The Effects of Vitamin D on the Expression of IL-33 and Its Receptor ST2 in Skin Cells; Potential Implication for Psoriasis

Interleukin 33 (IL-33) belongs to the IL-1 family and is produced constitutively by epithelial and endothelial cells of various organs, such as the skin. It takes part in the maintenance of tissue homeostasis, repair, and immune response, including activation of Th2 lymphocytes. Its involvement in pathogenesis of several inflammatory diseases including psoriasis was also suggested, but this is not fully understood. The aim of the study was to investigate expression of IL-33 and its receptor, ST2, in psoriasis, and the effects of the active form of vitamin D (1,25(OH)₂D₃) on their expression in skin cells. Here we examined mRNA and protein profiles of IL-33 and ST2 in 18 psoriatic patients and healthy volunteers by qPCR and immunostaining techniques. Potential effects of 1,25(OH)₂D₃ and its receptor (VDR) on the expression of IL-33 and ST2 were tested in cultured keratinocytes, melanocytes, fibroblasts, and basal cell carcinoma cells. It was shown that 1,25(OH)₂D₃ effectively stimulated expression of IL-33 and its receptor ST2’s mRNAs in a time-dependent manner, in keratinocytes and to the lesser extends in melanocytes, but not in fibroblasts. Furthermore, the effect of vitamin D on expression of IL-33 and ST2 was VDR-dependent. Finally, we demonstrated that the expression of mRNA for IL-33 was mainly elevated in the psoriatic skin but not in its margin. Interestingly, ST2 mRNA was downregulated in psoriatic lesion compared to both marginal tissue as well as healthy skin. Our data indicated that vitamin D can modulate IL-33 signaling, opening up new perspectives for our understanding of the mechanism of vitamin D action in psoriasis therapy.     

Antimicrobial and Cytotoxic Properties of Bisquaternary Ammonium Bromides of Different Spacer Length

A group of cationic gemini surfactants (bisquaternary ammonium bromides) with different spacer chain lengths (8–6–8, 8–7–8, 8–8–8, 8–9–8) was investigated, paying special attention to antimicrobial and the cytotoxic properties as well as their antimicrobial activity during long‐term storage. It was shown that the compounds investigated exhibit excellent antimicrobial activity against Gram‐positive bacteria (Staphylococcus aureus) and Gram‐negative bacteria (Pseudomonas aeruginosa) as well as antifungal properties (Candida albicans). The gemini surfactants tested had the differential level of cytotoxicity against normal lymphocytes. It was shown that the spacer chain length plays an important role in antibacterial activity and influences the cytotoxicity. The gemini surfactants with shorter spacer chain length, that had higher critical micelle concentration, showed generally weaker antibacterial properties, but on the other hand, these exhibited lower level of cytotoxicity. Furthermore, the aqueous solution of gemini surfactants exhibited the same antimicrobial activity even after 3 months.     

Viscoelastic properties and morphological characteristics of polymer‐modified bitumen blends

The state of dispersion, the viscoelastic properties and the mechanical properties (such as Young's modulus, ductibility, penetration, and Fraas breaking point) of polymer‐modified bitumen are investigated. Bitumen was modified with low‐density polyethylene from processed bags (PE_bags) and styrene‐butadiene random block copolymer (SBR). The blends were characterized by optical microscopy, dynamic mechanical thermal analysis (DMTA), and other conventional methods. Photomicrographs indicated that different morphologies were obtained; PE_bags gave dispersions with almost spherical polymer particles; whereas in the case of SBR, fibrillar domains were observed. DMTA measurements indicated significant changes of the storage and loss moduli of modified bitumen; depending on the polymer content in the bitumen matrix, these values were three to four times higher compared with neat bitumen. Blends with SBR showed a significantly increased resistance to cracking at low temperatures due to decrease of the glass transition temperature from ?14 to ?34°C. Contrary, PE_bags gave better results at higher temperatures where as a result of the increased resistance to permanent deformation the softening point of modified bitumen was shifted from 52 to 73°C. It was also investigated the influence of mixtures of PE_bags/SBR on the properties of bitumen as function of the composition and ratio between PE_bags and SBR. It was found that the best improvement in deformation resistance, permanent deformation, and cracking of bitumen was achieved with the addition of PE_bags/SBR mixture as the rubber increased the bitumen properties at low temperatures and the polyolefin at high temperatures. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Network films of conducting polymer-linked polyoxometalate-modified gold nanoparticles: Preparation and electrochemical characterization

