玄胡索散通过下调粒细胞集落刺激因子抑制脾脏髓源抑制细胞分化发挥抗乳腺癌作用

目的:探讨玄胡索散抑制乳腺癌小鼠脾脏髓源抑制细胞(MDSC)分化的作用机制。方法:4～5周龄BALB/c雌性小鼠48只,其中6只为正常对照组,其他42只采用小鼠左侧第二对乳腺皮下脂肪垫接种4T1细胞构建乳腺癌荷瘤小鼠模型,分为粒细胞集落刺激因子(G-CSF)对照组、G-CSF敲减组、模型对照组、玄胡索散小剂量组、玄胡索散中剂量组、玄胡索散大剂量组和环磷酰胺组,每组6只。其中G-CSF对照组和G-CSF敲减组分别采用shRNA慢病毒转染联合嘌呤霉素构建相应4T1稳转细胞模型。各组造模48 h后,玄胡索散小剂量组、玄胡索散中剂量组、玄胡索散大剂量组分别按2、4、8 g·kg^-1·d^-1玄胡索散灌胃,每天一次;环磷酰胺组按30 mg/kg腹腔注射环磷酰胺,隔天一次;其他组给予等体积0.5%羟甲基纤维素纳。各组连续给药25 d。苏木精-伊红染色观察脾脏组织病理学改变,流式细胞术测定脾脏MDSC亚群比例,免疫荧光法检测脾脏CD11b、Ly6G共表达,酶联免疫吸附测定外周血G-CSF浓度。在体外,建立荷瘤小鼠脾脏与4T1稳转株共培养体系,玄胡索散(30μ...     

基于网络药理和实验验证探究中药通过健脾作用治疗白细胞减少症的作用机制

摘要 目的 运用数据挖掘、网络药理学和实验验证探讨中药通过健脾作用治疗白细胞减少症的用药规律、药效物质基础及潜在的作用机制。方法 在中国知网、万方数据知识服务平台、维普网和PubMed数据库中检索健脾中药复方治疗白细胞减少症的临床文献,运用古今医案云平台在线分析软件和SPSS Modeler 18 统计分析软件寻求核心药物组;利用中药系统药理学数据库和分析平台（TCMSP）、GeneCards数据库、OMIM数据库检索、Cytoscape3.7.2软件、STRING数据库获取关键基因和主要有效成分,利用Metascape进行基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析;采用MTT法检测细胞增殖率,采用qPCR法检测关键基因信使核糖核酸（mRNA）水平表达。结果 共筛选得到90篇有效文献,共计91首中药复方,党参-当归-黄芪为核心药物组合。肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、白细胞介素-10（IL-10）、JUN为核心靶点,槲皮素、木犀草素、山奈酚、芒柄花素、豆甾醇为主要有效成分,其主要作用机制可能通过癌症的途径、TNF信号通路、p53信号通路等来实现。健脾中药黄芪、党参、当归提取物和有效成分芒柄花素、槲皮素对人单核细胞白血病细胞（THP-1）具有促进增殖作用,芒柄花素对化疗诱导的THP-1细胞生长具有促进增殖的作用,芒柄花素能够抑制炎症细胞因子IL-6、IL-1β、TNF-α和刺激抗炎因子IL-10、原癌基因JUN的分泌。结论 初步揭示黄芪等多种中药通过多成分、多靶点发挥健脾作用,参与抗肿瘤、抗炎、免疫调节等相关信号通路,治疗白细胞减少症。     

基于"WD倒谱"法分析人体脾组织的超声散射微结构特征

本文提出了一种对超声散射信号分析的新方法--“WD倒谱”法,并利用该方法对人体正常脾和脾增生组织的回波信号进行了分析,对软组织中散射子的平均间距进行了估计,结果表明：两种脾组织散射子的平均同距明显不同;“WD倒谱”能有效的反映软组织的微观结构特征,说明“WD倒谱”是软组织超声散射信号分析与软组织散射子平均间距定征的一种有效方法。     

灵芝多糖对小鼠脾脏树突状细胞的增殖作用

目的 观察灵芝多糖（GP）对小鼠脾脏树突状细（dendrirtie cells，DCs）的增殖作用。方法采用MTT法，以细胞因子（GM-CSF＋IL-4）作比较，观察不同质量浓度GP以及细胞因子＋不同浓度的GP对小鼠脾脏DCs的增殖作用。结果GP（5-80μg/mL）可明显刺激小鼠脾脏DCs增殖，与细胞因子组相比，其较高质量浓度组（20、40、80μg／mL）作用明显；GP＋细胞因子，与对照组相比均有显著的增殖作用，且明显高于细胞因子组。结论GP不仅能促进小鼠脾脏DCs的增殖，而且与细胞因子有显著的协同作用。具有类生长因子和协同生长因子的作用。     

