中药多糖对实验性糖尿病性视网膜病变防治作用的研究进展

多糖是药用植物的主要成分,是生物体中继蛋白质、核酸之后的另一类重要的信息分子。它们广泛存在于动物细胞膜、植物和微生物的细胞壁中。十个或十个以上的单糖通过糖苷键连接和缩合,形成聚羟基烷酮聚合物[1]。近几十年来,从不同种类的中草药中分离得到的多糖因其具有抗肿瘤、抗氧化、抗糖尿病、抗辐射、抗病毒、降血脂和免疫调节等重要生物活性而备受关注[2]。

水通道蛋白4和中枢神经系统疾病

水通道蛋白（aquaporins,AQPs）是近年来发现的一小型跨膜蛋白家族,它们广泛表达于众多类型细胞的质膜上,参与膜内外液体转运途径。目前在哺乳动物细胞膜上共发现13种AQPs（AQP0-AQP12）,在啮齿类动物及人类有7个分布于脑内,分别为AQP1、AQP3、AQP4、AQP5、AQP8、AQP9和AQP11,其中AQP4（（aquaporin-4））是中枢神经系统（central nervous system，cNs）分布最广泛的AQP。

Uptake of albumin nanoparticle surface modified with glycyrrhizin by primary cultured rat hepatocytes

AIM: To investigate the uptake difference between bovine serum albumin nanoparticle (BSA-NP) and bovine serum albumin nanoparticles with their surface modified byglycyrrhizin (BSA-NP-GL) and to develop a novel hepatocyte targeting BSA-NP-GL based on active targeting technology mediated by specific binding site of GL on rat cellular membrane. METHODS: Calcein loaded bovine serum albumin nanoparticles (Cal-BSA-NP) were prepared by desolvation process. Glycyrrhizin was conjugated to the surface reactive amino groups (SRAG) of Cal-BSA-NP by sodium periodate oxidization, which resulted in calcein-loaded bovine serum albumin nanoparticles with their surface modified by glycyrrhizin (Cal-BSA-NP-GL). The morphology of the two types of prepared nanoparticles (NP) was observed by transmission electron microscopy. The diameter of NP was measured with a laser particle size analyzer. The interaction between Cal-BSA-NP-GL and primary cultured hepatocytes was studied through cellular uptake experiments. The uptake amount of Cal-BSA-NPGL and Cal-BSA-NP by rat hepatocytes was determinedby fluorospectrophotometry. Uptake characteristics were investigated through experiments of competitive inhibition of specific binding site of GL. RESULTS: Both Cal-BSA-NP-GL and Cal-BSA-NP had regular spherical surfaces. The average diameter of CalBSA-NP-GL and Cal-BSA-NP was 77 and 79 nm respectively. The uptake amount of the two NP by hepatocytes reached its maximum at 2 h after incubation. The uptake amount of Cal-BSA-NP-GL by rat hepatocytes was 4.43-fold higher than that of Cal-BSA-NP. There was a significant difference in the uptake of Cal-BSA-NP-GL and Cal-BSA-NP by hepatocytes (P＜0.01). The uptake of Cal-BSA-NP-GL was inhibited when GL was added previously to isolated rat hepatocytes, and the uptake of Cal-BSA-NP was not affected by GL.CONCLUSION: A binding site of GL is present on the surface of rat hepatocytes, BSA-NP-GL may be internalized via this site by hepatocytes and can be used as a drug carrier for active targeting of delivery drugs to hepatocytes.

cAMP elevators inhibit LPS-induced IL-12 p40 expression by interfering with phosphorylation of p38 MAPK in Murine Peritoneal Macrophages

cAMP mediated signaling may play a suppressive role in immune response. We previously found that the cAMP-elevators (CTx and 8-Br-cAMP) inhibited IL-12, IL-la, IL-6 gene expression, but increased the transcriptional levels of IL-10 and IL-IRa in LPS-treated murine peritoneal macrophages. The present study examined a possible molecular mechanism involved in cAMP elevators-induced inhibition of IL-12 p40 expression in response to LPS. Our data demonstrated that cAMP elevators downregulated IL-12 p40 mRNA expression and IL-12 p70 production in murine peritoneal macrophages. Subsequent studies revealed that cAMP-elevators blocked phosphorylation of p38 MAPK, but did not affect the activity of NF-kB binding to IL-12 promoter (-136/-112). This is the first report that cAMP elevators inhibit LPS-induced IL-12 production by a mechanism that is associated, at least in part, with p38-dependent inhibition by cAMP signaling pathways.

The Notch-Hes pathway in mammalian neural development

A wide variety of neurons and gIial cells differentiatefrom common precursor cells in the developing nervoussystem. During this process, Notch-mediated cell-cell in-teraction is essential for maintenance of dividing cells andsubsequellt generation of cell type diversity. Activation ofNotch inhibits cellular differentiation, and abnormality ofthe Notch pathway leads to premature neuronal differenti-ation, the lack of some cell types, and severe defects of tis-sue morphogenesis. Recent data demonstrate that Notchfails to inhibit cellular differentiation in the absence of thebHLH genes Hes1 and He5, which functionally afitago-nize the neuronal bHLH genes such as theh1- These re-sults indicate that the two Hes genes are essential effecorsfor the Notch pathway and that neuronal differentiation iscontrolled by the pathway "Notch-+He1/Hs5,Mish1".

