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.

The effect of the Thr–Ser–Lys–Tyr peptide isolated from the brain of the obligate hibernating long-tailed ground squirrel Urocitellus undulatus (formerly Citellus undulatus, Spermophilus undulatus) on the polymerization/depolymerization of actin in vitro was studied by electron microscopy. Upon incubation of the peptide with globular (monomeric) actin at concentrations of 0.1 mg/mL (at a ratio of 1 : 1), the formation of single filaments of actin was observed. When the peptide was added to the formed actin filaments, no effects were observed, in particular, actin depolymerization. The possible involvement of the peptide in the polymerization of actin in vivo and a possible contribution to the restoration of the functional activity of the central nervous system after the hibernating animal leaves the state of hypothermia are discussed.

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).

The pioneer SOX2 transcription factor plays an important role in the regulation of gene expression by binding to condensed chromatin and inducing its decondensation. Experimental data on the preferred positions of SOX2 binding to DNA in the context of the nucleosome are contradictory: in some studies, binding to the inner segments of nucleosomal DNA is preferred, in others it binds to the edge segments. In the framework of this work, all possible variants of SOX2 binding to nucleosomal DNA at different distances from the nucleosome center (determined by the superhelix position parameter, SHL) and different orientations of the binding site relative to the nucleosome center (determined by the SHL sign) were analyzed by molecular modeling. It was shown that on an intact nucleosome binding is possible at positions SHL +2, SHL ±4, and SHL ±5, but if we assume a shift of nucleosomal DNA by one pair of nucleotides, binding becomes possible at positions corresponding to all integer values of the SHL. This observation helps to explain some of the contradictions between the experimental data.

The α-subunits of the Kv1.2 potassium voltage-gated channel, whose function is to regulate neuronal conductivity in the central nervous system, form heterotetramers with α-subunits of related Kv1 channels, which differ in composition and stoichiometry. To study heterotetrameric channels in vitro, concatemers have been constructed by sequentially connecting the Kv1 α-subunits. The method for constructing concatemers that allow reproducing the properties of native channels requires detailed study. In this work, concatemers (dimers) of Kv1.2 α-subunits (mKate2-Kv1.2-Kv1.2) labeled with the fluorescent protein mKate2 were constructed and their expression was carried out in mouse neuroblastoma Neuro-2a cells. It was shown that the Kv1.2 channel assembled from concatemers is almost identical in its properties, namely, intracellular distribution, ability to integrate into the plasma membrane, efficiency of interaction with a peptide blocker, as well as in its electrophysiological characteristics, to the Kv1.2 channel based on monomeric mKate2-Kv1.2 α-subunits.

It has been shown that the conversion of the nitrosonium (NO+) cation into the NO molecule in sodium nitroprusside under the action of a strong reducing agent, sodium dithionite, does not completely suppress the cytotoxic effect of sodium nitroprusside solution as a NO+ donor on MCF-7 tumor cell culture. The fact is that NO molecules and Fe2+ ions released from nitroprusside under these conditions form, together with thiol-containing ligands (thiosulfate as a degradation product of sodium dithionite and thiol groups of proteins), dinitrosyl iron complexes in which half of the nitrosyl ligands are represented in the form of cytotoxic nitrosonium cations. The amount of dinitrosyl iron complexes formed in this process is more than 3 times lower than the initial level of sodium nitroprusside and is the main reason for the weakening of the cytotoxic effect of sodium nitroprusside solution on cell culture.

The results of an in situ (leaves) study of electron transport in chloroplasts of two plant species of the genus Cucumis, the shade-tolerant species C. sativus (cucumber) and a light-loving species C. melo (melon) grown under conditions of strong (800–1000 μmoles m–2 s–1 of photons) and moderate (50–125 μmoles m–2s–1 of photons) illumination are described. The processes of electron transport were monitored by the electron paramagnetic resonance (EPR) signal from $${\text{P}}_{{{\text{700}}}}^{ + }$$ (the oxidized reaction center of photosystem 1), by light absorption (the difference signal A870–830 from $${\text{P}}_{{{\text{700}}}}^{ + }$$ ), and by the fluorescence yield of chlorophyll a. It has been shown that plants grown at high light intensity are characterized by faster changes in the redox state of Р700 compared to plants grown at low (moderate) light intensity. The data obtained are discussed in the context of the mechanisms of regulation of electron transport in chloroplasts of shade-tolerant and light-loving plant species of the genus Cucumis.

