Synthesis and comparative analysis of the cytotoxicity and mitochondrial effects of triphenylphosphonium and F16 maslinic and corosolic acid hybrid derivatives.

The cytotoxic profile and antiproliferative and mitochondrial effects of triterpene acid conjugates with mitochondriotropic lipophilic triphenylphosphonium (TPP) and F16 cations were evaluated. Maslinic and corosolic acids chosen as the investigation objects were synthesized from commercially available oleanolic and ursolic acids. Study of the cytotoxic activity of TPP and F16 triterpenoid derivatives against six tumor cell lines demonstrated a comparable synergistic effect in the anticancer activity, which was most pronounced in the case of MCF-7 mammary adenocarcinoma cells and Jurkat and THP-1 leukemia cells.

Synthesis and cytotoxic activity of some (+)-salsolidine derivatives.

On the basis of typical for secondary amino group reactions a number of derivatives of alkaloid (+)-salsolidine was synthesised. Cytotoxic properties of obtained compounds towards the HEK293, A549, MCF-7 and SH-SY5Y cell lines have been evaluated. As a result of the screening, the hit compound - 2-(chloroacetyl)-6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline () was identified, that inhibited the metabolic activity of A-549, MCF-7 and SH-SY5Y tumour cell lines with the IC values of 3.

Impact of a sugar-sweetened beverage tax on sugar producers in Ukraine.

Taxes on sugar-sweetened beverages can promote health and raise revenue. Whether these taxes negatively impact domestic sugar producers, an argument often made by opponents, is understudied. We extended a simulation model based on a uniform specific volume-based tax of UAH 4/L in Ukraine.

The globalizability of temporal discounting.

Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups.

[The role of glutamate in the pathogenesis of multiple sclerosis].

The results of recent studies indicate that the hyperactivation of the glutamatergic system plays an important role in the pathophysiology of multiple sclerosis (MS). In addition to the well-known direct toxic effect of the excessive extracellular level of the glutamate neurotransmitter on neurons, additional mechanisms of glutamate-induced cell damage have been described in the literature, including effects on oligodendrocytes, astrocytes, endothelial cells and immune cells. The study of these toxic effects will reveal the possible link between various pathological hallmarks of MS, such as axonal damage, oligodendrocyte death, demyelination, neurodegeneration, autoimmune reactions and dysfunction of blood-brain barrier.

Synthesis of new 1,3-thiazol derivatives of maleopimaric acid as anticancer, antibacterial and antifungal agents.

A series of new 1,3-thiazole derivatives of maleopimaric acid , were synthesized and evaluated for anticancer, antibacterial and antifungal activities. Evaluation of cytotoxic activity against human embryonic kidney 293 cells (HEK293), human neuroblastoma cell line (SH-SY5Y), hepatocellular carcinoma cell line (HepG2) and human T-cell lymphoblast-like line (Jurkat), showed that introduction of the aminothiazole fragment at position 6 of the diterpenoid molecule leads to decrease of cell viability. Substance 3 was found to be the most active against all tested cell lines, inhibiting cell viability with IC values in the range of 2-24 μM.

NMDA Receptors Regulate Genes Responsible for Major Immune Functions of Mononuclears in Human Peripheral Blood.

To determine the role of NMDA receptors in the functional regulation of immunocompetent cells, comparative assay was carried out for genes expressed in the mononuclears in peripheral blood of healthy persons under normal conditions and after blockade of these receptors. The genes, whose expression changed in response to blockade of NMDA receptors in mononuclears, encode the products involved in regulation of the major functions of immune cells, such as proliferation (IL4, VCAM1, and CDKN2A), apoptosis (BAX, MYC, CDKN2A, HSPB1, and CADD45A), activation (IL4R, IL4, VCAM1, and CDKN2A), and differentiation (IL4, VCAM1, and BAX).

[Inhibition of IAA oxidase activity of wheat anionic peroxidase by chitooligosaccharides].

The study demonstrated that chitooligosaccharides with a molecular weight of 5–10 kDa and a degree of acetylation of 65% exhibited an auxin-like effect in wheat plants and also played an important role in regulating the activity of polysaccharide (chitin)–specific anion isoenzymes of peroxidase oxidizing indole acetic acid. Changes in the kinetic parameters of the interaction of the wheat anionic chitin-specific peroxidase with pI ∼3.5 with chitin oligomers in the presence of indoleacetic acid were pH-depended and indicated that chitooligosaccharides significantly impair the ability of the enzyme for oxidation at pH levels of 4.

[Search of (-)-Cytisine Derivatives as Potential Inhibitors of NF-κB and STAT1].

Design and synthesis ofnew derivatives of (-)-cytisine with a wide spectrum of pharmacological activity, represents the potential therapeutic interest for development of drug candidates for neurodegenerative disorders, inflammatory diseases, and treatment of nicotine addiction. We used HEK293 cell line transiently transfected with N F-κB and STATI luciferase reporter constructs to screen the (-)-cytisine derivatives for their potency to modulate basal and induced NF-κB and STAT1 activity. Currently, NF-κB, STAT1 and components of their signaling pathways are considered as attractive targets for pharmacological intervention, primarily in chronic inflammation, cancer, autoimmune, neurodegenerative and infectious diseases.

[DNA amplification using PCR with abutting primers].

DNA analysis of ñîmplex biological objects (wastewater, soil, archaeological and forensic samples, etc.) is currently of great interest. DNA of these objects is characterized by low suitability for research due to the violation of its integrity and chemical structure; thus, the detection of specific nucleic acid fragments can be achieved by PCR with contiguous primers.

