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GIZh-298 pharmacokinetics was studied in rats after different dosage regimens.The aim of this study was to study GIZh-298 pharmacokinetics after its multiple intragastric administration.Methods. The study was conducted on outbred male rats. The concentrations of GIZh-298 in the blood plasma were determined by HPLC with mass-spectrometric detection. Pharmacokinetic parameters were evaluated using a model-independent method.Results. After single and multiple (4 times with a dosage interval of 3 hours) intragastric administrations at 60 mg/kg dose, the test substance in the blood plasma was determined for 4 hours. The mode of administration of GIZh-298 did not affect the value of its half-life and the mean residence time. It has been established that GIZh-298 accumulates in the rats.

Current global warming and climate change under the greenhouse effect call for a thorough understanding of the spatial distribution of greenhouse gases in different atmospheric layers. Lidar systems are the most effective for remote greenhouse gas monitoring. We design a two-channel infrared OPO lidar optical system for remote DIAL/DOAS sensing of carbon dioxide and water vapor in the atmosphere. In this work, optimal geometric parameters of the transceiving channel of the lidar optical system are chosen, a need to focus laser radiation at a distance of 1 km from an observation point is demonstrated, and numerical simulations confirm the possibility of detecting lidar signals ranging from 10−7 to 10−10 W in the informative spectral range 4800–5100 cm−1 (1960–2083 nm). Laboratory experiments with the main components of the lidar system with experimentally confirmed parameters, which simulate atmospheric measurements of CO2 absorption at a calibrated sensing wavelength of 2005 nm (4987 cm−1) (pressure of 1 atm; CO2 concentration corresponding to the midlatitude summer background atmosphere) in the informative spectral range of the lidar system, enable selecting a pair of wavelengths with resonant absorption of the target gas near 2005 nm to study the background state of the atmosphere in the surface layer. Efficiency of the lidar optical system is confirmed by in situ test experiments, where backscattering signals from a topographic target with an albedo of ∼0.15 spaced 168 m apart from an observer are recorded at 60 mV when operating along a horizontal atmospheric path. The lidar system we design can be used in measuring complexes at carbon test sites. It can also be used for atmospheric monitoring in industrial centers, at background measuring stations, and in swamp areas.

The third article in a series of publications devoted to the results of studying the current radiation situation in the territories of the Bryansk region bordering the Republic of Belarus presents results of studies of the content of radionuclides (137Cs and 90Sr) in samples of agricultural food products produced in the personal subsidiary plots of the population. The regularities of changing 137Cs and 90Sr content in samples of cow’s milk and potatoes depending on the level of radioactive contamination of the territory were studied; the present values of the quantities characterizing the distribution of the ratio of the activity concentration of radionuclides in agricultural food products to the density of radioactive contamination of the soil of the territory were deter -mined. The ratios of average values of 137Cs activity concentration in milk from stalled and grazing periods for cattle were analyzed. The results of the study show that some dairy product samples (less than 1%) do not meet the radiological safety criterion. Exceedances of the hygienic standards were not found in the studied samples of potatoes, vegetables, and meat of farm animals.

Introduction. Today, prevalence of neurodegenerative diseases increases. In recent years, more studies have revealed a new knowledge about the role of microglia in the development of these diseases. Animal experiments showed that peripheral inflammation causes activation of microglia in brain. All this points to the essential role of the cells in the development of neurodegeneration. Under the influence of various factors, microglia can change the phenotype and participate in both repair and damage to brain cells. Chronic herpesvirus infection caused by HSV-1 is another known factor in the development of neurodegenerative pathology. However, the exact pathogenetic mechanisms are still unknown, nevertheless, studying the virus effect on microglia has great potential. The goal of our study in this connection was to assess the effect of HSV-1 on microglia polarization in mouse strain with normal susceptibility to this virus and in strain which is more resistant to the action of HSV-1. For this purpose, changes in the cytokine profile were detected. A comparison of interstrain differences in the expression of cytokine genes was also compared in control groups. Materials and methods. The study involved infecting C57BL/6 and BALB/c mice with herpes simplex virus type 1, an isolation of microglia was based on separation steps using a discontinuous gradient density, the cytokine profile was assessed by gene expression levels using a real-time reverse transcription PCR. To calculate the relative fold gene expression of samples the 2–ΔΔCt method was used. Statistical significance was determined using the Mann–Whitney U-test. Results. There were found no interstrain differences in cytokine gene expression in control groups of different mouse strains. At the same time, gene expression differed in the experimental groups: in BALB/c mice, the expression of genes for both pro-inflammatory and anti-inflammatory cytokines increased; in C57BL/6 mice, a slight increase in the expression of IL-1β genes was observed. Conclusion. The data indicate the formation of different microglial phenotypes after HSV-1 infection in different mouse strains. Apparently, in BALB/c mice there is a switch from the pro-inflammatory M1 phenotype of microglia to the anti-inflammatory M2 phenotype, while in C57BL/6 mice the attenuation of the infectious process occurs through a return to the original M0 phenotype.

