RNAi Knockdown of in Maternal Expression of Prader-Willi Syndrome Genes.

Background/objectives: Euchromatic histone lysine methyltransferase 2 (EHMT2, also known as G9a) is a mammalian histone methyltransferase that catalyzes the dimethylation of histone 3 lysine 9 (H3K9). On human chromosome 15, the parental-specific expression of Prader-Willi Syndrome (PWS)-related genes, such as and , are regulated through the genetic imprinting of the PWS imprinting center (PWS-IC). On the paternal allele, PWS genes are expressed whereas the epigenetic maternal silencing of PWS genes is controlled by the EHMT2-mediated methylation of H3K9 in PWS-IC.

CLINICAL FEATURES OF THE COURSE OF HIRSCHSPRING'S DISEASE INCHILDREN OF THE FIRST YEAR.

The purpose of the work - to investigate the peculiarities of the clinical course of Hirschsprung's disease in children of the first year of life and to determine the significance of symptoms in the verification of the disease. From 1980 to 2021, at the pediatric surgery clinic of the National Medical University named after O.O.

Suppression of systemic inflammation and signs of acute and chronic cholangitis by multi-kinase inhibitor 1-(4-Cl-benzyl)-3-chloro-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione.

An aberrant activity of growth factor receptors followed by excessive cell proliferation plays a significant role in pathogenesis of cholangitis. Therefore, inhibition of these processes could be a fruitful therapeutic strategy. The effects of multi-kinase inhibitor 1-(4-Cl-benzyl)-3-chloro-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione (MI-1) on the hepatic and systemic manifestations of acute and chronic cholangitis in rats were addressed.

FOXP1 negatively regulates intrinsic excitability in D2 striatal projection neurons by promoting inwardly rectifying and leak potassium currents.

Heterozygous loss-of-function mutations in the transcription factor FOXP1 are strongly associated with autism. Dopamine receptor 2 expressing (D2) striatal projection neurons (SPNs) in heterozygous Foxp1 (Foxp1) mice have higher intrinsic excitability. To understand the mechanisms underlying this alteration, we examined SPNs with cell-type specific homozygous Foxp1 deletion to study cell-autonomous regulation by Foxp1.

An essential role for MEF2C in the cortical response to loss of sleep in mice.

Neuronal activity and gene expression in response to the loss of sleep can provide a window into the enigma of sleep function. Sleep loss is associated with brain differential gene expression, an increase in pyramidal cell mEPSC frequency and amplitude, and a characteristic rebound and resolution of slow wave sleep-slow wave activity (SWS-SWA). However, the molecular mechanism(s) mediating the sleep-loss response are not well understood.

Pyrrole derivatives as potential anti-cancer therapeutics: synthesis, mechanisms of action, safety.

Pyrrole derivatives (PDs) chloro-1-(4-chlorobenzyl)-4-((3-(trifluoromethyl)phenyl)amino)-1H-pyrrole-2,5-dione (MI-1) and 5-amino-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrole-3-one (D1) were synthesised as inhibitors of several protein kinases including EGFR and VEGFR. The aim of the study was to reveal the exact mechanisms of PDs' action EGFR and VEGFR are involved in. We observed, that both PDs could bind with EGFR and VEGFR and form stable complexes.

Water-soluble pristine C fullerene attenuates acetaminophen-induced liver injury.

Oxidative stress has been suggested as the main trigger and pathological mechanism of toxic liver injury. Effects of powerful free radical scavenger С fullerene on rat liver injury and liver cells (HepG2 line) were aimed to be discovered. Acute liver injury (ALI) was simulated by single acetaminophen (APAP, 1000 mg/kg) administration, on a chronic CLI, by 4 weekly APAP administrations.

Antitumor effects and hematotoxicity of C-Cis-Pt nanocomplex in mice with Lewis lung carcinoma.

Background: Cisplatin (Cis-Pt) is a widely used anticancer drug but its therapeutic efficiency is limited by hemato-, cardio-, hepato-, nephro- and neurotoxicity. Complexation of Cis-Pt with C fullerene nanoparticle will allow to enhance the antitumor activity of the drug and to reduce its side toxic effects.

Aim: To estimate the antitumor effects of С60-Cis-Pt nanocomplex in Lewis lung carcinoma (LLC) and analyze hematological toxicity in tumor-bearing mice.

Synthesis and biological activity of 4-amino-3-chloro-1-pyrrole-2,5-diones.

4-Amino-3-chloro-1-pyrrole-2,5-dione derivatives were designed and synthesized as potential tyrosine kinase inhibitors. One of them has been shown to inhibit growth of cancer cell lines and in vivo tumors. To determine the impact of side groups on biological activity the ability of different 4-amino-3-chloro-1-pyrrole-2,5-diones to interact with ATP-binding domains of growth factor receptors and with model cell membranes were aimed to be discovered.

