The influence of salicylic (SA) and jasmonic (JA) acids as signaling systems mediators on the generation of H2O2 and expression of genes encoding protective proteins was studied in the leaves of wheat Triticum aestivum L. upon infection with the pathogen of septoriosis Septoria nodorum Berk. It was found that presowing treatment of seeds with SA and JA decreased the development of the fungus on the leaves of wheat and had a stimulating effect on the production of H2O2 in the area of infection. An increased expression of genes encoding oxalate oxidase AJ556991.1 and anionic peroxidase TC 151917 was shown in infected tissues with the method of polymerase chain reaction.

Effects of water-soluble phenolic antioxidant sodium 3-(3'-tret-butyl-4'-hydroxyphenyl)-propyl thiosulfonate (TS-13), potassium 3,5-dimethyl-4-hydroxybenzyl thioetanoate (BEP-11-K) and potassium 3-(3',5'-ditretbutyl-4'-hydroxyphenyl)-propionate (potassium phenosan) on tumor cells proliferative activity and the role of redox-dependent and calcium-dependent signaling mechanisms in realization of tumor cell response to the antioxidant action were studied. Potassium phenosan and BEP-11-K were found to stimulate proliferation and ARE-inducing phenolic antioxidant TS-13 was found to inhibit tumor cell growth in culture. The tumor cell growth rate depended on the rate of intracellular reactive oxygen species production and was decreased by apocynin (a NADPH-oxidase inhibitor) and antimycin A (an ubiquinol-cytochrome c oxidoreductase inhibitor). TS-13 action on tumor cells was accompanied by a transient increase in intracellular reactive oxygen species production and the intracellular calcium concentration, whereas cell incubation with potassium phenosan and BEP-11-K did not influence the reactive oxygen species level and intracellular calcium ions. Cyclosporine A blocked the inhibitory effect of TS-13. Thus, it can be reasonably speculated that phenolic antioxidant TS-13 starts mitochondria-dependent apoptosis in tumor cells by the opening of permeability transition pores.

Biologically active regulatory peptide, tripeptide Pro-Gly-Pro (PGP) was used as C-terminal fragment for peptide drugs Semax and Selank. In recent years the independent effects of PGP were observed. The question was raised, whether PGP contributes to the effects ofpeptide drugs containing PGP as a fragment. The genome-wide analysis was performed to investigate the influence of PGP on the transcriptome of ischemic rat brain cortex tissues. The gene expression alterations caused by the action of the tripeptide PGP were compared with the gene expression of the control group "ischemia" at 3 and 24 h after permanent occlusion of left middle cerebral artery. The altered expression was detected for 29 genes at 3 h and 57--at 24 h. The proteins encoded by these genes have variety of functions: cytokines, transport proteins, transcription factors, transmembrane receptors, etc. Biological processes, which are related to the genes with altered expression, were distinguished. The influence of PGP on the diversity of biological processes in different systems of the organism is demonstrated for the first time. The process "Immune response" was the most statistically notable at 24 h after occlusion. The expression of the immune system genes was predominately down regulated.

Some ribonucleases (RNases) produce selective toxic effect on the cancer cells. The mechanism of this antitumor activity remains largely unclear. The subject of this review is the RNases interaction with cellular components, resulting in the induction of apoptosis of tumor cells. Cell surface structures, which are potential acceptors of the exogenous RNase are discussed: acidic lipids and glycoproteins, heparansulfate-containing proteoglycans, actin, and RNA-associated proteins. Cell membranes of normal and malignant cells differ according to the composition of these components, which largely determines the selectivity of RNases for the latter. Different types of RNA are examined as intracellular targets of the RNases activity, evidence is presented demonstrating the possibility of exogenous RNases intervening in the process of RNA interference. The role of potassium channels, NF-kappaB-dependent.signaling pathway and various caspases in apoptosis induced by exogenous RNases is discussed. Evidence is also presented showing that the sensitivity of cells to exogenous RNases is linked to the expression of certain oncogenes, namely RAS, KIT, AML1-ETO. It is suggested that discovering the details of the mechanisms of RNases cytotoxic effect in malignant cells susceptible to their activity, will in the future serve as a foundation to developing new tools of targeted anticancer therapy.

