Vol 165, No 3 (2018)

We studied the effect of long-term prenatal administration of caffeine on the behavior and learning of rats in postnatal ontogeny. Experiments were carried out on male rats born by females receiving caffeine solution as the only source of fluid throughout gestation. The control group consisted of pups obtained from females receiving drinking water throughout pregnancy. It was found that long-term caffeine intake by female rats during pregnancy determined increased locomotor activity of the offspring. Rat pups born from mothers treated with caffeine during pregnancy faster reached the underwater platform in the Morris maze, i.e. demonstrated better spatial memory formation than control animals.

Correlations between extracellular matrix components in mouse lungs were examined during various terms of BCG-induced granulomatosis (on postinfection days 3, 30, 60, 90, and 180). During the development of pathological process, the revealed dynamic interrelations between structural units of proteoglycans and hydroxyproline weakened. Most correlations were observed on postinfection day 180. They reflect the relationships not only between the structural units of proteoglycans but also between collagens, presumably determining the maximum degree of fibrosis at this period. The established correlations characterize the systemic nature of reactions in extracellular matrix and its versatile implications determined by the processes going on in the organs and tissues during the onset and development of generalized pathology.

Activation of lysosomal proteolysis and increased coenzyme Q10 level were revealed in the liver and brain of rats with individual typological features under conditions of food deprivation. Changes in cathepsin B activity in these tissues were different in behaviorally active and passive animals. We observed indirect modulating effect of coenzyme Q10 in the regulation of activity of lysosomal endopeptidases in the brain of animals with different behavior during adaptation to metabolic stress.

Effect of different Ca²⁺ concentrations in the bathing solution [Ca²⁺]_o on the parameters of single isometric contraction and slow force response to stretching was studied in isolated preparations of healthy and hypertrophied myocardium of male and female Wistar rats. In all groups of experimental animals, the increase in calcium concentration was followed by a decrease in the myocardium slow response intensity. We revealed a complementary relationship between the current and medium-term systems of myocardial contractility regulation by the length of the myocardium aimed at the maintenance of the constant level during adaptation to the load. Slow responses of the hypertrophied rat heart myocardium were suppressed in comparison with those in the healthy myocardium and their intensity did not depend on animal sex.

We studied the effects of low-intensity broadband red light on electrical activity of the heart and oxidative modification of proteins in the myocardium of rats after asphyxia. It was shown that low-intensity red light reduced the content of oxidatively modified proteins in rat heart after oxidative stress caused by asphyxia. Exposure to low-intensity red light normalized ECG parameters in rats after asphyxia.

We carried out a comparative analysis of circadian rhythms of melatonin secretion in Caucasian menopausal women with and without insomnia depending on the 3111T/C polymorphism of the Clock gene. Melatonin levels was measured in the saliva 4 times a day (06.00-07.00, 12.00-13.00, 18.00-19.00, and 23.00-00.00 h). Carriers of the TT genotype with insomnia demonstrated significantly higher level of melatonin in the early morning hours compared to the carriers of the minor allele C (12.60±7.58 and 8.98±8.62 pg/ml, respectively, p=0.023). In the control group, no statistically significant differences were revealed. The carriers of the TT genotype with sleep disorders have higher morning melatonin level compared to control group women (12.60±7.58 and 5.48±4.74 pg/ml, respectively, p=0.005) and low nocturnal melatonin level (6.42±4.97 and 12.52±10.40 pg/ml, respectively, p=0.039).

We analyzed proliferative and apoptotic activity of bone marrow monocyte lineage cells in the offspring of mothers with experimental toxic injury to the liver. Rat pups were examined at different times of ontogeny. Inhibition of proliferative activity and increase in apoptotic activity in bone marrow monocyte cells of experimental rat pups in comparison with intact ones were found.

The possibility of correction of morphological changes in the myocardium and biochemical parameters of the blood with 3-hydroxypyridine acetylcysteinate in a dose of 25 mg/kg was studied in the model of doxorubicin-induced chronic heart failure in rats. It was found that 3-hydroxypyridine acetylcysteinate in a dose of 25 mg/kg produced less pronounced cardio-protective effect in experimental chronic heart failure than 3-hydroxypyridine succinate.

The kinetics of ozone interaction with 14 saturated and unsaturated fatty acids with different molecular structures was studied and velocity constants of these reactions were measured. The relationships between the measured constants and some parameters of fatty acid (length of the aliphatic chain, number of double bonds, location of the double bonds, and its configuration) were detected. The highest velocity constant is recorded for monounsaturated oleic fatty acid: 2.58×10⁵ (M×sec)^—1. Other studied fatty acids had 1.5-5-lower constants depending on their molecular structures.

Protein G is present in group G streptococcus strain (G4223); the IgG-binding part of this protein contains three IgG-binding domains and binds human IgG with very high activity. We obtained two recombinant polypeptides G4223 and G₁4223 with high IgG-binding activity. Polypeptide G₁4223 consisting of three IgG-binding domains and W region has higher molecular weight and is characterized by higher affinity for IgG than polypeptide G4223 consisting of only three IgG-binding domains. It was shown that polypeptide affinity depends on its structure and size.

Structural changes in the liver of CBA mice were studied during the development of experimental hepatocarcinoma-29 inoculated into the hip. A decrease in the volume density of hepatocyte cytoplasm, mitochondria, endoplasmic reticulum, and lipid inclusions and an increase in the volume density of lysosomal structures during tumor growth were observed. All stages of intracellular autophagy were recorded by the method of electron microscopy. These stages included the appearance of autophagosomes, autophagolysosomes, and secondary lysosomes in the hepatocyte cytoplasm. Fragments of cytoplasm, glycogen rosettes, mitochondria, and fragments of endoplasmic reticulum with ribosomes were found in autophagosomes. The obtained data indicate the development of non-selective autophagy in the liver during distant tumor growth in aimed at the maintenance of intracellular homeostasis in hepatocytes and energy and trophic homeostasis of organism.

