Green synthesis of zinc oxide nanoparticles using Amygdalus scoparia Spach stem bark extract and their applications as an alternative antimicrobial,anticancer, and anti-diabetic agent

For the first time in this study, Zinc oxide nanoparticles were biosynthesized by the eco-friendly and cost-effective procedure using Amygdalus scoparia stem bark extract then used as antibacterial, antifungal, anticancer, and anti-diabetic agents. The characterization techniques confirmed the biosynthesis, crystalline nature, structure, size, elemental composition of ZnO NPs and bioactive compounds that exist in A. scoparia extract accounting for Zn²⁺ ion reduction, capping and stabilization of ZnO NPs. The ZnO NPs displayed remarkable inhibitory activity against E. coli, E. aerigenes, S. aureus, P. oryzae, F. thapsinum, and F. semitectum compared to antibiotic standards. The ZnO NPs showed significant inhibitory effects on cancer cell lines, while it had no toxic effect on Vero normal cell line. The ZnO NPs (30 mg/kg)-treated diabetic rats showed significantly higher levels of insulin and lower AST, ALT and blood glucose compared with the STZ induced diabetic group and other treated groups (P < 0.05). The ZnO NPs- and extract-treated rats showed significantly higher levels of IR, GluT2, and GCK expression and lower TNFα expression compared with the STZ induced diabetic rats. Our findings showed that ZnO NPs represented an outstanding performance for biological applications.     

Synthesis of Benzophenones and in vitro Evaluation of Their Anticancer Potential in Breast and Prostate Cancer Cells

Breast and prostate cancers are frequently treated with chemotherapy. Several novel chemicals are being reported for this purpose, particularly synthetic and natural benzophenones. This work reports the synthesis of substituted 2-hydroxybenzophenones through 1,4-conjugate addition/intramolecular cycloaddition/dehydration of nitromethane on key intermediate chromones. Structures were extensively studied by means of 2D NMR spectroscopy and single-crystal XRD. Their cytotoxicity was evaluated in vitro in two breast cancer cell lines (MDA-MB-231 and T47-D) and one prostate cancer cell line (PC3). The most potent compound exhibited good cytotoxic effects against the three cancer cell lines (IC₅₀ values ranging from 12.09 to 26.49 μm ) and induced cell-cycle retardation only on prostate cancer cells, which suggested that it might exert cell-type-specific effects.     

2-Phenyloxazole-4-carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (K_i) values in the sub-micromolar range and a good selectivity index (K_{i MAO-A}/K_{i MAO-B}>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity.     

Hit to Leads with Cytotoxic Effect in Leukemic Cells: Total Synthesis Intermediates as a Molecule Treasure Chest

A previously designed and developed 12-step total synthesis that includes [1,1′-biphenyl]-2-amine and carbazole intermediates and that ultimately produces the carbazole alkaloid carbazomycin G was exploited as a screening compound library with the goal of identifying potential lead compound(s) with cytotoxic effect. These compounds were investigated by using in-vitro tests involving the two human cell lines HL-60 and MOLM-13, which both model acute myeloid leukaemia (AML). The in-vitro biological test results were used together with the molecular structures of the various intermediates in a concise SAR analysis. Several of the intermediates revealed cytotoxicity (IC₅₀<10⁻⁴ M), although the final natural product carbazomycin G did not reveal cytotoxicity versus the two said human cell lines.     

骨组织工程PLGA/TCP复合材料的性能研究

骨组织工程的支架要求有与人骨在功能梯度上相一致的材料结构、几何结构和生理功能。PLGA／TCP复合材料具有适用于骨组织工程支架的综合性能。以快速成形技术低温沉积工艺的成形效果来评价材料的成形性能，以体外降解试验来评价材料的降解性能，以国家标准的方法来评价材料的细胞毒性，对PLGA和TCP不同配比下的性能进行了研究，发现TCP含量的增加有利于降低材料的细胞毒性，加快了材料的降解，但同时降低了材料的成形性能。从骨组织工程的临床应用来看，低的细胞毒性是需要首先得到保证的，成形性能则通过其他方式来改善。     

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.     

Pro-Inflammatory Effect of Gliadins and Glutenins Extracted from Different Wheat Cultivars on an In Vitro 3D Intestinal Epithelium Model

There is a need to assess the relationship between improved rheological properties and the immunogenic potential of wheat proteins. The present study aimed to investigate the in vitro effects of total protein extracts from three modern and two landrace Triticum aestivum commercial flour mixes, with significant differences in gluten strength (GS), on cell lines. Cytotoxicity and innate immune responses induced by wheat proteins were investigated using Caco-2 monocultures, two dimensional (2D) Caco-2/U937 co-cultures, and three dimensional (3D) co-cultures simulating the intestinal mucosa with Caco-2 epithelial cells situated above an extra-cellular matrix containing U937 monocytes and L929 fibroblasts. Modern wheat proteins, with increased GS, significantly reduced Caco-2 cell proliferation and vitality in monoculture and 2D co-cultures than landrace proteins. Modern wheat proteins also augmented Caco-2 monolayer disruption and tight junction protein, occludin, redistribution in 3D co-cultures. Release of interleukin-8 into the cell medium and increased U937 monocyte migration in both 2D and 3D co-cultures were similarly apparent. Immuno-activation of migrating U937 cells was evidenced from cluster of differentiation 14 (CD14) staining and CD11b-related differentiation into macrophages. The modern wheat proteins, with gluten polymorphism relatedness and increased GS, were shown to be more cytotoxic and immunogenic than the landrace wheat proteins.     

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.