Том 70, № 5 (2025)

Pioneer transcription factors from the "Yamanaka cocktail" carry out cellular reprogramming. These proteins bind to heterochromatin, promote its opening and attract proteins to alter the epigenetic landscape and activate transcription. However, the literature lacks information on which chromatin proteins are attracted through direct protein-protein interactions with pioneer transcription factors. In this work, we predicted potential protein-protein complexes of three proteins from the "Yamanaka cocktail" (SOX2, OCT4, and KLF4) using neural network algorithms and performed structural and functional analysis of the resulting complexes.

The aim of this work was to analyze the interactions of methyl-β-cyclodextrin and amphotericin B (AmB) with spectrin, actin, and hemoglobin by the method of molecular docking. The protein structures were taken from PDB. The full-atom models of proteins were "cleaned" from water molecules and buffer components, surface charge arrangement was performed, and cells were selected for "blind" docking. The structural formula of methyl-β-cyclodextrin and amphotericin B were taken from PubChem and converted to HyperChem. Geometry optimization was performed using the MM+ model potential, rigid/fixed structures were optimized using the semi-empirical quantum chemical method PM3. The protein-ligand complex interactions were described using PLIP. The total binding energy for all complexes ranged from –4.4 to –10.3 kcal/mol. The complexes were formed due to hydrogen, van der Waals bonds, and salt bridges. Visualization of the most energetically advantageous positions confirmed that both amphotericin B and methyl-β-cyclodextrin localized in the central cavities of hemoglobin and actin, and in the distal sites of α- and β-subunits of spectrin. Amphotericin B formed more stable complexes with each of the proteins: the strength of hydrogen bonds and the number of hydrophobic contacts with the proteins were higher than for complexes with methyl-β-cyclodextrin.

The protein corona has a significant impact on the biodistribution, pharmacokinetics and therapeutic functionality of nanosystems, which determines the need for an in-depth study of the factors influencing its formation. The auxiliary substances included in the nanoparticles, in particular polyvinyl alcohol, can affect their physico-chemical properties, thereby affecting the formation of a protein corona. In this work, nanoparticles based on a copolymer of lactic and glycolic acids loaded with paclitaxel were synthesized by single emulsification using various concentrations of polyvinyl alcohol. The obtained nanoparticles were characterized by dynamic and electrophoretic light scattering methods. The adsorption models of Langmuir, Freundlich, Langmuir-Freundlich, and Brunauer, Emmett and Teller were used to describe the process of protein adsorption on the surface of nanoparticles. The obtained data indicate that the concentration of adsorbed proteins decreases when the residual polyvinyl alcohol concentration on the particle surface is increased. The revealed relationship will allow optimizing the design of nanosystems based on a copolymer of lactic and glycolic acids in order to increase the effectiveness of therapy.

The functional activity and morphological characteristics of the musculature of planarians have been studied. A physiological study conducted on isolated muscle cells of the planarian Procerodes littoralis (Turbellaria, Platyhelminthes) showed that caffeine in concentrations of 1–10 mM and depolarization caused by a high content of potassium ions (20–75 mM) had a dose-dependent stimulating effect on the musculature of planarians. Tapsigargin and cycloplazonic acid, calcium reuptake blockers in the sarcoplasmic reticulum store, reduced the number of muscle responses induced by both caffeine and depolarization. In addition, contractions of single P. littoralis muscle fibers induced by a medium with a high content of potassium ions were inhibited by ryanodine, which in mM concentrations is a blocker of the ryanodine calcium channels of the sarcoplasmic reticulum. The data obtained suggest that intracellular calcium store, as an intracellular source of calcium ions, play a role in the mechanism of contractile muscle response in flatworms. Histochemical examination using frozen sections and staining with fluorescently labeled phalloidin demonstrated the conservative organization of the body wall musculature of Schmidtea mediterranea planarians. The musculature of the body wall contains circular, diagonal and longitudinal muscle fibers. The thinnest circular fibers are densely packed in the outer layer of the musculature. The longitudinal fibers are the thickest and are mostly assembled in pairs. The diagonal fibers extend in two directions at an angle of 110–115 degrees to each other. Dorso-ventral muscle bundles penetrate the planarian body. The intestinal lumen is surrounded by thin longitudinal muscle fibers. Experiments have shown that planarians can be successfully used as a model object for studying the mechanisms of muscle contraction in flatworms.

It is known that microgravity leads to significant changes in the functioning of human physiological systems. In vitro, mechanosensitive cells also adapt to microgravity, demonstrating a rearrangement of cytoskeletal elements and functional activity. The effect of long-term microgravity simulated on a randomization position device (Gravite^®) was studied on cultured multipotent mesenchymal stromal cells of umbilical cord tissue. After 21 days of exposure, the cells retained high viability and a characteristic stromal phenotype. The expression of CD90 and CD105 markers involved in cell-to-cell and cell-to-matrix adhesion increased on their surface. The cytokine profile changed, and the concentration of pleiotropic cytokines MCP-3, GM-CSF, and PDGF-AA, which potentiate metalloproteinase activity, increased. The expression of the genes encoding MMP1 and osteocalcin increased, and decreased in case of osteopontin. The main extracellular matrix proteins — fibronectin, collagen, and osteopontin — were visualized in both experimental groups, while collagen was more pronounced in microgravity. The described changes indicate adaptive changes in the local microenvironment and remodeling of the extracellular matrix in response to prolonged exposure to simulated microgravity while the functional activity of mesenchymal stromal cells is maintained.

