Biofizika

The problem of stretching a flexible polymer with given conditions at the ends, under the action of a fixed force, is considered. A mathematical model is constructed for different energy functions describing the elasticity of the polymer and different immobilization methods. It is shown that the dependence of stretching on the polymer length is linear. Numerical results are given. The results obtained allow to improve the analysis of experimental data on polymer stretching. The theory offers several verifiable predictions, and experimental methods are proposed to improve the accuracy of measurements.

Diabetes mellitus is considered one of the most common metabolic diseases in the developed world and is associated either with impaired insulin secretion or with cell resistance to the action of this hormone (type 1 and 2 diabetes, respectively). In both cases, the common pathological change is an increase in blood glucose levels – hyperglycemia, which can ultimately cause serious damage to organs and tissues of the body. Mitochondria are believed to be one of the main targets of diabetes at the intracellular level. The present study addressed the functional state of mitochondria in the C57BL/Ks–db+/+m inbred mice carrying the recessive diabetes-db gene (diabetic mice). Histological analyses of the left ventricle of the hearts from diabetic and control mice were performed. In cardiac tissue samples from diabetic mice, an increase in the intensity of the eosin stain was observed implying that the structure of cytoplasmic proteins was distorted. In addition, it was shown that respiratory control and Ca2+ capacity in the mitochondria of diabetic mice decreased compared to controls. Changes in mitochondrial dynamics and mitophagy under these conditions were analyzed.

The study of the cytotoxic activity of two polyacrylic acid-based compounds containing gold (aurumacryl) and silver (argacryl) against a panel of human tumor cell cultures (769-P, Caki-2, SK-RC-1 renal carcinoma lines, BT-474 breast carcinoma, NCI-H211 small cell lung carcinoma) was carried out in vitro. The results obtained were analyzed in comparison with the data established earlier for other cell cultures (MCF-7 breast carcinoma, A-549 lung carcinoma, HCT116 colon carcinoma, Mel Me melanoma). The IС50 cytotoxic index of drugs for the nine tested tumor cell lines ranged from 0.8 to 5.2 µg/ml for aurumacryl and from 0.2 to 14.4 µg/ml for argacryl (in terms of gold and silver content, respectively), varying depending on the type of tumor. Significant differences have been found in the spectra of the lethal effect of aurumacryl and argacryl against tumor cells of various natures.

An important direction in cancer prevention is the development of novel strategies that can be used in the treatment by affecting the mechanisms of the regulatory pathways and genomic elements involved in malignant transformation. Strategy proposed in this study is to initiate cell death mechanisms in response to the depletion of the energy resources within a cancer cell due to the uncontrolled spread of mobile genetic elements throughout its genome. The calculation results obtained using a preliminary mathematical model that simulates cellular bioenergetic balance, taking into account the energy consumption for retrotransposition of the mobile elements such as LINE-1 and SINE, show that this scenario is plausible. Intracellular resources undergo a critical redistribution when affecting the genomic defense mechanisms and the LINE-1 transcription rate. This leads to a sharp increase in energy consumption for retrotransposon transcription that causes a significant decrease in the pool of free ATPs in the cell.

Radiation therapy holds a key position in the arsenal of cancer treatment methods. This non-invasive technique has been actively used for several decades and has demonstrated high effectiveness in combating various types of malignant tumors. Despite significant advancements in ionizing radiation delivery technologies and the introduction of targeted radiosensitizing drugs and immunotherapy, classical radiation therapy faces limitations related to the radioresistance of tumor cells. This resistance is caused by numerous factors, such as genetic mutations, the metabolic characteristics of cancer cells, their ability to repair DNA, the presence of a tumor microenvironment, and many others. Tumor radioresistance reduces the success of treatment, making it necessary to explore new approaches to enhance the effectiveness of radiation therapy. This review discusses the main principles of radiation therapy and the properties of cancer cells that affect their radiosensitivity. It examines both existing methods for overcoming the radioresistance of cancer cells and prospects for further development, which could significantly improve the effectiveness of cancer treatment.

