Digital transformation affects all social spheres bringing to life interactive technologies and virtual reality. Since the virtual (digital) space depends on the digital and creative solutions that form its technological base, insofar the legal regime of copying creative solutions affects both the freedom of creativity necessary for sustainable development and public control which is significant for maintaining the manageability of sovereign states and integrational unions.Aim. Improving the legal regime for the protection of interactive works to create a universal and harmonious information space where the rights of authors and the economic interests of software developers are protected, as well as digital sovereignty is guaranteed.Tasks. The concept development for legal protection of interactive works and the political and legal modeling of the digital (information) space presuppose the implementation of international agreements in the field of intellectual rights, as well as solution of several tasks to formalize the results of the creative activity that are perceived through digital technologies.Methods. Political and legal modeling of the digital space is carried out by introducing terminological certainty and creating a system of the interactive works protection. Such legal construction should provide effective public control while preserving creative freedom in digital space.Results. The protection of the copyright and moral rights of the authors of interactive works differs significantly from the legal protection of audiovisual artworks and literature. While the form of objective expression in computer programs may be similar to a literary artwork, their perception by the target audience is fundamentally different in that it models a virtual (digital) space, which the state administration seeks to control in recent years.Conclusion. The state administration’s tendency to digital sovereignty makes sense only if the target audience demonstrates high demand for interactive artworks published under the state jurisdiction. Since the information space is universal, the digital sovereignty of the state is inextricably linked with participation in integration unions that ensure the p roper quality of the results of creative work and create the digital space that is necessary under digital transformation for the interactive art development and the prosperity of creative corporations.
Background and Aims At present, there is no doubt about the relationship between the state of the kidneys and the cardiovascular system, which is reflected in the concept of the cardiorenal continuum. The emerging data suggest that miRNAs may be one of the links connecting the kidneys and the cardiovascular system. However, information about the role of epigenomic changes in the development of damage to the heart and blood vessels in chronic kidney disease remains not fully understood. Target. The aim of the work was to evaluate changes in the expression levels of microRNA-21, 133,203, as well as the nuclear transcription factor κB (NFκB) in the tissues of the myocardium and aorta in the development of remodeling of the heart and blood vessels with a chronic reduction in the mass of active nephrons in the experiment. Method Systolic blood pressure (BP, mm Hg), myocardial mass index (MMI, mg/g), relative expression levels of miRNA-21, -133, -203 and NFκB in myocardium and aorta were analyzed in rats Wistar-Kyoto (WKY) with 5/6 nephrectomy (Nx) and duration of experimental exposure 2 mo (n = 9). Controls were sham operated (SO) animals (n = 9). The reverse transcription reaction for ‘complementary’ DNA (cDNA) preparation was carried out under the StemLoop-technology separately for the studied miRNA. The following primers were used in PCR: microRNA-21–5'-GCCCGCTAGCTTATCAGACTGATG-3_, microRNA-133–5_-GCCCGCAGCTGGTAAAATGGAAC-3_, microRNA-203–5_-GCCGGTGAAATGTTTAGGACC-3_ and U6–5_-GCGCGTCGTGAAGCGTTC-3_, and common reverse 5_-GTGCAGGGTCCGAGGT-3. The semi-qualitative evaluation of the miRNA expression level (in relative units, RU) under the 2-(ΔΔCt) protocol at the laboratory referent (0.09) was used in calculations. NFκB expression was quantified using a StemLoop technology and RealTimePCR compared to the expression of the reference-gene GAPDH. Data were analyzed using Student's t-test and the Mann–Whitney, a P<0.05 was considered statistically significant. Results In rats WKY with an experimental decrease of the nephron mass in comparison to control, significantly higher levels (median [interquartile rang]) of blood pressure (145.5[135.0; 155.0] vs 117.5[110.0; 120.0] mm Hg; P<0.001) NFκB expression in the myocardium (1.25[0.87; 1.87] vs 0.89[0.31; 1.15] relative units; P<0.01) and aorta (0.87[0.57;1.63] vs 0.35[0.22; 0.87] relative units; P<0.05). The expression level of miRNA-21 in the myocardium increased in rats with NE (1.48[0.54; 3.73] vs 0.37[0.06; 1.62] relative units; P<0.01) relative to the SO group, but did not change significantly in the aorta (p>0.05). Relative expression levels of microRNA-133 and -203 both in the myocardium and in the aorta of WKY rats with NE were more than 10 times lower compared to those of the SO group (p<0.001). BMI in rats 2 months after NE increased relative to the SO group (p<0.05). Conclusion An experimental decrease in the number of functioning nephrons not only leads to an increase in blood pressure and myocardial mass in WKY rats, but also causes epigenomic changes in the myocardium and blood vessels, in particular, activation of signaling pathways associated with NFκB in the myocardium and aorta of rats. Possibly, it is accompanied by growth in expression of NFκB-associated proliferative, proinflammatory and profibrotic cytokines. It is possible that microRNA-21 is also involved in the formation of fibrosis and myocardial remodeling. However, specific mechanisms of miRNA involvement in the pathogenesis of heart and vascular remodeling require further study.
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