An overview of data on studies of multi-vector, as well as the persistence of unidirectional synaptic modulation in various types of motor units is presented. As is known, modulators of synaptic transmission are numerous. These include: the main mediator directly involved in this synapse, neuropeptides (endorphins and enkephalins, calcitonin, substance P, etc.), fatty acid derivatives (arachidonic acid and eicosanoids), gaseous mediators (NO, CO, and H₂S), as well as purines and pyrimidines (extracellular ATP, adenosine, etc.). Using the example of data analysis based on the results of the action of the most effective neuromodulators, purines, both their constant and variable effects in the synaptic modulation of various types of skeletal muscles were revealed.

Changes in the activity of the angiotensin converting enzyme and the production of reactive oxygen species in the rat aorta during diabetes induction by alloxan have been studied. The activity of the angiotensin converting enzyme in the aortic segments was determined by the hydrolysis of hippuryl-L-histidyl-L-leucine, and the formation of reactive oxygen species was determined by the oxidation of dichlorodihydrofluorescein. It has been shown that the activity of the angiotensin converting enzyme increases with an increase in blood glucose concentration to a maximum value at a glucose concentration of 12 mM and does not increase with a further increase in glucose levels. In contrast to the activity of the angiotensin converting enzyme, the formation of reactive oxygen species increases with increasing glucose concentration over the entire studied concentration range (up to 24 mM). Experiments with enalapril, an angiotensin converting enzyme inhibitor, have shown that it completely prevents an increase in the rate of formation of reactive oxygen species up to glucose concentration of 12 mM (100% contribution of activation of angiotensin converting enzyme to an increase in the formation of reactive oxygen species), but further the effectiveness of enalapril decreases (about 30% contribution of activation of angiotensin converting enzyme to an increase in formation of reactive oxygen species).

Deletions in mitochondrial DNA are recognized factors in mitochondrial disorders and aging. The aim of this study was to investigate the prevalence of large-scale mtDNA deletions in peripheral blood samples of offspring whose parents, "Mayak" PA workers, were exposed to combined external γ- and internal α-radiation during the preconception period. Using long-extension PCR, deletions of 4977 bp and sizes ranging from 7436 to 8044 bp were detected. It was found that the prevalence of deletions in the studied groups of these offspring tended to increase, but no statistically significant differences were found compared to the control group.

Covalent complexes of prourokinae, miniplasmin, and thrombin with QD nanoparticles containing aldehyde, amino, and carboxyl groups on the surface were obtained. It was shown that under the selected immobilization conditions, the listed enzymes immobilized on QD nanoparticles fully retained their enzymatic activity, and the formed complexes were stable colloids. The coating density of nanoparticles with enzymes reached 50–100 molecules per a particle. The immobilization of enzymes on carboxylic nanoparticles was performed using carbodiimide. Unlike the technology with carboxyl groups, the immobilization of enzymes on aldehyde nanoparticles does not require the use of carbodiimide to form a covalent complex and does not require a procedure for washing reagents before adding enzymes to nanoparticles, which improves the reproducibility of the immobilization procedure. It has been shown that particles with immobilized thrombin, when incubated with fibrinogen or blood plasma, form microemboli, which in vitro are completely destroyed by plasmin in the physiological concentration of the latter.

Disulfiram, a well-known anti-alcohol drug with minimal side effects, as well as other dithiocarbamates are being investigated as part of the Drug Repurposing program in order to expand their use, including in oncology. In this work, using the example of human tumor cells BT474, it was found that the action of oxidized disulfiram metabolites generated by aerobic oxidation of diethyldithiocarbamate in the presence of the catalyst cobalamin (vitamin B_12b) causes stress in the endoplasmic reticulum, and the integrated stress leads to cell death by paraptosis. The ability of substances of this class to cause non-apoptotic types of cell death is of interest for the development of new approaches in oncotherapy.

The development of new personalized approaches to non-drug treatment of functional disorders and impairments is a priority area of scientific and technological development in Russia. This review analyzes innovative research line using automatic modulation of non-invasive sensory stimuli (transcranial magnetic and electrical stimulation, acoustic, optical, and audiovisual stimuli) by rhythmic components of a subject's electroencephalogram for therapeutic purposes. When considering numerous examples of successful therapeutic use of sensory stimulation automatically modulated by feedback signals from rhythmic components of the electroencephalogram, an analysis of the observed effects is undertaken depending on the conditions and parameters of the organization of these electroencephalogram-controlled stimulations. The main advantages of the approach under consideration are considered, such as the optimal involvement of neuroplasticity mechanisms and resonance mechanisms of the brain in the therapeutic process. Prospects for the development of this line of research are outlined using the example of the author's own research.