We present the results of near-Earth interplanetary space, magnetosphere, and atmosphere monitoring during large-scale solar wind disturbances at the end of August 2005. The monitoring was carried out using ground-level cosmic ray (CR) observations made at the worldwide network of neutron monitors as well as muon telescopes in Yakutsk and Novosibirsk. As a result of the analysis performed by different methods, we have obtained variation properties of CRs of different rigidities in Earth’s orbit, their pitch angle anisotropy, orientation and configuration of the interplanetary magnetic field, changes in the planetary system of geomagnetic cutoff rigidities during geomagnetic disturbances, as well as mass average air temperature over CR stations equipped with muon telescopes. For the periods of geomagnetic disturbances, we have determined parameters of magnetospheric ring current and magnetopause currents.

The pharmacokinetics of a new antiparkinsonian drug ADK-1113 after single intravenous and intragastric administrations in mice at doses of 10 and 20 mg/kg was studied. The absolute bioavailability was 10.1–16.3 % that indicates on potential possibility of preparing a dosage form for oral administration.

Introduction. It has been established that the presence of homologous recombination deficiency in a breast tumor is associated with the effectiveness of treatment. But despite the high chemosensitivity of the tumor to DNA-damaging agents, complete pathological responses to treatment are very rare. And this process may be based on a change in the somatic status of BRCA1, that is, a reversion and return of the wild-type allele occurs and the DNA repair function is restored.Aim. To evaluate changes in the presence of chromosomal aberrations and the expression profile of the main genes of homologous recombination in cell models of breast cancer under the influence of cisplatin and docetaxel.Materials and methods. The study was conducted on breast cancer tumor cell cultures: MCF-7, MDA-MB-231 and MDA-MB-468. A cell model of drug resistance was obtained for two drugs: cisplatin and docetaxel. RNA and DNA were isolated from cell suspension using the RNeasy Plus Mini Kit and QIAamp DNA Mini Kit (Qiagen, Germany), respectively. The expression level of homologous recombination genes was assessed using reverse transcription polymerase chain reaction. To assess the presence of chromosomal aberrations, microarray analysis was performed on DNA chips.Results. Restoration of normal copy number for the BRCA1, CDK12, CHEK1 and RAD51D genes in MCF-7 under the influence of cisplatin was shown. For BRCA2 and PALB2, amplifications were detected. A statistically significant increase in the expression of the BRCA1 (p = 0.04), BRCA2 (p = 0.02), PALB2 (p = 0.01) and RAD51D (p = 0.05) genes was also shown. MDAMB-231 shows that all identified loci with deletions, where the BRCA2, BARD1, CHEK2, PALB2 and RAD54L genes are localized, are restored to normal copy number by cisplatin. The appearance of amplifications was registered for BRCA1, BRIP1, FANCL, RAD51B, PARP1. A similar result was shown for docetaxel. An increase in the expression level is typical for the genes BRCA1 (p = 0.02), BRCA2 (p = 0.02), CHEK2 (p = 0.05), FANCL (p = 0.04), PALB2 (p = 0.05), RAD51C (p = 0.02), PARP1 (p = 0.02), which corresponds to the appearance of amplifications. In the MDA-MB-468 cell culture, an increase in the copy number of only the BRCA1 gene is observed. The effect of docetaxel has no effect on this cell culture. The level of BRCA1 expression increases in direct proportion to the duration of drug action.Conclusion. Thus, the study showed that under the influence of cisplatin, reversion of not only homologous recombination gene mutations, but also other disorders can occur.

