Effect of particle size on the shaping of ceramics by slip casting

The effect of the nanometric-ranged particle size of the starting powder through a simple and well-established shaping method, slip casting, has been studied. Several alumina suspensions with the same viscosity (but different solid content suspensions) and different particle size (11, 44, 190 and 600 nm) were prepared and shaped into a dense body. The green and sintered densities ranged between 30–67% and 63–99% of the theoretical value, respectively. These values, together with the microstructure observations reveal the effect of the solid content of the suspensions and the characteristics of the ceramic powder, leading to the determination of an optimal particle size. Based on both processability (rheological behaviour) and microstructure (density and grain size) it has been determined that particles with sizes ranging 100–300 nm are the best for preparing concentrated suspensions with low viscosity and bodies with density close to the theoretical value when using conventional pressureless sintering densification.     

Dielectric properties of polyethylene terephthalate/polyphenylene sulfide/barium titanate nanocomposite for application in electronic industry

Polymer/ceramic nanocomposites designed for application as electronic packaging were prepared using corotating twin‐screw extruder. The dielectric properties of the composites made from polyethylene terephthalate (PET), polyphenylene sulfide, and barium titanate were studied as a function of BaTiO₃ fraction in the range between 0.75 and 1.5 wt%. Processing parameters were optimized in order to obtain the nanocomposites with appropriate dielectric properties like dielectric permittivity ε′, dielectric losses ε″, and their temperature stability in a wide frequency range. The measurements showed the increase of the dielectric permittivity value ε′ in the composites in comparison to both pure polymers. The dielectric loss factor tgδ of the composites was found to be much smaller than that of the pure PET. The weak influence of the ceramics on the temperature stability of the dielectric properties of the composites was stated. POLYM. ENG. SCI., 50:1613–1619, 2010. © 2010 Society of Plastics Engineers     

Electrochemical properties of two-component polymers of palladium and pyrrolidine and piperazine derivatives of C60

Redox-active films have been generated via electrochemical reduction in a solution containing palladium(II) acetate and [C₆₀]fullerene, or derivatives of C₆₀. The C₆₀ derivatives include piperazine (piperazine-C₆₀), pyrrolidine (CH₃-pyr-C₆₀), and a pyrrolidine salt, [(CH₃)₂-pyr-C₆₀]⁺ attached to the fullerene unit. In these films, fullerene moieties are covalently bonded to palladium atoms to form a polymeric network. The polymer yields involving the piperazine and pyrrolidine derivatives of C₆₀ are significantly lower than the yield of the C₆₀/Pd film. The CH₃-pyr-C₆₀/Pd and [(CH₃)₂-pyr-C₆₀]⁺/Pd films are electrochemically active in the negative potential region due to the reduction of the fullerene moiety. Reduction of the CH₃-pyr-C₆₀/Pd film is accompanied by the transport of supporting electrolyte cations from the solution into the film. In the first reduction step of the [(CH₃)₂-pyr-C₆₀]⁺/Pd film, both cations and anions of the supporting electrolyte are involved. The piperazine-C₆₀/Pd film exhibits electrochemical activity at both negative and positive potentials. In the negative potential region, reduction of the fullerene cage takes place. Oxidation of the piperazine moiety is responsible for the observed current in the positive potential range. Here, the oxidation process of this polymer is significantly influenced by the presence of metallic palladium particles in the film.     

