The Role of Smad3 in the Realization of the Growth Potential of Different Types of Neural Progenitor Cells and the Secretory Function of Neuroglia.

The features of the participation of Smad3 in the functioning of neural stem cells (NSC), neuronal committed precursors (NCP), and neuroglial elements were studied in vitro. It was found that this intracellular signaling molecule enhances the clonogenic and proliferative activities of NCP and inhibits specialization of neuronal precursors. At the same time, Smad3 does not participate in the realization of the growth potential of NSC.

Effect of Xe/O Inhalation on Hemostasis in Experimental Thromboplastin Pneumonitis.

We studied the effectiveness of Xe/O mixture inhalation (30% Xe and 70% O, 20 min for 5 days) in a model of experimental thromboplastin pneumonitis. Inhalation of the studied mixture decreased the intensity of the inflammatory process in the lung tissue assessed by the temperature response of animals, changed lung weight and lung weight coefficient. At acute stage of pneumonitis, an increase in xenon consumption was recorded due to its retention in the gas exchange zone and a natural decrease in oxygen consumption due to partial alveolar/capillary block.

Xenon Antiaggregant Effects.

In in vitro model of short-term therapeutic inhalation of Xe/O mixture, xenon in millimolar concentrations led to a pronounced decrease in induced platelet aggregation in the platelet-enriched blood plasma. The maximum and statistically significant decrease occurred in response to induction by collagen (by ≈30%, p≤0.01) and ADP (by ≈25%, p≤0.

Pharmacokinetics of Dihydroquercetin after Single and Repeated Administration to Rats.

The pharmacokinetic properties of dihydroquercetin (DHQ) were studied after single and repeated (for 3 days) administration to rats in the form of a starch suspension at a dose of 25 mg/kg. Blood samples were collected using a permanent catheter in the jugular vein in 2, 5, 10, 20, and 30 min and in 1, 2, 4, and 6 h after administration. Before the repeated administration (5 min), blood sample was collected to assess the concentration of DHQ at the zero time point.

Features of Intracellular Signal Transduction in Neural Stem Cells under the Influence of Alkaloid Songorine, an Agonist of Fibroblast Growth Factor Receptors.

We performed a comparative in vitro study of the involvement of NF-κB, PI3K, cAMP, ERK1/2, p38, JAKs, STAT3, JNK, and p53-dependent intracellular signaling in the functioning of neural stem cells (NSC) under the influence of basic fibroblast growth factor (FGF) and FGF receptor agonist, diterpene alkaloid songorine. The significant differences in FGFR-mediated intracellular signaling in NSC were revealed for these ligands. In both cases, stimulation of progenitor cell proliferation occurs with the participation of NF-κB, PI3K, ERK1/2, JAKs, and STAT3, while JNK and p53, on the contrary, inhibit cell cycle progression.

Age-Related Features of the Response of Cancer Stem Cells and T Cells in Experimental Lung Cancer.

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.

Effect of IQ-1 on the Infarct Size and the Parameters of Cardiodynamic Indicators in the Acute Period after Myocardial Ischemia/Reperfusion in Rats.

The effect of a new JNK inhibitor IQ-1 (11H-indeno[1,2-b]quinoxalin-11-one oxime) was studied in male Wistar rats in a model of acute myocardial ischemia/reperfusion. Area at risk and myocardial infarct zones were studied in two series of experiments: 16 h after a single dose of IQ-1 (25 mg/kg intraperitoneally during cardiac ischemia) and on day 5 after its course administration (25 mg/kg intraperitoneally during cardiac ischemia and daily over 4 days). On day 5 after ischemia/reperfusion, cardiodynamic indicators were also studied: systolic, end-diastolic, and minimum pressure in the left ventricle, stress-time index, as well as the maximum rates of pressure rise and fall in the left ventricle (+dP/dt and -dP/dt).

Influence of a Decrease in Blood Viscosity on Arterial Pressure in Normotensive and Spontaneously Hypertensive Rats.

We investigated the effect of a decrease in blood viscosity on the mean BP during isovolumic hemodilution and vasodilating activity of the endothelium in normotensive Wistar rats and spontaneously hypertensive rats (SHR). Blood viscosity was reduced by isovolumic hemodilution (replacement of 10% of circulating blood with an equal volume of plasma). Hemodilution caused the same reduction in blood viscosity by 16% in both groups of rats.