Summary: The inwardly rectifying K+ channel Kir5.1 (Kcnj16) is essential in renal salt handling and blood pressure control. However, the underlying mechanisms are not fully understood. Here, we integrated transcriptomics and metabolomics to comprehensively profile the changes in genes and metabolites in the Dahl salt-sensitive (SS) rat lacking Kcnj16 to identify potential mechanisms. Consistent with the phenotype of knockout (KO) rats, the transcriptomic profile predicted reduced blood pressure, kidney damage, and increased ion transport. Canonical pathway analysis suggested activation of metabolic-related pathways while suppression of immune response-related pathways in KO rats. Untargeted metabolomic analysis revealed different metabolic profiles between wild-type (WT) and KO rats. Integration of transcriptomic and metabolomic profiles suggested altered tricarboxylic acid (TCA) cycle, amino acid metabolism, and reactive oxygen species (ROS) metabolism that are related to SS hypertension. In conclusion, besides increased ion transport, our data suggest suppressed immune response-related and altered metabolic-related pathways of SS rats lacking Kir5.1.

Mast cell tumour is one of the most common cutaneous neoplasms in dogs, ranging from well differentiated to aggressive tumors with metastases. Currently, prognosis and therapeutic definitions of canine cutaneous MCTs are based on the histological grade of malignancy. Clinical examination and treatment were performed in Dnipro veterinary clinics and pathological analysis in the Department of Animal Anatomy, Histology and Pathomorphology, Dnipro State Agrarian and Economic University (Dnipro, Ukraine). Thirty-six dogs with a history of skin neoplasia were examined. Skin MCTs were diagnosed in 23 males and 13 females, aged between 5 and 15 years. No breed predisposition was found out in tested cohort. MCTs were located on the trunk (44.4%), limbs (33.4%) and less frequently on the head and neck, axillary, inguinal and perineal areas (22.2%). MCT was detected in 8 animals where the malignancy was systemic and develops metastatic spread to internal organs. Pathological diagnosis included cytopathological examination of tumor material, pathological analysis of samples obtained by incisional biopsy using haematoxylin/eosin and toluidine blue staining. According to the diagnostic criteria (smear cellularity, presence of cells with basophilic cytoplasmic granularity, size and number of cytoplasmic granules, presence or absence of mitotic figures, nuclear pleomorphism, presence or absence of binucleations or multinucleations, anisokaryosis), benign mast cell tumour (high grade) was diagnosed in 23 animals and malignant mast cell tumour (low grade) in 13 animals. These results were confirmed by histopathological methods using haematoxylin and eosin staining. Additional staining of histological sections with toluidine blue allowed differentiation of benign mast cell tumours into high-grade (38.9%) and intermediate-grade (5%).

Abstract To date, numerous mechanisms have been identified in which one cell engulfs another, resulting in the creation of ‘cell-in-cell’ (CIC) structures, which subsequently cause cell death. One of the mechanisms of formation of these structures is entosis, which is presumably associated with possible carcinogenesis and tumour progression. The peculiarity of the process is that entotic cells themselves actively invade the host cell, and afterwards have several possible variants of fate. Entotic formations are structures where one cell is engulfed by another cell, creating a cell-in-cell structure. The nucleus of the outer cell has a crescent shape, while the inner cell is surrounded by a large entotic vacuole. These characteristics differentiate entosis from cell cannibalism. It’s worth noting that entotic formations are not necessarily harmful and may even be beneficial in some cases. In this article we will consider the mechanism of entosis and variants of entotic cell death, and also put forward hypothesis about possible variants of participation of this process on the formation and progression of cancer. This article also presents our proposed classification of functional forms of entosis.

The article examines the peculiarities of reproduction of archetypes in the translation of an artistic work. The interpretation of the concept of ‘archetype’, its classifi cations and levels of its mental representation in the text are studied herein. While examining the issue of universal and ethnocultural archetypes, the author of the article introduces the term ‘culturally determined archetypes’. The article contains the proposals as to the actions that are to be taken by a translator in the process of reproduction of the source language archetype in the target language, outlines what exactly it is necessary to pay attention to in order to properly translate the archetype. It is noted that if the archetypes are translated inadequately or inaccurately, the integrity of the literary work may be violated due to the partial loss of the symbolic meaning, or the emotional impact on the reader. It is proposed to include the archetypal analysis of the source and target texts to the translation studies analysis.

