2-Arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropanoic acids as selective and effective carboxylesterase inhibitors with powerful antioxidant potential.

A series of 2-arylhydrazinylidene-3-oxo acids (AHOAs) was prepared by dealkylation of alkyl-2-arylhydrazinylidene-3-oxo-3-alkanoates with AlBr. Using X-Ray, NMR spectroscopy, and quantum mechanical calculations (QM), the existence of AHOAs in a thermodynamically favorable Z-form stabilized by two intramolecular H-bonds was established. All AHOAs had acceptable ADME parameters.

Powerful Potential of Polyfluoroalkyl-Containing 4-Arylhydrazinylidenepyrazol-3-ones for Pharmaceuticals.

4-Arylhydrazinylidene-5-(polyfluoroalkyl)pyrazol-3-ones (4-AHPs) were found to be obtained by the regiospecific cyclization of 2-arylhydrazinylidene-3-(polyfluoroalkyl)-3-oxoesters with hydrazines, by the azo coupling of 4-nonsubstituted pyrazol-5-oles with aryldiazonium chlorides or by the firstly discovered acid-promoted self-condensation of 2-arylhydrazinylidene-3-oxoesters. All the 4-AHPs had an acceptable ADME profile. Varying the substituents in 4-AHPs promoted the switching or combining of their biological activity.

Comparison of Methods for MicroRNA Isolation from Extracellular Vesicles Obtained from Ascitic Fluids.

Secreted extracellular vesicles (EVs) contain active biomolecules, including miRNAs, composition of which reflects epigenetic changes occurring in cells during pathological processes, in particular, malignant transformation. The accumulated pool of data on the role of EVs in carcinogenesis has stimulated investigations of the EV-derived cancer markers. The most important factor limiting development of this scientific direction is lack of "gold standards" both for methods of EV isolation from biological fluids and for analyzing their molecular content, including composition of miRNAs.

New Multifunctional Agents for Potential Alzheimer's Disease Treatment Based on Tacrine Conjugates with 2-Arylhydrazinylidene-1,3-Diketones.

Alzheimer's disease (AD) is considered a modern epidemic because of its increasing prevalence worldwide and serious medico-social consequences, including the economic burden of treatment and patient care. The development of new effective therapeutic agents for AD is one of the most urgent and challenging tasks. To address this need, we used an aminoalkylene linker to combine the well-known anticholinesterase drug tacrine with antioxidant 2-tolylhydrazinylidene-1,3-diketones to create 3 groups of hybrid compounds as new multifunctional agents with the potential for AD treatment.

[Identification regulatory noncoding RNAs of human papilloma virus type 16 (Papillomaviridae: Alphapapillomavirus: Human papillomavirus) in cervical tumors].

Introduction: High carcinogenic-risk human papillomaviruses (hrHPVs) are recognized as etiological agents of cervical cancer. Constant expression of the viral oncoproteins, E6 and E7, is required for maintenance of the malignant phenotype of tumor cells. The exact mechanism of regulation of viral oncogenes expression in tumor cells is not fully elucidated.

Extracellular Vesicles from Uterine Aspirates Represent a Promising Source for Screening Markers of Gynecologic Cancers.

Extracellular vesicles (EVs), including exosomes, are key factors of intercellular communication, performing both local and distant transfers of bioactive molecules. The increasingly obvious role of EVs in carcinogenesis, similarity of molecular signatures with parental cells, precise selection and high stability of cargo molecules make exosomes a promising source of liquid biopsy markers for cancer diagnosis. The uterine cavity fluid, unlike blood, urine and other body fluids commonly used to study EVs, is of local origin and therefore enriched in EVs secreted by cells of the female reproductive tract.

Novel potent bifunctional carboxylesterase inhibitors based on a polyfluoroalkyl-2-imino-1,3-dione scaffold.

An expanded series of alkyl 2-arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropionates (HOPs) 3 was obtained via Cu(OAc)-catalyzed azo coupling. All were nanomolar inhibitors of carboxylesterase (CES), while moderate or weak inhibitors of acetylcholinesterase and butyrylcholinesterase. Steady-state kinetics studies showed that HOPs 3 are mixed type inhibitors of the three esterases.

Synthesis of 2-arylhydrazinylidene-3-oxo-4,4,4-trifluorobutanoic acids as new selective carboxylesterase inhibitors and radical scavengers.

A series of 2-arylhydrazinylidene-3-oxo-4,4,4-trifluorobutanoic acids was synthesized via dealkylation of ethyl 2-arylhydrazinylidene-3-oxo-4,4,4-trifluorobutanoates under the action of a Lewis acid. Under the same conditions, ethyl 2-arylhydrazinylidene-3-oxobutanoates were also found to undergo dealkylation rather than the previously described cyclization into cinnolones. Study of the esterase profile of these compounds showed that trifluoromethyl-containing acids, in contrast to non-fluorinated analogs, were effective and selective inhibitors of carboxylesterase (CES), without substantially inhibiting structurally related cholinesterases (acetylcholinesterase and butyrylcholinesterase).

Synthesis, molecular docking, and biological evaluation of 3-oxo-2-tolylhydrazinylidene-4,4,4-trifluorobutanoates bearing higher and natural alcohol moieties as new selective carboxylesterase inhibitors.

To search for effective and selective inhibitors of carboxylesterase (CES), a series of 3-oxo-2-tolylhydrazinylidene-4,4,4-trifluorobutanoates bearing higher or natural alcohol moieties was synthesized via pre-transesterification of ethyl trifluoroacetylacetate with alcohols to isolate transesterificated oxoesters as lithium salts, which were then subjected to azo coupling with tolyldiazonium chloride. Inhibitory activity against porcine liver CES, along with two structurally related serine hydrolases, acetylcholinesterase and butyrylcholinesterase, were investigated using enzyme kinetics and molecular docking. Kinetics studies demonstrated that the tested keto-esters are reversible and selective mixed-type CES inhibitors.