Age-Related Features of the Early Period of Liver Regeneration after Partial Hepatectomy in Rats.

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.

Xenon-Induced Recovery of Functional Activity of Pulmonary Surfactant (In Silico Study).

To understand the nature of xenon-induced recovery of the functional activity of pulmonary surfactant during inhalation of a gas mixture of Xe/O, the mechanisms of the ongoing processes were studied in silico. Impaired ability of pulmonary surfactant to maintain low surface tension preventing alveolar atelectasis occurs due to formation of aggregates of its phospholipids and a decrease in their lateral mobility. Aggregated lipid systems, whose structure can explain the loss of lateral mobility of surfactant phospholipids, were modeled in silico at the molecular level.

Anti-Inflammatory Effect of Technologically Processed Antibodies to the Molecules of the Major Histocompatibility Complex in a Model of Acute Inflammation In Vivo.

The anti-inflammatory effect of technologically processed antibodies (TPA) to immune targets (MHC I and MHC II) was assessed in the carrageenan-induced rat paw edema model. The parameters "increase in edema" and "suppression of edema" significantly decreased (p<0.05) against the background of treatment with TPA and the reference drug indomethacin compared to the placebo group.

Regenerative Potential of Granulocyte Colony-Stimulating Factor Immobilized by Using Electron-Beam Synthesis Nanotechnology in an Experimental Model of Ovarian Reserve Depletion.

The pharmacological activity of granulocyte CSF (G-CSF) immobilized using electron-beam synthesis nanotechnology (imG-CSF) was evaluated in an experimental model of ovarian reserve depletion. The effectiveness of the drug was compared with that of its unmodified form. Depletion of the ovarian follicular pool in female Sprague-Dawley rats was caused by a single intravenous injection of the antitumor drug etoposide in the maximum tolerated dose.

Pharmacokinetics of a New Neuroprotector - Indenoquinoxalinone Derivative after Intravenous Administration in Rabbits and Rats.

The specific JNK inhibitor and NO donor 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) demonstrated pronounced neuroprotective properties in an in vivo model of ischemic stroke in rats. The pharmacokinetic behavior of IQ-1 was studied in two animal species (rats, rabbits) after intravenous administration in a dose of 1 mg/kg. IQ-1 concentrations in venous blood plasma were measured by the liquid chromatography-tandem mass spectrometry method.

The Role of JNK and p53 in the Regulation of Secretory Function of Neuroglial Cells of Various Types in β-Amyloid-Induced Neurodegeneration.

We studied the effect of JNK and p53 inhibitors on the production of neurotrophic factors stimulating the realization of the growth potential of neural stem cells by neuroglial cells of various types under conditions of simulation of induced β-amyloid neurodegeneration in vitro. It was shown that β-amyloid stimulates the production of neurotrophins by astrocytes and microglial cells, but does not affect the functioning of oligodendrocytes. JNK and p53 were not involved in the secretion of neurotrophins by intact astrocytes.

Pharmacological Effects of a New Soluble Guanylate Cyclase Stimulator in Experimental Ischemic Stroke.

We studied the action of a new indolinone derivative GRS, acetylsalicylic acid (ASA), and their combination on platelet aggregation, vasodilatory endothelial function, neurological status, and cerebral infarction area in experimental focal cerebral ischemia/reperfusion in rats. GRS compound (10 mg/kg), ASA (10 mg/kg), and their combination in the same doses were administered orally once a day as a suspension in 1% starch solution over 5 days after pathology modeling. Sham-operated and control animals were administered 1% starch solution.

Assessment of Ante- and Postnatal Development of the Offspring of Male Rats Crossed in Delayed Periods after Treatment with Methotrexate in Low Doses.

We studied ante- and postnatal development of the offspring of intact female rats crossed with males injected with low doses of methotrexate 3 and 6 months before mating. The time of crossing corresponded to the manifestation of the cytostatic effect on spermatogonial stem cells. The offspring of methotrexate-treated males was characterized by increased preimplantation losses and fetal growth restriction in the antenatal period and inhibition of physical development, delayed formation of sensory-motor reflexes, and impaired learning abilities in the postnatal period.