Relevance. To introduce the GK-2 compound into clinical practice, it is necessary to conduct a preclinical study of its pharmacokinetics, in particular, the distribution of the studied drug in organs and tissues. The aim is to study the tissue availability of a new original compound GK-2 in rats after its intraperitoneal administration. Methods. Quantitative determination of GK-2 in blood plasma and organ/tissue homogenates of rats was carried out by high-performance liquid chromatography with mass spectrometric detection. Results. The distribution of GK-2 in organs and tissues with varying degrees of vascularization was studied in rats. It was found that after a single intraperitoneal injection of GK-2 at a dose of 150 mg/kg, the studied compound was recorded in blood plasma for 2 hours, its half-life (t1/2el) was 0.4 hours. In organs and tissues, GK-2 was detected from 1.5 to 2 hours. The tissue availability of GK-2 in the liver — blood plasma system was 18.68; "kidneys — blood plasma" — 1.26; "spleen — blood plasma" — 0.68; "skeletal muscles — blood plasma" — 0.31. For the target organ, the brain, the tissue availability was 0.24. In the brain, the time to reach the maximum concentration of GK-2 (0.77 mcg/g) was 0.34 hours. It was found that GK-2 is excreted more slowly from the brain (t1/2el was 0.75 h) than from other organs and tissues (from 0.31 h for the spleen and up to 0.47 h for the kidneys).

This study presents results of radiation-hygienic surveys of the Bryansk Oblast settlements bordering the Republic of Belarus. The data were obtained in the course of implementation of measures of the “Program of joint activities of Russia and Belarus within the framework of the Union State for the protection of the population and rehabilitation of the territories affected by the Chernobyl NPP accident” in 2019–2022. The second part of the study presents structure of population’s food preferences (diet). A general description of the diets of residents is given and the main types of local food products at the present stage of the radiation accident are identified. The current levels of consumption of locally produced food (and products of local origin) by residents of different age categories have been assessed. The obtained results of assessing the levels of food consumption have been compared with our own results of earlier studies and with the results of studies on the population of Russia and Belarus. Similarly with previous years, among agricultural food products the most consumed products are milk and potatoes and among natural food products are mushrooms. The established levels of consumption of local dairy products and beef have decreased over the past ten years and the resident consumptions of mushrooms and potatoes are in the same levels as before.

Abstract Sodium-glucose co-transporters (SGLTs) in the kidneys play a pivotal role in glucose reabsorption. Several clinical and population-based studies revealed the beneficial effects of SGLT2 inhibition on hypertension. Recent work from our lab provided significant new insight into the role of SGLT2 inhibition in a non-diabetic model of salt-sensitive hypertension, Dahl salt-sensitive (SS) rats. Dapagliflozin (Dapa) blunted the development of salt-induced hypertension by causing glucosuria and natriuresis without changes in the Renin–Angiotensin–Aldosterone System. However, our initial study used male SS rats only, and the effect of SGLT2 inhibitors on hypertension in females has not been studied. Therefore, the goal of this study was to determine whether SGLT2 inhibition alters blood pressure and kidney function in female Dahl SS rats. The result showed that administration of Dapa for 3 weeks prevented the progression of salt-induced hypertension in female rats, similar to its effects in male SS rats. Diuresis and glucose excretion were significantly increased in Dapa-treated rats. SGLT2 inhibition also significantly attenuated kidney but not heart fibrosis. Despite significant effects on blood pressure, Dapa treatment caused minor changes to electrolyte balance and no effects on kidney and heart weights were observed. Our data suggest that SGLT2 inhibition in a non-diabetic model of salt-sensitive hypertension blunts the development of salt-induced hypertension independent of sex.

Purpose. To investigate the anthropogenic communication of the Cherkasy oblast as an ecosystem-forming component of the modern landscape structure of the area of research. Research materials and methods. Methods. On the principle of natural-anthropogenic coexistence general scientific and specific scientific research methods were applied. Results. The peculiarities of natural conditions and natural resources are determined by the geographical location within the borders of the Dniester-Dnieper and Left Bank-Dnieper forest-steppe regions of the East European plain country. The class of road landscapes of the study area is formed by the following types of roads, namely: automobile, dirt, forest and field roads, railways. In the landscape structure of Zvenyhorod district, the length of highways, unpaved roads, field and forest roads, railways. Uman district and Cherkasy district have the highest index of connectivity in terms of road length. The lowest indicators of the index of communication in terms of the length of highways in Zolotoniskyi district. Uman district has the highest index of communication in terms of the length of dirt roads, and Zvenigorodsky district has the lowest. Zolotoniskyi district and Cherkasy district have the highest index of communication in terms of the length of field and forest roads. The lowest indicator is Zvenigorodsky district, Uman district. Cherkasy district has the highest communication index in terms of railway length and Zvenigorodsky district has the lowest. Conclusions. The Zolotonisky district of Cherkasy region has the highest index of general anthropogenic communicability, i.e. it has the highest degree of anthropogenic transformation of the territory and anthropogenic load

