Bile acids as constituents for dental composites: in vitro cytotoxicity of (meth)acrylate and other ester derivatives of bile acids.

Methacrylic derivatives of bile acids have been synthesized for use as monomers in dental composites. Polymeric dental materials are known to leach cytotoxic unreacted monomers and degradation products. In this study, the in vitro cytotoxicity of bile acids and their derivatives towards 3T3 fibroblasts has been evaluated by colorimetric MTT assay and compared with that of the common dental monomers BisGMA, UDMA and TEGDMA. In general, the bile acids and their derivatives induced mitochondrial dysfunction at similar or higher concentrations than the commercial dental monomers. Certain monomers did not influence MTT response over their entire range of solubility.     

Synthesis and biological activity of phthalimide‐based polymers containing 5‐fluorouracil

The attachment of anticancer agents to polymers is a promising approach towards reducing the toxic side‐effects and retaining the potent antitumour activity of these agents. A new tetrahydrophthalimido monomer containing 5‐fluorouracil (ETPFU) and its homopolymer and copolymers with acrylic acid (AA) and with vinyl acetate (VAc) have been synthesized and spectroscopically characterized. The ETPFU contents in poly(ETPFU‐co‐AA) and poly(ETPFU‐co‐VAc) obtained by elemental analysis were 21 mol% and 20 mol%, respectively. The average molecular weights of the polymers determined by gel permeation chromatography were as follows: M_n = 8900 g mol^?1, M_w = 13 300 g mol^?1, M_w/M_n = 1.5 for poly(ETPFU); M_n = 13 500 g mol^?1, M_w = 16 600 g mol^?1, M_w/M_n = 1.2 for poly(ETPFU‐co‐AA); M_n = 8300 g mol^?1, M_w = 11 600 g mol^?1, M_w/M_n = 1.4 poly(ETPFU‐co‐VAc). The in vitro cytotoxicity of the compounds against FM3A and U937 cancer cell lines increased in the following order: ETPFU > 5‐FU > poly(ETPFU) > poly(ETPFU‐co‐AA) > poly(ETPFU‐co‐VAc). The in vivo antitumour activities of all the polymers in Balb/C mice bearing the sarcoma 180 tumour cell line were greater than those of 5‐FU and monomer at the highest dose (800 mg kg^?1). © 2002 Society of Chemical Industry     

Synthesis,characterization, and antitumor activity of poly(maleic anhydride‐co‐vinyl acetate‐co‐acrylic acid)

The ternary copolymerization of maleic anhydride (MA), vinyl acetate (VA), and acrylic acid (AA) [P(MA‐co‐VA‐co‐AA)], which is considered to be an acceptor–donor–acceptor system, was carried out in 1,4‐dioxane with benzoyl peroxide as an initiator at 70°C under a nitrogen atmosphere. Constants of complex formation for the monomer systems in the study were determined by UV–visible (hydrogen‐bonding complex) and ¹H‐NMR (charge transfer complex) methods, respectively. The results show that polymerization of the P(MA‐co‐VA‐co‐AA) system proceeds by an alternating terpolymerization mechanism. It is shown that the synthesized copolymers have typical polyelectrolyte behavior, ability for reversible hydrolysis–anhydrization reactions, and semicrystalline structures. In these cases, including radical polymerization, and formation of semicrystalline structures, the hydrogen‐bonding effect plays a significant role. The in vitro cytotoxicities of the synthesized terpolymer and alternating copolymer were evaluated using Raji cells (human Burkitt lymphoma cell line). The antitumor activities of prepared anion‐active copolymers were studied using methyl–thiazol–tetrazolium colorimetric assay and 50% of the cytotoxic dose of each copolymer and terpolymer were calculated. Hydrolyzed P(MA‐co‐VA‐co‐AA) and P(MA‐alt‐AA) copolymers have sufficiently high antitumor activity, which depends on the amount of hydrogen‐bonding carboxylic groups and their regular distribution in the side chain of functional macromolecules. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 3425–3432, 2006     