[Cellular test systems for the search for transcription factor activity modulators].

Test systems for monitoring activities and the search for substances activating or inhibiting transcription factors as biotargets have been designed on the basis of luciferase constructs containing binding sites for transcription factors CREB, NFAT, NF-kB, p53, STAT1, GAS, VDR, HSF1, and HIF1alpha. An assessment of the functional activity of reporter constructs has been carried out using their transient transfection into HEK293 cells followed by treatment with specific inducers. The functional activity of all reporter constructs was observed based on the increased luciferase expression.

Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation.

Background: Noopept (N-phenyl-acetyl-L-prolylglycine ethyl ester) was constructed as a dipeptide analog of the standard cognition enhancer, piracetam. Our previous experiments have demonstrated the cognition restoring effect of noopept in several animal models of Alzheimer disease (AD). Noopept was also shown to prevent ionic disbalance, excitotoxicity, free radicals and pro-inflammatory cytokines accumulation, and neurotrophine deficit typical for different kinds of brain damages, including AD.

[Morphological features of transgenic tobacco plants expressing the AINTEGUMENTA gene of rape under control of the Dahlia mosaic virus promoter].

Transgenic tobacco plants expressing the AINTEGUMENTA gene of rape under control of the 35S promoter and the promoter of dahlia mosaic virus were obtained. The transgenic plants were characterized by increase in the length of the leaves, flower sizes, stem height, and weight of seeds; at the same time, the degree of increase was greater in the case of use of the dahlia mosaic virus promoter as a regulator of transcription. Ectopic expression of the AINTEGUMENTA gene promoted prolongation of leaf growth, while sizes of epidermal cells of the leaves remained unchanged.

[Metabolic changes in wheat (Triticum aestivum L.) plants under action of bioregulator stifun].

Under action of growth-stimulating concentrations of bioregulator stifun on wheat plants, an increase of functional activity of nucleoli of meristematic cells; contents of lectin (wheat germ agglutinin); and activity of proteinases, tripsin inhibitors, and ATPase activity was established. The pool of free amino acids was increased under bioregulator use. Levels of methionine, phenylalanine, cysteine, lysine, and tyrosine were increased.

NMDA receptors as a possible component of store-operated Ca²⁺ entry in human T-lymphocytes.

Elevation of intracellular Ca²⁺ in T-lymphocytes as a consequence of T cell antigen receptor activation triggers transcriptional programs resulting in effector cytokine secretion and immune response coordination. Increase of Ca²⁺ concentration in T-lymphocytes follows both the Ins(1,4,5)P(3)-dependent release from an intracellular store and subsequent influx from extracellular milieu. Flow cytometry and the fluorescent dye Fluo-4AM have been used to demonstrate that noncompetitive NMDA receptor antagonist (+)-MK801 inhibits Ca²⁺ influx in T cells induced by thapsigargin.

[New approaches to the real-time detection of nucleotide mismatches by means of chimeric hybridization probes].

New approaches to the detection of impaired nucleotides based on the allele specific ligation of a "C probe" followed by rolling circle amplification have been developed. The detection of amplification products was realized by using enzymatic and deoxyribozyme digestion of fluorescently-labeled DNA-RNA-DNA chimeric oligonucleotide structures in cycling probe technology (CPT) in real-time mode.

[Immunogenicity of N-protein of Puumala hantavirus for noninbred mice in the intramuscular administration of its gene DNA].

The outbreaks of hantavirus infections in some regions of the Russian Federation in some years involve considerable material and social losses. In this connection, the designing of the most effective types of vaccines is an urgent task. The authors have created plasmid constructions containing the gene of hemorrhagic fever with renal syndrome virus, with whose Intramuscular injection there is a specific immune response and plasmid DNA is detectable in the adjacent tissues within a month after injection.

[Correlation between the effect of chemotherapy on complement conformation and on CA-125 antigen in the blood plasma of patients with ovarian carcinoma].

Correlation was investigated between blood-plasma levels of C3(H2)O (conformation pattern of C3 component of the complement) and tumor-associated marker CA-125 in patients with ovarian cancer before and after chemotherapy. Since a drop in CA-125 level after chemotherapy was associated with similar changes in C3(H2)O fraction, it seems reasonable to suggest that change in conformation of C3 is a response of the immune system to cancer.

[The symbiosis between oriental goat's rue and the root nodule bacteria Rhizobium galegae: specificity and competitiveness].

Competitiveness and genetic variation of the Rhizobium galegae strains from the collection of the All-Russia Institute of Agricultural Microbiology, Russian Academy of Agricultural Sciences, causing nodulation of oriental goat's rue under conditions of Bashkortostan soils (lacking this rhizobial species) were studied. It was demonstrated that of all the tested strains, the strains CIAM 0702 and CIAM 0704, each carrying two megaplasmids of 1500 and 2000 MDa, were the most competitive. RAPD (random amplified polymorphic DNA) analysis showed that R.

[DNA macroarray analysis of gene expression changes in rat brain after single administration of 2-aminoadamantane compound].

We have used the Rat Atlas cDNA Array ("BD Bioscience") to assess changes in mRNA expression of 588 genes in rat brain after acute treatment of 2-aminoadamantane compound--Ladasten. Drug exhibits the psychostimulating and anxyolitic actions. The analysis of results of hybridization on macrochips and their corroboration by quantitative real-time RT-PCR has allowed to reveal 12 genes, expression of which changes in response to ladasten in rat brain cells.