Reconciling the controversial data on the effects of C fullerene at the organismal and molecular levels using as a model Drosophila melanogaster.

Fullerenes have attracted attention since their discovery as structural units of complex carbon nanostructures capable of transporting drugs and macromolecules. As such artificial nanomaterials are applied in biology and medicine, they are routinely scrutinized for their effects on living organisms. The results of such studies range from direct destabilizing effects on DNA molecules to amelioration of the toxic effects of known genotoxic agents.

Effect of С fullerenes on the intensity of colon damage and hematological signs of ulcerative colitis in rats.

The application of pristine С fullerene aqueous colloid solution (CFAS; 0.5 mg/kg body weight) for rats experienced acute colitis, either intraperitoneally or intrarectally (1) restores the colonic mucosa healing and epithelial barrier integrity, evidenced by autopsies and histological findings and the normalization of phenolsufonphthalein dye daily excretion; (2) attenuates the consequences of hemorrhages, such as signs of anemia and increased platelet count; (3) improves the liver redox status suppressing the lipid peroxidation (malonic dialdehyde and protein carbonyl group levels tended down) and stimulating the antioxidant defense system (glutathione peroxidase activity grew up). In addition, CFAS intrarectally increases the monocyte count and decreases content of neutrophil granulocytes, i.

Comparative Analysis of the Antineoplastic Activity of C Fullerene with 5-Fluorouracil and Pyrrole Derivative In Vivo.

The antitumor activity of pristine C fullerene aqueous solution (CFAS) compared to 5-fluorouracil (5-FU) and pyrrole derivative 1-(4-Cl-benzyl)-3-Cl-4-(CF-fenylamino)-1H-pyrrol-2.5-dione (MI-1) cytostatic drugs was investigated and analyzed in detail using the model of colorectal cancer induced by 1.2-dimethylhydrazine (DMH) in rats.

Interaction of C60 fullerene complexed to doxorubicin with model bilipid membranes and its uptake by HeLa cells.

With an aim to elucidate the effects of C60 fullerene complexed with antibiotic doxorubicin (Dox) on model bilipid membranes (BLM), the investigation of the electrical properties of BLM under the action of Dox and C60 fullerene, and of their complex, C60+Dox,was performed. The complex as well as its components exert a clearly detectable influence on BLM, which is concentration-dependent and also depends on phospholipid composition. The mechanism of this effect originates either from intermolecular interaction of the drug with fatty-acid residues of phospholipids, or from membranotropic effects of the drug-induced lipid peroxidation, or from the sum of these two effects.

[MORPHOFUNCTIONAL STATE OF BLOOD CELLS AFTER CHRONIC EXPOSURE OF THE PROTEIN KINASES INHIBITOR MALEIMIDE DERIVATIVE].

The effect of the protein kinases inhibitor maleimide derivative (MI-1, 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione), inhibitor of VEGF-R1,2,3, FGF-R1, EGF-R(h), PDK1, Src(h), Syk(h), YES, ZAP70 et al. with antineoplastic activity, on blood cells parameters of rats after chronic exposure has been studied. Administration of MI-1 at doses 0.

Effects of 5-Amyno-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrol-3-one Intake on Digestive System in a Rat Model of Colon Cancer.

Introduction: Pyrrol derivate 5-amyno-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrol-3-one (D1) has shown antiproliferative activities in vitro, so investigation of the impact of D1 intake on gut organs in rats that experienced colon cancer seems to be necessary.

Materials And Methods: D1 at the dose of 2.3 mg/kg was administered per os daily for 27 (from the 1st day of experiment) or 7 (from the 21st week of experiment) weeks to rats that experienced 1,2-dimethylhydrazine (DMH)-induced colon cancer for 20 weeks.

[MORPHOFUNCTIONAL PARAMETERS OF BLOOD CELLS OF THE RAT WITH 1,2-DIMETHYLHYDRAZINE-INDUCED COLON CARCINOGENESIS].

Morphofunctional parameters of blood cells of the rats with dimethylhydrazine induced colon carcinogenesis have been investigated. The reduction of Mean corpuscular hemoglobin (MCH) and Mean corpuscular hemoglobin concentration (MCHC) whereas increasing of reticulocytes number and indirect bilirubin after 20 weeks of experiment of dimethylhydrazine (DMH)-induced colon carcinogenesis indicate the hemolysis of red blood cells due to the DMH influence during tumors development. The moderate increasing of monocytes and platelets number, as well as increment of eosinophilic granulocytes number have been observed.

Disrupted coupling of gating charge displacement to Na+ current activation for DIIS4 mutations in hypokalemic periodic paralysis.

Missense mutations at arginine residues in the S4 voltage-sensor domains of NaV1.4 are an established cause of hypokalemic periodic paralysis, an inherited disorder of skeletal muscle involving recurrent episodes of weakness in conjunction with low serum K(+). Expression studies in oocytes have revealed anomalous, hyperpolarization-activated gating pore currents in mutant channels.

