迷迭香酸药理作用及其递送系统的研究进展

迷迭香酸是从迷迭香等植物中分离得到的一种多酚类化合物,具有显著的抗氧化、抗炎、抗微生物、抗肿瘤及神经保护等作用。然而,由于溶解度差、渗透性低、光不稳定性、体内靶向性差、代谢速率快等缺点,限制了其药理活性及临床产品开发。药物递送系统能够在改善药物的理化性质、保护药物稳定性、发挥更佳给药途径和提高生物利用度等方面具有显著优点。通过对迷迭香酸的药理作用及新型药物载体用于迷迭香酸递送的研究进展进行综述,为迷迭香酸的药物开发和临床应用提供参考。     

南京市中老年人高尿酸血症检出情况及相关因素的分析

目的:了解南京市中老年(45岁以上)人群高尿酸血症的检出情况及相关因素. 方法:用随机整群抽样的方法选取社区居民5 423人,对其血尿酸、肌酐、胆固醇、三酰甘油、血糖进行测定,并调查其饮食等情况. 结果:社区人群中老年人群高尿酸血症患病率为15.0%,男20.1%,女10.6%.男性和女性高尿酸血症患病率在50岁年龄组明显升高,并在以后的年龄组中维持较高水平.高尿酸血症病人血胆固醇、三酰甘油、肌酐、尿酸、血糖、血压、体质指数(BMI)水平均高于非高尿酸血症者.BMI较高(1.512)、患高血压(1.859)为危险因素,而喜热食(0.687)则可能为保护因素. 结论:南京市中老年人高尿酸血症以50岁以上为多见.肥胖、患高血压为高尿酸血症的危险因素.     

Mechanisms of occupational asthma induced by isocyanates

Isocyanates are some of the most important low molecular weight chemicals associated with occupational asthma. These compounds are often volatile and they are highly reactive on mucous membranes, especially the conjunctivae and respiratory tract. Despite numerous data derived from experimental and clinical investigations, there is no agreement concerning the real mechanisms involved in isocyanate-induced occupational asthma. In fact, the cause of occupational asthma is multifactorial. The aim of this paper is to review the involved physiological causes of isocyanate-induced asthma; the main mechanisms are immunological, pharmacological and/or irritative.     

Liquid biopsy in lymphoma: Molecular methods and clinical applications

In this article, we broadly review the application of cfDNA analysis to the diagnosis and management of lymphoma. We introduce the advantages of cfDNA measurement over conventional tissue biopsy and describe how cfDNA may be utilized for both genotyping and detection of minimal residual disease. First, we discuss genotyping, beginning with differences in identifying mutations from the blood plasma vs. from circulating cells. We review the technical distinctions between PCR- and NGS-based assays and describe two important applications of NGS-based cfDNA tests, namely the identification of resistance mutations and classification of disease subtype. We discuss difficulties in genotyping diseases with low burden of tumor cells and the application of cfDNA assays in these contexts. Second, we describe the utility of ctDNA measurement in assessing MRD. We cover recent advances in the assessment of pre-treatment disease burden as a prognostic biomarker, detection of molecular response to therapy, and early detection of relapsing disease. Third, we explore select emerging areas of research in ctDNA technologies that show promise in boosting the performance of existing ctDNA-based assays. These include cell-free DNA fragment structure analysis or ‘fragmentomics’, epigenetic modifications, and novel circulating analytes such as tumor-educated platelets and extracellular vesicular DNA. We also discuss alternative analytes to blood plasma for tumor detection, such as urine, saliva, and stool. Finally, we present a case that highlights potential applications of ctDNA approaches to the management of patients with lymphoma, while also defining important prerequisite advances before this can be fully realized. We close with a look to the future of cfDNA applications, outlining one potential timeline and path forward towards routine clinical application.     

组织工程表皮与单核白血病细胞共培养的致敏性检测模型

背景:大量研究表明体外构建的组织工程皮肤可用于化学物质的刺激性检测。目的:构建组织工程表皮和单核白血病细胞共培养体外模型,并用致敏物初步验证。方法:利用人源性角质形成细胞构建组织工程表皮,和单核白血病细胞进行共培养,干预24h后,ELISA法检测空白对照组,溶剂对照组,二硝基氟苯处理组和十二烷基硫酸钠处理组培养液中白细胞介素1β的质量浓度,流式细胞术检测各组中单核白血病细胞表面标记物CD86和CD54的平均荧光强度。结果与结论:角质形成细胞气液界面培养14d后,苏木精-伊红染色结果显示构建的组织工程表皮含有8～10层细胞结构,泛角蛋白免疫组化染色阳性。二硝基氟苯处理组培养液中白细胞介素1β质量浓度,单核白血病细胞表面标记物CD86和CD54的平均荧光强度均高于溶剂对照组(P<0.05)。实验成功构建了组织工程表皮和单核白血病细胞共培养的致敏物检测模型。     

TRUE Gene Silencing : Unique Gene Silencing by the tRNA Maturase tRNase ZL under the Direction of Small-guide RNA

