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The responses of tumor stem cells and various populations of CD4 and CD8 T cells of young and aged C57BL/6 mice were studied in a lung cancer model. Using Lewis lung carcinoma cell line, an orthotopic model of lung cancer was modeled. Cancer stem cells, circulating tumor cells, and various populations of CD4 and CD8 T cells in the blood and lung tissue were studied by cytometry. We revealed age-related differences in the content of various populations of CD4 and CD8 T cells in the blood and lungs of intact young and aged mice. Age-related features of the reaction of various populations of cancer stem cells and CD4 and CD8 T cells in the blood and lungs of animals in the Lewis lung carcinoma were shown., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Regenerative processes in the liver were studied in 3-month-old (young) and 9-month-old (aged) male Wistar rats on day 1 after 30 and 70% hepatectomy. Regardless of the resected liver volume, shifts in the biochemical parameters of the serum in aged rats were more pronounced than in young animals. After 30% hepatectomy, no age differences in the rate of hepatic regeneration were found, while after 70% liver resection this parameter was higher in young rats. Hepatectomy in young rats led to recruitment of MSC, hepatocyte precursors, endothelial and epithelial progenitor cells into the liver parenchyma and increased fluidity of the plasma and mitochondrial membranes of hepatocytes. In aged rats, the recruitment of MSC, hepatocyte precursors, and endothelial progenitor cells into the injured liver was impaired and the rigidity of the mitochondrial membranes of hepatocytes increased., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

We studied the effects of the extract of the terrestrial part of Aconitum baicalense in BALB/c female mice at the early stages after the injection of N-methyl-N-nitrosourea (MNU). The extract reduced inflammatory activity and tumor growth in the mammary gland. The antitumor and anti-inflammatory effects of the extract are based on the inhibition of cancer stem cells, hematopoietic stem cells, and hematopoietic progenitor cells that promote inflammation. The extract of A. baicalense disrupted the recruitment of epithelial progenitor cells and angiogenesis precursors to the mammary gland preventing neovascularization and transformation of epithelial cells into tumor cells., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

The effect of ketanserin on inflammation, liver fibrosis, and microviscosity of the plasma and mitochondrial membranes of hepatocytes was studied on young (3 months) and old (9 months) male Wistar rats with experimental liver cirrhosis. Ketanserin reduced inflammation, area of the connective tissue, and liver damage and improved serum biochemical parameters in rats of both age groups; in old rats, the effects were more pronounced than in young animals. In old rats, ketanserin reduced polarity of hepatocyte plasma and mitochondrial membranes in the area of protein-lipid contacts, which determined higher effectiveness of ketanserin during the treatment of liver cirrhosis in aged animals., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

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 + CD24 - ) are proposed as the early diagnostic marker of breast cancer, and short-living HSC, hematopoietic progenitor cells, and angiogenic precursors (CD45-CD117 + FLK-1 + ) as predictors of the formation of tumor microenvironment., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

We studied the age-related characteristics of the response of stem cells and liver in male Wistar rats to administration of carbon tetrachloride (CCl 4 ) 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 (CD45 hi CD133 + ) 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.

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.

The changes in endothelial progenitor cells and progenitor cells of angiogenesis, pericytes and smooth muscle cells, were studied in female C57BL/6 mice with a combination of metabolic impairments induced by injections of sodium glutamate and lung emphysema modeled by the administration of cigarette smoke extract. It was observed that sodium glutamate significantly enhances pathological changes in the lungs (inflammation and lung emphysema) induced by the administration of cigarette smoke extract. Recruiting of endothelial progenitor cells (CD45 - CD31 + CD34 + and CD31 + CD34 + CD146 - ) and progenitor cells of angiogenesis (CD45 - CD117 + CD309 + ) was registered in the injured lungs. Angiogenesis impairment induced by combined exposure is related to altered migration of pericytes (CD31 - CD34 - CD146 + ) and smooth muscle cells (CD31 - CD34 + CD146 + ) in emphysema-like enlarged lung tissue.

The title of the article should read:"Role of β Cell Precursors in the Regeneration of Insulin-Producing Pancreatic β Cells under the Influence of the Pegylated Form of Glucagon-Like Peptide 1".

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.