The ability of Keggin-type phosphododecamolybdate (PMo₁₂O₄₀³⁻, PMo₁₂) to undergo chemisorption on solid surfaces (including gold) is explored here to convert (by ligand place-exchange and phase transfer to aqueous solution) the alkanothiolate-modified Au nanoparticles of controlled size (prepared in toluene) into a stable colloidal solution of PMo₁₂-protected gold nanoparticles, PMo₁₂-AuNPs, the sizes of which are ca. 4-5 nm as determined by transmission electron microscopy. By dip-coating, PMo₁₂-AuNPs were assembled on carbon electrode substrates. The step-by-step assembly, by which alternate exposures to the solutions of PMo₁₂-AuNPs and either anilinium cations or pyrrole monomers, was utilized to grow in controlled manner hybrid network films in which the negatively charged PMo₁₂-AuNP deposits were linked, or electrostatically attracted, by ultra-thin, positively charged conducting polymer (polyaniline or polypyrrole) structures. The three-dimensionally distributed PMo₁₂-AuNPs immobilized within the polypyrrole-based composite film exhibited some electrocatalytic reactivity towards reduction of hydrogen peroxide.     

2'-O-Lysylaminohexyl oligonucleotides: modifications for antisense and siRNA

A novel type of oligonucleotide has been developed, characterized by the attachment of a lysyl moiety to a 2'-O-aminohexyl linker. A protected lysine building block was tethered to 2'-O-aminohexyluridine, and the product was converted into the corresponding phosphoramidite. Up to six modified nucleosides were incorporated in dodecamer DNA and RNA oligonucleotides using standard phosphoramidite chemistry. Each of the building blocks contributes one positive charge to the oligonucleotide instead of the negative charge of a wild-type nucleotide. Thermal denaturation profiles indicated a stabilizing effect of 2'-O-lysylaminohexyl chains that was more pronounced in RNA duplexes. Incubation of the oligonucleotides with 5'-exonuclease revealed an exceptionally high stability against enzymatic degradation. Incorporation of up to three modifications into functional antisense and siRNA oligonucleotides targeted at ICAM-1 showed that the gene-silencing activity was higher with an increasing number of lysylaminohexyl nucleotides. Compared with wild-type antisense or siRNA, compounds with three modifications led to equal or higher ICAM-1 downregulation.     

The effect of phosphate source on the sintering of carbonate substituted hydroxyapatite

Carbonate hydroxyapatite (CHAp) was synthesized by a wet precipitation method. In the synthesis, calcium oxide, H₃PO₄ and (NH₄)₂HPO₄ were applied as reactants. NH₄HCO₃ in the amount of 0.05–0.20 mol per 0.3 mol of H₃PO₄ or (NH₄)₂HPO₄ was used as the source of CO₃^2? groups. Sintering was carried out using powders and uniaxially pressed samples of carbonate and non-carbonate hydroxyapatites. The influence of synthesis conditions as well as sintering atmosphere on sinterability and phase composition of the final ceramic materials was evaluated. It was found that using properly synthesized CHAp powders and CO₂ atmosphere during heat-treatment it was possible to obtain dense CHAp ceramics with 1% of CaCO₃ as the secondary phase at the temperature 300–350 °C lower than that required for non-carbonate hydroxyapatite. Chemical stability and bioactive potential of CHAp–CaCO₃ ceramics were confirmed by in vitro tests.     