Calcium propionate, as an approved food additive, is widely used as a mold inhibitor in food and feed. It is recognized as safe, but when metabolized in the gastrointestinal tract, it can affect the body’s metabolism both directly and indirectly through the intestinal microbiota. The effect of various doses of calcium propionate on the body of model animals, with the study of the quantitative and qualitative composition of their intestinal microbiome, was investigated in this experiment. Four groups of male laboratory rats were formed, which for 20 days consumed: a high-fat diet with the addition of 0.0%, 0.5%, 1.0%, 2.0% calcium propionoate. We determined changes in body weight, the condition and mass indices of the internal organs, biochemical blood parameters, the functional state of the nervous system using the “open field” method, as well as changes in the intestinal microbiota. Adding calcium propionate to a high-fat diet does not affect the rate of animals’ weight gain, nor the amount of feed and water consumed. High dose consumption of calcium propionate caused a decrease in the relative weight of the spleen and an increase in the relative weight of the kidneys, without affecting the functional state of the nervous system. With the addition of calcium propionate to a high-fat diet, only minor changes in some biochemical blood parameters were observed (increased De Ritis ratio and Ca/P ratio, moderate dyslipidemia). Calcium propionate had the most significant changes in the quantitative and qualitative composition of the intestinal microbiota in laboratory rats. Among the representatives of the microflora, the most sensitive to this substance against the background of a high-fat diet were obligate microorganisms from the genera Bifidobacterium and Lactobacillus. The antimicrobial action of calcium propionate was also demonstrated by the pathogenic Staphylococcus aureus. Amid a deficiency of obligate microflora, proliferation of transient microflora was found – facultative anaerobic and aerobic microorganisms (bacteria of the genera Klebsiella, Enterococcus, Clostridium, fungi of the genus Candida). Further research will be aimed at studying the effect of calcium propionate in various doses on the biological systems of different age group laboratory animals in a long-term experiment.

The pharmacokinetics of dimeric dipeptide mimetic of nerve growth factor GC-2 in the rat blood plasma after different routes of administration was studied. The drug was administered at dose of 150 mg/kg by single and repeatedly. After single intravenous and intraperitoneal injection, GC-2 was detected for 2 h, its half-life was 0.4 h. GC-2 absolute bioavailability after single intraperitoneal injection was 84.62 %, that indicates the prospect of development its injectable (intramuscularly) dosage form. After 4-fold (1.5 h dosing interval) intraperitoneal injection dose-independent pharmacokinetic parameters of GC-2 practically do not change compared to single administration. This indicates that GC-2 is not accumulated in the body of rats. The hypothesis of the linearity of the pharmacokinetics of GC-2 in the rats blood plasma after single intraperitoneal administration at doses of 50, 100 and 150 mg/kg was tested. It was found that the kinetics of GC-2 in the rat blood plasma is linea.

The diversity of macroinvertebrates, the structure of their communities in Bolshiye Koty Bay (Lake Baikal) was studied by a DNA metabarcoding approach using an Illumina MiSeq system. Internal primer mlCOIintF in combination with jgHCO2198 of the Folmer fragment of the COI gene were used for macroinvertebrate metabarcoding. A total of 118009 reads of the COI gene fragment (at least 313 bp in length) were obtained. The correlation of the Spearman coefficient (S = 0.6, p < 0.05) with the abundance of macroinvertebrates in the samples before DNA extraction showed that the number of reads can serve as an indirect characteristic of the abundance of a species (operational taxonomic unit, OTU). 115 OTUs belonging to the higher taxa of macroinvertebrates were identified: Porifera, 1; Platyhelminthes, 3; Annelida, 38; Arthropoda, 55; Mollusca, 18. At a high level of resolution (with homology with GenBank reference sequences ≥ 95 %, coverage ≥ 90 %), 46 taxa of macroinvertebrates comprising three communities were registered: one dominated by molluscs (Choanomphalus conf. maacki) and two dominated by chironomids (Orthocladius grega rius Linev., Sergentia baicalensis Tshern.). Communities are characterized by low species diversity according to Shannon (from 0.7 to 1.2 bits), high concentration of dominance according to Simpson (from 0.5 to 0.7) and low evenness according to Pielou (from 0.3 to 0.4). Dominants and subdominants in the communities account for 91 to 96 % of COI gene fragment reads. The spatial distribution of the dominant species identified in the communities is influenced by the geomorphological features of the bottom and the composition of sediments in the area studied. The approach proposed for studying the structure of macroinvertebrate communities based on DNA metabarcoding and next generation sequencing can be recommended for express assessment of the state of aquatic ecosystems in the monitoring.