Brain serotonin (5-HT) system plays an important role in the control of normal and pathological behavior. 5-HT2A receptors are widely implicated in the regulation both normal functions and psychopathologies, especially schizophrenia and depression. Here, we investigated implication of 5-HT2A receptor in mechanisms of neurotrophic factors BDNF and GDNF action. We found that the acute intracerebroventricular injection of BDNF produced considerable increase in 5-HT2A receptor functional activity in ASC mice. Moreover, BDNF injection led to the increasing of 5-HT2A receptor gene expression in the hippocampus and its decrease in the frontal cortex without any effects in the midbrain. On the contrary, GDNF injection failed to alter 5-HT2A receptor functional activity, but increased the 5-HT2A receptor gene expression in the frontal cortex without any effects in the hippocampus and midbrain. Thus, an effect of the central administration of the neurotrophic factors BDNF and GDNF on the 5-HT2A receptor functional activity and gene expression was shown. The results indicate the implication of 5-HT2A receptor in the mechanisms of BDNF and GDNF action.

Glutamate antibodies intranasally administered to Wistar rats at a dose of 300 μg/kg reduced the elevated levels of expression of Aifml, Casp3, and Parp 1 genes in the prefrontal cortex and Aifml and Casp3 genes in the hippocampus on the third day after administration of the β-amyloid fragment Aβ25-35 into the Meynert nuclei of the brain. Changes in Aifm1, Bax, Casp3, and Parp 1 gene expression were not found in the hypothalamus, and changes in Bax gene expression were not found in the brain structures studied. The discovered features of gene expression in the prefrontal cortex and hippocampus are considered in terms of development of various cell-death programs, which are modulated by glutamate antibodies.

Transgenic tobacco plants expressing Arabidopsis thaliana ARGOS and ARGOS-LIKE genes under the control of the chalcone synthase promoter of Petunia hybrid L., as well as the estradiol inducible XVE system, have been obtained. The part of transgenic plants with flower-specific expression of the target genes was characterized by increased flower size, caused by an increase in cell size and quantity in the case of the ARGOS gene and by a stimulation of cell growth via stretching in the case of the ARGOS-LIKE gene. An enhanced expression level of the NtEXPA1, NtEXPA4 genes encoding expansins, NtEXGT gene encoding endo-xyloglucan transferase, and the AINTEGUMENTA-like gene was detected in the flowers of transgenic tobacco plants. In the case of inducible expression of ARGOS and ARGOS-LIKE genes, an increase in leaf, stem and flower size was revealed in several lines of transgenic plants as compared to control. Expression of the ARGOS gene also affected cell number and size in this case, while the ARGOS-LIKE gene mainly influenced cell size via stretching. Inducible expression of the ARGOS gene in flowers mainly provided an enhanced containment of AINTEGUMENTA-like mRNA, while ARGOS-LIKE gene expression resulted in the activation of NtEXPA1 and NtEXGT genes.

We identified 40 miRNAs with inherited aberrant expression by multiple parallel sequencing of human HeLa cells irradiated with X rays and mitomycin C. Twenty-two miRNAs were repressed and 15 miRNAs were induced after radiation and mytomycin C treatment. The expression of three miRNAs (miR-10b-5p, miR-148a-3p, and miR-340-5p) decreased after X-ray exposure and increased after mitomycin C treatment. The spectrum of aberrantly expressed miRNAs after X-ray and mitomycin C treatment is different, except for three miRNAs (mir-100-5p, miR-99b-5p, miR-501-3p), which showed the inherited decreased expression after both mutagens. It has been ascertained that for five miRNAs (miR-21-3p, miR-182-5p, miR-19b-3p, miR-30a-3p, and miR-30e-3p) with increased inherited expression, the targets are well-described tumor suppressor genes. For 9 miRNAs (miR-99b-5p, miR-148a-3p, miR-365a-3p, miR-193a-3p, miR-100-5p, miR-99a-5p, miR-29b-3p, miR-340-5p, and miR-23b-3p) with reduced inherited expression, the targets are oncogenes. The obtained results provide further support of the idea that induced epigenetic changes in the genome should be considered when assessing the long-term genetic effects of ionizing radiation and chemical compounds.

The influence of small doses of exogenic nitrite on reversible and irreversible oxidative modifications of water-soluble proteins of rat cardiac and skeletal muscle was studied with the aid of redox 2D-electrophoresis and colorimetric determination of protein carbonyl group, correspondingly. To explain the absence of significant changes under hypoxia induced by nitrite the known hypothesis about nitrite inhibition of some sites of mitochondrial electron transporting chain decreasing free radical quantity was discussed.

