UV radiation from the sun in the B-region (UVB, 290–320 nm) and A-region (UVA, 320–400 nm) is a key genotoxic environmental factor that causes DNA damage, which threatens the integrity of the genome in living cells. If DNA defects remain unrepaired, they can cause potentially carcinogenic mutations. UV-induced damage in DNA involves direct or photosensitized reactions, and the chemical nature and quantity of photoproducts depend on the wavelength of UV radiation. UVB photons, by direct absorption by DNA bases, cause the formation of two main types of pyrimidine dimeric photoproducts. Under the action of UVA, mainly thymine dimers are formed in DNA, and only of one type; they can be formed either as a result of direct photon absorption or by transferring energy to thymine bases from sensitizing molecules. In addition, UVA effectively induces sensitized reactions of oxidative DNA damage. This review presents current knowledge about the fundamental mechanisms of photochemical reactions in DNA and discusses the role of various DNA photoproducts in the initiation of genotoxic processes. When considering oxidative reactions in DNA, attention is paid to the properties of pterins, riboflavin, protoporphyrin IX, and melanin as potential cellular photosensitizers for the generation of reactive oxygen species involved in these reactions.
In the process of cellular transcription, short-lived intermediates called elongation complexes are formed. They contain matrix DNA, RNA, DNA-dependent RNA polymerase, and transcription factors that regulate transcription parameters. The accumulated biochemical and structural data on transcriptional elongation complexes allow us to consider them as independent functional units. This article provides an analysis of published experimental and theoretical works, on the basis of which a hypothesis is put forward about the joint structural and functional evolution of the components of transcriptional elongation complexes.
Using methods of flow cytometry and fluorescence analysis, a comparative analysis was conducted on the mechanisms of the response of human cervical carcinoma cells to thymoquinone, the main component of black cumin oils (Nigella sativa), under hypoxia and normoxic conditions. It was found that thymoquinone induced the death of tumor cells under both standard conditions (5
The effectiveness of drugs with various mechanisms of antitumor action, representing the following classes of compounds: precious metal polyacrylates (aurumacryl and argacryl), binuclear dinitrosyl iron complexes (B-DNIC-cysteine), and nitrosoalkyl ureas (metinur, dimethinur, chlonisol, and nimustine) has been studied on the advanced solid tumors. The range of tumor models included xenografts of human melanoma BRO, the first generation of spontaneous breast cancer in mice, Lewis lung carcinoma, adenocarcinoma Ca-755, melanoma B-16, and leukemia P-388 (solid form). The mass of tumors when exposed to the drugs varied from 120 to 420 mg, and the time to start using the drugs ranged from 5 to 12 days of tumor growth. It was shown that it is possible in principle to achieve a very high antitumor effect with late initiation of treatment and the effect of drugs on advanced tumors.
The aim of the work was to study specific changes in internal organs against the background of metabolic disorders in rats with experimental obesity. Experimental obesity was initiated by feeding rats a high-fat diet for 12 weeks. The diet of the experimental animals included standard feed enriched with lard. A histological examination of the internal organs and a biochemical blood test were performed. After 12 weeks of a high-fat diet, the rats showed an increase in body weight and metabolic disorders, which consisted in a significant increase in blood levels of glucose, triglycerides, total cholesterol, and renal metabolites. Organ-specific changes were characterized by the development of fatty liver and kidney degeneration, adaptive reactions in the small intestine, and structural changes in the vascular system.
Flax (Linum usitatissimum L.) is a valuable agricultural crop and an important source of fiber and seeds necessary for industry and agriculture. The imperfect ascomycete Fusarium oxysporum is one of the most dangerous pathogens of flax. In the process of coevolution with plants, Fusarium oxysporum has developed several strategies at the molecular level to ensure successful infection. One such strategy is the use of small SIX effector proteins that facilitate infection and influence the host’s immune response. The authors of this work investigated the relationship between the expression patterns of DIM2 methyltransferase, five SIX genes, and the virulence level in three contrasting Folini strains: highly virulent MI39, medium-virulent F476, and weakly virulent F200. It was found that Folini infection releases genes SIX1 and SIX13, which are exclusively associated with the parasitic stage of development, and genes whose activity is increased outside the plant in MI39: SIX7ab, SIX10, and SIX12ab. The greatest difference in the expression of SIX genes between the resistant and susceptible varieties was observed on day 5 after inoculation with a highly virulent strain for the SIX12 and SIX13 genes, determining their possible role in the formation of the protective response of the resistant variety. A unique pattern of changes in the expression of the DIM2 DNA methyltransferase gene, with a high level at an early stage of infection development and a sharp drop on day 7 was found. DIM2 activity also significantly differed between contrasting flax varieties in the early and late stages of infection.
