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The viscosity of plasma and mitochondrial membranes of hepatocytes was studied in young (3-month-old) and old (9-month-old) male Wistar rats. It was shown that viscosity of hepatocyte plasma and mitochondrial membranes in young rats under optimal vital functions in the area of protein—lipid membrane contacts was significantly lower than in old rats. No age-related differences in the viscosity of lipid—lipid membrane contacts and in the polarity of protein—lipid contacts and lipid layers were found. Liver cirrhosis induced by carbon tetrachloride and ethanol administration was associated with increased fluidity of the plasma and mitochondrial membranes of hepatocytes in rats of both age groups. The decrease in membrane viscosity in young rats occurred due to a decrease of the viscosity in the area of protein—lipid and lipid—lipid contacts, while in old rats in the area of protein—lipid contacts. Carbon tetrachloride and ethanol did not affect the polarity of lipid contacts and lipid layers.

We studied the age-related characteristics of the response of stem cells and liver in male Wistar rats to administration of carbon tetrachloride (CCl4) and ethanol. It was shown that modeling of liver cirrhosis caused inflammation, fibrosis, damage to sinusoidal capillaries, necrosis, and disturbances in the functional activity of hepatocytes in young rats. These processes were accompanied by mobilization of profibrotic mesenchymal stem cells (MSC), proinflammatory hematopoietic stem cells (HSC) and lymphocytes (CD45hiCD133+) from the bone marrow into the blood and migration to the liver. On the other hand, the number of hepatocyte precursors expressing Sox9 (cells of Hering's canal), immature cholangiocytes, Ito cells, oval cells, and endothelial cells of the liver sinusoids) sharply increased in the liver. In young rats, mobilization and migration of MSC, HSC, and hepatocyte precursors against the background of liver cirrhosis were more intensive than in old animals. The higher resistance of old rats to exposure is associated with age-related changes in the niches as well as in mobilization and migration of cells.

For evaluation of the effect of high-fat diet on the development of diabetic complications, the rats were maintained on standard or high-fat diet. In 3 weeks, diabetes mellitus was modeled by single intraperitoneal injection of streptozotocin. Changes in hematological parameters, physical and biochemical parameters of the urine, and in the development of thermal allodynia were different after 15-week standard and high-fat diets.

We studied the formation of injuries in lung endothelium and the response of angiogenesis cells during modeling of pulmonary emphysema in male and female C57BL/6 mice with metabolic disorders. Hemodynamic disturbances and reduction in the area of the microvasculature caused by combined pathology in male mice were more pronounced than in females. Mobilization and migration of angiogenic precursors were impaired in both male and female mice. In males, activity of recruiting endothelial progenitor cells, vascular smooth muscle cells, luminal cells of nascent vessels and pericytes into the lungs was additionally reduced. In females, accumulation of endothelial progenitor cells (CD45-CD31+CD34+), vascular smooth muscle cells, and pericytes in the lungs was observed, which indicated activation of endothelial regeneration. Sex differences in the reaction of the lung endothelium and angiogenesis cells can be explained by genetic factors of lipid and glucose metabolism.

We studied the effects of spiperone, a selective blocker of dopamine D2 receptors, on the model of pulmonary emphysema provoked by administration of elastase and D-galactosamine hydrochloride to female C57BL/6 mice and characterized by activation of proteases in the lungs and systemic deficiency of its inhibitor α1-antitrypsin. In this model, spiperone prevented the development of inflammatory reaction and reduced the area of emphysematous expanded alveolar tissue. The expression of angiogenic marker CD31 in the lungs increased under these conditions. Regeneration of the damaged microvascular bed under the action of spiperone resulted from recruiting of Notch1+ endothelial progenitor cells (CD45-CD31+CD34+) into the lungs and blockade of the inhibitory effect of dopamine on phosphorylation of VEGF-2 receptors in endothelial cells of different maturity. In addition, spiperone produced a protective effect on hepatocytes and restored the production and secretion of α1-antitrypsin by these cells.