How Substitution Combines with Non-Covalent Interactions to Modulate 1,4-Naphthoquinone and Its Derivatives Molecular Features—Multifactor Studies

Substitution is well-known to modulate the physico-chemical properties of molecules. In this study, a combined, multifactor approach was employed to determine a plethora of substitution patterns using –Br and –O-H in 1,4-naphthoquinone and its derivatives. On the basis of classical Density Functional Theory (DFT), 25 models divided into three groups were developed. The first group contains 1,4-naphthoquinone and its derivatives substituted only by –Br. The second group consists of compounds substituted by –Br and one –O-H group. As a result of the substitution, an intramolecular hydrogen bond was formed. The third group also contains –Br as a substituent, but two –O-H groups were introduced and two intramolecular hydrogen bonds were established. The simulations were performed at the ωB97XD/6-311++G(2d,2p) level of theory. The presence of substituents influenced the electronic structure of the parent compound and its derivatives by inductive effects, but it also affected the geometry of the 2 and 3 groups, due to the intramolecular hydrogen bonding and the formation of a quasi-ring/rings. The static DFT models were applied to investigate the aromaticity changes in the fused rings based on the Harmonic Oscillator Model of Aromaticity (HOMA). The OH stretching was detected for the compounds from groups 2 and 3 and further used to find correlations with energetic parameters. The evolution of the electronic structure was analyzed using Hirshfeld atomic charges and the Substituent Active Region (cSAR) parameter. The proton reaction path was investigated to provide information on the modulation of hydrogen bridge properties by diverse substitution positions on the donor and acceptor sides. Subsequently, Car–Parrinello Molecular Dynamics (CPMD) was carried out in the double-bridged systems (group 3) to assess the cooperative effects in double –O-H-substituted systems. It was determined that the –O-H influence on the core of the molecule is more significant than that of –Br, but the latter has a major impact on the bridge dynamics. The competitive or synergic effect of two –Br substituents was found to depend on the coupling between the intramolecular hydrogen bridges. Thus, the novel mechanism of a secondary (cooperative) substituent effect was established in the double-bridged systems via DFT and CPMD results comparison, consisting of a mediation of the bromine substitutions’ influence by the cooperative proton transfer events in the hydrogen bridges.     

Analysis of the Potential Genetic Links between Psoriasis and Cardiovascular Risk Factors

Cardiovascular risk factors are one of the most common comorbidities in psoriasis. A higher prevalence of hypertension, insulin resistance and type 2 diabetes, dyslipidemia, obesity, metabolic syndrome, depression, as well as cardiovascular disease was confirmed in psoriatic patients in comparison to the general population. Data suggest that psoriasis and systemic inflammatory disorders may originate from the pleiotropic interactions with many genetic pathways. In this review, the authors present the current state of knowledge on the potential genetic links between psoriasis and cardiovascular risk factors. The understanding of the processes linking psoriasis with cardiovascular risk factors can lead to improvement of psoriasis management in the future.     

Breast Cancer: Targeting of Steroid Hormones in Cancerogenesis and Diagnostics

Breast cancer is the most common malignancy in women with high mortality. Sensitive and specific methods for the detection, characterization and quantification of endogenous steroids in body fluids or tissues are needed for the diagnosis, treatment and prognosis of breast cancer and many other diseases. At present, non-invasive diagnostic methods are gaining more and more prominence, which enable a relatively fast and painless way of detecting many diseases. Metabolomics is a promising analytical method, the principle of which is the study and analysis of metabolites in biological material. It represents a comprehensive non-invasive diagnosis, which has a high potential for use in the diagnosis and prognosis of cancers, including breast cancer. This short review focuses on the targeted metabolomics of steroid hormones, which play an important role in the development and classification of breast cancer. The most commonly used diagnostic tool is the chromatographic method with mass spectrometry detection, which can simultaneously determine several steroid hormones and metabolites in one sample. This analytical procedure has a high potential in effective diagnosis of steroidogenesis disorders. Due to the association between steroidogenesis and breast cancer progression, steroid profiling is an important tool, as well as in monitoring disease progression, improving prognosis, and minimizing recurrence.