GPR55 Receptor Activation by the N-Acyl Dopamine Family Lipids Induces Apoptosis in Cancer Cells via the Nitric Oxide Synthase (nNOS) Over-Stimulation

GPR55 is a GPCR of the non-CB1/CB2 cannabinoid receptor family, which is activated by lysophosphatidylinositol (LPI) and stimulates the proliferation of cancer cells. Anandamide, a bioactive lipid endocannabinoid, acts as a biased agonist of GPR55 and induces cancer cell death, but is unstable and psychoactive. We hypothesized that other endocannabinoids and structurally similar compounds, which are more hydrolytically stable, could also induce cancer cell death via GPR55 activation. We chemically synthesized and tested a set of fatty acid amides and esters for cell death induction via GPR55 activation. The most active compounds appeared to be N-acyl dopamines, especially N-docosahexaenoyl dopamine (DHA-DA). Using a panel of cancer cell lines and a set of receptor and intracellular signal transduction machinery inhibitors together with cell viability, Ca²⁺, NO, ROS (reactive oxygen species) and gene expression measurement, we showed for the first time that for these compounds, the mechanism of cell death induction differed from that published for anandamide and included neuronal nitric oxide synthase (nNOS) overstimulation with concomitant oxidative stress induction. The combination of DHA-DA with LPI, which normally stimulates cancer proliferation and is increased in cancer setting, had an increased cytotoxicity for the cancer cells indicating a therapeutic potential.     

Magic Peptide: Unique Properties of the LRR11 Peptide in the Activation of Leukotriene Synthesis in Human Neutrophils

Neutrophil-mediated innate host defense mechanisms include pathogen elimination through bacterial phagocytosis, which activates the 5-lipoxygenase (5-LOX) product synthesis. Here, we studied the effect of synthetic oligodeoxyribonucleotides (ODNs), which mimic the receptor-recognized sites of bacterial (CpG-ODNs) and genomic (G-rich ODNs) DNAs released from the inflammatory area, on the neutrophil functions after cell stimulation with Salmonella typhimurium. A possible mechanism for ODN recognition by Toll-like receptor 9 (TLR9) and RAGE receptor has been proposed. We found for the first time that the combination of the magic peptide LRR11 from the leucine-rich repeat (LRR) of TLR9 with the CpG-ODNs modulates the uptake and signaling from ODNs, in particular, dramatically stimulates 5-LOX pathway. Using thickness shear mode acoustic method, we confirmed the specific binding of CpG-ODNs, but not G-rich ODN, to LRR11. The RAGE receptor has been shown to play an important role in promoting ODN uptake. Thus, FPS-ZM1, a high-affinity RAGE inhibitor, suppresses the synthesis of 5-LOX products and reduces the uptake of ODNs by neutrophils; the inhibitor effect being abolished by the addition of LRR11. The results obtained revealed that the studied peptide-ODN complexes possess high biological activity and can be promising for the development of effective vaccine adjuvants and antimicrobial therapeutics.     

Control of mechanized surfacing of stamping tools with modulation of conditions

The results of investigations of the effect of the regulated parameters of low-frequency modulation on the characteristics of deposited beads in reconditioning of the working surfaces of dies of stamping tools are presented. The effect of the frequency and duty ratio of the modulated conditions on the mechanical properties of the deposited layer and the structure of its metal is described. Recommendations are issued for the effective application of technology with the controlled modulated conditions in the reconditioning of the working edges of the dies of the stamping tools.     

Natural and Designed Toxins for Precise Therapy: Modern Approaches in Experimental Oncology

Cancer cells frequently overexpress specific surface receptors providing tumor growth and survival which can be used for precise therapy. Targeting cancer cell receptors with protein toxins is an attractive approach widely used in contemporary experimental oncology and preclinical studies. Methods of targeted delivery of toxins to cancer cells, different drug carriers based on nanosized materials (liposomes, nanoparticles, polymers), the most promising designed light-activated toxins, as well as mechanisms of the cytotoxic action of the main natural toxins used in modern experimental oncology, are discussed in this review. The prospects of the combined therapy of tumors based on multimodal nanostructures are also discussed.     

X-ray Fluorescence Determination of Element Contents in Milk and Dairy Products

The concentrations of minerals (Na, Mg, P, S, Cl, K, and Ca) and trace elements (Mn, Fe, Ni, Cu, Zn, Rb, Sr, and Br) in different types of milk, dairy products, and infant formulas have been determined using wavelength-dispersive X-ray fluorescence analysis (WDXRF). Freeze-dried samples pressed as tablets of 4 g have been analyzed. Calibrations have been established using both plant and milk standard reference materials. The matrix correction method based on the power function of Compton scattered intensity was applied. The paper provides calibration data, detection limits for each element, and testing the accuracy of the proposed technique. The elemental compositions of the samples obtained by WDXRF were compared with the previously reported data from different countries.     

Oxidation resistance before and after heat treatment for compacted Al<Subscript>2</Subscript>O<Subscript>3</Subscript>–SiC–C mixtures with aluminum-chromium-phosphate binder

Oxidation resistance has been examined for compacted Al₂O₃–SiC–C mixtures, which contain an aluminum-chromium-phosphate binder without firing (DTA method) and ones that have been previously fired and given isothermal heat treatment at 800°C (as indicated by the mass loss). To obtain oxidation-resistant materials, the content of silicon carbide should not exceed 10 wt.% and the recommended graphite content is not more than 20 wt.%. Translated from Novye Ogneupory, No. 2, pp. 38 – 43, February, 2009.     

Interaction of Boron Carbide with Nickel Oxide

Thermodynamic methods and x-ray analysis have been applied to the chemical interactions in 0.9625 B₄C + 0.05 NiO + 0.0375 C, B₄C + NiO, B₄C + 4 NiO + 3 C mixtures; stages occur in the processes there that correspond to various temperature ranges. It is found that NiB always contains small amounts of lower borides, whose quantity does not exceed 2 mass% when the synthesis conditions are optimal.