Using an experimental model of dysbiosis caused by the antibiotic gentamicin sulfate, the effect of low-intensity electromagnetic radiation of extremely high frequencies (42.2 GHz, 100 µW/cm2, pulse modulation by a meander with a frequency of 1 Hz, exposure for 30 min per day for 10 consecutive days, starting from the 4th day after induction of dysbiosis) on the fatty acid composition of the thymus, blood plasma, activity of antioxidant enzymes, the content of malondialdehyde and lactate in the blood of laboratory rats was studied. A significant decrease in the content of myristic, palmitic, stearic, palmitoleic, oleic and linoleic fatty acids in the thymus of animals was shown. The activity of antioxidant enzymes, the content of fatty acids and malonic dialdehyde in the blood did not change. The content of lactate in the blood plasma decreased. Irradiation of animals with dysbiosis normalized the fatty acid composition of the thymus and the content of lactate in plasma. The high efficiency of low-intensity extremely-high-frequency electromagnetic radiation with certain parameters in dysbiosis opens up fundamentally new possibilities for using radiation in this range for the prevention and treatment of a number of pathological conditions associated with dysbiosis.

Intracellular heat shock protein 90 (Hsp90) performs important functions related to the folding, stabilization, and degradation of various proteins in the cell, and prevents protein aggregation and denaturation under various types of stress. There are two isoforms of Hsp90, that is, the inducible Hsp90α isoform and the constitutive Hsp90β isoform. Hsp90β is thought to play a key role in the functioning of housekeeping proteins, while Hsp90α plays an important role in the cellular response to stress. We explored the roles of two Hsp90 isoforms in the resistance of human HT1080 fibrosarcoma cells to Hsp90 inhibitors and a number of antitumor drugs with different mechanisms of action for the first time. Both Hsp90 isoforms have been shown to make a comparable contribution to cell resistance to Hsp90 inhibitors and one Hsp90 isoform is not able to completely compensate for the absence of another Hsp90 isoform under the influence of Hsp90 inhibitors. Both Hsp90 isoforms are also involved in cell resistance to cytotoxic anticancer drugs, with Hsp90α likely playing a more important role than Hsp90β in protecting cells from the cytotoxic effects of sorafemib and nocodazole. For cisplatin, each of the Hsp90 isoforms is able to largely compensate for the absence of the other isoform. For doxorubicin, bortezomib, sorafenib, paclitaxel, and nocodazole, the absence of one of the Hsp90 isoforms led to a significant decrease in cell resistance to anticancer drugs, which was especially pronounced in the case of paclitaxel and nocodazole. The Hsp90 inhibitor 17-AAG potentiates the effect of cytotoxic drugs on cells, providing the most pronounced synergy with paclitaxel and nocodazole. As a result, the important role of both Hsp90 isoforms in cell resistance to Hsp90 inhibitors and anticancer drugs with different mechanisms of action was determined for the first time. The data we obtained indicate the prospects of developing Hsp90α- or Hsp90β-specific inhibitors for antitumor therapy and their combined use with known antitumor drugs.

Fluorescent confocal microscopy has shown the presence of the family of septin proteins types 2, 3, 5, 7, and 9 in the somatic muscle of the earthworm Lumbricus terrestris. Septins of types 2 and 9 lack their specific concentration in the cholinergic synapse zone, whereas septins of types 3 and 5, and especially type 7, have a quantitatively expressed binding localization at the zone of the motor end plate. It is assumed that septins of types 3 and 5 and, above all, type 7 may be participants in the mechanisms of modulation of the quantal secretion of the mediator.