Various stem cells were studied in female BALB/c mice at the early terms after administration of N-methyl-N-nitrosourea to search early diagnostic markers and therapeutic targets. At these terms, damage to the epithelium and endothelium, inflammation, and fibrosis were observed in the mammary gland, but the tumor was not detected. Cancer stem cells, hematopoietic stem cells (HSC), hematopoietic progenitor cells, angiogenic precursors, and epithelial progenitor cells were found in the blood and mammary gland. Cancer stem cells (CD44

We studied the formation of injuries in lung endothelium and the response of angiogenesis cells during modeling of pulmonary emphysema in male and female C57BL/6 mice with metabolic disorders. Hemodynamic disturbances and reduction in the area of the microvasculature caused by combined pathology in male mice were more pronounced than in females. Mobilization and migration of angiogenic precursors were impaired in both male and female mice. In males, activity of recruiting endothelial progenitor cells, vascular smooth muscle cells, luminal cells of nascent vessels and pericytes into the lungs was additionally reduced. In females, accumulation of endothelial progenitor cells (CD45

We studied the effects of elastase, cigarette smoke extract, D-galactosamine hydrochloride, and tyrosine kinase inhibitor SU5416 on endothelial progenitor cells and angiogenesis precursors, as well as on Notch-1 expression by immature endothelial cells. Simultaneously with pulmonary emphysema, different damaging factors with diverse mechanisms of action caused pathological changes in the microvascular network of the lungs and destroyed the alveolar endothelium in female C57Bl/6 mice. D-galactosamine hydrochloride disturbed mobilization of endothelial progenitor cells expressing VEGFR (CD45-CD309+) and angiogenesis progenitors (CD45-CD309+CD117+) and their migration into emphysema expanded lungs. Elastase inhibited VEGFR-expressing endothelial progenitor cells, while cigarette smoke extract inhibited cells with CD45-CD31+CD34+ phenotype. In pulmonary emphysema provoked by elastase or D-galactosamine hydrochloride, angiogenesis was provided by endothelial cells with CD45-CD31+CD34+ phenotype, whereas in emphysema modeled with SU5416 or cigarette smoke extract, it was provided by the endothelial VEGFR-expressing cells and mature CD31+ endothelial cells, respectively. Replenishment of immature endothelial cells damaged by elastase and SU5416 involved Notch-1+ angiogenesis precursors and Notch-1+ endothelial progenitor cells with VEGFR.

Biological activity of a new pegylated form of an of glucagon-like peptide-1 (GLP-1) analogue pegGLP-1 was studied in C57Bl/6 mice under normal conditions and during modeling of streptozotocin-induced type I diabetes mellitus. pegGLP-1 differs from GLP-1 (7-37) by polyethylene glycol residue covalently bound to His7, Lys26, and Lys34 of the GLP-1 molecule. It was shown that single intragastrical administration of pegGLP-1 induced an increase in GLP-1 level in blood serum of healthy mice. The maximum level of this parameter was observed in 4-8 h. pegGLP-1 elimination half-time was 8.5 h and mean retention time was 15 h. Administration of pegGLP-1 to animals with modeled type I diabetes mellitus was followed by an increase in the levels of GLP-1 and insulin in blood serum, produced a hypoglycemic effect, and improved the parameters of glucose-tolerance test. Biological activity of pegGLP-1 was higher than activity of GLP-1.

The regenerative potential of stem and progenitor cells from ischemic testes of C57Bl/6 mice was studied in vitro (cell culture) and in vivo (mouse model of busulfan-induced suppression of spermatogenesis). Spermatogonial stem cells with phenotypes CD117-CD90+ and CD51-CD24+CD52+ from ischemic testes demonstrated 33-fold and 7-fold increments of cell mass and generated colonies in vitro. Epithelial (CD45-CD31-Sca-1+CD49f+) and endothelial (CD45-CD31+) precursors exhibited lower self-renewal capacity. On day 30 after injection of stem and progenitor cells from ischemic testes to the rete testis zone of the testes of busulfantreated animals, an increase in the count of CD117-CD90+ spermatogonial stem cells, total count, and mobile sperm count in the testes of recipient mice was observed. In addition, we observed an increase in Sca-1+ cell count, recovery of the spermatogenic epithelium in the seminiferous tubules, and appearance of immature Leydig cells in "busulfan" testes; the level of tissue testosterone and fertility index also increased.