The effects of the pegylated form of glucagon-like peptide 1 (pegGLP-1) on oligopotent β cell precursors (CD45 - TER119 - CD133 + CD49f low ) in the pancreas were studied in C57Bl/6 mice. Under conditions of streptozotocin-induced type 1 diabetes mellitus, intraperitoneal injection of pegGLP1 increased the content of β cell precursors and dithizone-stained cells in the pancreas. β Cell precursors of mice with diabetes demonstrated high self-maintenance potential. In contrast to pegGLP-1, native GLP-1 did not affect β cell precursors in diabetic animals. Treatment of a culture of β cell precursors from mice with diabetes induced the yield of dithizone-stained mononuclears. In conditioned mediums of dithizone-positive cells obtained as a result of differentiation of β cell precursors from mice with diabetes, insulin was detected after administration of pegGLP-1 (10 -7 M) and glucose (3 mmol/liter); the level of insulin increased with increasing glucose concentration (to 20 mmol/liter). The in vitro effect of pegGLP-1 did not differ from the effect of GLP-1 (10 -7 M).

Course administration streptozotocin to male C57Bl/6 mice induces a complex of symptoms typical of type 1 diabetes mellitus: hyperglycemia and insulin deficiency, focal inflammatory infiltration of the pancreas, destructive changes in the Langerhans islets, damage to the insular apparatus (reduced number of PDX1 + cells and insulin expression by the secreting cells). Male reproductive disorder are serious complications of type 1 diabetes mellitus. In "diabetic" mice, interstitial edema with inflammatory infiltration and microvascular disorders in the testicular tissue are observed, the number of endothelial precursors (CD45 - /CD31 + ) and the total number and percentage of motile spermatozoa decreased, immature spermatogenic epithelium cells are desquamated of into the lumen of the tubules. Disturbances in the proliferation and differentiation of various spermatogonial stem cell populations (c-kit - /CD90 + , c-kit + /CD90 + , and CD51 - /CD24 + /CD52 + ) in diabetes can be explained by the inhibitory influence of inflammatory factors on testosterone-producing Leydig cells.

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 His 7 , Lys 26 , and Lys 34 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 properties of spermatogonial stem cells, endothelial progenitor cells, and the epithelial progenitors of C57Bl/6 mice under conditions of metabolic disorders were studied using the model of busulfan-induced suppression of spermatogenesis and in vitro culture technique. Spermatogonial stem cells CD117-CD90 + and epithelial progenitors CD45-CD31-Sca-1 + CD49f + derived from the testes of mice with metabolic disturbances demonstrated 17- and 28-fold increase in the respective cell mass and generated cell colonies in vitro. In contrast, spermatogonial stem cells with immune phenotype CD51-CD24 + CD52 + had reduced selfrenewal capacity. Spermatogonial stem cells CD117-CD90 + and CD117 + CD90 + as well as endothelial progenitors CD45-CD31 + derived from the testes of donor mice with metabolic disorders demonstrated high transplantation capacity in C57Bl/6 mouse testes damaged by cytostatic busulfan.

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.

Using the model of hypogonadism in C57Bl/6 male mice, we showed that injection of streptozotocin to newborn animals and high-fat diet induced serum IFN-γ and IL-17 elevation, glucose metabolism disturbances, insulin resistance, destructive changes of the Langerhans islets (deficit of PDX1 + β cells), while the number of oligopotent β cell precursors (CD45 - TER119 - CD133 + CD49f low ) increased. Diabetes played the role of an inducer of testicular tissue inflammation (pan-hemopoietic cell infiltration, increase of IL-2, IL-17, and IL-23 content) and reproductive system disturbances in mice (decrease in free testosterone concentration, suppression of spermatogenesis, and infertility). The development of hypogonadism was paralleled by an increase in the count of spermatogonial stem cells (CD117 + CD29 + CD90 + ), multipotent mesenchymal stromal cells (CD45 - CD31 - CD90 + CD106 + ), hemangiogenesis precursors (CD45 - CD117 + Flk1 + ), and epithelial cells (CD45 - CD31 - CD49f + CD326 + ).

