Vol 69, No 4 (2024)

Knowledge of the nature of intermolecular interactions and amino acid residues unveiling their origin is necessary to enable alteration of the stability of intermolecular complexes. In this work, using Nt.BspD6I nickase as an example, it was shown that hydrophobic interactions have an influence on the protein’s ability to oligomerization and that chemical and geometric complementarity of external surfaces is a necessary condition for the formation of stable homo complexes.

The method for the extraction of quercetin from plant cells with the use of ultrasound in combination with metastable fraction from aqueous solution is proposed. The procedure enabled more efficient isolation of the cytoplasmic part due to etching and/or mechanical destruction of the cell membrane. The oxidized water fraction has the most pronounced extracting properties, but changes the properties of quercetin by oxidizing the chromophore part of the molecule. According to the criterion of pigment preservation, the best extraction solution is the reduced water fraction. To analyze the extract samples the following analytical methods were used: UV-Vis spectrometry, protein gel electrophoresis, 1H-NMR spectrometry, and QCM weighing, as well as scanning electron microscopy.

This review discusses the current understanding of the molecular mechanisms of pathological hyperexcitation and synchronization of neuronal networks in epileptogenesis, including potassium, GABA, membrane (cellular), and synaptic (network) models. The focus of these models is the disturbance of the balance between excitation and inhibition involving multiple positive and negative feedback loops (PFL/NFL) in neuronal networks. This paper considers current ideas about (1) the robustness of dynamical systems with many NFLs, and (2) degeneracy, i.e., the ability of heterogeneous elements (channels, currents) to replace each other, as the basis for the stable functioning of hyperexcited networks in channelopathies and ion channel hyperexpression. In this work, a potential mechanism of spontaneous seizure onset and potassium accumulation in the intercellular space is proposed; it is based on potassium- and calcium-induced activation of a group of cation channels (HCN, Kir2.x, hERG, Nav1.х, and ВКСа) and ensures the robustness and high sensitivity of epileptiform activity to external and internal factors due to degeneracy and PFLs formation.

Rotenone, Rhodamine 123, and Janus green B, inhibitors of mitochondria function, are currently investigated to create pharmacological agents that induce mitochondrial dysfunction and apoptosis. Since impaired mitochondrial function is associated with overproduction of reactive oxygen species, it seems relevant to compare DNA damage induced by the said inhibitors in Ehrlich ascites carcinoma cells and murine lymphocytic leukemia P388 and DNA damage induced by the direct effect of ionizing radiation (X-rays) that induces an increase of reactive oxygen species. The alkaline comet assay was used for measuring the level of DNA damage. The level of Rotenone-induced DNA damage was comparable to that one induced by very low-dose radiation (4 Gy) for both cell types. Post-irradiation incubation of cells led to a reduction in the level of DNA damage, indicating that damage to DNA is repaired. Treatment of Ehrlich ascites carcinoma cells with Rhodamine 123 and subsequent washing them for removal of excess dye did not cause an increase in the level of DNA damage, however, exposure to very low dose radiation (4 Gy) in the presence of Rhodamine 123 induced an increase in the level of DNA damage, which was significantly reduced after 1-hour incubation. It can be assumed that pre-treatment of cells with Rotenone or Rhodamine 123 that disrupt mitochondrial function contributed to the maintenance of the integrity of nuclear DNA in irradiated cells. Exposure to Janus green B caused an increase in the level of DNA damage and cell death. The alkaline comet assay revealed that damage induced by these compounds can be considered single- and double-strand breaks and alkali-labile (apurinic/apyrimidinic) sites in DNA.

The review is devoted to modern ideas about paraptosis, as one of the types of regulated cell death, in comparison with other types of cell death. Paraptosis is a form of cell death caused by endoplasmic reticulum stress, accompanied by an accumulation of damaged or misfolded proteins, extensive non-autophagic vacuolation of cisterns of endoplasmic reticulum and, in some cases, mitochondria, with subsequent damage to mitochondria, the cytoskeleton, and cell death. The knowledge regarding the molecular mechanisms of paraptosis is of interest for the treatment of cancers resistant to apoptosis-inducing agents.

