Danshensu Promotes Cholesterol Efflux in RAW264.7 Macrophages

Contemporary research suggests that macrophage foam cell and cholesterol efflux defect play pivotal role in atherogenesis. We reported on the heretofore unknown therapeutic effect of Danshensu (DSS) in reducing intracellular cholesterol level and unraveled the mechanism of DSS promotes cholesterol efflux. Oxidized low‐density lipoprotein stimulation of Raw264.7 cells into foam cells, which were treated with DSS and co‐treated with Simvastatin and Rosiglitazone. PPARγ, ABCA1, ABCG1, SR‐BI, CD36, and LXR‐α mRNA were quantified by Real‐Time PCR. Western blotting was used to determine protein expression of PPARγ, ABCA1 and CD36. Cellular cholesterol handling was studied by measurement of intracellular lipid droplets concentration and cholesterol efflux. DSS significantly reduced scavenger receptor CD36 and its orthologue SR‐BI. In addition, DSS stimulated the upregulation of cellular cholesterol exporters ABCA1 and ABCG1 to reduce intracellular lipid accumulation. DSS can reduce lipid deposition in Raw264.7 foam cells by balancing CD36 and ABCA1 protein expression.     

Perilla Oil Reduces Fatty Streak Formation at Aortic Sinus via Attenuation of Plasma Lipids and Regulation of Nitric Oxide Synthase in ApoE KO Mice

Consumption of n‐3 polyunsaturated fatty acids (PUFA) is associated with a reduced incidence of atherosclerosis. Perilla oil (PO) is a vegetable oil rich in α‐linolenic acid (ALA), an n‐3 PUFA. In this study, antiatherogenic effects and related mechanisms of PO were investigated in atherosclerotic mice. Apolipoprotein E knockout (ApoE KO) mice (male, n = 27) were fed high‐cholesterol and high‐fat diets containing 10 % w/w lard (LD), PO, or sunflower oil (SO) for 10 weeks. Plasma triglyceride, total cholesterol, and low‐density lipoprotein cholesterol concentrations reduced in the PO and SO groups compared to the concentrations in the LD group (P < 0.05). The PO group showed reduced fatty streak lesion size at the aortic sinus (P < 0.05) compared to the sizes in the LD and SO groups. A morphometric analysis showed enhancement of endothelial nitric oxide synthase expression and reduction of inducible nitric oxide synthase expression in the PO group compared to that in the LD group (P < 0.05). Furthermore, aortic protein expression of intercellular cell adhesion molecule 1 and vascular cell adhesion molecule 1 was diminished in the PO group compared to that in the LD and SO groups (P < 0.05). These findings suggested that PO inhibited the development of aortic atherosclerosis by improving the plasma lipid profile, regulating nitric oxide synthase, and suppressing the vascular inflammatory response in the aorta of ApoE KO mice.     

瑞苏伐他汀遗传药理学研究进展

胆固醇水平升高是动脉粥样硬化发病的主要原因。瑞苏伐他汀为临床常用的抑制胆固醇合成的药物,其药动学和药效学存在显著个体差异。药物转运体、药物代谢酶、药物靶点的遗传多态性对瑞苏伐他汀的体内代谢和临床疗效个体差异具有重要作用。本文阐述了药物转运体、细胞色素P450酶和其他相关基因的遗传多态性对瑞苏伐他汀药动学和药效学的影响,为临床制定个体化用药方案提供参考。     

Focused ion beam-scanning electron microscope: exploring large volumes of atherosclerotic tissue

Atherogenesis is a pathological condition in which changes in the ultrastructure and in the localization of proteins occur within the vasculature during all stages of the disease. To gain insight in those changes, high-resolution imaging is necessary. Some of these changes will only be present in a small number of cells, positioned in a 'sea' of non-affected cells. To localize this relatively small number of cells, there is a need to first navigate through a large area of the sample and subsequently zoom in onto the area of interest. This approach enables the study of specific cells within their in vivo environment and enables the study of (possible) interactions of these cells with their surrounding cells/environment. The study of a sample in a correlative way using light and electron microscopy is a promising approach to achieve this; however, it is very laborious and additional ultrastructural techniques might be very valuable to find the places of interest.
In this report we show that the focused ion beam-scanning electron microscope is a powerful tool to study biological specimens in a correlative way. With this microscope one can scan for the area of interest at low magnification, in this case the atherosclerotic plaque, and subsequently zoom in, for further analysis on an ultrastructural level, rendering valuable and detailed two- and three-dimensional information of, in this case, the endothelial cells and the vessel wall. Moreover, in combination with pre-embedment labelling of surface exposed antigens, the method allows insight into the 3D distribution of these markers.     

