Modulating Properties of Piroxicam,Meloxicam and Oxicam Analogues against Macrophage-Associated Chemokines in Colorectal Cancer

The mechanisms underlying the antineoplastic effects of oxicams have not been fully elucidated. We aimed to assess the effect of classic and novel oxicams on the expression/secretion of macrophage-associated chemokines (RTqPCR/Luminex xMAP) in colorectal adenocarcinoma cells, and on the expression of upstream the non-steroidal anti-inflammatory drug (NSAID)-activated genes NAG1, NFKBIA, MYD88, and RELA, as well as at the chemokine profiling in colorectal tumors. Meloxicam downregulated CCL4 9.9-fold, but otherwise the classic oxicams had a negligible/non-significant effect. Novel analogues with a thiazine ring substituted with arylpiperazine and benzoyl moieties significantly modulated chemokine expression to varying degree, upregulated NAG1 and NFKBIA, and downregulated MYD88. They inhibited CCL3 and CCL4, and their effect on CCL2 and CXCL2 depended on the dose and exposure. The propylene linker between thiazine and piperazine nitrogens and one arylpiperazine fluorine substituent characterized the most effective analogue. Only CCL19 and CXCL2 were not upregulated in tumors, nor was CXCL2 in tumor-adjacent tissue compared to normal mucosa. Compared to adjacent tissue, CCL4 and CXCL2 were upregulated, while CCL2, CCL8, and CCL19 were downregulated in tumors. Tumor CCL2 and CCL7 increased along with advancing T and CCL3, and CCL4 along with the N stage. The introduction of arylpiperazine and benzoyl moieties into the oxicam scaffold yields effective modulators of chemokine expression, which act by upregulating NAG1 and interfering with NF-κB signaling.     

Vibrational spectra of two BEDT-TTF-based organic conductors: charge order

Infrared and Raman investigations of two phases of bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) based organic conductors with the same CF₃CF₂SO₃⁻ anion: β′-(BEDT-TTF)₂CF₃CF₂SO₃ and δ′-(BEDT-TTF)₂CF₃CF₂SO₃, are shortly reviewed and compared with the most typical infrared properties of the family of (BEDT-TTF)₂RR′SO₃ organic conductors, where R = SF₅, CF₃, and R′ are CH₂, CF₂, CHF, CHFCF₂, and CH₂CF₂. The role of the molecular structur and spatial organization of the counterions is discussed. Presented at 2-nd International Conference on Functional Materials and Devices, ICFMD 2008, June 16–19, 2008, Kuala Lumpur, Malaysia     

Impact of TiO2 nanoparticles on morphology and performance of crosslinked polyimide organic solvent nanofiltration (OSN) membranes

Chemically crosslinked polyimide organic–inorganic composite nanofiltration membranes suitable for application in harsh organic solvents were successfully prepared by phase inversion of dope solutions. TiO₂ nanoparticles were dispersed in these dope solutions, comprising polyimide (PI) in N,N-dimethylformamide/1,4-dioxane. The impact of TiO₂ on the resulting PI membranes was investigated using SEM, TGA, water contact angle, dope viscosity measurements and mechanical strength. The presence of TiO₂ nanoparticles within the membrane matrix was proved by the detection of a peak characteristic of TiO₂ in the WAXS pattern. SEM pictures of the cross-section of the PI/TiO₂ membranes showed dramatically changed morphology compared to reference membranes with no TiO₂ addition. Macrovoids present in reference membranes were suppressed by increasing loading of TiO₂ nanoparticles, and eventually disappeared completely at a TiO₂ loading above 3 wt.%. Decreasing water contact angle and an increase in ethanol flux indicated that hydrophilicity increased as nanoparticle loading increased. The effect of TiO₂ on the functional performance of the membranes was evaluated by measuring flux and rejection using cross-flow filtration. Perhaps surprisingly, the presence of TiO₂ improved the compaction resistance of the membranes, whereas rejection and steady flux were almost unaltered.     

Immersions of spheres and algebraically constructible functions

Let Λ be an algebraic set and let (n is even) be a polynomial mapping such that for each there is r(λ) > 0 such that the mapping g _λ  =  g(· , λ) restricted to the sphere S ⁿ (r) is an immersion for every 0  <  r  <  r (λ), so that the intersection number I(g _λ|S ⁿ (r)) is defined. Then is an algebraically constructible function. I. Karolkiewicz and A. Nowel supported by the grant BW/5100-5-0286-7.     

Quantitative EPR study on free radicals in the natural polyphenols interacting with metal ions and other environmental pollutants

Quantitative electron paramagnetic resonance (EPR) method was applied to characterise radicals stabilised in polyphenolic matrices of various biogenic materials: lichens, mosses, composts, soils, peats, brown coals and sewage sludge sediments. The investigations were carried out on raw materials and extracted fractions of humic acids (HA). General trends of g value and spin concentration changes were found. These parameters in lichens strongly depend on lichen species and air pollution. Determination of the g value and semiquinone spin concentration allows to assess degree of transformation of organic matter in compost, soil, peat and lignite. Application of gaseous ammonia as a base penetrating the organic matrices extends the possibilities and usefulness of the method. Interaction of metal ions with humic materials is illustrated by interaction of VO2+ ion with peat and lignite HA as well as demineralised (raw and carbonised) brown coal. Our investigations demonstrate that quantitative EPR is a rapid and effective monitoring method to study the influence of various environmental factors on substances containing polyphenolic matrices.     