An experimental model of dysbacteriosis caused by gentamicin sulfate, an antibiotic, was used to investigate the effect of low-intensity electromagnetic radiation of extremely high-frequencies (42.2 GHz, 0.1 mW/cm2, pulse modulation by a meander with a frequency of 1 Hz, exposure duration 30 min per day for 10 consecutive days, starting from the fourth day after the induction of dysbacteriosis) on the fatty acid composition of the thymus, blood plasma, activity of antioxidant enzymes, the amount of malondialdehyde and lactate in blood of laboratory rats. A significant decrease in the amount of myristic, palmitic, stearic, palmitoleic, oleic and linoleic fatty acids in the thymus in animals was shown. The activity of antioxidant enzymes, the amount of fatty acids and malondialdehyde in the blood remained unchanged. Lactate level in blood plasma decreased. Irradiation was shown to result in normalization of the fatty acid composition of the thymus and the amount of lactate in plasma in animals with dysbacteriosis. Due to its high efficacy, low-intensity extremely high-frequency electromagnetic radiation knowing certain parameters in dysbiosis opens up fundamentally new possibilities that could use these frequency spectrum bands to prevent and treat a number of pathological conditions associated with dysbiosis.

Using Doppler flowmetry and tissue optical oximetry, a comprehensive spectral analysis of the oscillatory components of the myogenic, neurogenic and endothelial components of microvascular tone and an assessment of the oxygen transport dynamics in the cerebral cortex of rats at the age of 4, 18 and 23 months were performed. Regional differences of age-dependent changes in the regulatory mechanisms of microcirculation and the efficiency of tissue oxygen extraction were revealed. It was found that at the age of 18 months, microcirculatory changes are observed in the frontal and parietal cortical areas and are manifested as a decrease in sympathetic regulation of microcirculation, a decrease in precapillary myogenic resistance, vasodilation and an increase in the contribution of the capillary unit to microcirculation. In the parietal cortical area, these changes contribute to the activation of tissue oxidative metabolism and to an increase in oxygen consumption. With further aging, microvascular endothelial dysfunction develops and the contribution of the endothelial component to the total perfusion level of all cortical areas decreases. These disorders in 23-month-old rats are accompanied by an increase in the contribution of sympathetic regulation of microcirculation in the frontal cortex, a decrease in the contribution of the capillary unit to the microcirculation in the occipital area, and the development of stagnant processes in the venous area of the microcirculatory bed of the parietal cortex, reducing the efficiency of tissue oxygen extraction from the blood.

We analyze specific options for the development of the current epidemic situation due to regularly updated SAR-CoV-2 strains and compare methods for modeling the spread of infection. The relevance of the development of scenario modeling methodology is due to the renewed waves of growth in COVID cases in a number of regions in 2024 as an unusual variant of a pulsating epidemic process. The next surges of infections are determined by the activity of the evolutionary branch of the BA.2.86 Pirola strains, which have managed to split, which are better in affinity and antibody avoidance than the previously dominant Omicron EG.5 or XBB.1.5 lines. Strains in 2023 retained sufficient transmissibility with reduced affinity for the ACE2 receptor and a lower replication rate compared to Delta, but the persistence time of the virus increased. In the situation of immunization of the population, the trend of virus evolution has changed with an emphasis on the complication of the phylogenetic tree and with the selection of Spike protein variants that provide balanced characteristics for replication and evasion of antibodies. The potential for variability of coronavirus proteins is clearly not exhausted, and methods for predicting their promising mutations are under development. Methods for computational research of epidemic scenarios based on those modified by expanding the set of statuses of individuals in office “SIR” models are discussed. Variants of systems of equations based on SIR do not describe the resumption of COVID waves, which was already observed in 2020. Status transition schemes based on fundamental aspects are poorly suited for describing nonlinear oscillatory regimes of the epidemic, even when second-order oscillatory equations are included in the linear SIR scheme. The models developed by the author for decaying COVID waves based on equations with delay and with threshold effects were modified to take into account that the new Omicron lines change fluctuation regimes. The changes in oscillation modes that we have identified with an increase in repeated cases are not described only by restructuring the parameters of the equations with damping functions. According to the observed epidemic graphs of COVID waves, the models require a restructuring of regulatory functions. We propose to model aspects of the transition phases of the modern epidemic using special computational tools and based on the nature of nonlinear oscillations. An original method for forming a structure for a hybrid model is substantiated based on a set of right-hand sides of differential equations with heterogeneous delayed regulation parameters that generate relaxation oscillations and are redefined when the criteria for the truth of predicates are violated. It has been shown that changes in the binding affinity of S-protein variants with ACE2 are a key indicator for modeling periods of attenuation and activation of waves associated with the evolution of the virus, as in 2024 for the JN.1 strain. The new hybrid model with evet time describes event-based transformations in the shape of epidemic waves associated with disturbances in the mutational landscape of the coronavirus, which can now be established by monitoring mutations and the frequency of occurrence of strains.

