L-Cysteine/Silver Nitrate/Iodate Anions System: Peculiarities of Supramolecular Gel Formation with and Without Visible-Light Exposure.

In this study, novel anion photo-responsive supramolecular hydrogels based on cysteine-silver sol (CSS) and iodate anions (IO) were prepared. The peculiarities of the self-assembly process of gel formation in the dark and under visible-light exposure were studied using a complex of modern physico-chemical methods of analysis, including viscosimetry, UV spectroscopy, dynamic light scattering, electrophoretic light scattering, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. In the dark phase, the formation of weak snot-like gels takes place in a quite narrow IO ion concentration range.

Preparation of Composite Hydrogels Based on Cysteine-Silver Sol and Methylene Blue as Promising Systems for Anticancer Photodynamic Therapy.

In this study, a novel supramolecular composite, "photogels", was synthesized by mixing of cysteine-silver sol (CSS) and methylene blue (MB). A complex of modern physico-chemical methods of analysis such as viscosimetry, UV spectroscopy, dynamic and electrophoretic light scattering, scanning electron microscopy and energy-dispersive X-ray spectroscopy showed that MB molecules are uniformly localized mainly in the space between fibers of the gel-network formed by CSS particles. Molecules of the dye also bind with the surface of CSS particles by non-covalent interactions.

Effects of Isoxazolyl Steroids on Key Genes of Sonic Hedgehog Cascade Expression in Tumor Cells.

Activation of the Hedgehog (Hh) signaling pathway is often associated with the progression of various types of cancer. The purpose of study was to search for inhibitors of the Hh signaling pathway among eight compounds belonging to the group of isoxazolyl steroids. The evaluation of the effectiveness of the compounds was based on the analysis of their cytotoxicity, effect on the cell cycle, on the expression of key Hh-signaling-pathway genes (Ptch1, Smo, and Gli1) and putative target genes MMP-2 and MMP-9.

Fluoride-Ion-Responsive Sol-Gel Transition in an L-Cysteine/AgNO System: Self-Assembly Peculiarities and Anticancer Activity.

Supramolecular hydrogels based on low-molecular-weight compounds are a unique class of so-called "soft" materials, formed by weak non-covalent interactions between precursors at their millimolar concentrations. Due to the variety of structures that can be formed using different low-molecular-weight gelators, they are widely used in various fields of technology and medicine. In this study, we report for the first time an unusual self-assembly process of mixing a hydrosol obtained from L-cysteine and silver nitrate (cysteine-silver sol-CSS) with sodium halides.

Impact of dihydropyrimidinase-related protein 2 in memory formation on rats and its possible role in neuronal back remodeling.

The article concerns the problem of molecular mechanisms of memory formation. In this study the effects of polyclonal antibodies to serotonin-modulating anticonsolidation protein (SMAP) complex and its component dihydropyrimidinase-related protein 2 (DRP2) have been analyzed. Intra-cerebral administration of polyclonal anti-SMAP antibody significantly enhanced elaboration and strengthened memory formation in two complex behavioral conditioned models.

Cysteine-Silver-Polymer Systems for the Preparation of Hydrogels and Films with Potential Applications in Regenerative Medicine.

Herein, the problem concerning the poorer mechanical properties of gels based on low molecular weight gelators (LMWGs)-L-cysteine and silver nitrate-was solved by the addition of various polymers-polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG)-to the initial cysteine-silver sol (CSS). The physicochemical methods of analysis-viscosimetry, UV spectroscopy, DLS, and SEM-identified that cysteine-silver hydrogels (CSG) based on PVA possess the best rheological properties and porous microstructure (the average pore size is 2-10 µm) compared to gels without the polymer or with PVP or PEG. Such gels are able to form cysteine-silver cryogels (CSC) and then porous cysteine-silver films (CSF) with an average pore size of 10-20 µm and good mechanical, swelling, and adhesion to skin characteristics as long as the structure of CSS particles remains stable.

L-Cysteine and -acetyl-L-cysteine-mediated synthesis of nanosilver-based sols and hydrogels with antibacterial and antibiofilm properties.

The need of the synthesis of a new generation of medicines aimed at combating bacteria and biofilms that cause various infections is a great urgency. There has been a gradual decrease in the conventional techniques of treatment with the use of antibiotics. Consequently, much effort has focused on the search for new methods and approaches to obtain antibacterial drugs and determine their rational use such that microorganisms do not acquire resistance.