Oxozinc carboxylates: a predesigned platform for modelling prototypical Zn-MOFs' reactivity toward water and donor solvents

Two unique adducts of an oxozinc carboxylate cluster with H(2)O and THF were isolated and structurally characterized, [Zn(4)(μ(4)-O)(O(2)CR)(6)(H(2)O)(THF)]·2(THF) and [Zn(4)(μ(4)-O)(O(2)CR')(6)(THF)(3)] (where R = benzoate and R' = 9-antracenecarboxylate anion). The study shows that the zinc centers of the Zn(4)O core can easily form unique coordination environments without breaking of the Zn-O(carboxylate) bonds.     

Voltammetric Detection of a Specific DNA Sequence of Avian Influenza Virus H5N1 Using HS‐ssDNA Probe Deposited onto Gold Electrode

The working principle of a genosensor is based on the mechanism of ion‐channel mimetic sensors. The analytical signals generated upon hybridization processes were recorded by a redox active marker [Fe(CN)₆]^3?/4? present in the sample solution using voltammetric techniques. The developed genosensor was suitable for determination of 20‐mer complementary oligonucleotide sequence, and also of the PCR products containing the complementary 20‐mer sequence in various positions, with detection limits in the 10 pM range. The noncomplementary 20‐mer oligonucleotide sequence as well as the PCR product without complementary region generated very weak response. The good discrimination of the position of the complementary part in the PCR products was observed.     

Oxozinc carboxylate complexes: a new synthetic approach and the carboxylate ligand effect on the noncovalent-interactions-driven self-assembly

An atom-efficient and mild synthesis of a series of oxozinc carboxylates [Zn(4)(μ(4)-O)(O(2)CR)(6)] [where R = Ph (2a), p-PhC(6)H(4) (2b), p-MeC(6)H(4) (2c), and p-MeSC(6)H(4) (2d)] from well-defined alkylzinc precursors and H(2)O is described. The molecular and crystal structures of the resulting complexes have been determined by single-crystal X-ray diffraction. A closer examination of their crystal structure provides a direct picture of the effect of the nature of substituents on the molecular self-assembly of the octahedral oxozinc through noncovalent interactions. It was revealed that these discrete oxozinc clusters can form diverse types of noncovalent assemblies ranging from structures representing zeolitic topologies in the case of 2a to soft porous materials with gated voids or open channels for the remaining molecular clusters.     

An unusual nicotinamide derivative, 4-pyridone-3-carboxamide ribonucleoside (4PYR), is a novel endothelial toxin and oncometabolite

Our recent studies identified a novel pathway of nicotinamide metabolism that involves 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) and demonstrated its endothelial cytotoxic effect. This study tested the effects of 4PYR and its metabolites in experimental models of breast cancer. Mice were divided into groups: 4T1 (injected with mammary 4T1 cancer cells), 4T1 + 4PYR (4PYR-treated 4T1 mice), and control, maintained for 2 or 21 days. Lung metastasis and endothelial function were analyzed together with blood nucleotides (including 4PYR), plasma amino acids, nicotinamide metabolites, and vascular ectoenzymes of nucleotide catabolism. 4PYR metabolism was also evaluated in cultured 4T1, MDA-MB-231, MCF-7, and T47D cells. An increase in blood 4PYR in 4T1 mice was observed at 2 days. 4PYR and its metabolites were noticed after 21 days in 4T1 only. Higher blood 4PYR was linked with more lung metastases in 4T1 + 4PYR vs. 4T1. Decreased L-arginine, higher asymmetric dimethyl-L-arginine, and higher vascular ecto-adenosine deaminase were observed in 4T1 + 4PYR vs. 4T1 and control. Vascular relaxation caused by flow-dependent endothelial activation in 4PYR-treated mice was significantly lower than in control. The permeability of 4PYR-treated endothelial cells was increased. Decreased nicotinamide but enhanced nicotinamide metabolites were noticed in 4T1 vs. control. Reduced N-methylnicotinamide and a further increase in Met2PY were observed in 4T1 + 4PYR vs. 4T1 and control. In cultured breast cancer cells, estrogen and progesterone receptor antagonists inhibited the production of 4PYR metabolites. 4PYR formation is accelerated in cancer and induces metabolic disturbances that may affect cancer progression and, especially, metastasis, probably through impaired endothelial homeostasis. 4PYR may be considered a new oncometabolite.Subject terms: Mechanisms of disease, Pathogenesis, Breast cancer     

Biochemical and Molecular Investigation of the Effect of Saponins and Terpenoids Derived from Leaves of Ilex aquifolium on Lipid Metabolism of Obese Zucker Rats

Ilex paraguariensis, the holly tree, is a plant with recognized biological properties, whose aqueous infusions are known as “Yerba mate”, that regulate lipid metabolism, reduce obesity, and improve brain stimulation. In the present study, the effect of standardized saponin and terpenoid fractions of a European taxon, Ilex aquifolium, on blood biochemical parameters in a rat model of metabolic disorder, (fa/fa) Zucker, are presented. The profiles of the volatile fractions of two species and six European varieties of Ilex were investigated. After selecting the best variety, the saponin and terpenoid fractions were isolated and standardized, and animals were fed 10 mg kg⁻¹ b.w. for 8 weeks. A statistically significant decrease in liver adiposity was observed, confirmed by histology and quantitative identification (gas chromatography–mass spectrometry analyses of hepatic lipids. RT-qPCR analysis of gene expression in the aorta revealed that the administration of the terpenoid fraction downregulated LOX-1, suggesting a reduction in atherosclerotic stimuli. In addition, a statistically significant reduction (p < 0.05) in PPARγ for the saponin fraction was observed in the liver. The expression of the ACAT-1 gene in the liver, responsible for the formation of cholesterol esters, increased significantly in the group receiving the terpenoid fraction compared to the control, which was also confirmed by the analysis of individual blood biochemical parameters. The opposite effect was observed for saponins. Taking the above into account, it is shown for the first time that Ilex aquifolium can be a source of compounds that positively influence lipid metabolism.