Flax is an important agricultural crop grown to produce fiber and oil. Depending on the purpose of cultivation, flax is divided by morphotype into fiber flax, characterized by a long stem with low branching, and linseed flax, which has a large number of seeds and inflorescences. Data from single-nucleotide polymorphisms are usually used to characterize samples with different morphotypes, however, analysis of the pattern of mobile element insertions can complement the picture, since mobile elements make up a significant part of the plant genome and are subjected to targeted selection along with single-nucleotide polymorphisms. In this study, we analyze the pattern of the location of new insertions of mobile elements in flax samples with different morphotypes and breeding status and identify sequences characteristic of different groups of samples. An analysis of the location of mobile elements in old-world and kryazhs varieties shows a relationship between the pattern of the distribution of insertions and climatic data, which confirms the presence of directional selection among the insertions.
All complex living organisms consist of two interconnected domains: information and energy (the brain and the systems of internal and external mobility of the body). Adaptation to the external environment is based on the perception and processing of information. The external actions of the organism are the result of the influence of the information system on the energy system. The cost of exchange transactions between the body’s domains can be defined as the biophysical multiplier effect in which there is an oscillatory exchange of energy quanta for quanta of the body’s characteristic action time. This cost varies during ontogenesis from childhood to old age. This explains age-related changes in the scales of perception of time and space intervals.
A new computational approach has been developed for predicting and prioritizing neoantigens, peptides that arise during tumor transformation and are promising candidates for creating anticancer vaccines. The IIS indicator is an integral indicator of immunogenicity that combines two key parameters: the affinity of the peptide to MHC I and its ability to elicit an immune response. The developed modular system, implemented in Python, uses an efficient computing strategy that includes a preliminary calculation of immunogenicity to reduce computational load. The platform supports analysis for both individual HLA alleles and population data, which allows it to be used to develop both personalized and universal vaccines. The results of the work include a ranked list of candidates with verification against the IEAtlas and IEDb databases. The system is available in an open repository on GitHub and represents a significant step forward in identifying targets for cancer immunotherapy.
The effect of UV radiation on bovine serum albumin solutions was studied, and differences in the photomodification of bovine serum albumin molecules in different media were revealed. The formation and properties of complexes formed by albumin and lysozyme molecules have been studied. A change in the spectral characteristics and hydrodynamic radius of protein complexes under the action of UV light is shown. It was found that a change in the ionic strength of the solution at pH 5.5 does not affect the absorption spectrum of albumin, which confirms the stability of its conformation. In the Na-phosphate buffer at pH 5.5, albumin exists mainly in the form of dimers with a hydrodynamic radius of 5.14 nm, while monomeric and dimeric forms are present in distilled water, which indicates the heterogeneity of the aggregate state of the system. It has been shown that UV irradiation causes dose-dependent photooxidation of tyrosine residues to form dityrosine, which is reflected in the albumin spectrum in the 300–320 nm band. At the same time, the photolability of albumin is higher in buffer than in water. Under the influence of UV light, the size and number of aggregates increase, which is associated with the destruction of intramolecular bonds and the formation of molten globules. The addition of lysozyme to albumin in buffer solution does not change the absorption spectrum of albumin at 250–290 nm. Molecular docking has shown that Trp, Tyr, and Phe residues are not shielded during the formation of the albumin–lysozyme complex. Hydrodynamic analysis confirmed the formation of an albumin–lysozyme complex ( 5 nm) predominantly with the monomeric form of albumin. UV irradiation affects the interaction of bovine serum albumin with lysozyme: at low doses (755 and 1510 J/m2), the optical density of the complex decreases, while complex formation is impeded at high doses (3020 J/m2). In the irradiated samples, lysozyme reduced the intensity of the aggregation of albumin molecules, which indicates its stabilizing role. In aqueous solutions, exposure to UV light reduced the size of the albumin–lysozyme monomer complex and promoted the formation of larger aggregates.
