条件。方法：构建PX458空载质粒转染J774A.1细胞株,进行7-AAD染色。选择BD FACSAria II流式细胞分选仪的100 μm喷嘴以及initial、4-way purity、purity、yield、fine tune、single cell 6种分选模式分选J774A.1细胞的GFP阳性转染株,比较仪器各部分参数变化对分选效率的影响。结果：在仪器稳定的液流条件下,100 μm喷嘴各分选模式所得细胞纯度均达80%以上,其中purity模式分选效率最高,达95.7%±1.0%。结论：使用BD FACSAria II流式细胞分选仪100 μm喷嘴分选PX458空载转染的J774A.1细胞选择purity分选模式最合适。     

甲基化芯片检测电离辐射诱导人外周血淋巴细胞DNA甲基化水平的变化

目的：筛选正常人细胞基因组中电离辐射后甲基化水平发生变化的基因,为在其中寻找新型辐射损伤标志物奠定研究基础。方法：⁶⁰Co γ射线照射人外周血全血,照射剂量为0、0.5和2.0 Gy。利用Illumina 450K芯片检测外周血淋巴细胞基因组DNA甲基化水平的变化,筛选甲基化水平差异的基因,利用GO功能富集分析基因的分子功能和参与的生物学途径。结果：0.5和2.0 Gy γ射线照射下人外周血淋巴细胞基因组DNA甲基化水平显著上调的基因有1 311个,显著下调的基因286个。GO功能富集分析表明,按富集度大小排列,差异基因在生物途径水平上排在首位的是“细胞过程”（富集度=5.86）,在细胞定位水平上排在首位的是“细胞”（富集度=7.48）,在分子功能水平上排在首位的是“结合”（富集度=5.27）。进一步细分后得到差异基因显著富集在与转录调控及转录因子活性相关的功能上,与以往的研究结果认为DNA甲基化参与转录调控和基因表达相一致;甲基化水平差异基因还显著富集在核苷连接（GO：0001882）上,并在其中寻找到与DNA修复相关的基因RAD50、RAD54L和INIP,以及与维持染色体结构稳定相关的基因HIST1H4K、SMC1B。结论：正常人外周血淋巴细胞基因甲基化水平受电离辐射影响,可进一步研究将这些与DNA修复、维持染色体结构稳定相关的基因甲基化水平作为辐射损伤标志物的可行性。     

用直接投入增菌法进行药品包装材料控制菌检查的探索性研究

目的:对复合膜、硬片、铝箔、瓶盖、垫片、干燥剂等药品包装材料构建微生物限度检查-控制菌检查的新方法,为加强药品包装材料的微生物质量控制提供一种检测新思路.方法:分别取代表性复合膜、硬片、铝箔、瓶盖、垫片、干燥剂样品,用代表性菌株制备人工污染样品,采用国家药品包装材料标准规定的方法(以下简称供试液增菌法)以及本研究建立的...     

Recurrent perseveration correlates with abnormal repetitive locomotion in adult mink but is not reduced by environmental enrichment

We analysed the relationship between abnormal repetitive behaviour (ARB), the presence/absence of environmental enrichment, and two types of behavioural disinhibition in farmed American mink, Neovison vison. The first type, recurrent perseveration, the inappropriate repetition of already completed responses, was assessed using three indices of excessive response repetition and patterning in a bias-corrected serial two-choice guessing task. The second type, disinhibition of prepotent responses to reward cues, a form of impulsivity, was tested in a locomotive detour task adapted from primate reaching tasks: subjects were required to walk around, rather than directly into, a transparent barrier behind which food was visible. In older adult females, recurrent perseveration positively predicted pre-feeding abnormal repetitive locomotion (ARL) in Non-enriched housing. High-ARL subjects also performed repeated (same-choice) responses more rapidly than low-ARL animals, even when statistically controlling for alternated (different-choice) response latency. Mink performed much less ARL following transfer to Enriched housing, but there was no corresponding change in recurrent perseveration. Thus, elevated recurrent perseveration is not sufficient for frequent ARL; and while captive environments do determine ARL frequency, in mink, they do not necessarily do so by modifying levels of perseveration. Disinhibition of prepotent responses to reward cues, meanwhile, did not predict ARL. In a separate sample of differentially housed young adults, neither type of behavioural disinhibition predicted ARL, and again, whether or not housing was enriched did not affect behavioural disinhibition despite affecting ARL. Thus, the relationship between recurrent perseveration and ARB may only develop with age; longitudinal studies are now required for confirmation.     