Internal cation mobility in molten CsCl-NdCl3 system at 1073 K

CsCl-NdCl₃ is the next of binary MCl-NdCl₃ systems (M: alkali metal) investigated for determination of relative internal mobilities of cations (b_Cs, b_Nd) by countercurrent electromigration method (Klemm's method). The results have been presented as isotherms of internal mobilities of Cs⁺ and Nd³⁺ ions on NdCl₃ equivalent fraction (y_Nd). It has been found that internal mobility of cesium cations is higher than neodymium ones in the entire composition range (what is typical for nonsymmetrical MCl-LnCl₃ systems (M: Li, Na, K; Ln: La, Nd, Dy)) and decreases with increase of NdCl₃ concentration in the melt. Generally, dependence of internal mobility of lanthanide cations in melts with alkali metal chlorides on lanthanide (i.e. its atomic number and concentration) seems strongly related to stability of chloride complex anions of lanthanides in the melt. Investigated systems may be divided into two classes. The first class includes MCl-NdCl₃ systems (M: Li, Na) characterized by decrease of b_Nd with increase of NdCl₃ concentration. The second includes KCl-LnCl₃ systems (Ln: La, Nd, Dy) and presented here CsCl-NdCl₃ system, and is characterized by increase of b_Ln with concentration of Ln³⁺ cation. The dependence of b_Nd on NdCl₃ concentration at 1073 K was fitted (as for other systems) by a simple equation of the form: , where is the internal mobility of Ln³⁺ cations in pure molten LnCl₃, a the difference between internal mobility of Ln³⁺ cations in pure molten LnCl₃ and infinitely diluted LnCl₃ in molten alkali metal chloride (extrapolated), and yLnCl₃ is the equivalent fraction of LnCl₃.     

Tracking of Glycans Structure and Metallomics Profiles in BRAF Mutated Melanoma Cells Treated with Vemurafenib

Nearly half of patients with advanced and metastatic melanomas harbor a BRAF mutation. Vemurafenib (VEM), a BRAF inhibitor, is used to treat such patients, however, responses to VEM are very short-lived due to intrinsic, adaptive and/or acquired resistance. In this context, we present the action of the B-Raf serine-threonine protein kinase inhibitor (vemurafenib) on the glycans structure and metallomics profiles in melanoma cells without (MeWo) and with (G-361) BRAF mutations. The studies were performed using α1-acid glycoprotein (AGP), a well-known acute-phase protein, and concanavalin A (Con A), which served as the model receptor. The detection of changes in the structure of glycans can be successfully carried out based on the frequency shifts and the charge transfer resistance after interaction of AGP with Con A in different VEM treatments using QCM-D and EIS measurements. These changes were also proved based on the cell ultrastructure examined by TEM and SEM. The LA-ICP-MS studies provided details on the metallomics profile in melanoma cells treated with and without VEM. The studies evidence that vemurafenib modifies the glycans structures and metallomics profile in melanoma cells harboring BRAF mutation that can be further implied in the resistance phenomenon. Therefore, our data opens a new avenue for further studies in the short-term addressing novel targets that hopefully can be used to improve the therapeutic regiment in advanced melanoma patients. The innovating potential of this study is fully credible and has a real impact on the global patient society suffering from advanced and metastatic melanomas.     

Role of HMOX1 Promoter Genetic Variants in Chemoresistance and Chemotherapy Induced Neutropenia in Children with Acute Lymphoblastic Leukemia

Whilst the survival rates of childhood acute lymphoblastic leukemia (ALL) have increased remarkably over the last decades, the therapy resistance and toxicity are still the major causes of treatment failure. It was shown that overexpression of heme oxygenase-1 (HO-1) promotes proliferation and chemoresistance of cancer cells. In humans, the HO-1 gene (HMOX1) expression is modulated by two polymorphisms in the promoter region: (GT)n-length polymorphism and single-nucleotide polymorphism (SNP) A(−413)T, with short GT repeat sequences and 413-A variants linked to an increased HO-1 inducibility. We found that the short alleles are significantly more frequent in ALL patients in comparison to the control group, and that their presence may be associated with a higher risk of treatment failure, reflecting the role of HO-1 in chemoresistance. We also observed that the presence of short alleles may predispose to develop chemotherapy-induced neutropenia. In case of SNP, the 413-T variant co-segregated with short or long alleles, while 413-A almost selectively co-segregated with long alleles, hence it is not possible to determine if SNPs are actually of phenotypic significance. Our results suggest that HO-1 can be a potential target to overcome the treatment failure in ALL patients.     

