Bulletin of Experimental Biology and Medicine最新文献

A full-length humanized chimeric antibody 10H10ch that specifically interacts with the surface glycoprotein E of flaviviruses was obtained. To construct it, we used variable fragments of the heavy and light chains of the monoclonal antibody 10H10 that form the active center of the antibody and a fragment of the constant part of the heavy chain of the human IgG1 antibody. The resulting full-length chimeric humanized antibody 10H10ch specifically interacted with the E protein of flaviviruses pathogenic to humans, such as tick-borne encephalitis, Zika, West Nile, and dengue viruses. An immunochemical assessment of the interaction constants of the 10H10ch antibody with a panel of native and recombinant flavivirus antigens by ELISA and biolayer interferometry showed that the dissociation constant (Kd) of the chimeric antibody is in the nanomolar region and is comparable to that of the high-affinity mouse monoclonal antibody 10H10. The possibility of using the resulting chimeric humanized antibody 10H10ch for the diagnosis, prevention, and treatment of various flavivirus infections is discussed.

We studied interrelationships between behavioral parameters, metabolic processes, and cytokine content in the blood of male and female rats at different stages of postnatal ontogeny after intrauterine stress (mothers were forced to swim in cold water from the 10th to the 16th day of pregnancy). Correlations between behavioral and metabolic parameters in prenatally stressed rats were revealed at an earlier age (day 21 of life) than in controls. In comparison with intact rats, in males exposed to intrauterine stress no relationships between these parameters were revealed at older age, while in females, their direction and character change on day 60 of life. In prenatally stressed males, correlations of the blood levels of IL-6 were revealed: inverse relationships with behavioral parameters on the days 21 and 30 and direct relationships with metabolic parameters on day 60 of life. In prenatally stressed females on day 30 of life, we observed negative correlations between IL-4 levels and metabolic parameters that were absent under normal conditions. Thus, intrauterine stress leads to reorganization of the relationships between the parameters of metabolic and immune processes, which are essential for the purposeful behavior of mammals. The effects of stress seem to depend on the sex of the offspring and stage of postnatal development.

A positive correlation was found between the level of global seismic activity and dynamics of cortisol concentration in blood serum of male rabbits (r=0.33, p=0.01) and Campbell's dwarf hamsters (r=0.38, p=0.04). For a small group of healthy volunteers (n=5), we also found a positive correlation between cortisol levels and the number of major earthquakes, excluding aftershocks (r=0.36, p=0.009) and a negative correlation with IL-18 levels (r=-0.28, p=0.04). The body response to earthquakes is not delayed, and the numerous aftershocks do not seem to affect the biological indicators under study. These facts showed that the earthquakes themselves do not affect the cortisol level via the changes of the environmental parameters. In contrast, the underlying biotropic factor is an unknown trigger responsible for an increase in the number of potent earthquakes. Evidently, it is important to take into account the level of global seismicity as a marker of this trigger provoking the rise of glucocorticoid hormones.

We studied the radical-binding and antioxidant activities of the alkaloid tryptanthrin (TR) and its new synthetic derivative tryptanthrin oxime (TR-Ox), as well as the cytoprotective activity of TR-Ox under conditions of oxidative stress. The antiradical activity of TR-Ox was revealed in the test of binding with stable chromogen radical 2,2-diphenyl-1-picrylhydrazyl and in the superoxide radical generation test (riboflavin photoreduction reaction with detection by NBT reduction). TR-Ox was inferior to ionol and dihydroquercetin by the antiradical activity. In these tests, TR did not exhibit antiradical activity. TR-Ox did not show iron-chelating activity (in the test with the formation of the o-phenanthroline-Fe²⁺ complex and its destruction in the presence of chelating agents). In brain homogenate, TR-Ox significantly reduced the increase in spontaneous chemiluminescence. Under conditions of oxidative stress induced by 15 mM H₂O₂ in the SH-SY5Y neuroblastoma cell culture, TR-Ox exhibited cytoprotective activity and increased the number of viable cells.

We studied the effect of NF-κB blockade on the state of various pools of progenitor cells of the nervous tissue and the psychoneurological status of experimental animals with modeled Alzheimer's disease. Administration of scopolamine hydrobromide to C57BL/6 mice for 4 weeks was accompanied by the development of "persistent" disturbances in the orientation and exploratory behavior and mnestic function. An ameliorating effect of the NF-κB inhibitor on these cognitive disorders typical of senile dementia was revealed. At the same time, we observed an increase in the content of neural stem cells and committed neuronal precursors in the subventricular zone of the brain.

