After traumatic brain injury (TBI), inflammation develops in the CNS, an active participant of which is the complement system. Activated complement fragments trigger inflammation and subsequently considerably affect reparative and regenerative processes. This work was aimed to abate neuroimmune disorders after experimental TBI by blocking excessive inflammation at early post-traumatic stages with a monoclonal antibody to complement component 3 (C3). The experiments were carried out on 65 male Wistar rats using a weight drop TBI model. To correct neuroinflammation, the rats were administered with a novel recombinant anti-C3 neodeterminant monoclonal antibody (C3A8, 100 mg/kg, i.v.), which blocks the activation of the alternative complement pathway. A recombinant human interleukin-1 receptor antagonist (rIL-1RA, 50 mg/kg, s.c.) was used as a reference compound. Both preparations were administered once, 30 min or 24 h after TBI (regimens 1 and 2, respectively). The study parameters were blood corticosterone levels, cytotoxic and proliferative activity of splenocytes, and behavioral responses in the plus maze test. The data obtained indicate that on day 7 after TBI, in rats treated with a C3A8 antibody in the regimen 1, post-traumatic weight loss was decreased, cytotoxic and proliferative activity of splenocytes increased, motor and exploratory activity also increased with a significant decrease in the level of anxiety. The administration of rIL-1RA in the above regimens, as well as their co-administration, had no significant effect on the study parameters.

Intercellular communication plays a huge role in the vital activity of living organisms. At present, far less studied is distant cellular communication, in which, along with autocrine and paracrine regulations by soluble factors (e.g. cytokines and growth factors), of particular interest is communication by means of microparticles via their ligand-receptor interaction with target cells, direct membrane fusion, or internalization by endocytosis. This study aimed at evaluating in vitro the effect of microparticles produced by natural killer cells of the NK-92 cell line on the content and activation of markers associated with apoptosis initiation in trophoblast cells of the JEG-3 cell line. Microparticles derived from NK-92 cells caused caspase-8 activation in trophoblast cells with the formation of an intermediate fragment and no final cleavage to active caspase-8. We found no significant changes in the content of the various cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP) isoforms (long isoform, FLIP L ; short isoform, FLIP S ) in trophoblast cells after their treatment with microparticles derived from natural killer cells. In contrast, distant interaction of trophoblast cells with natural killer cells modeled by the transwell system increased the content of FLIP S in trophoblast cells. We demonstrated that microparticles produced by natural killer cells were able to transfer their cargo to target cells, including the cytotoxic protein granzyme B. Furthermore, we could observe an increase in the caspase-3 and caspase-9 activities in trophoblast cells.

Background. Heat stress (HS) induces the cellular secretion of heat shock proteins (HSP ) and extracellular nanovesicles (ENVs). The biological link between these phenomena is poorly understood. In the case of colorectal cancer (CRC) cells, the secretion of HSP s and ENV may be involved in the clinical response to intraperitoneal therapy of peritoneal carcinomatosis.Material and Methods. Established colon cancer cell lines COLO 320, HCT 116, HT29 and DLD 1 were used. ENVs were isolated from culture media by differential ultra-centrifugation and analyzed by dynamic light scattering, nanoparticle tracking analysis, atomic force microscopy and flow cytometry. Super-paramagnetic particles (SPMP ) covered by antibodies to the membrane form of Hsp70 were used for isolation and quantification of Hsp70(+) ENVs. Vesicular microRNA was assayed by RT-qPC R.Results. HS induces the secretion of ENVs by CRC cells, the resistance to HS correlates with the activity of HS-induced ENVs secretion. HS induces the secretion of a specific population of ENVs enriched by membrane form Hsp70 (mHsp70). The microRNA content of mHsp70(+) ENVs has qualitative and quantitative features. The concentration of miR-126-3p, -181-5p, -155-5p, -223 is increased in mHSP 70(+) ENVs secreted by three CRC cell lines.Conclusion. HS induces the secretion of mHSP 70(+) ENVs by CRC cells. This phenomenon may be involved in a clinical response to intraperitoneal chemo-hyperthermic perfusion therapy of peritoneal carcinomatosis.

