4-Thiazolidinone derivative Les-3833 effectively inhibits viability of human melanoma cells through activating apoptotic mechanisms

Aim To evaluate cytotoxic action of 4-thiazolidinone derivative Les-3833 and study the mechanisms of its pro-apoptotic action toward human melanoma cells and human tumor cell lines of other tissue origin. Methods The effect of Les-3833 or doxorubicin on the viability of 9 cell lines was studied using MTT assay, while human melanoma cells of WM793 line were additionally examined using light and fluorescent microscopies for evaluating cytomorphological changes. The Western-blot and flow cytometric analyses were carried out to study signaling pathways of melanoma cell cycling and death. Results Les-3833 was the most efficient against melanoma cells. Its half maximal inhibitory concentration (IC50) was 0.22 μg/mL for WM793 cells and 0.3 μg/mL for SK-Mel- 28 melanoma cells. For human lung A549, breast MCF-7, colon HCT116, and ovarian SKOV3 carcinoma cell lines IC50 was in between 2.5 to >5.0 μg/mL. Les-3833 was relatively not toxic (IC50 > 5 μg/mL) for human embryonic kidney HEK293 cells. Results of Annexin V/PI staining of melanoma cells and activation of caspase 3, PARP, MAPK, and EndoG protein suggest apoptosis in Les-3833-treated cells. Les- 3833 also induced ROS production in melanoma cells and their arrest in G0/G1 phase of cell cycle. Conclusion Novel 4-thiazolidinone derivative Les-3833 is effective against human melanoma cells in vitro, and such effect is tumor specific since it is much less pronounced in human carcinoma and leukemia cells. In melanoma cells Les-3833 induces apoptosis (morphological changes and increased pro-apoptotic proteins), ROS production, and arrest in G0/G1 phase of cell cycle

A PERFORMANCE INTERPRETATION OF THE VIENNESE CLASSICS BY THE EXAMPLE OF FANTASIA FOR PIANO, CHORUS AND ORCHESTRA IN C MINOR, OP. 80 BY LUDWIG VAN BEETHOVEN

The relevance of the study is determined by the need to cover the significance, uniqueness and means of performance of one of the masterpieces of the Viennese Classical School — Fantasia in c minor, op. 80 for mixed choir, piano and orchestra by Beethoven. The aim of this publication was to study the problems of performance interpretation of the legacy of the Viennese Classical School using the example of L. Beethoven’s Fantasia for piano, soloists, mixed chorus, and orchestra. Research methods were: creation of an information background; comparative analysis and structuring of information; identification of the categories that make the basis of the problem; generalization of obtained data. The materials based on audio and video recordings of the work by prominent representatives of the performing arts were used. The literature on the stylistic and compositional atmosphere of the era of Viennese classicism, as well as on features of the genres of the work was also used. The results of the study revealed the interrelationship of all components of the problem being studied. They evidenced the inseparability of such elements as genre, musical form, instrumentation, manner of performance, a certain historical period, as well as the stylistic orientation prevailing within it. Its main categories were identified while studying the chosen topic, as well as their dependency on the temporal, stylistic, individual, and psychological (performers’ personalities) context was established. These facts became a theoretical and methodological contribution to art science, history of performance, as well as music pedagogy. As a conclusion of the study on performing interpretation of the Viennese classics using the example of Fantasia by Beethoven, its genre stylistic and compositional technical universality was determined; the process during which the piano becomes a solo concert instrument; the role of improvisation in the large-scale synthetic genre; development of a single performance concept by the conductor, pianist and choirmaster, diversity of artistic and psychological types of performance while preserving the main author’s idea. The research of this topic has wide prospects in the future, thanks to its volume, multi-vector nature, connection with a wide range of musical subjects, and sensitivity to individual styles of interpretation in the context of different epochs. This is emphasized by the value of classical heritage, the need to preserve and popularize it

Putative anticancer potential of novel 4-thiazolidinone derivatives: cytotoxicity toward rat C6 glioma in vitro and correlation of general toxicity with the balance of free radical oxidation in rats

