Vol 70, No 3 (2025)

Determination of interaction parameters of low molecular weight compounds with DNA is difficult in cases where compounds do not exhibit appreciable fluorescence or their spectral changes are difficult to interpret. To solve this problem, an approach involving the use of known fluorescent dyes competitively binding on DNA is proposed. This approach uses a model describing the competitive binding of two extended ligands on a linear DNA matrix. This model allows approximation of experimental data and determination of binding parameters corresponding to two non-fluorescent types of ligands. The first type of ligands exhibits intercalation binding to DNA and competes with ethidium bromide, while the second type binds along a narrow groove and competes with Hoechst 33258 dye.

In this work, computer-based molecular dynamics studies of the interaction of the pharmacological pair “vector–receptor” have been carried out to model promising mechanisms and processes of specific drug delivery to the tumor. The purpose of these computational molecular dynamic calculations is to study the interaction processes and determine the spatial positions of the RGD peptide + αvβ3-integrin receptor system, which is solvated with water. The configuration positions of the RGD-peptide + αvβ3-integrin system in 100 ns relaxed states were obtained from molecular dynamic modeling. In this case, two RGD peptides were modeled located outside and inside the αvβ3-integrin receptor. One of the two RGDs is a peptide of the original PDB file localized inside the αvβ3-integrin receptor. The other RGD peptide is located outside the receptor in its initial position, freely diffuses throughout the entire area of the modeling cell, and naturally comes into contact and binds to αvβ3-integrin.

Light-induced redox transformations of P700, the reaction center of photosystem I, were studied by EPR method depending on the illumination conditions of plant leaves (intensity and spectral composition of the active light). Within the framework of a mathematical model, the key stages of electron transfer along the noncyclic electron transport chain containing photosystems I and II and mobile transporters (plastoquinone, plastocyanin, ferredoxin) and the processes of trans-thylakoid proton transfer associated with ATP synthesis were considered. The mechanisms of pH-dependent regulation of electron transport in chloroplasts at the acceptor and donor sites of photosystem I have been analyzed. The modeling results are in agreement with experimental data on the kinetics of light-induced transformations of P700 in chloroplasts of higher plants. The results obtained are discussed in the context of "short-term" pH-dependent mechanisms of electron transport regulation in chloroplasts in situ.

Changes in the qualitative composition and quantitative content of metabolites of the phosphoinositide cycle have been studied and their participation in the process of excitation conduction along nerve conductors and regeneration of damaged somatic nerves under the action of insulin-like growth factor-1 have been established. It was shown that during nerve excitation there is a decrease in the level of phosphatidylinositol and phosphatidylinositol-4,5-diphosphate and an increase in the content of phosphatidylinositol-4-monophosphate and phosphatidylinositol-3,4,5-triphosphate, which indicates the intensification of phosphoinositide metabolism under conditions of depolarization of the nerve fiber membrane, and there is also a redistribution of fatty acids in the composition of phosphatidylinositol, diacylglycerol and free fatty acid fractions. Nerve transection is accompanied by accumulation of all forms of phosphoinositides and a decrease in the level of diacylglycerol in both proximal and distal sections of the nerve conductor, apparently as a result of inactivation of phosphoinositide-specific phospholipase C. Against the background of intramuscular injection of insulin-like growth factor-1 at a concentration of 100 ng/kg, intensification of phosphoinositide metabolism, accumulation of diacylglycerol and decrease in the level of free fatty acids were observed. The methods of Raman spectroscopy, registration of action potentials and growth cones revealed the restoration of the physico-chemical state of the lipid bilayer and functional activity in the proximal segment of somatic nerves using insulin-like growth factor-1, which correlates with the data we obtained on the changes in the composition of the lipid fraction of damaged nerve conductors against the background of the drug action. We believe that insulin-like growth factor-1 is one of the factors of axonal regeneration and restoration of functioning of damaged nerve conductors, exerting its effect as a result of activation of phosphoinositide-specific phospholipase C and phosphatidylinositol-3-kinase signaling pathways.

The radioprotective efficacy of granulocyte colony-stimulating factor in the form of pegfilgrastim at fractionated irradiation was evaluated on male ICR (CD-1) mice. Mice were exposed to five daily exposures to X-rays at a dose of 2.5 Gy. Three hours after each exposure, pegfilgrastim was injected subcutaneously into mice at a dosage of 0.5 μg/g. The drug was also administered daily 3–7 days after the last irradiation. The efficacy of this therapeutic regimen was evaluated on the basis of the degree of DNA damage in spleen cells 30 min after the last irradiation, hematologic parameters – after 30 min and 3 days, Schiffbases, trieno and oxodiene conjugates in the liver – after 30 min, thymus and spleen weight, the number of karyocytes in the femur, the content of thiobarbiturate-reactive products in the liver – after 3 days, as well as on the basis of 30-day survival. The application of the therapeutic regimen under study contributed to a significant correction of irradiation-induced oxidative stress: according to the criteria of the content of Schiff bases, trieno and oxodieno conjugates, the group receiving pegfilgrastim corresponded to the intact mice, the content of thiobarbiturate-reactive products in the liver decreased relative to the irradiated control, but the parameters of intact mice were not reached. Pegfilgrastim administration did not compensate for the irradiation-induced bone marrow cell death 3 days after the last irradiation and could eventually ensure the survival of only 3 mice out of 14 individuals receiving the drug. Thus, for effective application of pegfilgrastim during fractionated irradiation at a total dose of 12.5 Gy it is necessary to increase the number of irradiation sessions with decreasing dose of each session, or to decrease the total radiation dose. Joint use of pegfilgrastim with other radioprotective drugs with other mechanisms of action is also promising.

Changes in the level of some markers of apoptosis (lipid asymmetry of plasma membranes, production of reactive oxygen species, nitric oxide, concentration of ionized calcium) of human blood lymphocytes modified by exposure to hydrogen peroxide (10−5 mol/l) and UV light (254 nm, 1510 J/m2) in the presence of cycloastragenol (10−8–10−4 mol/l) were studied. The intensity of apoptotic lymphocyte death processes was found to decrease after UV-light exposure in the presence of cycloastragenol (10−8 mol/l). The cytoprotective effect of cycloastragenol on lymphocytes was found to be due to a decrease in the level of intracellular reactive oxygen species and calcium ions, an increase in the activity of catalase and glutathione reductase and nitric oxide production. Possible mechanisms of cycloastragenol action as a regulator of apoptotic death of lymphocytes induced by UV radiation and hydrogen peroxide exposure are discussed.