Oxygen uptake-heart rate relationship in élite wheelchair racers

The American College of Sports Medicine (ACSM) recommends that, as a general rule for health purposes, individuals should exercise at 40%–85% of their maximal oxygen uptakes. Moreover, it has been suggested that 55%–90% of the maximal heart rate may be used as an alternative estimate of these percentage maximal oxygen uptake values. The present study examined the relationship between percentage peak heart rate (% HR_peak) and percentage peak oxygen uptake (% ) during steady-state incremental intensity wheelchair propulsion of 16 élite, male wheelchair racers (WR). Oxygen uptake was determined during each submaximal exercise stage and heart rate (HR) was continuously monitored. The was subsequently determined using a separate protocol. Linear regression equations of % HR_peak versus % for each participant included % HR_peak values corresponding to 40%, 60%, 80% and 85% . The linear regression equation, derived as the group mean of the slope and intercept terms determined for each individual, was: . The group mean of the individual correlation coefficients for the relationship was 0.99. The values of % HR_peak for each of the % values below 85% were significantly greater (P<0.01) than those suggested by the ACSM. This suggests that the ACSM guidelines below 85% , based on % HR_peak, may underestimate the relative exercise intensity (i.e. % ) in the WR population. However, in élite level WR, % HR_peak can be recommended as an alternative estimate of % at wheelchair propulsion intensities of 85% or more. Electronic Publication     

Non-redundancy of cytidine deaminases in class switch recombination

Class switch recombination (CSR), somatic hypermutation, and gene conversion are immunoglobulin diversification mechanisms that are strictly dependent on the activity of the activation-induced cytidine deaminase (AID). The precise role and substrate(s) of AID in these processes remain to be well defined. The closest homologue of AID is APOBEC-1, a bona fide mRNA-editing enzyme, which shares with AID the ability to deaminate cytidines within single-stranded DNA in vitro and in prokaryotic cells. To determine whether APOBEC-1 can therefore substitute for AID in activated B cells, we expressed human AID, a catalytic mutant thereof, and rat APOBEC-1 in AID-deficient murine B cells. Whereas AID rescued CSR, neither the inactive mutant nor APOBEC-1 could complement AID deficiency. This indicates that cytidine deaminase activity is necessary but not sufficient to initiate CSR, and suggests that AID is specifically targeted to its cognate substrate, the immunoglobulin genes or a distinct mRNA, by an as-yet-unknown mechanism.     

Lymphotoxin but not tumor necrosis factor functions to maintain splenic architecture and humoral responsiveness in adult mice

To compare the function of the tumor necrosis factor (TNF) and lymphotoxin (LT)α/β systems in the mature immune system, these two pathways were blocked with soluble receptor-immunoglobulin (R-Ig) fusion proteins in normal adult mice. Inhibition of LTα/β signaling using LTβR-Ig or a blocking monoclonal antibody against murine LTβ had profound effects. The spleen lacked discrete B cell follicles and the marginal zone was altered. Less marked changes were detected in lymph nodes. LTα/β inhibition also prevented germinal center formation in the spleen and impaired Ig production in response to sheep red blood cells (SRBC) immunization. These results show that the LTα/β system is required for the maintenance of splenic architecture and normal immune responses, and not simply for the development of peripheral immune organs during ontogeny. In contrast, inhibition of the TNF/LTα pathway with TNF-R55-Ig did not affect the splenic architecture or the anti-SRBC response. Splenic defects and impaired antibody responses are seen in TNF-deficient mice, suggesting that TNF is important during development. Therefore relative to TNF, the LT system has the dominant influence on splenic organization and anti-SRBC Ig formation in the adult mouse.     

益精养血方对帕金森病大鼠多巴胺能神经元Caspase-3表达的影响

目的研究益精养血方对帕金森病(Parkinson's disease,PD)大鼠多巴胺能神经元Caspase-3表达的影响。方法将微量6-羟多巴胺(6-OHDA)立体定向注射于SD大鼠中脑右侧黑质以建立大鼠帕金森病模型,将造模成功的实验动物随机分为模型组、实验(中药)组,每组6只;另纳入6只正常大鼠为正常组。正常组和模型组大鼠生理盐水灌胃,实验组大鼠益精养血方灌胃,各30天。灌胃结束两周后进行行为学检测,免疫组织化学方法观测黑质酪氨酸羟化酶(TH)、Caspase-3的表达。结果实验组大鼠的旋转圈数比治疗前明显减少(P<0.05),实验组损毁侧与健侧黑质TH阳性细胞数量百分比较模型组显著提高(P<0.05),实验组损毁侧黑质Caspase-3表达的OD值比模型组显著降低(P<0.05)。结论益精养血方可使帕金森病大鼠多巴胺能神经元Caspase-3的表达降低,明显抑制神经细胞凋亡。