根据基因表达谱与基因功能模块研究大鼠抑郁症发病的分子机制

用Willner法构造大鼠抑郁症模型,由基因芯片检测8例模型和8例正常大鼠的基因表达谱,识别差异表达基因,寻找差异表达基因功能模块并构建基因表达相关网络,研究大鼠抑郁症模型的分子病理机制.在基因本体(GO)功能体系中寻找显著富集差异表达基因的疾病相关功能模块,提取疾病相关功能模块中的基因构造表达相关网络.从中选择显著多地与其它基因共表达的基因定义为HUB基因,并进一步研究其与疾病的关系.筛选得到207个差异表达基因及13个差异表达基因功能模块,主要涉及神经肽激素活性、信号传导通路、核糖体生成以及蛋白质转运与降解.在共表达相关网络中进一步识别了4个差异表达的HUB基因.利用基因功能模块和表达相关网络研究疾病机制的结果显示,抑郁症的发病可能涉及单胺递质的释放、信号传导以及神经肽激素调节等通路协同作用.     

聚氨酯软骨-骨双层复合材料的构建及性能研究

关节软骨损伤是临床上的常见病,由于其组织再生能力差,可能导致骨性关节炎的发生,因此,研究开发骨-软骨移植替代材料非常重要。目的就是设计一体化软骨-骨双层复合材料,以解决软骨与骨的整合问题。该双层复合体上层软骨材料为聚氨酯,软骨下骨为羟基磷灰石/聚氨酯复合支架材料,两层结构中引用了同一种材料——聚氨酯,将双层结构有机黏合在一起,使黏合更牢固。下层多孔HA/PU复合支架材料的孔与孔之间相互贯通,孔隙率约为83%,孔径范围分布在200～600μm。体外细胞相容性实验表明,该一体化双层复合材料为细胞的黏附、增殖以及生存活力的维持提供了有利环境。上述结果表明该双层复合材料有望用于软骨组织工程修复。     

Role of cell polarity dynamics and motility in pattern formation due to contact-dependent signalling

A key challenge in biology is to understand how spatio-temporal patterns and structures arise during the development of an organism. An initial aggregate of spatially uniform cells develops and forms the differentiated structures of a fully developed organism. On the one hand, contact-dependent cell–cell signalling is responsible for generating a large number of complex, self-organized, spatial patterns in the distribution of the signalling molecules. On the other hand, the motility of cells coupled with their polarity can independently lead to collective motion patterns that depend on mechanical parameters influencing tissue deformation, such as cellular elasticity, cell–cell adhesion and active forces generated by actin and myosin dynamics. Although modelling efforts have, thus far, treated cell motility and cell–cell signalling separately, experiments in recent years suggest that these processes could be tightly coupled. Hence, in this paper, we study how the dynamics of cell polarity and migration influence the spatiotemporal patterning of signalling molecules. Such signalling interactions can occur only between cells that are in physical contact, either directly at the junctions of adjacent cells or through cellular protrusional contacts. We present a vertex model which accounts for contact-dependent signalling between adjacent cells and between non-adjacent neighbours through long protrusional contacts that occur along the orientation of cell polarization. We observe a rich variety of spatiotemporal patterns of signalling molecules that is influenced by polarity dynamics of the cells, relative strengths of adjacent and non-adjacent signalling interactions, range of polarized interaction, signalling activation threshold, relative time scales of signalling and polarity orientation, and cell motility. Though our results are developed in the context of Delta–Notch signalling, they are sufficiently general and can be extended to other contact dependent morpho-mechanical dynamics.     

Walking on water: revisiting the role of water in articular cartilage biomechanics in relation to tissue engineering and regenerative medicine

The importance, and the difficulty, of generating biosynthetic articular cartilage is widely recognized. Problems arise from obtaining sufficient stiffness, toughness and longevity in the material and integration of new material into existing cartilage and bone. Much work has been done on chondrocytes and tissue macromolecular components while water, which comprises the bulk of the tissue, is largely seen as a passive component; the ‘solid matrix’ is believed to be the main load-bearing element most of the time. Water is commonly seen as an inert filler whose restricted flow through the tissue is believed to be sufficient to generate the properties measured. We propose that this model should be turned on its head. Water comprises 70–80% of the matrix and has a bulk modulus considerably greater than that of cartilage. We suggest that the macromolecular components structure the water to support the loads applied. Here, we shall examine the structure and organization of the main macromolecules, collagen, aggrecan and hyaluronan, and explore how water interacts with their polyelectrolyte nature. This may inform the biosynthetic process by identifying starting points to enable developing tissue properties to guide the cells into producing the appropriate macromolecular composition and structure.     

生物活性玻璃/PLA-PEG-PLA/聚乳酸组织工程支架在SBF溶液中的降解和矿化

通过测定pH值、质量损失率、SEM、XRD和FTIR,系统研究了生物活性玻璃/聚乳酸-聚乙二醇-聚乳酸嵌段共聚物（PLA-PEG-PLA）/聚乳酸组织工程支架在模拟体液（SBF）中的降解和生物矿化性能。研究结果表明：随着支架在SBF溶液中浸泡时间的延长,SBF的pH值和支架的质量呈下降趋势;生物活性玻璃的存在使pH值升高,而PLA-PEG-PLA嵌段共聚物的存在使pH值降低。XRD、FTIR图谱和SEM图像表明：在SBF中浸泡一定时间后,有无定型或结晶不完善的磷灰石在生物活性玻璃/PLA-PEG-PLA/聚乳酸组织工程支架表面沉积形成,并且PLA-PEG-PLA共聚物降解速度比聚乳酸快;在SBF中浸泡7天后,PLA-PEG-PLA共聚物的含量已经很难通过FTIR检测出来。     