It was demonstrated that fibroblast growth factor bFGF influences the process of heme synthesis, the proliferation activity and viability of bone marrow mesenchymal stem cells in culture under hypoxic conditions. The addition of fibroblast growth factor bFGF (7 ng/ml) to the medium under above conditions led to the accumulation of aminolevulinic acid--an early porphyrin and heme precursor, an increase in CD 71 expression--a transferrin receptor, and also a decrease in porphyrin pigments and heme contents--a late precursor and end products of heme synthesis, respectively. It was found that cultivation of the cells under hypoxic conditions and bFGF is an optimum to maintain high viability and proliferation capacity of the mesenchymal stem cells.

The tobacco plant genes NtEXPA1 and NtEXPA4 encode the α-expansin proteins involved in the regulation of cell growth and extension. We examined the levels of expression of these genes in various plant organs and under the effect of exogenous phytohormones. The highest levels of NtEXPA1 expression were registered in the terminal bud and in the young growing leaves and flowers. NtEXPA1 expression ceased once the leaves stopped growing. The NtEXPA4 gene showed a similar expression profile, except for higher levels of mRNA in the leaves. In young leaves located near the terminal bud, high levels of NtEXPA1 and NtEXPA4 are induced by auxins. In the lower leaves, expansin expression is differentially regulated by brassinosteroids, which inhibit NtEXPA1 and upregulate NtEXPA4. We further showed that expression of the transgenic ARGOS-LIKE results in upregulation of NtEXPA1 and a reduction in the NtEXPA4 mRNA. In turn, overexpression of NtEXPA1 resulted in an increased size of the leaves and stems because of the larger size of the individual cells.

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. It was shown that in the morphine-self-injected rats SMAP level in the cingulate cortex is significantly upregulated (p = 0.01), while in the hypothalamus it was left unchanged. In the 2nd series of studies the rats with stable level of morphine intake were administered intraperitoneally with anti-SMAP rabbit polyclonal antibodies (experimental group) or non-immune γ-globulins (control group). Soon after antibodies administration the animals of the experimental group demonstrated manifold decrease of morphine intake lasted for 8 days (p < 0.008), whereas it did not change in the controls. SMAP upregulation in the brain cingulate cortex in the rats with stable morphine intake, obviously, indicates to its engagement in positive reinforcement effect of morphine. Blockade of SMAP activity with anti-SMAP antibodies in the nerve cells induced sharp decrease of morphine intake due to disturbances of transduction through intracellular serotonin's signal channels.

We have shown that antioxidant N-acetylcysteine (NAC, 2-10 mM) quickly (for 2 hours) and completely inactivates the activity of matrix metalloproteinases (gelatinases MMP-2 and MMP-9, and collagenases MMP-1 and MMP-8) secreted by transformed mouse fibroblasts 3T3-SV40 into the medium. The same MMP inhibition took place in the cell-free conditioned medium of HT-1080 fibroblasts, which suggests a direct chemical interaction between NAC and MMP resulting in the loss of MMP activity. Besides inhibitory effect, NAC decreased MMP-1 and MMP-9 (but not MMP-2) production in the cell medium. However, the level of MMP-1 and MMP-9 inhibitor (TIMP-1) remained normal, indicating a shift in the balance between the enzyme and inhibitor. The correlation between MMP-2 level and tissue enzyme inhibitor TIMP-2 was similar in control and NAC treated cells. At the same time, reorganization of type I collagen at the cell surface occurred. All together permits the conclusion that NAC action results in the extracellular matrix remodeling and changing in cellular functions.

According to the Neurodevelopmental hypothesis, the long-lasting cognitive deficit in schizophrenia and other types of neuropathology may occur by injurious factors, such as hypoxia, traumas, infections that take place during pre- and postnatal development, at least at early stages. These pathological conditions are often associated with the high production of pro-inflammatory cytokine interleukin-1B (IL-1B) by the cells of immune and nervous systems. We investigated the expression of genes involved in the neuroplastic regulation (Fgf2 and Timp2) in medial prefrontal cortex and dorsal and ventral regions of hippocampus of adult rats that were treated with IL-1beta between P15 and P21. The learning impairment in IL-1beta-treated rats is accompanied by lower FGF-2 mRNA levels in medial prefrontal cortex and ventral (not dorsal) hippocampus, but TIMP-1 was not affected. No differences in TIMP-1 and FGF-2 mRNA expressions were observed in untrained IL-1beta-treated when compared to control rats.

Synthetic glucocorticoids are able to activate apoptosis in the cells by regulating the transcription of the respective genes. Effect of dexamethasone on apoptosis is an established fact. However, its influence on another program of cell death autophagy, is currently unproven. Therefore, in this paper we have analyzed the influence of dexamethasone on the expression of bcl-2 and mTOR genes in T-lymphocytes from healthy donors. The results showed that dexamethasone reduced the expression of bcl-2 and mTOR genes. However, the nature of the effect of dexamethasone on mTOR and bcl-2 expression was different: the expression of bcl-2 gene in the long-term cultivation was maintained at the same reduced level, while the expression of mTOR was first reduced and then increased.