Bacterial nanocellulose (BNC) prepared by the methods of "green" bionanotechnological synthesis is considered a promising food additive and food ingredient. At the same time, the risk of reducing the bioavailability of minerals due to their adsorption on BNC fibers having a high specific surface area and high adsorption and ion exchange capacity cannot be excluded. We studied the effect of oral administration of BNC on the accumulation of macronutrients and trace elements included in the diet in the liver and kidneys of laboratory animals. Male Wistar rats received BNC at doses of 0 (control), 1, 10, and 100 mg/kg body weight as part of their diet for 8 weeks. The content of 30 macronutrients and trace elements in the liver and kidneys was determined by inductively coupled plasma mass spectrometry. It was found that BNC at all doses did not significantly change the content of the main essential macronutrients and trace elements in the organs (Ca, Cr, Cu, Fe, K, Mg, Mn, Na, P, Se, and Zn), which indicates the absence of a negative effect on their bioavailability. Among other elements, a statistically significant decrease in the content of As, B, Cd, Co, and Pb in the liver and an increase in Al, B, Ba, Ni, and Pb in the kidneys were revealed (more than 20% of the control). The revealed decrease in the bioaccumulation of cobalt can indicate inhibition of assimilation of certain chemical forms of this trace element under the action of BNC.

We studied cytotoxicity and accumulation of boron and lithium by cultured human fibroblasts and human and mouse skin melanoma cell cultures. The cytotoxicity of boron and lithium drugs was assessed by MTT tests in the boron and lithium concentration range of 10-640 μg/ml. Cell viability was significantly reduced after incubation with boron and lithium at concentrations >160 μg/ml. To assess accumulation of boron and lithium, the concentration of elements was measured using inductively coupled plasma atomic emission spectrometry. Melanoma cells more intensively accumulated lithium in comparison with boron. The results indicate the possibility of safe application of lithium salts in concentrations minimally required for successful neutron capture therapy.

Under the influence of inflammation, pancreatic β cells can transdifferentiate into cells with a different phenotype. When inflammation decreases, the opposite process is possible. We studied the effect of intramuscular injection of 5-amino-2,3-dihydrophthalazine-1,4-dione sodium salt (APH) on the structural and functional characteristics of the pancreatic islets in rats with experimental type 2 diabetes mellitus. Insulin-producing, glucagon-producing, and proliferating cells were identified by immunohistochemistry. After APH administration, an increase in the number of β cells, a decrease in the number of α cells and cells synthesizing both insulin and glucagon (insulin-glucagon-positive) were observed; mitotic activity of β cells did not change. It is likely that APH promotes transdifferentiation of α cells into β cells by changing the microenvironment of endocrine cells and reducing inflammation in pancreatic islets.

The effect of nitric oxide (NO) supplied to the sweep gas of the oxygenator on the formation of gaseous microemboli during cardiopulmonary bypass has been studied in animal experiments (female pigs). It was shown that NO added to the sweep gas of the oxygenator during cardiopulmonary bypass significantly decreased the number and volume of microemboli (the number of microemboli over 1 h of cardiopulmonary bypass was 1197 (568; 2436) vs 55,478 (15,217; 331,480) in the control; p=0.016). The decrease in the number and volume of all bubbles was accompanied by a significant decrease in the concentration of neuron-specific enolase, a marker of brain injury, 6 h after the end of cardiopulmonary bypass to 7.7 (7.5; 8.7) ng/ml vs 11.2 (9.2; 18.3) ng/ml in the group without NO (p=0.047).

The effect of a new antibiotic peptomide A-70 on changes in the mesenterial lymph nodes caused by experimental peritonitis was studied. Differences in the morphological changes in rat lymph nodes in peritonitis and against the background of antibiotic therapy were revealed. Lymph nodes responded to peritoneal inflammation by reducing the area of cortical structures and expansion of the sinus system, which indicates a decrease in drainage-detoxification and immune function and determines unfavorable outcome of peritonitis. Antibiotic therapy reduced inflammatory manifestations and toxic pressure on the lymph system and potentiated the reactive response of the mesenteric lymph nodes: the size of lymphoid nodes and the paracortical T-dependent zone increased against the background of shrinkage of the sinus system, which attested to activation of the lymphopoietic function and immune response of lymph nodes in peritonitis. The observed changes attested to favorable prognosis of peritonitis treated with antibiotic peptomide A-70.