We carried out a comparative study of the features of osteogenesis from the progenitor osteogenic periosteal cells in rabbit and human. At the initial stages, high osteogenic potential of both human and rabbit periosteal cells was observed. However, at the later stages, the cell response favors resorption of the new bone tissue formed from periosteal cells in rabbits, but does not affect the bone tissue formed from human progenitor osteogenic periosteal cells. These functional characteristics of rabbit periosteal cells should be considered when planning the experiment.

Dihydroquercetin is a natural flavonoid with antioxidant properties that are determined by its ability to scavenge free radicals and chelate transition metal ions. Chemiluminescent studies showed that iron (II) ions in complex with dihydroquercetin are inactive and cannot catalyze decomposition of hydrogen peroxide (Fenton reaction).

We studied the effect of radioprotector indralin (B-190) alone or in combination with monizol on BP and HR in rabbits, reduction of blood supply and spleen weight in rats and (CBA×C57Bl/6)F1 hybrids mice, and on blood loss from a wound on tip of the tail in mice. Being an α1-adrenomimetic, indralin caused hypertensive reaction with the development of bradycardia, reduced blood supply and spleen weight, and sharply reduced blood loss from the wound. Monizol as nitrate reduced BP without affecting HR and reduced blood loss from the wound. Monizol administered prior to indralin eliminated radioprotector-induced hypertensive reaction, reduced bradycardia by more than 2 times, and attenuated the effect of indralin on spleen weight and blood loss from the wound by 1.6-1.8 times. Monizol administered after indralin had no effect on shifts in peripheral blood supply caused by the radioprotector.

The glycolipid biosurfactant complex from actinobacterium Rhodococcus ruber IEGM 231 inhibits the innate and adaptive immunity parameters after intraperitoneal and intramuscular injection. Marked suppression of antibody production, bactericidal potential, and production of proinflammatory cytokines by peritoneal macrophages, detected in vivo, do not agree with the previously detected immunostimulatory activity of biosurfactants towards the immunocompetent cell cultures; this fact indicates an important role of the cell environment in the formation of immune response under the effect of bacterial glycolipids.

We performed a cytogenetic analysis of the results of CRISPR/Cas9-correction of G2019S mutation in LRRK2 gene associated with Parkinson’s disease. Genome editing was performed on induced pluripotent stem cells derived from fibroblasts of a patient carrying this mutation. A mosaic variant of tetraploidy 92 XXYY/46,XY (24-43% cells from various clones) was found in neuronal precursors differentiated from the induced pluripotent stem cells after gene editing procedure. Solitary cases of translocations and chromosome breaks were observed. These data confirm the importance of the development of new approaches ensuring genome stability in CRISPR/Cas9-edited cultures.

Cancer-testis antigens, effective markers of tissue malignant transformation, are characterized by heterogonous transcription depending on the pathological features of breast cancer. We performed screening of transcription profile of cancer-testis antigens specific for breast tumor tissues in female patients with and without regional metastasis. The relative expression of 16 genes (MAGEA1, MAGEA2, MAGEA3, MAGEA4, MAGEB1, MAGEB2, GAGE1, GAGE3, GAGE4, MAGEC1, BAGE, XAGE3, NY-ESO1, SSX2, SYCP1, and PRAME1) was analyzed by RT-qPCR method in biopsy specimens of the mammary gland tissues obtained during surgery from 25 patients. Differential transcription activity of cancer-testis antigens genes was observed in patients with metastatic (enhanced expression of MAGEA2, MAGEB1, and XAGE3 genes) and non-metastatic (enhanced expression of GAGE3 and PRAME1 genes) breast cancer.

The dynamics of the development of the pancreatic islet cells in the porous TiNi scaffold was studied by electron microscopy. Changes in the metabolism of glucose and glycosylated hemoglobin and parameters of the peripheral blood and bone marrow were shown after transplantation of pancreatic islet cells on porous permeable TiNi scaffold during alloxan-induced diabetes. The cells administered on the porous biocompatible scaffold produced more prolonged anti-diabetic effect and normalized hemopoiesis parameters in comparison with their intraperitoneal administration. The experiment on pancreatic islet cells showed that porous permeable TiNi scaffold is a unique cell incubator acceptable for usage for tissue engineering.

Incubation of Yersinia pseudotuberculosis cells grown on a solid medium with pseudotuberculous diagnostic bacteriophage for 20 min at 37oC led to a significant decrease in the concentration of both components of the system. This effect was absent when the bacteria were grown in a fluid medium. At the same time, this incubation regimen promoted vesicle formation and typical morphological changes in bacteria grown in both surface and suspension cultures. Co-incubation of the bacteriophage with suspension of vesicles isolated from the suspension culture of Y. pseudotuberculosis grown at 10oC (but not 37oC) led to a decrease in plaque-forming activity of the bacteriophage.

We developed a new experimental model for studies of orientation and exploratory behavior in humans. This method allows analysis of variants of orientation and exploratory behavior in humans, including risky behavior, and cognitive and individual typological parameters. The model allows distinguishing examinees with high and low orientation and exploratory activity, which helps to determine their psychoemotional status. Surprisingly, individuals in emotional strain demonstrated longer orientation and exploratory behavior. This allows them to achieve the results more rapidly during purposeful behavior under similar conditions. This model provides the tool for evaluation of the electrophysiological, autonomic, and biochemical mechanisms of orientation and exploratory behavior of humans.