Biophysics最新文献

Aerosols made of highly charged nanoparticles of nonvolatile substances are of interest for the development of new highly effective methods of targeted drug delivery. However, for safe use, it is necessary to study their possible damaging effect on cell membranes. Human erythrocytes were selected as a model system. The experiments were carried out under conditions of partial dehydration of cells with exposure of a part of the surface of red blood cells to air to ensure contact of the sprayed particles with the cell membrane. It was found that while highly charged nanoaerosolic particles during direct electron spraying are capable of disrupting the structure of the lipid monolayer they do not cause damage to the cell membrane of erythrocytes. Thus, the results of this work can be used in the development of an electro-spraying method for the delivery of medicinal drugs to wound surfaces, the olfactory bulb, etc. The developed devices can also be used in studies of the interaction of nanoaerosols of various substances with the cell membrane.

The aim of this work was to evaluate the effects of gel materials containing taxifoline pentaglutarate and a conjugate of taxifolin with glyoxylic acid on the healing of skin wounds caused by acetic acid. It was shown that collagen materials containing polyphenols accelerated re-epithelialization and formation of granulation tissue compared with the control (collagen alone). The data obtained indicate that taxifolin derivatives can be considered as promising agents that not only cross-link collagen molecules, but also have a wound-healing effect. In turn, materials based on collagen and these polyphenols can be considered as dual purpose materials, that is, as wound-healing agents and as a delivery system of biologically active substances to the area of injury.

A new method has been developed that allows rats to use visual rather than olfactory or tactile information when searching for food. It has been found that visually impaired white Wistar rats are not well suited for experimental studies on learning related to visual images. There is no linear relationship between the time of foraging after 96 hours of fasting.

2,3-Diphosphoglycerate is present in large quantities in mammalian red blood cells and controls the affinity of hemoglobin to oxygen. The level of 2,3-diphosphoglycerate changes with the development of certain pathologies, such as chronic lung diseases, anemia, and hyperthyroidism. 31P NMR spectroscopy has shown that reducing the number of washings of rat erythrocytes significantly increases the stability of 2,3-diphosphoglycerate in these samples. The level of 2,3-diphosphoglycerate does not change for 3.5 h with a single wash and for 4 h without washing. At the same time, with standard double washing, the content of 2,3-diphosphoglycerate decreases after 2.5 h. Analysis of its distribution between red blood cells and removed plasma, as well as analysis of the serum of one animal, showed that all the 2,3-diphosphoglycerate remains in the suspension of red blood cells and is absent in the plasma and serum. The results we obtained should be taken into account when working with intact erythrocytes.

The development of cryopreservation methods for testicular spermatozoa makes it possible to safely and economically reproduce genetically diverse agricultural and numerous endangered animal species. The effect of the TSKY peptide (Thr–Ser–Lys–Tyr) isolated from the brains of winter-sleeping ground squirrels (Spermophillus undulatus) in a state of deep hibernation on the physiological activity of bovine sperm cells was studied. A decrease in the activity of bovine rapidly moving spermatozoa was shown when the TSKY peptide was added at the thawing stage after cryopreservation of reproductive cells in liquid nitrogen (–196°C).

Binuclear dinitrosyl iron complexes with cysteine, which are donors of nitrosonium (NO+) cations, exhibit high antitumor activity when exposed to a formed tumor (Lewis lung carcinoma) with a mass of 0.42 g (12 days after grafting), causing an 11-day inhibition of tumor growth by 90% and an increase in the time of doubling the tumor mass by 9.3 times compared with the control. At the early stage of the administration of the complexes, on the next day after the tumor grafting, their noticeable effect on the tumor growth rate was not observed. It is assumed that the difference in the antitumor effect of dinitrosyl iron complexes with cysteine, depending on the size of the tumor, is due to the different ratio between the level of immunocompetent cells (macrophages) that selectively tolerate these complexes and retain this ability, and the concentration of tumor cells that accept the complexes. Upon late administration of dinitrosyl iron complexes with cysteine, this ratio increases due to a decrease in the number of tumor cells available to immunocompetent cells, it is limited to cells localized only in the peripheral (“surface”) layer of the tumor.