Assembly and disassembly of mammalian chromosome pellicle

By means of indirect double immunofluorescent staining, the coordination of PI antigen and perichromonucleolin (PCN), the constituent of nuclear periphery and nucleolus respectively, in the assembly and disassembly of chromosome pellicle during mitosis was studied. It was found that in 3T3 cells, during mitosis PI antigen began to coat the condensing chromosome .surface earlier.than PCN did. However, both of them completed their coating on chromosome at approximately the same stage of mitosis, prometaphase metaphase. The dissociation of PI antigen from chromosome pellicle to participate the formation of nuclear periphery took, place also ahead of that of PCN. At early telophase PI antigen had been extensively involved in the formation of nuclear periphery, while PCN remained in association with the surface of decondensing chromosomes. At late telophase, when PI antigen was localized in an fairly well formed nuclear periphery, PCN was in a stage of forming prenucleolar bodies.

Human chromosome pellicle antibody recognizing centromere protein-C(CENP-C),the main component of the kinetochore

Recently the antichromosome antisera from several scleroderma patients have been found to recognize the pellicle of metaphase and anaphase chromosomes. In order to identify the pellicle components, we used these antichromosome antisera to screen a human embryonic cDNA library. The sequences of the positive clones are identical to the cDNA gene sequence of CENP-C (centromere protein C), a human centromere autoantigen. This result suggusts that CENP-C is a component of the pellicle of human metaphase and anaphase chromosomes.

五加科植物多糖的抗肿瘤作用研究进展

多糖在自然界中分布广泛,资源丰富,主要存在于动物细胞膜、植物和微生物细胞壁中,是除病毒以外一切有生命的有机体必不可少的组成成分,同维持生物机能密切相关,和蛋白质、脂类、核酸一起成为构成生命的四大基本物质。多糖不仅是细胞的结构物质和能源物质,更是具有多种生理功能的生物活性物质,在生命现象中参与了细胞的各种活动。

Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss

Diabetic retinopathy （DR） is one of the most common retinal diseases world-wide. It has a complex pathology that involves the vasculature of the inner retina and breakdown of the blood-retinal barrier. Extensive research has determined that DR is not only a vascular disease but also has a neurodegenerative component and that essentially all types of ceils in the retina are affected, leading to chronic loss of visual function. A great deal of work using animal models of DR has established the loss of neurons and pathology of other cell types, including supporting glial cells. There has also been an increased emphasis on measuring retinal function in the models, as well as further validation and extension of the animal studies by clinical and translational research. This article will attempt to summarize the more recent developments in research towards understanding the complexities of retinal neurodegeneration and functional vision loss in DR.

The dehydration dynamics of a model cell membrane induced by cholesterol analogue 6-ketocholestanol investigated using sum frequency generation vibrational spectroscopy

Dehydration of a surface is the first step for the interaction between biomolecules and the surface. In this study, we systemati- cally investigated the influence of cholesterol analog 6-ketocholestanol （6-KC） on the dehydration of model cell membrane, using sum frequency generation vibrational spectroscopy. In pure DI water environment, two separate dehydration dynamic components were observed in neutrally charged and isotopically labeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine （DMPC） and positively charged 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine（chloride salt） （DMEPC） bilayer： a large-amplitude fast component and a small-amplitude slow component, which originated from the water molecules with a weak and a strong water-membrane bound strengths, respectively. Dehydration of a negatively charged mixed DMPC/DMPG bilayer lead to the membrane-bound water being reorganized to ordered structures quickly. It is evident that the water-membrane bound strengths depend largely on the charge status of the lipid and has an order of neutrally charged membrane〈〈positively charged mem- brane〈〈negatively charged membrane. In an ionic environment, KC1 solution can not only dehydrate DMPC bilayer, but also prevent the 6-KC fiom further dehydrating this model cell membrane. We observed that the dehydration dynamics behavior of DMPC bilayer in the presence of the chaotropic anions is similar to that of the negatively charged DMPG bilayer because of the penetration of chaotropic anions into the DMPC bilayer. The degree of dehydration difficulty in kosmotropic anions fol- lows a Hofmeister series and linearly correlates with the hydration Gibbs free energy of the anions. Our results provide a molecular basis for the interpretation of the Hofmeister effect of kosmotropic anions on ion transport proteins.

Lipid profiling of mammalian cells with in situ matrix-assisted laser desorption ionization-mass spectrometry

The analysis of cellular lipids and phospholipids has been of continuously increasing research interest due to the importance of these molecules in psychological process.In this work,a mass spectrometry-based method for direct,in situ analysis of lipids in cells was reported.Mammalian cells were directly cultured on ITO-coated glass and then analyzed by matrix-assisted laser desorption ionization-mass spectrometry(MALDI-MS).The matrix application process was achieved by electrospray coating,which produced a homogenous layer of matrix crystal on the sample.The detection results and reproducibility are satisfactory.With this method,a profile of abundant membrane lipids is generated,which is characteristic of cell type.In conclusion,this in situ MALDI-MS cellular lipid analysis method provides a platform for sensitive and robust molecular profiling of mammalian cells.