莪术醇通过降解ECM改变细胞周期抑制A549细胞增殖

目的:探讨莪术醇抑制A549细胞增殖作用及分子机理。方法:MTT法观察莪术醇对A549细胞增殖的抑制作用;天狼猩红染色法检测莪术醇对A549细胞层分泌胶原的影响;流式细胞术检测细胞周期阻滞。结果:莪术醇对A549细胞增殖有抑制作用,并能抑制细胞胶原分泌;细胞周期分析显示,莪术醇作用细胞24h,主要通过增加G1期细胞比例来抑制细胞增殖,作用48h主要影响了细胞的G2期。结论莪术醇能抑制肺腺癌A549细胞增殖,其机制可能是与莪术醇抑制ECM中胶原的分泌、诱导细胞周期阻滞有关。     

Cell-derived nanovesicles from mesenchymal stem cells as extracellular vesicle-mimetics in wound healing

Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers. Recently, extracellular vesicles(EVs), naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins, lipids, and nucleic acids, have drawn wide attention due to their ability to promote wound healing and tissue regeneration. However, current exploitation of EVs as therapeutic agents...     

Low-molecular-weight fucoidan enhances the proangiogenic phenotype of endothelial progenitor cells

Endothelial progenitor cell (EPC) transplantation is a potential means of inducing neovascularization in vivo. However, the number of circulating EPC is relatively small, it may thus be necessary to enhance their proangiogenic properties ex vivo prior to injection in vivo. Fucoidan has previously been shown to potentiate in vitro tube formation by mature endothelial cells in the presence of basic fibroblast growth factor (FGF-2). We therefore examined whether fucoidan, alone or combined with FGF-2, could increase EPC proangiogenic potency in vitro. EPC exposure to 10 microg/ml fucoidan induced a proangiogenic phenotype, including cell proliferation (p < 0.01) and migration (p < 0.01); moreover, differentiation into vascular cords occurred in the presence of FGF-2 (p < 0.01). This latter effect correlated with upregulation of the cell-surface #alpha6 integrin subunit of the laminin receptor (p < 0.05). Compared to untreated HUVEC, untreated EPC #alpha6 expression and adhesion to laminin were enhanced two-fold. Fucoidan treatment further enhanced HUVEC but not EPC adhesion to laminin. These results show that fucoidan enhances the proangiogenic properties of EPC and suggest that ex vivo fucoidan preconditioning of EPC might lead to increased neovascularization when injected into ischemic tissues.     

Pancreatic stellate cell migration: role of the phosphatidylinositol 3-kinase(PI3-kinase) pathway

Pancreatic stellate cells (PSCs) are implicated as key mediators of pancreatic fibrogenesis and are found in increased numbers in areas of pancreatic injury. This increase in number may be due to increased local proliferation and/or migration of PSCs to affected areas from surrounding tissue. We have recently shown that PSCs can migrate and that this migration is stimulated by PDGF in a predominantly chemotactic manner [Gut 52 (2003) 677]. However, the signalling mechanisms responsible for PDGF-induced PSC migration are not known. Aims: (i) To determine whether PDGF-induced PSC migration is mediated by the PI3-kinase pathway. (ii) To investigate whether cell migration is influenced by cell proliferation and whether an interaction exists between the PI3-kinase pathway and the ERK1/2 pathway (known to mediate cell proliferation) in PSCs exposed to PDGF. Methods: (i) PI3-kinase activity was assessed by measuring the activation (phosphorylation) of its downstream substrate Akt in rat PSCs incubated with PDGF (10ng/mL) for 5min, 15min, 60min, and 24hr in the presence or absence of the specific PI3-kinase inhibitor wortmannin. (ii) The role of the PI3-kinase pathway in PSC migration was examined by assessing PSC migration through a porous membrane after exposure to PDGF in the presence and absence of wortmannin for 24hr. (iii) The relationship between migration and proliferation was assessed by examining migration of PSCs exposed to PDGF in the presence and absence of mitomycin C, an inhibitor of cell proliferation. (iv) The interaction between PI3-kinase and ERK1/2 was examined by incubation of PSCs with PDGF in the presence and absence of wortmannin, followed by assessment of ERK1/2 activation by western blot. Results: PDGF increased Akt activation in PSCs as early as at 5min of incubation and this increase was sustained for 24hr. Inhibition of PI3-kinase by wortmannin decreased basal as well as PDGF-induced migration and also inhibited ERK1/2 activation. Inhibition of PSC proliferation with mitomycin C significantly reduced (but did not abolish) basal and PDGF-induced PSC migration. Conclusions: (i) The PI3-kinase pathway is induced in PSCs after exposure to PDGF and this induction is sustained for at least 24hr. (ii) The PI3-kinase pathway plays a role in PDGF-induced PSC migration and is partially involved in mediating ERK1/2 activation. (iii) PSC migration is dependent, at least in part, on cell proliferation.     