[Potential cytostatic effect of the maleimide derivative 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1-H-pyrrol-2,5-dione].

The cytostatic/cytotoxic effects of the maleimide derivative 1-(4-Cl-Benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrol-2,5-dione (MI-1) have been estimated on epithelial derived human cell cultures (Colo 205, MCF-7, and Hela). The anticancer and toxic effects of MI-1 have been investigated on DMH-induced cancer development and normal colon morphology in rats. The results showed that the compound studied has low cytotoxicity but produces a strong antiproliferative effect on cell cultures and partially suppresses colon cancer development in DMH-induced model.

[Mechanisms of nephrotoxicity of novel anticancer compound maleimide derivative MI-1].

The features of the impact of the maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF3-fenilamino)-1H-pyrrole-2,5-dione (MI-1) on the viability and apoptosis-induced cell death of renal proximal and distal tubular epithelial cells and the amount of total and phosphorylated ERK1/2 were studied in order to establish possible mechanisms of nephrotoxicity induced by of MI-1. The viability and apoptosis of renal epithelial tubular cells after incubation with MI-1 were perfomed by 3,4,5-dymetyltiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT)-test and by flow cytometry after staining with specific antibodies to annexin V, respectively. The amount of ERK 1/2 was determined by Western blotting.

[Effect of dihydropyrrol and maleimide derivatives on the state of the liver and colon in normal rats and those with colorectal carcinogenesis induced by dimethylhydrazine].

No liver and colon alterations in rats, caused by cytostatic compounds 5-amino-4-(1,3-benzothyazol-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrol-3-one (D1) and 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrol-2,5-dione (MI-1) when administered over a long time were found, as evidenced by the histopathological data and the data of activity of transaminases, alkaline phosphatase and lactate dehydrogenase in the blood serum. D1 and MI-1 in vivo decrease the total area of DMH-induced colon tumors in rats by 46-60%. Furthermore, D1 and MI-1 partially protect the liver and colon mucosa from toxic effects caused by 1,2-dimethylhydrazine (DMH) reducing DNA oxidative modifications, as evidenced by urine 8-hydroxydeoxyguanosine level.

Impact of dihydropyrrol derivative on the normal colonic mucosa of DMH-induced colon cancer rats compared with 5-fluorouracil.

Aim: To compare the effects of cytostatic compound dihydropyrrol derivative (D1, 5-amyno-4-(1,3-benzothyazol-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3Н-pyrrol-3-one) and 5-fluorouracil (5-FU) on the normal colonic mucosa of tumor-bearing rats and to estimate the relationships between proliferation of normal colonic mucosa and tumor growth parameters.

Methods: 1,2-dimethylhydrazine (DMH) carcinogenic model was used. Male Wistar rats were treated by dimethylhydrazine (20 mg/kg of body weight (b.

Comparative study of membranotropic action of single- and multi-walled carbon nanotubes.

The aim of the present work is the investigation of the interactions of single-walled and multi-walled carbon nanotubes (further referred as SWCNTs and MWCNTs, respectively) with bimolecular lipid model membrane (BLM) and cellular plasma membrane (PM). The findings demonstrate that both SWCNTs and MWCNTs (in concentration range of 10⁻⁴ to 10⁻¹ mg ml⁻¹) are capable to penetrate through the region of hydrophobic fatty acid residues of phospholipids and to form molecular associates in the bilayer that have conductive properties of molecular pores type. The formed pores were shown to enable phosphatidylserine externalization from inner to outer PM leaflet.

The intracellular Ca²⁺ channels of membrane traffic.

Regulation of organellar fusion and fission by Ca ( 2+) has emerged as a central paradigm in intracellular membrane traffic. Originally formulated for Ca ( 2+) -driven SNARE-mediated exocytosis in the presynaptic terminals, it was later expanded to explain membrane traffic in other exocytic events within the endo-lysosomal system. The list of processes and conditions that depend on the intracellular membrane traffic includes aging, antigen and lipid processing, growth factor signaling and enzyme secretion.

Effect of iron-doped multi-walled carbon nanotubes on lipid model and cellular plasma membranes.

The aim of the present work was the study of the interaction of multi-walled carbon nanotubes filled with iron (Fe-MWCNTs) with bimolecular lipid model membrane (BLM) and cellular plasma membrane (PM). The findings demonstrate that the Fe-MWCNTs adsorb on the BLM surface with possible partial build up in the hydrophobic area of fatty acid residues of lipids and increase its specific conductivity and capacity. Furthermore, upon interaction with the PM, the Fe-MWCNTs form channels which allow the flow of water to the cells and the externalization of phosphatidylserine from the inner to the outer PM leaflet.