Dynamic Modelling and Prediction of Cytotoxicity on Microelectronic cell Sensor Array

A real‐time cell electronic sensing (RT‐CES) system has been used for label‐free dynamic measurements of cell responses to toxicant. Cells are grown onto the surfaces of the microelectronic sensors. Changes in cell number expressed as cell index (CI) have been recorded on‐line as time series. The CI data are used for dynamic modelling or parameter estimation for cell cytotoxicity process. We consider two dynamic modelling approaches, namely data‐based system identification and first principle modelling. It is shown that data‐based system identification can provide a quick solution for the cytotoxicity dynamic models and is effective for short‐term predictions. It, however, can be poor for long‐term predictions, particularly if there is no output correction, i.e., when the model is used for simulation. In view of this, the first principle modelling approach by considering fundamental physical principles such as toxicant transport is explored. For long‐term prediction or simulation, the prediction performance for some of cytotoxicity process is dramatically improved using the models obtained from the latter approach. This happens only if the underlying mechanism is truly understood. Through several cytotoxicity modelling and validation studies, it is shown that the black box modelling and first principle modelling both should be considered in challenging modelling problems such as the cytotoxicity. Pros and cons of the two modelling approaches are discussed.     

Effect of B2O3 on the structural and in vitro biological assessment of mesoporous bioactive glass nanospheres

In this paper, the boron-containing mesoporous bioactive glass (MBG) nanospheres have been successfully synthesized by modified sol-gel method assisted by surfactant, and the effect of boron substitution on structure and bioactivity was evaluated by combining experiments and ab initio molecular dynamics (AIMD) simulations. All of the samples exhibit regularly uniform mesoporous spherical microstructure with an average size of about 60 nm, and the boron-containing MBGs show higher specific surface area with the value up to 416.20 m²/g. The simulated body fluid (SBF) immersion test confirms that the deposited hydroxyapatite (HA) evidently increases with the increasing of boron content, indicating that the biological behavior has been significantly improved resulting from incorporation of boron. Additionally, our results also reveal that B₂O₃ substitution has positive impact on cell proliferation of human periodontal ligament cells (hPDLCs) at lower extracted concentration. Furthermore, AIMD simulation is employed to understand the relationship between structural changes and in vitro bioactivity in terms of structural information, especially the boron coordination number. The results illustrate that the boron-containing MBG nanospheres with excellent bioactivity are great potential for biomedical applications.     

Fabrication, in vitro Degradation and Cytotoxic Assay of Different Cystalline Phases Calcium Polyphosphate

1Introduction Mostofthematerialsusedhistoricallyarecalcium phosphatessuchashydroxyapatite(HA),tricalciumphosphates(TCP),tetracalciumphosphate(TTCP),and cominationofthevariousphasesofcalciumphosphates[1].Calciumphosphatematerialshavesomeoutstandingprop ert…     

Phototoxicity and fluorotoxicity combine to alter the behavior of neutrophils in fluorescence microscopy based flow adhesion assays

The use of fluorescent probes that allow visualization of leukocyte-endothelial cell (EC) interactions has greatly informed our understanding of leukocyte recruitment. However, effects of these agents on the biological functions of leukocytes are poorly described, leading to concerns about the interpretation of such data. Here we used two flow-based neutrophil adhesion assays to compare the effects of phase contrast illumination (PCI) with high intensity illumination (HII) used for fluorescent microscopy, in the presence or absence of five commonly used fluorochromes. Isolated neutrophils were either (1) perfused across P-selectin to establish a population of rolling cells, which were subsequently activated with fMLP; or (2) perfused across EC activated with TNF-alpha. In the absence of fluorescent dyes, HII did not affect levels of leukocyte adhesion; however, subsequent neutrophil behavior was dramatically altered when compared with cells under PCI, for example, dramatically reducing their migration velocities. In the presence of fluorescent dyes, the effects of HII were exacerbated, although the precise nature of the biological effects of these probes was agent specific. Thus, for the first time, our experiments describe the effects of fluorescent microscopy on the separate stages of the neutrophil recruitment process and reveal a previously unsuspected effect of HII on neutrophil migration.     