The possible role of the formation of intracellular reactive oxygen species in the cytotoxic effect of gold (aurumacryl) and silver (argacryl) polyacrylates on tumor cells (an MCF7 cell culture) was studied. For this purpose, the effect of the antioxidant N-acetyl cysteine, known as a free radical scavenger, on the cytotoxic effect of drugs and on the value of the specific reactive oxygen species marker was investigated. Argacryl was found to have higher cytotoxic activity than aurumacryl, with an IC50 coefficient of 55 and 300 μg/mL, respectively, at 24 h exposure. It has been shown that the generation of reactive oxygen species is one of the key mechanisms in realizing the cytotoxic effect of aurumacryl, while the cytotoxic effect of argacryl is not associated with the production of intracellular reactive oxygen species in tumor cells under the influence of the drug. These results indicate that gold and silver polyacrylates, as active cytotoxic agents, have significant differences in the mechanism of action due to the nature of the metals contained in the preparations, which is in good agreement with the data we obtained earlier.

Pathological changes in blood vessels in diabetes are determined by oxidative stress. The effect of flavonoids on oxidative stress in blood vessels in diabetes has not been studied. In this work, we investigated the effect of flavononol dihydroquercetin on blood glucose levels, the activity of angiotensin converting enzyme, and the formation of reactive oxygen species in the aorta of rats with alloxan-induced diabetes. The activity of the angiotensin converting enzyme in the aortic segments was determined by the hydrolysis of hypuryl-L-histidyl-L-leucine and the formation of reactive oxygen species was evaluated by the oxidation of dichlorodihydrofluorescein. It has been shown that dihydroquercetin reduces blood glucose levels, angiotensin-converting enzyme activity, and formation of reactive oxygen species in the aorta of diabetic rats to the values of these parameters in the aorta of control rats. Dihydroquercetin also normalizes the glucose tolerance test in diabetic rats. The effects of dihydroquercetin disappear after stopping its consumption. Thus, dihydroquercetin may be useful for the treatment of diabetes, but its consumption should be continuous.

In this work, the state of mitochondria in neurons of the lateral vestibular nucleus of Deiters in mice after 8-hour vestibular stimulation was studied. It was shown that significant changes occurred in the mitochondria of Deiters neurons one hour after stimulation: an increase in area, disruption of the cristae structure, and the presence of mitophagosomes. At the same time, the level of mRNA of proteins-markers of mitochondrial biogenesis (PGC-1α), their division (DRP-1), and the fusion of the outer and inner mitochondrial membranes (MFN1, MFN2, OPA) increased, indicating the activation of mitogenesis in Deiters neurons as a result of stimulation of the vestibular system. The introduction per os of betahistine 30 min before stimulation at a dose of 300 mg/kg prevented mitochondrial disruptions and the formation of mitophagosomes. The obtained data indicate that under increased vestibular stimulation, Deiters neurons can undergo significant damage. The revealed mechanisms of mitochondrial damage allow us to define a potential strategy for the treatment of diseases associated with impaired mitochondrial dynamics (e.g., neurodegenerative diseases or ischemia).

Heat shock protein Hsp90 is an important cellular chaperone that contributes to the folding, stabilization, and regulation of specific target proteins involved in many cellular processes. Mammalian cells contain two isoforms of Hsp90, the inducible isoform Hsp90α and the constitutive isoform Hsp90β. Recently, we showed that knockout of the HP90AB1 gene encoding Hsp90β in human HT1080 fibrosarcoma cells (Hsp90β-KO cells) did not affect cell proliferation as well as resistance to heat shock and oxidative stress, while slightly reduced cell migration. This indicates the adaptation of cells and the cellular chaperone machinery to the loss of one of the key cellular chaperones, Hsp90β. In this work, using real-time quantitative PCR and Western blotting, we found that knockout of the gene encoding Hsp90β was accompanied by changes in the expression and content of individual chaperones and co-chaperones associated with Hsp90 and Hsp70 chaperone machineries. In the HSP90 family of chaperones/co-chaperones, an increase in the expression and content of the cytosolic isoform of Hsp90α remaining in the cell and upregulation of a number of important Hsp90 co-chaperones (FKBP4 and HOP) were observed. The expression and content of key chaperones, inducible Hsp70, constitutive Hsc70, and mitochondrial GRP75, were significantly increased in the HSP70 family of chaperones/co-chaperones. As a result, some mechanisms of adaptation of Hsp90 and Hsp70 chaperone machineries in response to the loss of one of the key chaperones, Hsp90β, by cells have been established for the first time. The Hsp90β-KO cells we created that do not express Hsp90β can be considered as a cellular model of pharmacological inhibition of Hsp90β function by promising Hsp90β-specific inhibitors created for tumor therapy. The revealed changes in Hsp90- and Hsp70-associated chaperones and co-chaperones in response to the loss of Hsp90β demonstrate probable changes in the cellular chaperone machinery in response to the suppression of Hsp90β by such inhibitors and can be taken into account when developing combined therapeutic strategies using Hsp90β-specific inhibitors.