Phenolics from purple grape, apple, purple grape juice and apple juice prevent early atherosclerosis induced by an atherogenic diet in hamsters

Knowledge of the effects of processing on the antioxidant properties of fruits is limited. We investigated the processing of apple (A) and purple grape (PG) and their juices (AJ and PGJ) in hypercholesterolemic hamsters. Five groups of eight hamsters each were fed an atherogenic diet for 12 wk. They received daily by gavage either 7.14 mL/(kg x day) of mashed A or PG, or the same volume of AJ or PGJ, or water as control. Plasma cholesterol, non-HDL cholesterol, liver superoxide dismutase and glutathione peroxidase activities, and thiobarbituric acid reactive substances were efficiently reduced by the fruits and their juices compared with controls, whereas plasma antioxidant capacity was increased and aortic fatty streak area was decreased from 48 to 93%. For each of these parameters, the efficacy was PGJ > PG > AJ > A. The results show for the first time that long-term consumption of antioxidants supplied by apple and purple grape, especially phenolic compounds, prevents the development of atherosclerosis in hamsters, and that processing can have a major impact on the potential health benefits of a product. The underlying mechanism is related mainly to increased antioxidant status and improved serum lipid profile.     

Self‐Assembled Monolayers on Gold for the Fabrication of Radioactive Stents

An innovative and easily applicable method for the fabrication of radioactive stents, to be used for the treatment of restenosis, is presented. By incorporating the β‐emitting radioisotopes ¹⁸⁶Re, ¹⁸⁸Re, ⁹⁰Y, or ³²P into sulfur‐containing adsorbates, it becomes possible to cover a gold surface with a radioactive self‐assembled monolayer (SAM). Two methods have been investigated. In the first, SAMs consisting of potentially radioactive rhenium‐, yttrium‐, and phosphorus‐containing adsorbates have been assembled on 2D gold substrates, after which they have been studied by wettability measurements, electrochemistry, and X‐ray photoelectron spectroscopy (XPS). The stability of these SAMs under simulated physiological conditions (phosphate buffered saline, PBS solution) for periods up to two months has been demonstrated. Alternatively, potentially radioactive monolayers have been prepared by exposure of SAMs of mono‐, bi‐, and tridentate ligands to a solution containing a radiometal (rhenium) in order to bind the metal to the monolayer. The polydentate ligands exhibit excellent binding capacity, leading to SAMs containing over 10^–10 mol/cm² of the radiometal, which is more than sufficient to make this system viable for the delivery of therapeutical dosages of radiation.     

石灰石分解特性及微观结构迁移规律研究

采用自建的热重分析仪进行石灰石煅烧分解的热重实验,得到了温度、煅烧气氛及粒径对石灰石分解过程的影响规律,利用扫描电镜(scanning electron microscopy,SEM)和比表面积及孔隙度分析仪重点考察了分解过程中煅烧产物微观结构的迁移变化规律。研究表明:温度是影响石灰石煅烧的关键因素,温度越高,反应越快;CO2分压和粒径的增大对石灰石分解反应有一定的抑制作用;石灰石煅烧产物比表面积和比孔容随煅烧时间的延续快速增加。超过完全分解时间继续煅烧,煅烧产物产生烧结,比表面积和比孔容减小;原始石灰石几乎为无孔形态,随着煅烧过程的进行,微孔、中孔和大孔出现,呈双峰结构分布,煅烧开始至2.5 min时段内中孔增长较多,2.5～6.5 min时段内微孔和大孔快速生成,烧结导致孔的数量减少。     

A SNOMED supported ontological vector model for subclinical disorder detection using EHR similarity

Electronic Health Records (EHR) form a valuable resource in the healthcare enterprise because clinical evidence can be provided to identify potential complications and support decisions on early intervention. Simple string matching, the common search algorithm, is not able to map a query to the similar health records in the database with respect to the medical concepts. A novel ontological vector model supported by the Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) is proposed in this paper to project the disease terms of a health record to a feature space so that each health record can be characterized using a feature vector, giving a fingerprint of the record. The similarity between the query and database health records was measured by similarity measures of their feature vectors and string matching score respectively. Three types of similarity measures were considered in this study, namely, Euclidean distance (ED), direction cosine (DC) and modified direction cosine (mDC). Medical history and carotid ultrasonic imaging findings were collected from 47 subjects in Hong Kong. The dataset formed 1081 pairs of health records and ROC analysis was used to evaluate and compare the accuracy of the ontological vector model and simple string matching against the agreement of the presence or absence of carotid plaques identified by carotid ultrasound between two subjects. It was found that the score generated by simple string matching was a random rater but the ontological vector model was not. In other words, the degree of health record similarity based on the ontological vector model is associated with the agreement of atherosclerosis between two patients. The vector model using feature terms at the SNOMED-CT level 4 gave the best performance. The performance of mDC was very close to that of ED and DC but the properties of mDC make it more suitable for the retrieval of similar health records. It was also shown that the ontological vector model was enhanced by the support vector classifier approach.