At present, epigenetic regulation is considered as a dynamic mechanism by means of which cells realize adaptive response to signals from both the inner medium and environment. DNA methylation, as bidirectional balance of the activity of histone-acetylation and -deacetylation (HDAC) enzymes, determines the conformation of chromatin thus playing the main role in "appropriate" gene expression. HDACs represent emerging therapeutic targets in the context of treating various forms of neurological and mental illness. A wide range of brain diseases are associated with imbalance between protein acetylation levels and tran- scriptional dysfunctions. Increasing evidence supports the notion that histone hypoacetylation and transcriptional dysfunction are involved in a large number of neurodegenerative conditions in vivo and in vitro. Histone deacetylase inhibitors (HDACIs) that affect the acetylation status of histones and other important cellular proteins--have been recognized as potentially useful therapeutic means for a broad range of human disorders. This review summarizes the current state of development of HDACIs based therapeutics and their application for the treatment of human brain neurodegenerative, ischemic, and cognitive pathologies. Treatment with various HDACIs can correct these deficiencies and has emerged as a promising new strategy for therapeutic intervention based on the experimental search and clinical testing of HDACIs representing compounds of various classes.

Molecular genetic analysis of lung tumors is often essential for the proper choice of therapy. EGFR mutation is a well-known marker of sensitivity to gefitinib, erlotinib and afatinib; ALK-translocations make tumor sensitive to several ALK inhibitors; low intratumoral expression of DNA repair genes (ERCC1, BRCA1, etc.) may increase the therapeutic index of platinum-based drugs. Usually these markers are evaluated using formalin-fixed paraffin-embedded tumor tissues. The goal of this work was to assess utility of archived cytological lung cancer specimens as an alternative source of material for molecular genetic testing. We analyzed paired histological and cytological lung adenocarcinoma specimens. Comparison of results within the pairs showed that cytological material can be used instead of histological material for qualitative analyses (detection of EGFR mutations or ALK-translocations); however, gene expression measurements, obtained by quantitative real-time PCR, may differ significantly in histological and cytological samples from the same patient.

Study the effect of inactivated influenza vaccines on the activity of innate and adaptive immunity genes (TLR3, TLR4 and B2M), RNA-interference Dicer1-gene, production of cytokines (antiviral IFN type I and II, regulatory IL10, IL17) and pro-inflammatory factors IL1-β, TNFα.

Now a number of CD4+ T-lymphocytes, known as Th1, Th2, Treg and Th17, is currently identified and well- studied. The methods basing on the targeted regulation of differentiation process of the Th-lymphocytes that carry out the immune response polarization attract an attention of scientists dealing with a correction of immune-mediated. In the present study, endogenous beta-galactoside-binding protein of the lectin family, galectin-3, was investigated as a regulator of T-cell homeostasis. A galectin-3 is known to be actively produced by tumor cells in malignant transformation and able to influence the processes of signal transduction, cell-cell cooperation and the implementation of programmed death. As cell differentiation processes are directly connected with the regulation of gene expression, we investigated the effect of recombinant galectin-3 on expression of mRNA of transcription.factors, which guide the differentiation of CD4+ lymphocytes. The study was performed on peripheral blood mononuclear cells of healthy individuals. The gene expression levels were evaluated by a real-time PCR. In the experiments in vitro, it has been first found the recombinant galectin-3 (0.5 mg/mL) up-regulating the expression of transcription factors Gata-3 and Rorc mRNAs and down-regulating the mRNA expression of transcription factors T-bet and FoxP3. Up to a concentration of 1 mg/mL recombinant galectin-3 stimulates Th-cells by dose-dependent manner, whereas at higher concentrations stimulating effect weakens, and inhibiting action starts prevailing. Thus, one can suppose that galectin-3 through regulation of lymphocytes differentiation promote development of allergic, autoimmune and neoplastic diseases that allows us to consider the galectin-3 as a.potential target for therapy of these diseases.

Changes in gene expression and isoform composition of giant sarcomeric protein titin (connectin) in cardiac muscle, as well as changes of its isoform composition in skeletal muscle (m. soleus) of chronically ethanol-fed rats have been studied using real-time RT-PCR and low percentage SDS-gel electrophoresis. The decrease of titin content in examined muscles and the decrease in titin gene expression in myocardium of chronically ethanol-fed rats have been shown. These changes indicate the development of pathologic process.