Synthesis and Biological Evaluation of New Isoxazolyl Steroids as Anti-Prostate Cancer Agents.

Steroids with a nitrogen-containing heterocycle in the side chain are known as effective inhibitors of androgen signaling and/or testosterone biosynthesis, thus showing beneficial effects for the treatment of prostate cancer. In this work, a series of 3β-hydroxy-5-ene steroids, containing an isoxazole fragment in their side chain, was synthesized. The key steps included the preparation of Weinreb amide, its conversion to acetylenic ketones, and the 1,2- or 1,4-addition of hydroxylamine, depending on the solvent used.

The impact of background γ-radiation on erythrocyte nuclear pathology, the serotonergic system, and cytochrome P-450 in hens (GALLUS GALLUS DOMESTICUS) from Azerbaijan.

High levels of background γ-radiation exist in the suburbs of Baku, Azerbaijan. We examined the impact of radiation on erythrocyte nuclear pathologies, levels of cytochrome P-450, and serotonin-modulating anticonsolidation protein (SMAP) in the tissues of the hens from three settlements with different levels of background radiation. Higher levels of radiation resulted in increased nuclear pathologies, upregulation of tissue SMAP levels, and downregulation of cytochrome P-450.

L-Cysteine as a reducing/capping/gel-forming agent for the preparation of silver nanoparticle composites with anticancer properties.

The present article reports the preparation of silver nanoparticles (AgNPs) homogeneously distributed in the gel matrix formed using only L-cysteine (CYS) as a bio-reducing agent. The physicochemical methods of analysis confirmed the formation of a gel-network from aggregates consisting of spherical/elliptical cystine-stabilized AgNPs (core) and cysteine/Ag complexes (shell) regardless of the used silver salt - AgNO, AgNO or AgOOCCH. CYS/AgNO and CYS/AgOOCCH aqueous solution systems needed the addition of electrolytes (Cl and SO) for the gelation process, but the gel-formation in CYS/AgNO occurred in one stage without any additional components.

L-Cysteine/AgNO low molecular weight gelators: self-assembly and suppression of MCF-7 breast cancer cells.

We report a new supramolecular hydrogel based on simple amino acids and silver salt compounds with low molecular weights. The in situ formation of silver nanoparticles during the self-assembly process endows the hydrogel with high cytotoxicity towards adenocarcinoma breast cells but no toxic effects towards embryonic fibroblasts.

Biological Evaluation of a New Brassinosteroid: Antiproliferative Effects and Targeting Estrogen Receptor α Pathways.

Brassinosteroids (BS), a class of plant-specific steroid hormones, are considered as new potential anticancer agents for the treatment of tumors of different origin, including hormone-dependent cancers. Effects of a synthetic brassinosteroid BS4 ((22R,23R,24R)-22,23-dihydroxy-24-methyl-B-homo-7-oxa-5α-cholest-2-en-6-one ((3aS,7aR,7bS,9aS,10R,12aS,12bS)-10-[(2S,3R,4R,5R)-3,4-dihydroxy-5,6-dimethylheptan-2-yl]-7a,9a-dimethyl-1,3a,4,7,7a,7b,8,9,9a,10,11,12,12a,12b-tetradecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one)) on hormone-dependent breast cancer cells and normal epithelial cells and its impact on the estrogen receptor signaling were evaluated. Cytotoxicity was assessed by MTT-test; expression of estrogen receptor α and survivin was measured by immunoblotting.

[Reparative mechanisms in retina and hypothalamus contributing to rhodopsin recovery in rabbit eyes with retinal dystrophy].

Purpose: To study the molecular reparatory mechanisms of the retina and hypothalamus in the context of experimental dystrophy of receptor apparatus in rabbit retina.

Material And Methods: Retinal dystrophy was induced in rabbit eyes by injecting monoiodacetic acid (MIA) intravenously. Indirect ELISA test was used to evaluate the levels of rhodopsin, heat shock protein 70 kDa (HSP70) in the retina, and serotonin-modulating anticonsolidation protein (SMAP) - that directly correlates with serotonin level - in the hypothalamus.

DNA integrity-protecting and survival-promoting activity of serotonergic system in sturgeon juveniles and sazans.