Inflammation, extracellular matrix proteins (hydroxyproline, connective tissue growth factor, collagen, and fibronectin), stem and progenitor cells (multipotent mesenchymal stromal cells, Clara cells, angiogenesis, precursors, endothelial and epithelial cells) were studied in female C57Bl/6 mice with experimental elastase-induced emphysema. Diffuse emphysema reduced the number of endothelial (CD45(-)CD31(+)CD34(+)) and epithelial (CD45(-)CD117(+)CD49f(+)) cells, induced microcirculation disturbances, and decreased the area occupied by the connective tissue. Emphysematous changes in the lungs were accompanied by infiltration of the alveolar septa with macrophages and lymphocytes, increase in the serum and lung concentrations of transforming growth factor-β, IL-1β, IL-2, IL-5, IL-10, and IL-13, and lung concentration of IL-17. In the lungs, inflammation was associated with marked increase in the number of multipotent mesenchymal stromal cells CD90(+)CD73(+)CD106(+)CD44(+)) and Clara cells (CD45(-)CD34(-)CD31(-)Sca1(+)) and overexpression of extracellular matrix proteins (hydroxyproline, connective tissue growth factor, collagen, fibronectin) and Clara cells protein. On the other hand, elastase reduced the number of angiogenic precursor cells (CD45(-)CD117(+)Flk1(+)).

Stem and progenitor cells were studied on mouse model of testicular ischemia. Testicular ischemia led to a decrease in free testosterone concentration. Hemodynamic changes, interstitial edema, and destruction of spermatogenic epithelium, Leydig, and Sertoli cells were observed in the testicular tissue. Accumulation of degenerative germ cells was accompanied by reduction in the count of spermatogonial stem cells with immunophenotype CD117(-)CD29(+)CD90(+) and CD117(+)CD29(+)CD90(+). Simultaneously with pathomorphological changes in the testes and suppression of spermatogenesis, ischemia reduced the count of hematopoietic progenitor cells, hematopoietic stem cells with immunophenotype Lin(-)CD117(+)Sca-1(+)c-kit(+)CD34(+) and Lin(-)CD117(+)Sca-1(+)c-kit(+)CD34(-), and multipotent mesenchymal stromal cells (CD45(-)CD31(-) CD90(+)CD106(+)) in the testicular tissue. The population of CD45(-)CD31(+)-endothelial cells in ischemic testicular tissue increased.

We studied the response of hematopoietic stem cells and progenitor cells to sympatholytic reserpine in intact C57Bl/6 mice and in animals with cyclophosphamide-induced leukopenia. The count of long-term hematopoietic stem cells (Lin(-)Sca-1(+)c-kit(+)CD34(-)) in the bone marrow of healthy mice increased in 7 min after reserpine injection and remained elevated in 2 h in parallel with elevated content of short-term stem (Lin(-)Sca-1(+)c-kit(+)CD34(+)) and progenitor (Lin(-)Sca-1(+)c-kit(+)) cells. Reserpine produced no effect on recruitment of hematopoietic stem and progenitor cells into the peripheral blood, but increased the serum level of granulocyte CSF and increased the count of metamyelocytes and neutrophilic granulocytes in the blood (in 2 h postinjection). Transplantation of bone marrow hematopoietic stem and progenitor cells from reserpine-treated donor C57Bl/6 mice to recipient CBA mice with 5-fluorouracil-induced leukopenia accelerated regeneration of the granulocytic lineage cells in leukemic mice. In cyclophosphamide-treated C57Bl/6 mice, reserpine reduced the level of short-term hematopoietic stem cells and increased the count of progenitor hematopoietic cells in the bone marrow in parallel with recruitment of the progenitors into the peripheral blood.

Comparative evaluation of the efficiency of prostatotropic agents was carried out in rat experiments. Serenoa repens plant preparation and polypeptides isolated from the cattle prostate were used for the treatment of benign hyperplasia. Drugs in parallel with sulpiride similarly led to shrinkage of the acinar epithelial area and to emergence of a trend to an increase of the stromal/epithelial proportion, more so after Serenoa repens treatment.

A pilot study evaluated the efficacy of the drug afalaza (mixture of affinity purified antibodies to PSA and endothelial NO-synthase) compared with the Serenoa repens extract in a model of chronic abacterial prostatitis in Wistar rats caused by suturing of prostate tissue by silk thread. Except for the animals of intact group, rats (n = 13 in each group) underwent intraperitoneal injection of distilled water (10 ml/kg), afalaza (at a doses of 5, 7.5 and 10 ml/kg) or an Serenoa repens extract (50 mg/kg) 1 month after surgery for 45 days. After infusion, the mass, volume, and prostate weighting factor were evaluated, and prostate tissue was examined histologically. 2.5 months after surgery, development of chronic abacterial prostatitis was observed in the control group. Compared with intact group, significant increase in weight, weighting factor, and volume of prostate were detected in control group. Against the background of administration of Serenoa repens extract and afalaza, these parameters were not significantly different from control values. The use of Serenoa repens extract prevented the development of atrophic processes and slowed the development of sclerotic processes. Administration of afalaza at all studied doses prevented the development of sclerotic changes, and a dose of 7.5 ml/kg prevented the development of atrophic processes with the effectiveness matching to Serenoa repens extract. Taking into account the high safety of afalaza, this drug is a promising treatment for chronic prostatitis.