Retinoic acid remodels extracellular matrix (ECM) of cultured human fetal palate mesenchymal cells (hFPMCs) through down-regulation of TGF-β/Smad signaling

The regulation of extracellular matrix (ECM) by retinoic acid (RA) is interesting in light of the fact that the ECM plays an essential role in morphogenesis and palatal shelf elevation. In the current study, we explored the effect of RA overexposure on ECM and the probable mechanisms in cultured human fetal palate mesenchymal cells (hFPMCs). RA dose-dependently inhibited cell proliferation and mRNA and protein levels of ECM components fibronectin, tenascin C and fibrillin-2. Zymography revealed that MMP-2 activity was suppressed by RA. Further analysis revealed that mRNA levels of MMP2 and TIMP2 were decreased, while the MMP2/TIMP2 mRNA ratio was increased, which might facilitate the ECM degradation. Because of the pivotal role of TGF-β/Smad pathway in palatogenesis we therefore checked the effect of RA on TGF-β/Smad signaling. The results indicated RA treatment increased Smad7 expression and decreased the levels of TGF-β1, TGF-β3, TGF-β type II receptor (TβRII) and phosphorylated Smad2 and Smad3. Activation of the Smad pathways by either exogenous TGF-β3 or recombinant adenoviruses for Smad3 attenuated RA-induced inhibition of cell proliferation and ECM components and rescued the RA-altered MMP2/TIMP2 mRNA ratio. In conclusion, these findings suggested that RA overexposure inhibited cell proliferation and disrupted the ECM network through down-regulation of TGF-β/Smad pathway.     

Polymer hydration and stiffness at biointerfaces and related cellular processes

The direct and indirect (by changing mechanical properties) effects of hydration at interfaces on cellular processes and tissue diseases are reviewed. The essential effect of substrate stiffness on cellular processes was demonstrated in the last decade. The combined effect of surface stiffness and hydration at interfaces has garnered much less attention, though hydration and dehydration play important roles in biological processes. This review focuses on the studies that demonstrate how hydration affects biological processes at interfaces. Elevated sodium and dehydration stimulate inflammatory signaling in endothelial cells and promote atherosclerosis. Various types of implant and blood contacting device coatings with varied surface stiffness and hydration have been reported. Effect of hydration on polymer modulus of elasticity and viscoelasticity was discussed taking into account cells adhesion, migration, proliferation, differentiation on surfaces with various degree of hydration. Future directions of research were considered, including the use of nanotechnology to regulate the hydration degree.     

Nanofiber technology in the ex vivo expansion of cord blood-derived hematopoietic stem cells

Umbilical cord blood (CB) can be used as an alternative source of hematopoietic stem cells (HSCs) for transplantation in hematological and non-hematological disorders. Despite several recognized advantages the limited cell number in CB one unit still restricts its clinical use. The success of transplantation greatly depends on the levels of total nucleated cell and CD34+ cell counts. Thus, many ex vivo strategies have been developed within the last decade in order to solve this obstacle, with more or less success, mainly determined by the degree of difficulty related with maintaining HSCs self-renewal and stemness properties after long-term expansion. Different research groups have developed very promising and diverse CB-derived HSC expansion strategies using nanofiber scaffolds. Here we review the state-of-the-art of nanofiber technology-based CB-derived HSC expansion.     

Modeling Sustained Treatment Effects in Tumor Xenograft Experiments

In cancer drug development, demonstrated efficacy in tumor xenograft models is an important step toward bringing a promising compound to human use. A key outcome variable is tumor volume measured over a period of time, while mice are treated with certain treatment regimens. A constrained parametric model has been proposed to account for special features, such as intrinsic tumor growth, or tumor volume truncations due to tumor size being either too large or too small to detect. However, since the drug concentration in the blood of a mouse or its tissues may be stabilized at a certain level and maintained during a period of time, the treatment may have sustained effects. This article extends the constrained parametric model to account for the sustained drug effects. The ECM algorithm for incomplete data is applied to estimating the dose-response relationship in the proposed model. The model selection based on likelihood functions is given and a simulation study is conducted to investigate the performance of the proposed estimator. A real xenograft study on the antitumor agent temozolomide combined with irinotecan against the rhabdomyosarcoma is analyzed using the proposed methods.     

2006-2008年韶关市流脑监测

目的了解韶关市2006-2008年健康人群中流行性脑脊髓膜炎(流脑)的带菌状况和血清保护性抗体水平,为制定防控对策提供依据。方法收集韶关市2006-2008年流脑监测资料,采集8个年龄组健康人群咽拭子并进行脑膜炎奈瑟菌分离培养,采集健康人群血清进行抗体水平检测,计算健康人群流脑带菌率、血清保护性抗体阳性率。结果 2006-2008年韶关市健康人群脑膜炎球菌的带菌率仅为0.14%,为C群脑膜炎奈瑟双球菌。A群IgG抗体的阳性率为67.69%(473/705),C群IgG抗体的阳性率为44.54%(314/705),3岁以下儿童C群流脑血清保护性抗体阳性率低于3岁以上年龄组(χ2=10.572,P0.01)。2006-2008年无流脑病例报告。结论韶关市健康人群脑膜炎球菌的带菌率很低,3岁以下儿童的C群IgG抗体水平较低,应加强免疫接种工作。     

Organic–Inorganic Surface Modifications for Titanium Implant Surfaces

This paper reviews current physicochemical and biochemical coating techniques that are investigated to enhance bone regeneration at the interface of titanium implant materials. By applying coatings onto titanium surfaces that mimic the organic and inorganic components of living bone tissue, a physiological transition between the non-physiological titanium surface and surrounding bone tissue can be established. In this way, the coated titanium implants stimulate bone formation from the implant surface, thereby enhancing early and strong fixation of bone-substituting implants. As such, a continuous transition from bone tissue to implant surface is induced. This review presents an overview of various techniques that can be used to this end, and that are inspired by either inorganic (calcium phosphate) or organic (extracellular matrix components, growth factors, enzymes, etc.) components of natural bone tissue. The combination, however, of both organic and inorganic constituents is expected to result into truly bone-resembling coatings, and as such to a new generation of surface-modified titanium implants with improved functionality and biological efficacy.