Biophysics最新文献

The use of ionizing radiation at an ultra-high dose rate (≥40 Gy/s), which is called FLASH irradiation, contributes to the preservation of healthy tissues with a level of tumor control comparable to that of irradiation at a standard dose rate. This review summarizes the current knowledge obtained in studies of irradiation of tumor and normal cell lines and animals, including tumor carriers, in conventional and FLASH modes. For comparison, data on FLASH irradiation with photons, electrons, and protons, as well as ions of helium and carbon, are also provided. The biophysical, molecular biological, and immunological aspects of FLASH exposure necessary for understanding radiation-induced processes in cells and tissues in order to improve tumor radiotherapy are discussed.

The effect of high-energy (660 MeV) proton irradiation at the phasotron accelerator in FLASH mode (80 Gy/s) compared with the standard proton exposure power of 3.0 Gy/min was studied. When irradiated in two modes at doses of 1.0 and 1.5 Gy, the induction of cytogenetic damage in bone marrow cells and the state of lymphoid organs (thymus and spleen) were evaluated; survival under total in vivo irradiation of mice was analyzed at doses of 7.0 and 8.0 Gy. The growth rate of a model tumor under ex vivo irradiation was determined at doses of 40 and 60 Gy. It has been shown that irradiation of animals in the FLASH mode at a dose of 1.5 Gy protected the proliferative activity of the spleen and also led to a decrease in cytogenetic damage in bone marrow erythrocytes according to the micronucleus test compared with the standard irradiation mode at a dose of 1.5 Gy, that is, a milder effect of the FLASH mode dose was observed. However, irradiation of mice in FLASH mode at high doses (7.0 and 8.0 Gy) led to earlier death of animals compared to the standard irradiation regime. A tumor node formed with further growth only after FLASH irradiation of a suspension of Ehrlich ascites carcinoma at a dose of 40 Gy; in all other groups a tumor was not formed.

The mitochondrial inhibitors rotenone and rhodamine 123 and the Janus Green B dye are being studied in order to develop pharmacological agents that cause mitochondrial dysfunction and apoptosis. Since mitochondrial dysfunction is associated with the production of reactive oxygen species, it seems relevant to compare the DNA damage induced by these substances to cells of ascitic Ehrlich carcinoma and murine lymphocytic leukemia P388 with exposure to a known inducer of reactive oxygen species, that is, ionizing (X-ray) radiation. The level of DNA damage was assessed using an alkaline version of the Comet assay. The level of DNA damage induced by rotenone was comparable to irradiation at a dose of 4 Gy in both cell types. Post-radiation incubation reduced the level of DNA damage, which indicates DNA repair. Treatment of Ehrlich’s ascitic carcinoma cells with rhodamine 123 followed by washing did not cause this increase; however, irradiation at a dose of 4 Gy in the presence of rhodamine 123 induced an increase in the level of DNA damage, which significantly decreased after 1 h incubation. It can be assumed that pretreatment of cells with rotenone and rhodamine 123, which impair the work of mitochondria, contributed to the preservation of the integrity of nuclear DNA in irradiated cells. Exposure to Janus Green B caused increased DNA damage and cell death. Based on the alkaline version of the Comet assay, damage induced by these compounds can be considered as single- and double-strand breaks and alkali-labile (apurine/apirimidine) sites in DNA.

A method of extraction of quercetin from a plant cell based on the combined action of ultrasound and a metastable fraction of an aqueous solution is proposed. This treatment leads to more efficient release of the cytoplasmic component due to etching and/or mechanical destruction of the plant cell envelope. The oxidized fraction of the solution has the most pronounced extractive properties; however, it acts on quercetin by oxidizing the chromophore part of the molecule. According to the criterion of pigment preservation, the best extraction medium is the reduced fraction of water. Analytical methods were used to analyze the extract samples: UV-Vis spectroscopy, gel electrophoresis of proteins, ¹H NMR spectroscopy, and QCM weighing, as well as scanning electron microscopy.

The aim of this study was to evaluate the kinetic parameters of the oxidation of some 3-aminopyridine-2(1H)-ones by hydrogen peroxide catalyzed by horseradish peroxidase and the affinity of horseradish peroxidase to these compounds. It has been shown that the oxidation of 3-aminopyridine-2(1H)-ones follows kinetics of the pseudo-first order. A hyperbolic decrease in the observed reaction rate constant (k_obs) was also found with an increase in the initial concentration of 3-aminopyridine-2(1H)-ones. The dependence of k_obs on the concentration of the enzyme was linear, suggesting competitive inhibition of oxidation by the reaction product. It was found that an increase in the polarity of the substituent in the fourth position leads to an increase in the rate of oxidation of pyridinones. V_max/K_m values were also higher for compounds carrying polar substituents in the fourth position. This kinetic parameter (V_max/K_m) reflects the substrate specificity of the enzyme. The data we obtained clarify the mechanisms of interaction between horseradish peroxidase and 3-aminopyridinones and suggest that 3-aminopyridinones can be used to develop sensitive methods for the detection of hydrogen peroxide and modification of immune enzyme analysis techniques.