光敏剂在光动力治疗中的应用研究进展

光动力疗法（PDT）以其超高时空分辨率、非侵入性及低毒副作用的优点,被认为是治疗癌症和各种非恶性疾病的有效疗法之一。本文主要综述了几类光敏剂发展历史、主要结构、特点及研究进展,分析了高性能光敏剂的开发动态,包括化学修饰;与具有特定细胞受体的其他配体缀合成复合光敏剂;采取纳米技术,如纳米颗粒输送,基于富勒烯的光敏剂等。基于此,指出具有临床应用前景的高性能光敏剂的基本特征、设计原则及发展趋势。     

近红外荧光磁性复合载药脂质体的制备及应用

拟建立以近红外荧光磁性复合脂质体(NFMSLs)为模型药物载体、盐酸多柔比星(DOX)为包封药物的药物输送系统,研究了近红外荧光磁性载药复合脂质体(DOX-NFMSLs)的制备、性质及初步应用.采用共沉淀法制备FeO4磁流体,CdTe掺杂Se制备近红外量子点CdSeTe,薄膜分散法制备DOX-NFMSLs.用DOX荧光分光光度法测定DOX-NFMSLs的包封率和体外药物释放率;用DOX-NFMSLs与HepG2肝癌细胞共孵育来进行细胞成像和细胞毒性实验.结果表明,近红外CdSeTe量子点粒径约为5nm,闪锌矿结构,发射波长824 nm.磷脂与胆固醇质量比为8∶1,药脂比为1∶20的DOX-NFMSLs平均粒径为252.9 nm,Zeta电位为-48.6 mV,理想释放药物温度为41℃,平均包封率为(74.84±0.89)％.DOX-NFMSLs对HepG2肝癌细胞有一定的抗癌效果.得到了具有良好磁响应、释药温度T=41℃、可近红外成像的载药脂质体.     

Multiwall Carbon Nanotubes Directly Promote Fibroblast–Myofibroblast and Epithelial–Mesenchymal Transitions through the Activation of the TGF‐β/Smad Signaling Pathway

A number of studies have demonstrated that MWCNTs induce granuloma formation and fibrotic responses in vivo, and it has been recently reported that MWCNT‐induced macrophage activation and subsequent TGF‐β secretion contribute to pulmonary fibrotic responses. However, their direct effects against alveolar type‐II epithelial cells and fibroblasts and the corresponding underlying mechanisms remain largely unaddressed. Here, MWCNTs are reported to be able to directly promote fibroblast‐to‐myofibroblast conversion and the epithelial–mesenchymal transition (EMT) through the activation of the TGF‐β/Smad signaling pathway. Both of the cell transitions may play important roles in MWCNT‐induced pulmonary fibrosis. Firstly, in‐vivo and in‐vitro data show that long MWCNTs can directly interact with fibroblasts and epithelial cells, and some of them may be uptaken into fibroblasts and epithelial cells by endocytosis. Secondly, long MWCNTs can directly activate fibroblasts and increase both the basal and TGF‐β1‐induced expression of the fibroblast‐specific protein‐1, α‐smooth muscle actin, and collagen III. Finally, MWCNTs can induce the EMT through the activation of TGF‐β/Smad2 signaling in alveolar type‐II epithelial cells, from which some fibroblasts involved in pulmonary fibrosis are thought to originate. These observations suggest that the activation of the TGF‐β/Smad2 signaling plays a critical role in the process of the fibroblast‐to‐myofibroblast transition and the EMT induced by MWCNTs.