The study concerns evaluation of engagement of serotonergic system in the mechanisms of antimutagenic protection and survival under adverse conditions. It is shown that under long-term exposure to oil and industrial pollution, simultaneous sharp increase of mutations level in the erythrocytes and downregulation of serotonin-modulating anticonsolidation protein (SMAP; Mekhtiev 2000) in the livers of the sturgeon juveniles (Acipenser gueldenstaedtii persicus) is observed. Mutation level was evaluated by the micronucleus analysis and SMAP level-by the indirect ELISA-test utilizing anti-SMAP immunoglobulins.

[ENGAGEMENT OF SEROTONIN-MODULATING ANTICONSOLIDATION PROTEIN IN REGULATION OF EMBRYOGENESIS OF LYMNEAE STAGNALIS AND LEWIS SARCOMA IN HYBRID MICE Fl C57B2/6 X DBA].

The article concerns study of the effects of a novel serotonin-modulating anticonsolidation protein (SMAP) being in a linear relationship with serotonin level, on embryogenesis of Lymneae stagnalis and Lewis sarcoma in hybrid mice Fl C57B2/6 X DBA. Inhibition of embryogenesis of Lymneae stagnalis on the stage of four blastomers and late blastula, lack of changes on the stage of trochofora and acceleration of metamorphosis under the effects of SMAP in a dose-dependent manner was observed. Short-term retardation (during the first 10 days) of development of Lewis sarcoma in mice and survival of 25% of transferring animals under high doses of SMAP was revealed.

Does serotonin-modulating anticonsolidation protein (SMAP) influence the choice of turning direction in carps, Cyprinus carpio, in a T-maze?

Serotonin-modulating anticonsolidation protein (SMAP) can impair the formation of memory traces in mammals and fish. We have studied the influence of SMAP on behavioral lateralization of juvenile carps Cyprinus carpio in a T-maze without food reinforcement in three experimental groups (n = 8 each): (1) negative control (intact animals); (2) experimental group (fish injected ICV with SMAP; 2 μl, 1.2 mg ml(-1)) and (3) active control group (fish injected ICV with inactivated SMAP).

[Character of changes of the level of serotonin-modulating anticonsolidation protein and of cytochrome P-450 in tissues of the eastern alburnoid Alburnoides bipunctatus eichwaldi from rivers of Azerbaijan].

The paper deals with study by the method of solid-phase indirect immunoenzyme analysis of levels of the novel serotonin-modulated anticonsolidation protein (SMAP) that is directly correlated with serotonin level as well as of biomarker cytochrome P-450 in the liver, gills, and brain of the eastern alburnoid (Alburnoides bipunctatus eichwaldi) caught in the rivers Khudat, Akstafachai, Kura, and Araks flowing at the territory of Azerbaijan. There was revealed a marked downregulation of cytochrome P-450 and SMAP in the liver and gills of the fish caught in the Akstafachai River relatively to values in the fish from the Khudat River not contaminated with pollutants. In the liver and gills in the fish from the Kura and Araks rivers, a significant differently directed changes of the cytochrome P-450 and SMAP levels were observed: downregulations of the cytochrome P-450 versus an upregulation of SMAP.

[Inhibition of morphine intake by antibodies to serotonin-modulating anticonsolidation protein in model of self-administration in rats].

The article concerns study of effects of polyclonal antibodies to serotonin-modulating anticonsolidation protein (SMAP) being in direct dependence on serotonin level and providing intracellular transduction of serotonergic signal, on positive reinforcement effect of morphine in rats. The task was formed in Wistar male rats in the model of morphine self-administration as a result of pressing of one of two levers attached to the wall, joined to the pump delivering each time 100 μg of morphine directly into the vena jugularis. In the 1st series of studies brain cingulate cortex and hypothalamus were taken from the rats achieved stable level of morphine intake and SMAP level was measured with indirect immune-enzyme assay.

[Adaptive increase of serotonergic system activity in tissues of half-migratory and migratory fish at increased water salinity].

The article deals with studies of the serotoninergic system activity in different tissues of half-migratory fish--the Caspian roach (Rutilus rutilus caspicus) and carpbream (Abramis brama orientalis)--and migratory fish--shemaya (Chalcalburnus chalcoides) caught in fresh and brackish waters, as well as in the common carp (Cyprinus carpio L.) tissues under effect of brackish water in model experiments. Using indirect solid-phase ELISA-test, the serotoninergic system activity was evaluated by measuring in the tissues of the studied fish the serotonin-modulated anticonsolidation protein (SMAP) which is in linear relationship with serotonin level.