Aim To evaluate the cytotoxic action of 4-thiazolidinone derivatives (ID 3288, ID 3882, and ID 3833) toward rat glioma C6 cells and to compare the effects of these compounds and doxorubicin on the balance of free radical oxidation (FRO) and antioxidant activity (AOA) in the serum of rats. Methods Glioma cells were treated with ID 3882, ID 3288, ID 3833, and doxorubicin, and their cytotoxicity was studied using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and Trypan blue exclusion test, light and fluorescent microscopy, and flow cytometric study of cell cycling and apoptosis, including measuring of Annexin V-positive cells. The contents of superoxide radical, hydrogen peroxide, hydroxyl radical, malonic dialdehyde, and hydrogen sulfide were measured in the serum of rats. Enzymatic activity of superoxide dismutase (SOD), catalase (Cat), and glutathione peroxydase (GPO) was determined. Results Among novel 4-thiazolidinone derivatives, ID 3288 was most toxic toward rat glioma C6 cells, even compared with doxorubicin. All applied derivatives were less active than doxorubicin in inducing reactive oxygen species-related indicators in the serum of rats. A similar effect was observed when enzymatic indicators of AOA processes were measured. While doxorubicin inhibited the activity of SOD, GPO, and Cat, the effects of 4-thiazolidinone derivatives were less prominent. Conclusion Novel 4-thiazolidinone derivatives differ in their antineoplastic action toward rat glioma C6 cells, and ID 3288 possesses the highest activity compared to doxorubicin. Measurement of indicators of FRO and AOA in the serum of rats treated with these compounds showed their lower general toxicity compared with doxorubicin’s toxicity

Obstetric phantom

The study guide is prepared for senior year students, intern doctors for specialty "Obstetrics and gynecology", young doctors. The material of the guide is presented as taking into account methodological needs, as well as modern obstetric knowledge based on principles of evidence-based medicine, which is the basis of the information provided in this publication

Theoretical-methodical approaches to monitoring of the level of socio-economic development of territorial units and national economy in conditions of decentralization

Theoretical-methodical approaches to monitoring of the level of socio-economic development of territorial units and national economy in conditions of decentralization / I. Irtyshcheva, M. Stegney, Y. Boiko, D. Voit, N. Hryshyna // Рerspectives : journ. on Economic Iss. – 2019. – No 2. – Р. 83–92.The paper outlines the nature and main components of provision of regions’ socio-economic development in conditions of decentralization. The condition of decentralization reform implementation in Ukraine and main problems of forming of efficient institutional architectonics to facilitate the reform implementation and to secure the improvement of the regions’ social and economic development at current stage are examined. Institutional forms and elements of decentralization are systematized and their nature and functioning principles are defined. The paper analyzes the peculiarities of traditional monitoring system of territorial units’ socio-economic development used in Ukraine. Improvement of methodical approaches to monitoring of socio-economic development is suggested. It is based on calculation of comparative integral estimations of dynamic coefficients of socio-economic development of national socio-economic system at three levels: global, national and regional. The use of suggested methodical approaches contributes to defining of an integral picture of socio-economic development, tendency vectors and misbalances of maintenance of social and economic results at the moment of estimation. Success of decentralization reform is manifested in the completeness of its implementation, which should result in not only adjustment of administrative-territorial structure of the country and improvement of institutional and managerial architectonics, but also in ex-tension of activity and efficiency of local communities in the context of their impact on the development of both education, medicine, social and housing infrastructure and the areas of culture, social provision, energy efficiency, transport, etc

Functional micelles formed by branched polymeric surfactants: Synthesis, characteristics, and application as nanoreactors and carriers