Unexpected impact of radiation friction: enhancing production of longitudinal plasma waves.

We study the penetration of ultra-intense (intensity I [Formula: see text] 10 W/cm) circularly polarized laser pulses into a thick subcritical plasma layer with accounting for radiation friction. We show that radiation pressure is enhanced due to radiation friction in the direction transverse to the laser pulse propagation, and that for stronger and longer laser pulses this mechanism dominates over the ordinary ponderomotive pressure, thus resulting in a substantionaly stronger charge separation than anticipated previously. We give estimates of the effect and compare them with the results of one and two dimensional particle-in-cell simulations.

Improving the accuracy of simulation of radiation-reaction effects with implicit Runge-Kutta-Nyström methods.

The Landau-Lifshitz equation provides an efficient way to account for the effects of radiation reaction without acquiring the nonphysical solutions typical for the Lorentz-Abraham-Dirac equation. We solve the Landau-Lifshitz equation in its covariant four-vector form in order to control both the energy and momentum of radiating particles. Our study reveals that implicit time-symmetric collocation methods of the Runge-Kutta-Nyström type are superior in accuracy and better at maintaining the mass-shell condition than their explicit counterparts.

Laser field absorption in self-generated electron-positron pair plasma.

Recently, much attention has been attracted to the problem of limitations on the attainable intensity of high power lasers [A. M. Fedotov et al.

[Oxidative modification and change of intramolecular hydrophobicity of hemoglobin A during incubation of human erythrocytes in Fenton's medium].

It has been established by method of fluorescentive spectroscopy with using of zond FNA (N-phenilnaftilamine) that under incubation of human erythrocytes in Fenton's system (under intensive generation of oxygen active forms) the hydrophobicity of major hemoglobin fraction is lowered. The changes in the state of hemoglobin A intramolecular structure are correlated with formation of oxidative modification products. It has been shown that aldehydes and ketones of neutral character, which may be oxidative modification products of hydrophobic aminoacid residues, have the highest coefficient of correlation (r =-0.

[Metabolic state of erythrocytes under gall-stone disease].

Metabolic state of erythrocytes is changed under gall-stone disease. The increase of glucose and glycated hemoglobin contents in erythrocytes is combined with intensification of glycolytic reactions and lowered activity of pentose phosphate pathway. These changes may have compensative importance.

[The deciduous teeth in children born to mothers with heart defects].

Stomatological examinations of infants aged 6 to 36 months, whose mothers suffer from heart diseases, have revealed that the number of infants with deciduous dental tissue abnormalities grows with the age of the infants, reaching the maximum in those aged 3 years: 63.88 percent. Caries and caries-complicated diseases were recorded in 3-year-old children.

[The treatment of herpetic stomatitis in children with ointments containing alpha- and gamma-interferons].

Clinical efficacies of ointments containing alpha- and gamma-interferon and characterized by antiviral activity (2.0 x 10(4) IU) were studied. Antiviral effect of these ointments used in the treatment of 168 children suffering from herpetic stomatitis was assessed from the clinical and immunologic viewpoints.

[Quantitative evaluation of the combined effect of external gamma radiation and internal alpha radiation from 239Pu based on biochemical indices of the organs of the rat immune system].

The combined effect of external gamma-radiation (137Cs, 103-26 mC/kg) and incorporated alpha-radiation (239Pu nitrate, 93-9.3 kBq/kg body mass) was estimated by changes in the nucleic acid metabolism and the number of cells in rat thymus, spleen and bone marrow. The data obtained were processed using a model of multiplicate action of the factors which is equivalent, in the case of low effects, to a traditional model of additive effects.

[Aminotransferase and lactate dehydrogenase activity in the blood of dogs exposed to the joint action of external gamma- and internal alpha-radiation].

After the effect of external gamma-radiation (6.5 to 51.6 mC/kg) and inhaled 239Pu submicron oxide, containing 25% of 241Am, (approximately 7 to 10 kBq/kg) delivered separately and in a combination, activities of alanine-aspartate aminotransferase and lactate dehydrogenase changed in an undulatory manner tending to increase at later times; the change rating was a function of type and level of radiation as well as the time lapsed from the onset of exposure.

[Alkaline phosphatase activity of the blood serum in dogs exposed jointly to external gamma irradiation and alpha radiation].

Alkaline phosphatase activity in dog blood serum was studied for two years following separate and combined exposure to gamma radiation (6.45 to 51.6 mC/kg) and inhaled submicron 239Pu oxide, containing 25 per cent of 241Am, in chronically effective amounts (approximately 7-10 kBq/kg).

[Lactate dehydrogenase and alkaline phosphatase activity of the serum and radiation-induced osteosarcoma in rats].

Alkaline phosphatase (AP) and lactate dehydrogenase (LDG) activities are stained in rat blood serum and osteogenic sarcomas of different histostructure, which developed following a combined exposure of 239Pu (92.5 kBq/kg of body mass) and gamma-irradiation (103.2 mC/kg), as well as following separate exposures to these factors at the same doses.

[Alkaline phosphatase and transaminase activity in the liver and blood serum of rats in the late periods following combined exposure to external gamma radiation and alpha radiation from plutonium-239].

A study was made of activity of alkaline phosphatase and alanine- and aspartate aminotransferase in rat liver and blood serum at remote times after external gamma-irradiation combined with internal exposure to 239Pu nitrate delivered in two chronically effective doses. The radionuclide was shown to be mainly responsible for the changes observed in activity of the enzymes under study. The degree to which the changes were manifest depended upon dose of plutonium administered.