Preventive and therapeutic types of environmental enrichment counteract beta amyloid pathology by different molecular mechanisms

Combined preventive and therapeutic physical/cognitive stimulation starting before disease onset and continuing over its progression reduce Alzheimer-related pathology in transgenic mice. We now report that exposure of TgCRND8 mice to an enriched environment as either a preventive or therapeutic approach is also capable to reduce Aβ burden, though with different plaque and cerebral amyloid angiopathy (CAA) morphology. Preventive treatment resulted in fewer and smaller plaques without affecting CAA, whereas in therapeutically treated mice beside reduction of CAA extent, numerous plaques of strongly diminished size were found, so that total plaque loads declined as well. These effects seemed to be mediated by distinct molecular pathways. In preventive but not therapeutic group a shift of Aβ(42/40) ratio towards Aβ(40) and up-regulation of Aβ clearing and degrading molecules were found. Contrariwise anti-oxidative defense mechanisms were induced only in therapy but not preventive group. We hypothesize that preventive enrichment lowers the amounts of plaque seeds and decelerates plaque growth by degradation and clearance of Aβ, while therapeutic enrichment mitigates growth and fusion of plaque seeds to large plaques by inhibiting further Aβ aggregation. This study provides an experimental basis for application of physical/cognitive training in both prophylaxis and therapy of Alzheimer's disease.     

Circulating tumor cells: finding the needle in the haystack

Localized and metastatic cancers give rise to circulating tumor cells (CTCs) which are detectable in the bloodstream. Recent studies have highlighted the prognostic significance of the presence and number of CTCs, particularly in patients with metastatic disease. Future studies are designed not only to detect CTCs, but also to characterize them. This review discusses current and developing methodologies for the isolation and characterization of CTCs as well as recent studies focusing on the clinical relevance of CTC detection and characterization.     

Environmental enrichment differentially modifies specific components of sensory-evoked activity in rat barrel cortex as revealed by simultaneous electrophysiological recordings and optical imaging in vivo

Environmental enrichment of laboratory animals leads to multi-faceted changes to physiology, health and disease prognosis. An important and under-appreciated factor in enhancing cognition through environmental manipulation may be improved basic sensory function. Previous studies have highlighted changes in cortical sensory map plasticity but have used techniques such as electrophysiology, which suffer from poor spatial resolution, or optical imaging of intrinsic signals, which suffers from low temporal resolution. The current study attempts to overcome these limitations by combining voltage-sensitive dye imaging with somatosensory-evoked potential (SEP) recordings: the specific aim was to investigate sensory function in barrel cortex using multi-frequency whisker stimulation under urethane anaesthesia. Three groups of rats were used that each experienced a different level of behavioural or environmental enrichment. We found that enrichment increased all SEP response components subsequent to the initial thalamocortical input, but only when evoked by single stimuli; the thalamocortical component remained unchanged across all animal groups. The optical signal exhibited no changes in amplitude or latency between groups, resembling the thalamocortical component of the SEP response. Permanent and extensive changes to housing conditions conferred no further enhancement to sensory function above that produced by the milder enrichment of regular handling and behavioural testing, a finding with implications for improvements in animal welfare through practical changes to animal husbandry.     

Olfactory enrichment improves the recognition of individual components in mixtures

Odor mixtures can exhibit synthetic (the mixture is qualitatively different from its components) or elemental properties (the components are recognizable). We tested how prior olfactory enrichment affects the recognition of individual components in binary mixtures. Experimental rats were exposed to pairs of similar odors for one-hour periods twice daily over 20 days. Spontaneous discrimination between the binary mixture and the individual components of similar pairs of odors was tested before and after the odor enrichment. We found that, after the enrichment period, rats could discriminate components in binary mixtures that had not been discriminated prior to the enrichment period, and that this increase in discrimination capability was not always specific to the odorants used during the enrichment period.     

固定化离子液体吸附分离八角茴香中莽草酸

目的研究固定化离子液体(SILs)对八角茴香提取液中莽草酸的吸附分离性能,并分离制备莽草酸。方法采用静态与动态吸附-解吸方法,研究SILs对莽草酸的吸附平衡和吸附动力学性能,并采用Freundlich型和Langmuir型方程拟合了303、313、323 K温度下的吸附等温线。结果 SILs对莽草酸具有良好的吸附特性,吸附等温线与Freundlich型和Langmuir型方程拟合效果均较好,且以Freundlich型方程拟合更佳。采用SILs对八角茴香中莽草酸进行富集分离,富集率为80.34%。结论该方法简便易行、富集率高,可用于八角茴香提取液(物)中莽草酸的富集分离。