The morphological structure and functional properties of musculature of flatworms Fasciola hepatica (Trematoda, Fasciolidae), parasites dangerous for agricultural animals and humans, have been studied. The histochemical staining of the body wall muscles of F. hepatica with fluorescently-labelled phalloidin has been performed and the stained samples were examined by fluorescent microscopy. Staining was observed both in longitudinal, circular, and diagonal muscle fibers of the body wall of the trematode, in the circular and diagonal muscle fibers surrounding the lumens of the branched intestine, and in the tubular structures of the reproductive tract. In the ventral and oral suckers of the trematode, tightly packed and intensively stained layers of muscle fibers were found. The physiological studies were conducted on the muscle strips prepared from F. hepatica. The results demonstrated that muscle preparations exhibit spontaneous contractile activity. Neuropeptide GYIRF, belonging to the FMRFamide-like peptide family, used at concentrations ranging from 1 µm to 10 µm, additionally stimulated the contractions of muscle preparations in F. hepatica, increasing the frequency and amplitude of contractions compared to their basic activity. The information obtained will be used in further investigation of muscle contraction mechanism in parasitic worms, the muscles of which are targets of antiparasitic drugs.

The problem of changes in myoneural transmission in the presence of an intercalating agent, ethidium bromide, which has a known inhibitory effect on neuromuscular transmission, has been investigated, but the nature of such an effect remains unclear. To solve the question of the possible participation in this process of known modulators of synaptic transmission – purines (ATP and adenosine), we evaluated their effects in the presence of this agent. After holding the neuromuscular frog preparation in a perfusing solution containing ethidium bromide, the amplitude of postsynaptic responses and muscle contraction forces decreased. Under these conditions, both purines additionally exerted their usual suppressive effect on both the amplitude of postsynaptic responses and the strength of skeletal muscle contraction. Thus, the inhibitory effect of ethidium bromide on neuromuscular transmission is not associated with an increase in the inhibitory effect of endogenous purines caused by the quantum release of the neurotransmitter.

The combination of two compounds such as the binuclear form of dinitrosyl iron complexes with glutathione (B-DNIC-G, 100 µM/kg, s/c) and sodium diethyldithiocarbamate (DETK, 500 µM/kg, i/p), administered eight times, causes two week-lasting complete inhibition of solid tumor development in mice after tumor transplantation (Lewis lung carcinoma). However, when the antitumor effect was evaluated on the 20th day after the end of drug administration, the maximum activityinhibition of tumor growth by 60% − was observed when drugs were administered in the order DETK, and then after an hour B-DNIC-G, while when drugs were used in reverse order, tumor growth inhibition was not greater than 30%. Based on the analysis of EPR measurements of tumor tissues (day 15 of tumor development), it was concluded that the inhibition of tumor growth was caused by nitrosonium cations released from B-DNIC-G during the breakdown of these complexes under the action of DETC. .