In type 2 diabetes mellitus, the regulation of blood flow oscillations in microvessels is disrupted by endogenous factors (products of lipid and carbohydrate metabolism, proinflammatory mediators, reactive oxygen species, etc.). At the same time, blood phagocytes show increased activity in the production of reactive oxygen species, but its association with microvascular disorders has not been established. The aim of the work is to evaluate the relationship between the processes regulating oscillations in blood flow in the microvessels of mouse skin and the kinetics of generation of reactive oxygen species in the blood. The object of the study is a model of type 2 diabetes mellitus in mice with monogenic obesity with the LEPR db/db mutation. The methods included laser Doppler flowmetry to register oscillations in blood flow and chemiluminescence analysis to measure the phagocytosis-dependent intensity of generation of reactive oxygen species. In type 2 diabetes mellitus, the normalized amplitude of oscillations in the myogenic frequency range was higher than in the controls. The kinetics of blood cell responses to opsonized zymosan was also changed: the amplitude, rate of development of the response, and production of reactive oxygen species increased; the lag period and Tmax decreased. Based on the Spearman rank correlation, strong correlations were found between the lag period of the response to zymosan and oscillations in cutaneous blood flow in the myogenic and Mayer intervals as well as between the rate of response and oscillations in the endothelial, neurogenic, and Mayer intervals in the controls. In mice with type 2 diabetes mellitus, a strong relationship was found between the response rate and oscillations in the neurogenic interval as well as between Tmax and oscillations in blood flow in the endothelial and neurogenic intervals. Thus, the development of type 2 diabetes mellitus affected the relationship of the regulatory components of microcirculation with the reactivity of blood cells, which may be a marker of metabolic disorders.
The most vulnerable stage of embryogenesis is the early embryonic period. It is here that natural selection for viability takes place, and it is here that the highest percentage of losses is observed—nature “checks” the viability of the embryo before allowing it to implant and begin to form a body. Solving the applied aspects of reproduction is closely related to the study of embryogenesis and the search for stimulating factors that target specific processes that determine the fate of the embryo and its potential for implantation at the blastocyst stage. In a model of early mouse embryos, premature embryo compactification was detected in the early stages of development in the presence of calcium ionophore A23187 (1.0 µM). Morphological signs of compactification appear 2 min after the addition of the ionophore and are accompanied by an increase in the concentration of cytosolic calcium (3.5 times). At the same time, the visible boundaries between the blastomeres disappear, and their contact area increases, which normally occurs in mammals at the late eight-cell stage. The observed effect under the influence of A23187 is reversible: after removing the ionophore from the environment, the morphology of the embryos is partially restored within 20–30 min. It has also been shown that A23187-induced compactification in the early stages stimulates in vitro development processes. In embryos that have been pretreated with an ionophore, the rate of cavitation increases, and hatching occurs faster compared to embryos that have not been exposed to A23187. It is concluded that a short-term sharp increase in intracellular calcium in the early stages of development is an incentive for triggering primary morphogenetic processes with the participation and control of the calcium-dependent phosphoinositol signaling cascade. Inhibition of the main components of phosphoinositol signaling leads to a delay in the onset of embryo cavitation, a dose-dependent decrease in the rate of cavitation or lack thereof when using a phospholipase C blocker, and a delay in the blastocyst in zona pellucida, which may indicate the inability of the embryo to implant in the uterus and continue its development.
The stability of binuclear dinitrosyl iron complexes with various thiol-containing ligands (glutathione, N-acetyl-L-cysteine, mercaptoethanol, mercaptosuccinate, and L-cysteine) exposed to air at room temperature and neutral pH, determined by the efficiency of oxygen oxidation of thiol-containing ligands, was evaluated. Complexes with glutathione and N-acetyl-L-cysteine were the most stable, while complexes with L-cysteine were the least stable. Similar ratios were obtained when evaluating the stability of the same complexes kept in aqueous solutions at pH 1–2, determined under these conditions by the protonation efficiency of the thiol group of thiol-containing ligands. The results obtained suggest the use of complexes with L-cysteine due to their low stability as the most effective donors of NO molecules and nitrosonium NO+ cations in experiments on the effects of binuclear dinitrosyl iron complexes on living organisms.
During radiotherapy of tumors, vessels of normal tissues can be in the irradiation zone. It has been shown that in this case, oxidative stress is initiated in the vessels, which subsequently leads to the development of atherosclerosis in them. In this work, the effect of low doses of ethanol on oxidative stress in the aorta of rats after irradiation was investigated. 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 evaluated by the oxidation of dichlorodihydrofluorescein. It has been shown that low doses of ethanol prevent an increase in the activity of angiotensin-converting enzyme and the formation of reactive oxygen species in the aorta of rats after irradiation. The effect depends on the dose of ethanol and the duration of exposure. With acute exposure (administration of ethanol into the mouth), the maximum effect is achieved 3 h before irradiation, and with chronic exposure (self-consumption of ethanol solutions by rats), the optimal dose decreases with increasing consumption time. The optimal dose of ethanol for chronic ethanol consumption (1 week) is 0.49 g /kg per day; it coincides with the dose that reduces the activity of angiotensin-converting enzyme in old animals and in animals treated with NO synthase inhibitor and dexamethasone, as well as with the dose that maximally reduces cardiovascular diseases in humans. The data obtained indicate the possibility of using low doses of ethanol to prevent vascular damage to normal tissues during radiotherapy of tumors.