Computer-Aided Search for 5-Arylideneimidazolone Anticancer Agents Able To Overcome ABCB1-Based Multidrug Resistance

ABCB1 modulation is an interesting strategy in the search for new anticancer agents that can overcome multidrug resistance (MDR). Hence, 17 new 5-arylideneimidazolones containing an amine moiety, as potential ABCB1 inhibitors, were designed, synthesized, and investigated. The series was tested in both parental (PAR) and multidrug-resistant (MDR) ABCB1-overexpressing T-lymphoma cancer cells using cytotoxicity assays. The ABCB1-modulating activity was examined in rhodamine 123 accumulation tests, followed by Pgp-Glo™ Assay to determine the influence of the most active compounds on ATPase activity. Lipophilic properties were assessed both, in silico and experimentally (RP-TLC). Pharmacophore-based molecular modelling toward ABCB1 modulation was performed. The studies allowed the identification of anticancer agents (p-fluorobenzylidene derivatives) more potent than doxorubicin, with highly selective action on MDR T-lymphoma cells (selectivity index >40). Most of the investigated compounds showed ABCB1-modulating action; in particular, two 5-benzyloxybenzylidene derivatives displayed activity nearly as strong as that of tariquidar.     

Coumarins from Seseli devenyense Simonk.: Isolation by Liquid–Liquid Chromatography and Potential Anxiolytic Activity Using an In Vivo Zebrafish Larvae Model

Different types of anxiety disorders have become the number one mental health issue in developed countries. The search for new, safer and effective drug-like molecules among naturally derived substances faces two difficulties: an efficient method of isolation compounds with a high-purity and high-throughput animal model for activity assay. Thus, the aim of the present study was to isolate by liquid–liquid chromatography high-purity rare coumarins from the fruits of Seseli devenyense Simonk. and evaluate their anxiolytic effect (defined as reversed thimotaxis) using a 5-days post-fertilization (dpf) Danio rerio larvae model. Liquid–liquid chromatography enabled the isolation of one simple hydroxycoumarin (devenyol) and four pyranocoumarins (cis-khellactone, d-laserpitin, isolaserpitin and octanoyllomatin). The anxiolytic effect was defined as a decrease in the time spent in the boundaries of the living space (also described as reversed thigmotaxis). Our results show that all isolated courmarins exerted a significant influence on the anxiety behavior (anxiolytic activity) in the zebrafish larvae model. According to our knowledge, this is the first report of anxiolytic activity of pyranocoumarins and devenyol.     

Evaluation of a Novel Plasmid for Simultaneous Gene Electrotransfer-Mediated Silencing of CD105 and CD146 in Combination with Irradiation

Targeting tumor vasculature through specific endothelial cell markers represents a promising approach for cancer treatment. Here our aim was to construct an antibiotic resistance gene-free plasmid encoding shRNAs to simultaneously target two endothelial cell markers, CD105 and CD146, and to test its functionality and therapeutic potential in vitro when delivered by gene electrotransfer (GET) and combined with irradiation (IR). Functionality of the plasmid was evaluated by determining the silencing of the targeted genes using qRT-PCR. Antiproliferative and antiangiogenic effects were determined by the cytotoxicity assay tube formation assay and wound healing assay in murine endothelial cells 2H-11. The functionality of the plasmid construct was also evaluated in malignant melanoma tumor cell line B16F10. Additionally, potential activation of immune response was measured by induction of DNA sensor STING and proinflammatory cytokines by qRT-PCR in endothelial cells 2H-11. We demonstrated that the plasmid construction was successful and can efficiently silence the expression of the two targeted genes. As a consequence of silencing, reduced migration rate and angiogenic potential was confirmed in 2H-11 endothelial cells. Furthermore, induction of DNA sensor STING and proinflammatory cytokines were determined, which could add to the therapeutic effectiveness when used in vivo. To conclude, we successfully constructed a novel plasmid DNA with two shRNAs, which holds a great promise for further in vivo testing.