Branched polymeric surfactants composed of grafted non-ionic polyethylene glycol (PEG) and anionic polyelectrolyte chains were synthesized via radical polymerization initiated by the comb-like PEG-containing polyperoxide. Above definite concentration in solution, these surfactants form micelle-like structures (MLS). The MLS formed by branched polymeric molecules are of larger size in comparison with size of MLS formed by the initial PEG-containing polyperoxide that is caused mainly by different mechanism of their self-organization and morphology of formed MLS. The availability of grafted polyelectrolyte chains in the MLS provides a possibility of their use as the containers for immobilization of bio-active substances and nucleation of the inorganic nanoparticles, as well as formation of their stable colloidal systems in water in a wide pH range. Noticeable compaction and narrowed size distribution of the MLS were revealed after immobilization of doxorubicin (Dox) molecules or Fe$_2$O$_3$ nanocrystals. MLS-based systems were used for delivery of Dox and maghemite particles at treatment of tumor cells. Both MLS-based formulations of Dox and Fe$_2$O$_3$ were efficiently engulfed by rat glioma C6 cells. A significant (10 times) decrease in the effective therapeutic dose of Dox was found when this drug was delivered by a MLS-based formulation of Dox. That effect might be explained by a specific structure and functionality of the novel carrier used for immobilization of drug that should be delivered to target cells

An economic management system for sustainable development in black sea region

Kramarenko, I. An economic management system for sustainable development in black sea region / I. Kramarenko, I. Irtyshcheva, S. Shults, M. Stehnei, K. Blishchuk, Y. Boiko, N. Popadynets, N. Samotiy, L. Rogatina, N. Hryshyna // Accounting. – 2020. – Vol. 6, № 4. – P. 387–394.The paper aims to develop a model for measuring economic system management efficiency of the Black Sea region of Ukraine through the context of sustainable development. The model includes the rates of social and economic efficiency, productivity, and performance. The proposed approach calculates the region’s economic system management efficiency. The respective evaluation criteria are systematized: economic and social efficiency of the region’s economic activity, productivity of the use of resources, and performance of the management system. The system of evaluation indicators by each criterion and mathematical apparatus to calculate them are suggested. The paper suggests methodical approaches to evaluate the economic system management efficiency in the region under transformation. They help determine the current level against similar indicators achieved within the country and the tendencies influenced by regional factors, form the “economic system management profile”, and identify the strengths and bottlenecks

Mechanisms to Manage the Regional Socio-Economic Development and Efficiency of the Decentralization Processes

Irtyshcheva, I. Mechanisms to Manage the Regional Socio-Economic Development and Efficiency of the Decentralization Processes / I. Irtyshcheva, I. Kramarenko, T. Vasyltsiv, Y. Boiko, O. Panukhnyk, N. Hryshyna, O. Hrafska, O. Ishchenko, N. Tubaltseva, I. Sirenko, N. Popadynets, I. Hryhoruk / International Conference on Human Interaction and Emerging Technologies. – Strasbourg, France : IHIET-AI 2021, AISC 1378, Springer, Cham. – 2021. – P. 694–701.The process of administrative and territorial reform in Ukraine urges most of the population to think about their future because the finalization of the reform stipulates that local governments are independent, and residents are responsible for their territories. To finish the process of administrative reform, it is necessary to efficiently use resources to achieve the ultimate decentralization objective. The paper aims to evaluate the efficiency of decentralization as an essential tool for the socio-economic development of regions. The efficiency of the reform implementation inUkrainian regions is suggested to be evaluated across the organizational-administrative and budgetary components. The parameters of analysisof the reform implementation efficiency in the regions across the suggested components are systematized. The absence of a consistent relationship between the organizational-administrative and budgetary components is confirmed

Mechanisms to Manage the Regional Socio-Economic Development and Efficiency of the Decentralization Processes

The process of administrative and territorial reform in Ukraine urges most of the population to think about their future because the finalization of the reform stipulates that local governments are independent, and residents are responsible for their territories. To finish the process of administrative reform, it is necessary to efficiently use resources to achieve the ultimate decentralization objective. The paper aims to evaluate the efficiency of decentralization as an essential tool for the socio-economic development of regions. The efficiency of the reform implementation inUkrainian regions is suggested to be evaluated across the organizational-dministrative and budgetary components. The parameters of analysis of the reform implementation efficiency in the regions across the suggested components are systematized. The absence of a consistent relationship between the organizational-administrative and budgetary components is confirmed