[Effect of serotonin-modulated anticonsolidation protein on formation of long-term memory in carps Cyprinus carpio in the model of active avoidance learning].

Effect of serotonin-modulated anticonsolidation protein (SMAP) that has property of disturbing formation of memory trace in mammals and of learning and memory in teleost fish was studied in the model of active avoidance learning. The experiment was performed in three stages: (1) fry of carps Cyprinus carpio L. was injected intracerebrovenricularly with the SMAP protein at a dose of 0.

[Molecular modeling of interaction of 17(20)Z- and 17(20)E-pregna-5,17(20)-dien-21-oyl amides with the nuclear receptor LXRbeta].

Aiming the search of novel regulators of lipid metabolism and their potential targets, in this study we performed molecular modeling of eight isomeric 17(20)Z- and 17(20)E-pregna-5,17(20)-dien-21-oyl amides differing in structure of the amide moiety. Analysis of the low energy conformers revealed that all 17(20)E-isomers had three main energy minima (corresponding to values of the dihedral angle theta20,21 (C17 = C20-C21 = 0) to approximately 0 degrees, to approximately 120 degrees and to approximately 240 degrees), the most occupied minimum was found to correspond to theta20,21 to approximately 0 degrees; while 17(20)Z-isomers had either one or two pools of low energy conformations. Molecular docking of these compounds to the ligand-binding site of the nuclear receptor LXRbeta (a potential target) indicates high probability of binding for E-isomers and the absence of that for Z-isomers.

[Synthesis and biological activity of probable 24-norbrassinolide biosynthetic precursors].

A number of 24-norbrassinolide biosynthetic precursors containing low polar functional groups (3beta3-OH, 3-keto-, delta2- or 2alpha,3alpha-epoxy-) in A-cycle and (22R,23R)-diol in the side chain has been prepared. Studies of these compounds as proliferation regulators in MCF-7 human breast cancer and LnCaP human prostate adenocarcinoma cells showed that most nonpolar (22R,23R)-derivatives effectively suppressed proliferation. Dependence of proliferation on concentration of studied compounds was found in human prostate carcinoma LnCaP cells (IC50 = 13-28 microM at 72 h of incubation in a medium containing 10% FBS; suppression of DNA biosynthesis).

[The role of serotonin-modulated anticonsolidation protein in memory formation in rats in a shuttle box].

Two series of experiments were carried out in Wistar male rats. In the first series, rats were trained to acquire conditioning in a shuttle box to 50% and 80% learning criteria. In the animals of the experimental group that achieved 50% learning criterion, a significant decrease in the levels of serotonin-modulated anticonsolidation protein (SMAP) (solid phase, indirect ELISA-test) was observed in the temporal cortex as compared to the animals of the active control group.

[Synthesis of secasterol and 24-episecasterol and their toxicity in MCF-7 cells].

A convergent synthesis of biosynthetic precursors of brassinosteroids - secasterol and 24-episecasterol with Δ²-bond in cycle A is described. The key stages in the construction of the side chain of these compounds were Julia olefination of steroid 22-aldehyde followed by asymmetric Sharpless dihydroxylation of the intermediate Δ²²-olefin. Toxicity of synthesized compounds against breast carcinoma MCF-7 cells was studied.

[Regulation of cholesterol biosynthesis and metabolism in Hep G2 cells by delta8(14)-15-ketoergostane derivatives].

The comparative study of effects of 5alpha-cholest-8(14)-en-15-on-3beta-ol (I), (22E)-5alpha-ergosta-8(14),22-dien-15-on-3beta-ol (II), (22S,23S)-22,23-oxido-5alpha-ergost-8(14)-en- 15-on-3beta-ol (III) and (22R,23R)-22,23-oxido-5alpha-ergost-8(14)-en-15-on-3beta-ol (IV) on HMG-CoA reductase, CYP27A1 and CYP3A4 genes expression in Hep G2 cells was performed. In the contrast to 15-ketocholestane derivative (I), 15-ketoergostane derivatives (II - IV) decreased the HMG- CoA reductase mRNA level; (22R,23R)-22,23-oxido-5alpha-ergost-8(14)-en-15-on-3beta-ol (IV) significantly increased CYP3A4 mRNA level (320% from control). Ketosterol (II) was found to be a more potent inhibitor of cholesterol biosynthesis in Hep G2 cells at a prolong incubation, compared with ketosterol (I).