The Role of cAMP-Dependent Intracellular Signaling Pathways in the Regulation of the Functions of Neural Stem Cells and Neuroglial Cells in Amyloid-β-Induced Neurodegeneration.

Under conditions of neurodegeneration modeled in vitro by the β-amyloid peptide-(25-35) fragment (Aβ), we studied the role of individual links of cAMP-dependent intracellular signaling pathways in determining the proliferation and differentiation status of neural stem cells (NSCs) and colony-stimulating activity of supernatants from neuroglial cells. The important role of intracellular cAMP and PKA in the inhibition of the progression of the NSC cell cycle and stimulation of the process of their specialization induced by Aβ was found. The selective ability of PKA to block the production of factors constituting colony-stimulating activity by neuroglial cells under conditions of their cultivation in vitro with a neurotoxic agent was revealed.

Effect of Paclitaxel on the Hemostatic Potential of the Blood in the Experiment.

The duration and severity of prothrombotic effects of the maximum tolerated dose of paclitaxel (40 mg/kg) were evaluated in intact outbred mice. Hemostasis was assessed before and on days 1, 2, 5, 7, 10, 15, 20, and 30 after a single injection of paclitaxel using standard coagulation tests (activated partial thromboplastin time, prothrombin time, fibrinogen concentration, and antithrombin III) and a "global" method, low-frequency piezothromboelastography. A pronounced prothrombotic effect of paclitaxel was revealed starting from the first day postinjection that consisted in intensification of fibrinogenesis up to the 7th day in parallel with activation of the anticoagulant mechanisms.

Pharmacological Effects of a New Indolinone Derivative in Experimental Pneumonitis in Rats.

We studied the effect of a new indolinone derivative GRS on animal survival and on functioning and histological structure of the lungs in rats with experimental pneumonitis. The rats of experimental groups were intratracheally administered 0.5% aqueous solution of carrageenan under intramuscular anesthesia.

The Role of Intracellular Signaling Molecules in Macrophage Activation by Peat Humic Acids.

Humic acids isolated by sodium pyrophosphate extraction from various types of peat activate macrophages in the classical proinflammatory pathway and stimulate nitric oxide production by these cells. This effect is mediated by activation of intracellular signaling pathways involving MAPK p38, PI3K, MEK 1/2 kinase, cAMP, and NF-κB via TLR-2 and TLR-4 receptors.

The Role of Cancer and Somatic Stem Cells in the Anti-Inflammatory and Antitumor Effects of Aconitum baicalense Extract on Experimental Breast Cancer.

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.

Comparative Analysis of Stress-Protective Activity and Prevention of Fatigue during Physical Load of Standardized Humic Acids from Peat and Officinal Preparations of Succinic Acid in Experiment.

The effect of humic acids and substances with similar action - derivatives of succinic acid (ethylmethylhydroxypyridine succinate) and combined agent consisting of succinic acid, nicotinamide, riboflavin, and riboxin on the performance and stress resistance of experimental rats was studied. Performance was assessed in the test of exhaustive forced swimming with a load, stress resistance was evaluated by the serum level of corticosterone and open field behavior, and the state of anaerobic metabolism was estimated by the serum level of lactate after swimming test. Humic acids from peat showed anti-stress activity comparable to that of the officinal preparation and preventive effect on fatigue during physical exercise.

Participation of cAMP-Mediated Signaling Transduction in the Regulation of the Secretory Function of Neuroglia during Ethanol-Induced Neurodegeneration.

We studied the involvement of cAMP and PKA in the regulation of the secretion of neurotrophic growth factors by macro-and microglial cells in the model of ethanol-induced neurodegeneration in vitro and in vivo. The stimulating role of cAMP in the secretion of neurotrophins by intact astrocytes and oligodendrocytes was shown, while PKA does not participate in this process. On the contrary, the inhibitory role of cAMP (implemented via PKA activation) in the production of neurogenesis stimulators by microglial cells under conditions of optimal vital activity was found.

Prevention of the Genotoxic Effects of Doxorubicin with Anthocyanin-Containing Complex from Sorbus aucuparia L. Fruit.

We studied the effect of an anthocyanin-containing complex from the fruits of S. aucuparia L. on doxorubicin-induced genotoxicity in bone marrow cells of C57BL/6 mice.