脉冲磁场对趋磁螺细菌AMB-1磁小体形成及相关基因表达的影响

本文利用Cmag测量、透射电镜观察等技术研究了脉冲磁场对不同初始状态的趋磁螺细菌AMB-1(Magnetospirillum magneticum AMB-1)磁小体形成的影响,并对其相关蛋白MamA、Mms13、Mms6和MagA编码基因的表达情况做了荧光实时定量反转录聚合酶链式反应(qRT-PCR).结果表明:同自然地磁场相比,50Hz、1mT脉冲磁场可促进AMB-1磁小体形成;当初始菌种为含有磁小体的AMB-1时,脉冲磁场促进指数期菌体magA基因的表达;而当初始菌种为不含磁小体的AMB-1时,则促进指数期菌体magA和mamA基因的表达.脉冲磁场虽然导致指数期细胞磁颗粒不均匀,但使磁小体链加长,含磁小体菌的平均磁颗粒数也较地磁场明显增加.实验结果为应用磁场干预磁小体形成,提高磁小体产率的研究提供了实验和理论依据,也有助于进一步了解磁场的生物学效应.     

小白鼠缺氧信息的获得、传导和储存的分子机理研究

通过不同缺氧程度小白鼠模型,同时利用心肌组织的核DNA片段的基因体外表达和mRNA体外翻译,观察到了心肌缺氧信息获得、传导和储存的分子机理.观察结果表明:心肌等胞质中氧代谢相关的已有基因的开关蛋白质复合体等参与了人工轻度快速缺氧信息的获得;心肌等胞质中已有n mRNA链状复合体中mRNA迅速翻译出蛋白质,心肌等组织可传导较严重快速缺氧信息;心肌等细胞核内已有氧代谢相关的活性核基因迅速表达出自己编码的蛋白质,心肌等以储存较长时间严重缺氧信息.昆明种小白鼠在中国西藏拉萨郊区自然缺氧条件下饲喂30天,长期缺氧信息的储存分子机制与上述小白鼠较长时间严重缺氧模型类似,同时原有的和新形成的细胞的核DNA片段上的氧代谢等相关的核基因分别表达出较多蛋白质,并引起小白鼠的耳朵和尾巴增长等体型的明显变化.     

聚乳酸组织工程支架在SBF溶液中的降解和矿化性能

本文利用扫描电镜、X射线衍射仪以及红外漫反射仪,并通过对聚乳酸组织工程支架在模拟体液(SBF)中的失重率、分子量以及模拟体液pH值变化的测试,系统地研究了聚乳酸组织工程支架在模拟体液中的降解和矿化性能。结果发现:在模拟体液中,随着时间的增长,聚乳酸组织工程支架的分子量不断下降;但是其重量并不随着时间的增长而减小,而是有升有降。X-射线衍射图谱和FTIR漫反射图谱研究表明,在模拟体液中,聚乳酸组织工程支架的表面有磷灰石沉积物出现。     

Microarray with Micro‐ and Nano‐topographies Enables Identification of the Optimal Topography for Directing the Differentiation of Primary Murine Neural Progenitor Cells

During development and tissue repair, progenitor cells are guided by both biochemical and biophysical cues of their microenvironment, including topographical signals. The topographical cues have been shown to play an important role in controlling the fate of cells. Systematic investigation of topographical structures with different geometries and sizes under the identical experimental conditions on the same chip will enhance the understanding of the role of shape and size in cell–topography interactions. A simple customizable multi‐architecture chip (MARC) array is therefore developed to incorporate, on a single chip, distinct topographies of various architectural complexities, including both isotropic and anisotropic features, in nano‐ to micrometer dimensions, with different aspect ratios and hierarchical structures. Polydimethylsiloxane (PDMS) replicas of MARC are used to investigate the influence of different geometries and sizes in neural differentiation of primary murine neural progenitor cells (mNPCs). Anisotropic gratings (2 μm gratings, 250 nm gratings) and isotropic 1 μm pillars significantly promote differentiation of mNPCs into neurons, as indicated by expression of β‐III‐tubulin (59%, 58%, and 58%, respectively, compared to 30% on the control). In contrast, glial differentiation is enhanced on isotropic 2 μm holes and 1 μm pillars. These results illustrate that anisotropic topographies enhance neuronal differentiation while isotropic topographies enhance glial differentiation on the same chip under the same conditions. MARC enables simultaneous cost‐effective investigation of multiple topographies, allowing efficient optimization of topographical and biochemical cues to modulate cell differentiation.     

聚(D,L-乳酸)基仿生聚合物材料的合成与表征

探索一种新型聚乳酸基仿生聚合物材料的制备新方法.具体实验步骤是:利用聚乳酸上叔碳原子的自由基反应活性,在过氧化二苯甲酰的催化作用下,将马来酸酐引入聚乳酸侧链上,以此提供高反应活性的酸酐键;然后利用酸酐基团与-NH2发生N-酰化反应这一特点,将脂肪族二胺引入聚乳酸侧链上,从而克服聚乳酸降解产物的体液环境呈酸性的缺陷;再用碳二亚胺作缩合剂,在二胺改性聚乳酸材料中共价引入一种细胞粘附肽段Arg-Gly-Asp-Ser(RGDS),赋予材料生物活性和生物特异性,这样就制备了一种新型聚乳酸基仿生材料.采用MALLS、FTIR和XPS对仿生材料进行结构表征;采用罗丹明比色法、茚三酮显色法和氨基酸分析仪检测法对仿生材料中的马来酸酐、二胺和粘附肽RGDS进行定量测定.结果表明,按文中所述之制备技术,在不改变聚乳酸材料主链结构的前提下,该仿生材料中粘附肽RGDS的含量是5.12μmol/g.这就形成了一种具有类似细胞外基质的新型仿生材料.