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.     

Therapeutic Effects of Saponins for the Prevention and Treatment of Cancer by Ameliorating Inflammation and Angiogenesis and Inducing Antioxidant and Apoptotic Effects in Human Cells

Saponins are natural compounds found in plants and have a diverse range of applications. However, the therapeutic potential of saponins in regulating cytotoxicity, angiogenesis, and inflammation in mammalian cells is yet to be explored. Here, we investigated the therapeutic effects of saponins from green tea by exploring the cytotoxic effects of saponins by inducing apoptosis in the human cancer cell lines hepatocellular carcinoma (HEPG2) and colorectal adenocarcinoma (HT29). The anti-angiogenesis effect of saponins was also investigated in human umbilical vein endothelial cells (HUVEC). We explored the ability of saponins to attenuate inflammation in a dose-dependent manner in normal human cells. It was found that saponins exhibit cytotoxic effects in cancer cells and not in normal cells at the same concentration. Cytotoxicity was measured by inducing apoptosis by enhancing caspase-3 (cas-3) activation and B-cell lymphoma-2 (Bcl-2)-associated X protein (BAX) gene expression and suppressing the antiapoptotic protein, Bcl-2. The inhibition of HUVEC proliferation was due to the suppression of the phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), vascular endothelial growth factor receptor-2 (VEGFR-2), and nuclear factor kappa B (NF-κB). We also observed the antioxidant potential of green tea-derived saponins against free radicals in reactive oxygen species (ROS)-induced cells. Here we observed that the saponins exhibited free radical scavenging activities and activated nuclear factorerythroid 2-related factor 2 (NRF-2) leading to the upregulation of antioxidant-related genes in human embryonic kidney 293 (HEK293) cells. Furthermore, we demonstrated that the anti-inflammatory effects were due to the suppression of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in HEK293 cells. The significance of the work is we are the first to report on the anti-cancer effects of saponins based on the anti-inflammatory, antioxidant, anti-angiogenesis, and apoptosis induction properties. In conclusion, green tea-derived saponins could be effective therapeutics for the treatment of cancer.     

Studies of Mercaptosuccinic Acid-Crosslinked Chitosan Hydrogel with Grafted Cinnamaldehyde and Silver Nanoparticles for Antibacterial Biomedical Application

For the effective clinical antibacterial application of biomaterials, such as for wound management and tissue repair, the biomaterials need to show proper antibacterial capability as well as non-cytotoxicity. Furthermore, the material needs to have suitable mechanical characteristics for further medical use. Chitosan hydrogel is a potential candidate for various antibacterial biomedical applications due to its amine functionalities that lead to antimicrobial characteristics. Nevertheless, its antimicrobial capability is dependent upon the degree of protonation of amine groups caused by the pH value. Moreover, its mechanical compressive strength may not be high enough for clinical use if not chemically or physically crosslinked. This study utilized a novel chemical crosslinker, mercaptosuccinic acid, to improve its mechanical characteristics. The natural antibacterial agent, cinnamaldehyde, was grafted onto the crosslinked chitosan to improve its antimicrobial capability. Meanwhile, to take advantage of the thiol functionality in the mercaptosuccinic acid, the bactericidal silver nanoparticles were incorporated through silver-thiol covalent bounding. NMR analyses indicated the chitosan was successfully mercaptosuccinic acid-crosslinked and grafted with cinnamaldehyde at different ratios. Combined the results from the mechanical assessment, swelling experiments, antimicrobial assessment, and cytotoxicity assay, the chitosan hydrogel with the highest crosslinked degree and grafted with cinnamaldehyde and silver nanoparticles is of great promise for further clinical uses.     

不同饮用水处理工艺中消毒副产物的生成潜能

对取自饮用水处理过程中的水样分别进行氯消毒和氯胺消毒,分析不同饮用水处理工艺对7类18种消毒副产物(DBPs)生成潜能的影响,测定的DBPs包括含碳DBPs[三卤甲烷(THMs)、卤乙酸(HAAs)、卤代酮(HKs)、三氯乙醛(CH)]和含氮DBPs[卤乙腈(HANs)、三氯硝基甲烷(TCNM)、总亚硝胺(TONO)]。结果表明,混凝、沉淀和过滤工艺均能有效降低卤代DBPs的生成潜能,活性炭吸附反而会增大TONO的生成潜能。混凝和砂滤工艺对去除含碳DBPs前体物更有效,氧化处理工艺则更有利于含氮DBPs前体物的去除。细胞毒性主要来源于HANs和HAAs,且其变化趋势大致与HANs和HAAs生成潜能一致。水中Br^-浓度的增加会显著增大溴代DBPs的生成潜能,并使细胞毒性大幅升高。