We compared the efficacy of Impaza (antibodies against endothelial NO-synthase in ultra-low doses) and Serenoa repens on the rat model of chronic aseptic prostatic inflammation. Administration of Serenoa repens in a dose of 50 mg/kg for 1.5 months prevented the development of prostate sclerosis and increased luminal area, but did delay the development of atrophic processes. In animals treated with Impaza (3 ml/kg for 1.5 months), atrophic changes in the prostate gland were practically absent. These findings indicate that Impaza can be used in complex therapy of abacterial prostatitis.

In experiments designed to study effect of taxan-containing agents on the progeny of Wistar rats, one of the parents was given a single intravenous injection of the antineoplastic drug paclitaxel 1, 3 and 6 months before crossing with the untreated partner. The number of systemic pathological changes in the off-springs of paclitaxel-treated females was significantly greater and their spectrum wider than in those of the treated males. Severity of toxic effects depended on the time of crossing after drug administration. The optimal time for obtaining less affected off-springs of treated females and males was 3 and 6 months after administration of paclitaxel.

The possibility of reducing the ovariotoxicity of antitumor drug etoposide with buserelin, a hypothalamic regulator of pituitary function, was studied in female Wistar rats. Quantitative analysis of ovarian structural and functional elements on serial sections through the entire organ showed that 3 months after combined treatment with etoposide and buserelin, the morphological picture of the ovarian glands did not differ from that in intact animals of the same age, while etoposide monotherapy led to earlier development of atrophic processes. Six months after treatment, the number of bi- and multilayer follicles was significantly higher in rats receiving combined therapy compared to animals treated with etoposide alone.

Morphological and functional state of the ovaries in female Wistar rats was assessed in the early and late periods after administration of antitumor drug vepesid in a single maximum tolerated dose. In the early period, the drug pronouncedly decreased the number of primordial follicles, bi- and multilayer follicles, and the total number of generative elements. The number of graafian vesicles and corpora lutea did not decrease. In the late period, exhaustion of the reserved potencies of gonads was more pronounced than in the control. Morphological alterations in the ovaries were accompanied by inhibition of the functional state of the female reproductive system in the period corresponding to the action on mature and primordial follicles. This inhibition manifested in increased postimplantation mortality.

Progeny of Wistar rats treated with vepesid 1, 3, and 6 months before mating is characterized by common pathological changes. These changes were more pronounced and more diverse in animals descending from females receiving the cytostatic compared to the progeny of treated males. The severity of toxic effects depended on the period between mating and vepesid treatment. Cytostatic treatment 3 months before mating was associated with minimum toxicity for the progeny.

Wistar rat pups from rats treated with first- and second-generation platinum-containing cytostatics (platidiam, carboplatin) 1, 3, and 6 months before mating with intact partners had similar disorders. The severity of these disorders depended in many cases on the chemical structure of the drug and sex of the parent treated with the cytostatic. The severity of toxic effects in the progeny of intact females mated with cytostatic-treated males decreased with prolongation of the period elapsing between the treatment and mating. Carboplatin produced a more potent toxic effect on the reproductive function of rats compared to platidiam.

Experiments on Wistar rats showed that cisplatin and carboplatin induced similar morphological alterations in the ovaries. Both agents reduced the number of structural and functional elements, but the effect of cisplatin was more pronounced. Morphological changes observed in the early period after injection of the preparations were accompanied by prolongation of the estrous cycle, which was longer in rats treated with carboplatin. Partial and reversible sterility was observed in females at the early terms after cisplatin treatment.

Pregnant rats exhibited regenerative anemia development 3 months upon a single intravenous injection of carboplatin in a maximum tolerated dose; the effect increased by the end of pregnancy. The character of changes in parameters of the peripheral and central erythron parts (increased level of erythrocyte hemolysis, decrease in the amount of erythrocytes, increase in the number of reticulocytes, development of erythropoietic hyperplasia in bone marrow and spleen) was indicative of the hemolytic type of anemia.