Recently, signaling by Wnt and its co-receptor, lipoprotein receptor-related protein (LRP) 5, has been suggested to be involved in the regulation of bone formation and bone mass. However, the mechanism by which Wnt signaling achieves this regulation is currently unknown. To assess the functional contribution of Wnt signaling to osteoblastic differentiation, we generated C2C12 cell lines that overexpress either Wnt3a or Wnt5a and treated these cell lines with bone morphogenetic protein (BMP)-2. Expression of bone matrix protein, matrix extracellular phosphoglycoprotein (MEPE), and matrix metalloproteinase (MMP)-13 was induced by BMP-2 in C2C12 cells overexpressing Wnt3a but not Wnt5a. Functional crosstalk between Wnt and BMP signaling during osteoblastic differentiation was also identified. We have now developed a unique system for downregulating gene expression that involves cutting a specific mRNA using the long form of tRNA 3′ processing endoribonuclease (tRNase ZL) under the direction of a small guide RNA (sgRNA). Any potential off-target effects of sgRNA would be expected to be much less serious than those induced by siRNA because the sgRNA targets complementary RNA of only 7–14 nt, a much smaller length of RNA than that targeted by siRNA. We compared the relative efficiency of the sgRNA/tRNase ZL and RNAi methods using an exogenous luciferase gene target. We found that our new method may be more effective at suppressing gene expression. Here, we also show that tRNaseZL, together with sgRNA, can downregulate expression of the endogenous human genes Bcl-2 and GSK-3β by degradation of their mRNAs. These data suggest that the TRUE (tRNase ZL-utilizing efficacious) gene silencing technology has the potential to be used as a therapeutic agent in the treatment of several diseases.     

N-正辛基-N′-琥珀酰基壳聚糖胶束的制备及特征研究*

目的：制备两亲性的N-正辛基-N’-琥珀酰基壳聚糖（OSC）胶束，并研究其制剂学特征。方法：采用超声方法制备OSC胶束，并考察OSC的胶束化行为、胶束的形态、粒径及￡电位。结果：OSC胶束具有较低的临界胶束浓度，胶束粒子呈较规则的球形，粒径为200～250nm，￡电位在-40．0～-30．0mV，且疏水链段取代度增加，粒径变大，临界胶束浓度降低。结论：OSC胶束具有较好的物理稳定性。     

黄连中5种小檗碱型生物碱在糖尿病大鼠体内的药动学

目的:研究灌胃黄连水提物后,其中所含的小檗碱、黄连碱、表小檗碱、药根碱及巴马汀等5种小檗碱型生物碱在糖尿病模型大鼠和正常大鼠体内的药动学行为.方法:采用腹腔注射链脲佐菌素诱发大鼠实验性糖尿病模型,与正常大鼠共同饲养6周后,灌胃给予黄连水提物,于给药后0.25,0.5,1.0,1.5,2,2.5,3,4,6,8,12和24 h眼底静脉丛取血,分离血浆后以LC-MS方法同时测定血浆中小檗碱、黄连碱、表小檗碱、药根碱和巴马汀的浓度,以DAS软件拟合求算相关药动学参数.结果:小檗碱型生物碱在正常大鼠体内的生物利用度较差,但在糖尿病模型大鼠体内,5种生物碱的cmax提高了1.7-3.3倍,AUXo-24提高了1.5-3.5倍.结论:糖尿病可能对5种生物碱在体内的吸收、分布、代谢和排泄过程中一个或多个环节产生影响,提高了其体内生物利用度,有利于其治疗作用的发挥.     

提高血氧分压对不同储存期血液红细胞影响的探讨

目的 探讨提高血氧分压在4℃保存条件下对不同储存期红细胞的影响。方法 在无菌条件下，分别对采集0、7、14d的库存血进行无菌氧处理，以提高血氧分压。分实验组和对照组（不加氧），测定血液红细胞在提高血氧分压后的血浆游离Hb浓度，血浆K^＋离子浓度，红细胞超氧化物歧化酶（SOD）活性，谷胱甘肽过氧化物酶（GSH-Px）活性。结果 与对照组比较，在4℃保存条件下，血液红细胞在提高血氧分压初期（1-2d），血浆游离Hb浓度和血浆K^＋离子浓度无明显变化（P〉0．05），红细胞SOD活性、红细胞GSH-Px活性有所提高（P〈0．05）；随着储存时间的延长，血浆游离Hb浓度增加，血浆K^＋离子浓度增高（P〈0．01），红细胞SOD活性和红细胞GSH-Px活性降低（P〈0．01）。结论 （1）红细胞能保持较高血氧分压和血氧饱和度；（2）血液红细胞在提高血氧分压的初期没有明显的溶血反应和其它损伤，红细胞抗氧酶活性有所提高。随着储存时间的延长，红细胞抗氧化酶活性下降，溶血反应加重，存在红细胞膜氧化损伤作用，这与氧自由基攻击红细胞膜发生过氧化反应及红细胞抗氧化酶活性降低有关。     

P基因在中国汉族及藏族群体中的多态性研究

目的：研究中国汉族和藏族两个群体中P基因3个外显子多态性。方法：利用PCR－RFLP多态性方法扩增P基因的3个外显子10、14、24,对其产物分别用HaeⅢ、MboⅡ、MaeⅢ酶切,4％琼脂糖凝胶电泳确定基因型。结果：A355A和G780G的等位基因频率在两个群中的差异具有显著性（χ^2＝24．54,χ^2=37.05,P＜0．001）,各基因型频率分布在两个群体间差异具有显著性（χ^2＝28．39,P＜0．001;χ^2=33.72,P＜0．001）;在两个群体内部男女基因型频率差异无显著性;IVS13－15的等位基因频率在两个群体中差异无显著性（χ^2＝2．06,P＜0．05）。汉族与藏族的基因型分布符合Hardy-Weinberg平衡。结论：P基因在不同的人群中具有很高的多态性。