Responses triggered by change/novelty of the stimuli are fundamental to adaptive behavior. By comparing the current observation with the previous one, living organisms can make predictions and change their actions. Brain mechanisms and its structures involved in the comparator function have not yet been fully elucidated. The evidence accumulated emphasizes the particular importance of the hippocampus in the comparator system; it is shown that novelty detection is carried out by hippocampal neurons through the implementation of the match-mismatch mechanism or divergence. This paper includes information on existing hypotheses that propose how these mechanisms are implemented, what other brain structures are involved in mismatch detection, how they are connected to the hippocampus, and what processes contribute to this function. It is assumed, in particular, that it is not novelty per se, but rather that one that contrasts with previously acquired experience and initiates the process of divergence. The arguments are analyzed that the theta rhythm plays a key role in the functioning of the hippocampus as a comparator. Theta oscillations caused by the appearance of a new signal/change in the environment, mediate, in particular, the mechanism of temporal coordination of structures involved in the comparator function. In the comparator system, the theta rhythm acts as a filter: it participates in the selection and transmission of a new signal to registration of information in the hippocampus. Increases in theta oscillations and their coherence in brain structures that process new information serve as a signal of mismatch, facilitating a change in behavioral strategy. Gamma-oscillations, like the theta rhythm, also play a significant role in the comparator system: during generation of the theta rhythm in the prefrontal cortex, temporal coincidence of gamma-oscillations in other brain regions with certain phase of the thetha cycle may serve as the comparator function in the process of memorization. A deeper understanding of the mechanisms of the comparator function or mechanisms of its damage will give us a better idea about the treatment of disorders, such as schizophrenia, Alzheimer’s disease, temporal lobe epilepsy and many others.

The effects of uridine and its monophosphoryl derivative both on the level of the main biochemical markers of myocardial damage in the blood and the electrical activity of the heart were investigated in a rat model of cardiomyopathy induced by isoprenaline. It was shown that the administration of isoprenaline (150 mg/kg, subcutaneously) caused an increase in the activity of serum enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT), leading to the elevated AST/ALT ratio or De Ritis ratio, and enhanced activity of lactate dehydrogenase in blood lymphocytes, which confirms the development of myocardial damage in experimental animals. ECG analysis has revealed prolonged RR, P-R, QT, QTc intervals and QRS complex, which indicates that the duration of depolarization and repolarization phases increases relative to the duration of the cardiac cycle in rats with isoprenaline-induced myocardial damage. Preliminary administration of uridine and uridine-5'-monophosphate to experimental animals at a dose of 30 mg/kg equally effectively prevented an increase in the enzymatic activity of AST and the De Ritis ratio, led to a decrease in the duration of P-R, QRS, QT and QTc intervals as well as to partial normalization of metabolic activity of rat blood lymphocytes. These findings suggest that uridine and uridine-5'-monophosphate have a similar protective effect on the contractile function of cardiomyocytes and can be used as agents for metabolic therapy in the treatment of ischemic heart disease.

The use of ultra-high dose-rate ionizing radiation, termed FLASH irradiation (≥40 Gy/s), contributes to healthy tissue sparing while maintaining tumor control compared to conventional dose rate irradiation. This review summarizes current knowledge dedicated to studies of tumor and normal cell lines, animals including tumor-bearing ones irradiated in conventional and FLASH dose rate irradiation modes. As a comparison, data on FLASH irradiation with photons, electrons, protons, helium and carbon ions are also presented. The biophysical, molecular biological and immunological aspects of FLASH effect which are essential for understanding the radiation-induced processes in cells and tissues in order to improve radiotherapy of tumors are discussed.

The effects on induction of cytogenetic damage to mouse bone marrow, generation of reactive oxygen species by whole blood cells, and on the thymus and spleen from exposure of mice to total-body proton radiation before and at the Bragg peak with a dose deposition of 0.1–1.5 Gy were investigated depending on the linear rate of energy loss. It was found that the level of polychromatophilic erythrocytes with micronuclei at all doses of proton radiation at the Bragg peak with the linear energy transfer 2.5 keV/μm was close to that of polychromatophilic erythrocytes with micronuclei for the corresponding doses of X-ray radiation with the linear rate of energy loss 2.0 keV/μm, and the level of cytogenetic damage induced by exposure to proton radiation up to the Bragg peak with the linear energy transfer 0.7 keV/μm was significantly lower. The coefficient of the relative biological effectiveness of proton irradiation calculated from the linear energy transfer by estimating micronuclei frequency at and before the Bragg peak was 1.15 and 0.63, respectively. Organ-specific differences in the patterns of pathophysiological effects on the thymus, spleen of mice and the state of the antioxidant system of blood cells depending on the linear energy transfer of protons were revealed by varying radiation doses.

Ongoing research continues to explore the phenomenology of the effect of synchronization between oscillations of a human resting heart rate and variations of the geomagnetic field in the period range 3–40 minutes. A total of 508 experiments have been conducted for the period 2012–2023 (each experiment lasted 100–120 minutes) to monitor the minute indicators of heart rate for three healthy women (55, 45, and 30 years old). 328, 113, and 67 measurements were made, respectively. The results indicate that, for each of these three volunteers, approximately 60% of the experiments yielded a wavelet spectrum of heart rate values that closely resembled the spectrum of synchronous variations of at least one of the horizontal components of the geomagnetic field (X or Y). Additionally, within the investigated frequency range of 3–40 minutes, three subbands were identified and in these sub-bands, the degree of synchrony of oscillations was maximal: 3.5 minutes, 10–12 minutes and 33–36 minutes. It can be concluded that the effect of biogeosynchronization is not uniformly implemented over the entire range from 3 to 40 minutes, but it is mainly evident in these sub-bands.