Splicing is a complex stage of gene expression regulated by many cis-elements represented by the specific pre-mRNA sequence motifs and trans-elements that are proteins and ribonucleoprotein complexes. Splicing disruption often leads to genetic disorders. A lot of pathogenic variants causing aberrant splicing are described in databases for human mutations, demonstrating a need for the development of the effective and safe splicing modulation tools and its application. Recent studies of the fundamental splicing regulation processes allow researchers to develop few tools for splicing modulation in order to be used as a therapeutic. In this review we describe the experience in antisense molecules application in vitro and in vivo according to the pathogenesis of the splicing disruption and affected components of its regulation; advantages and disadvantages of antisense oligonucleotides, modified small nuclear RNAs, spliceosome-mediated mRNA trans-splicing technology as a tools of therapy and tools for its delivery to the cells are also discussed.

   Atherosclerosis is considered as a chronic inflammatory disease characterized by dysfunction of the endothelium of the vascular wall, migration of immune cells, subendothelial accumulation of lipids and proliferation of vascular smooth muscle cells with further formation of atherosclerotic plaques. Research data suggests the potential importance of Toll-like receptors (TLRs) and other key components of the innate immune system in the pathologies associated with atherosclerosis. Toll-like receptor 4 (TLR4) may play a key role in the immunopathogenesis of atherosclerosis.

   The aim of this study was to explore the association of TLR4 gene expression in macrophages and polymorphic variants rs4986790 and rs4986791 with the development of atherosclerosis in the St. Petersburg population.

   The study included 671 individuals: 220 patients with atherosclerosis of various localizations (coronary, cerebral, lower extremity artery pool); 75 patients with familial hypercholesterolemia with/without manifestation of atherosclerosis; 376 individuals without cardiovascular pathology as the control group. Genotyping of polymorphic variants of the TLR4 gene was performed by PCR followed by restriction analysis. Analysis of the TLR4 gene expression level in was performed in differentiated in vitro macrophages of 13 patients with coronary atherosclerosis and 19 representatives of the control group by real-time PCR. Patients with coronary atherosclerosis were characterized by an increased level of TLR4 gene expression in macrophages when compared with the control group. The Asp299Gly and Thr399Ile variants of the TLR4 gene were not associated with atherosclerosis development in the population of St. Petersburg, including patients with familial hypercholesterolemia.

   Objective. We aimed to study the effect of water-soluble aryl C70 fullerene derivatives on the transcriptional activity of genes regulating oxidative metabolism.

   Methods. The toxicity of two derivatives of C70 with minor changes in the structure was studied using the MTT test on a culture of human embryonic lung fibroblasts as well as intracellular reactive oxygen species, expression of NOX4 and NRF2 genes and proteins. Fluorescence microscopy, real-time PCR-RT, and flow cytometry were used.
   Results. Both compounds equally caused a decrease in intracellular ROS during the day, an increase in the expression of the NOX4 gene and protein, and an increase in the expression of the NRF2 gene and protein. Probably, an increase in NOX4 expression is compensatory in response
to the development of an intracellular antioxidant state, and an increase in NRF2 expression is compensatory in response to NOX4 activation.

   Conclusion. Modification of the surface with substituents that enhance the antioxidant properties of the substance leads to a change in the mechanism of the influence of nanoparticles on genes, while minor differences in the structure of substituents do not significantly determine the effects.

   The populations of the indigenous ethnic groups of Central Asia are of considerable interest for population genomics, due to the specificity of their gene pools, which developed under various genetic and demographic conditions. The data on directional selection signals is an important addition to the existing data on the evolution of gene pools and the mechanisms of genetic adaptation of the Eurasian population. We used an array of genotypes for 1779819 SNPs in a sample of 128 people, including 5 populations of the population of Central Asia, to search for directional selection signals using tests for extended haplotype homozygosity (nSL, iHS). For the populations of Central Asia, it was found that all the studied populations differ greatly from each other in the composition of genes that demonstrate the influence of selection. The largest number of significant signals of natural selection was found in the populations of the Kyrgyz and Uzbeks. The CUEDC1, ERC1, FAM20C, and MRC1 genes are among the genome loci that carry the most pronounced signals of directional selection in populations.