Detecting environmental changes/novelty is of basic importance for adaptive behavior. By comparing the current context with the previous one, living organisms can make predictions and adjust their actions. The mechanisms and structures of the brain involved in the function of comparison have not yet been sufficiently elucidated. The available studies emphasize the special contribution of the hippocampus to the process of comparison; it is indicated that the identification of novelty is carried out by hippocampal neurons through the mechanisms of match/mismatch, or misalignment. Here, we provide information about existing hypotheses of how these mechanisms occur, which other brain structures are involved in detecting inconsistencies, how they are related to the hippocampus, and what processes contribute to this. In particular, it is assumed that it is not novelty in itself, but only novelty that contrasts with previously acquired experience that initiates the process of misalignment. The arguments that the theta rhythm plays a crucial role in the functioning of the hippocampus as a comparator are analyzed. Theta oscillations caused by the appearance of a new signal or a change in a situation mediate the mechanism of temporal coordination of structures involved in the comparison function. In comparison, the theta rhythm functions as an active filter: it participates in the selection and transmission of a new signal to the registration system in the hippocampus. An increase in theta oscillations and their coherence in the brain structures processing new information serves as a signal of misalignment, facilitating a change in behavior strategy. In addition to theta rhythm, gamma oscillations are also involved in comparison: during the generation of theta rhythm in the prefrontal cortex, the temporary coincidence of gamma oscillations in other areas of the brain with a certain phase of the theta cycle can perform the function of comparison during the memorization process. A deep understanding of the mechanisms of comparator function and its disorders can help in the treatment of pathologies such as schizophrenia, Alzheimer’s disease, and temporal lobe epilepsy.

Previously, we showed that taxifolin derivatives, taxifolin pentaglutarate and a conjugate of taxifolin with glyoxylic acid, improve the mechanical properties of collagen-based materials. In the process of degradation of such materials, biologically active polyphenols are released into the surrounding medium. Two approaches were used to assess the penetration of polyphenols through damaged skin. In the case of taxifolin pentaglutarate and taxifolin (used for comparison), a fluorescent label was introduced into the structure of the polyphenol. In the case of the conjugate, a fluorescent analogue was obtained. It has been shown that the application of polyphenolic compounds on the damaged skin leads to the formation of a fluorescent layer on its surface. Fluorescent derivatives of taxifolin and taxifolin pentaglutarate have been found to accumulate in hair follicles. In the case of taxifolin, fluorescence was observed in deeper layers of the dermis than in the case of taxifolin pentaglutarate, indicating better penetration of taxifolin. The fluorescent analog accumulated in the appendages of the skin to a lesser extent than other compounds. Thus, the data we obtained indicate the accumulation of polyphenols in the hair follicles, from which they can gradually be released into the surrounding tissue. In general, the results we obtained indicate that biologically active polyphenols are able to exert a prolonged effect when applied topically. This may be important in the treatment of burns, in particular in the treatment of second-degree burns, in which many skin derivatives remain intact.

Transplantation of immature nerve tissue is a promising biotechnological approach to repair damaged brain tissue. The success of transplantation therapy depends on a genetic program for the differentiation of donor neuronal precursors and the accuracy of neural connections both in the neurotransplants themselves and in the recipient’s brain. The degree of specificity of synaptic contacts during transplantation of the hippocampal formation into the rat neocortex was studied. Using the method of electron microscopy, it was shown that in the transplants themselves mainly specific forms of synapses were differentiated, which were topographically correctly located on the soma-dendritic surface of neurons. The axons of the transplanted neurons growing into the recipient’s brain formed synaptic contacts with normally unusual neurons. During the formation of nonspecific axonal connections, they modified the composition and distribution of neurotransmitter vesicles in presynaptic terminals, as well as inducing structural and chemical reorganization in postsynaptic dendrites.

The effectiveness of ¹H-NMR-based metabolomic analysis for the detection of metabolic changes during carcinogenesis was assessed based on a comparison of the quantitative composition of metabolites in the blood plasma of healthy rats and rats that receiving M-1 sarcoma grafts. Plasma was collected from the rats under study on day 12 and day 36 after sarcoma transplantation to identify metabolites associated with tumor development. Analysis of the NMR spectra using multivariate statistical methods showed differences in the composition of metabolites for the groups of animals under study as soon as on day 12 after sarcoma transplantation; on day 36 the differences were significant. Twenty three metabolites were quantified. On day 12, only the lactate and allantoin levels were significantly different between the groups, while on day 36, the levels of nine metabolites were different between the two groups. All of the identified metabolites are involved in cancer metabolism, which makes ¹H-NMR spectroscopy a promising method for cancer diagnosis.