Traumatic brain injury (TBI) is a multifactorial disease that can lead to the development of neurological diseases. To correct violations of physiological functions, anti-inflammatory cytokines are used, in particular, the IL-1 receptor antagonist (IL-1RA). The aim of this work is to evaluate the effectiveness of the rIL-1RA preparation for the correction of post-traumatic neuroinflammation. TBI in rats was simulated by dropping a 115 g weight from a height of 120 cm into the center of the parietal region, and the drug was injected subcutaneously at a dose of 50 mg/kg 60 min after injury. We studied blood corticosterone levels and behavioral responses in the “Open field” test. To characterize the activation pattern of microglia in different parts of the brain, the expression of the Iba1 marker and morphological changes of cells were evaluated. Counting the total number and changing the shape and size of Iba1-positive microglial cells on 7th day after TBI showed that in animals treated with rIL-1RA the number of activated microglial cells was significantly higher than in intact animals, but the degree of their activation was significantly lower. Studies of CNS function disorders after TBI showed that motor and orientation-exploratory activities were significantly inhibited, which, together with the disturbance of the emotional status of the animals, indicates the development of a neurological deficit in intact rats. In animals treated with rIL-1RА, changes in behavioral characteristics were less pronounced. The decrease in neurological deficit in treated animals was directly related to the normalization of the state of microglia. The data obtained in the work indicate that the use of rIL-1RA 1 h after TBI allows correction of motor, orientation-exploratory activity and reduce microglia activation in different parts of the CNS.

Abstract—We studied the effect of intranasal administration of RAIL gel (Il-1b antagonist) to rats with experimental chronic cerebral ischemia caused by permanent occlusion of the common carotid arteries on the main parameters of the thiol-disulfide system and the expression of heat shock protein (HSP70) in the brain. It was found that chronic cerebral ischemia leads to disruption of the thiol-disulfide system—a decrease in the activity of glutathione peroxidase (GP), glutathione transferase (GT), and glutathione reductase (GR), a deficiency of reduced thiols and GSH, and a decrease in the content of cysteine and methionine associated with an increase in the oxidized form of glutathione in the brain of animals. In parallel, we found an increase in the content of the nitrosative stress marker, nitrotyrosine, and a decrease in the concentration of the endogenous cytoprotective protein HSP70. Intranasal administration of RAIL for 18 days led to a 58.2% increase in the reduced intermediates of the thiol-disulfide system (SH-group) and a 100% increase in the GSH level, while the content of its oxidized form decreased by 36.3% compared to the control. RAIL increased the activity of GR by 96.1%, GP by 68.1%, and GT by 137.7% relative to control. After the course of intranasal administration of RAIL gel, the concentration of the HSP70 protein in the cytosol of the brain homogenate of animals increased by 98.4%, and in mitochondria by 142.8% compared with the control parameters. Treatment with RAIL has a neuroprotective effect aimed at stabilization of thiol-disulfide equilibrium and activation of HSP70-dependent mechanisms of endogenous neuroprotection.

Here, the autoproteolytic activity of human recombinant anti-Mullerian hormone (rAMH), a potential antineoplastic drug, was investigated. It was shown that the hormone is not only able to activate itself by the limited proteolysis, but also specifically interacts with the proteolytic inhibitor aprotinin. The involvement of the rAMH specific proteolysis site in interaction with a specifi c receptor type II (MISRII) was found. The data obtained may be useful to clarify some aspects of the native AMH biochemistry and pharmacodynamics of the recombinant hormone.

Two monoclonal antibodies were developed and were shown to block the complement system alternative pathway (AP) activation at the stage of assembly and activation of C3 convertase. The humanized antibody hC34 specific to a binding site on α’2 determinant of С3с fragment inhibited in vitro the human complement activation by 90% at a dose of 3 μg/ml of blood serum. The antibody 3А8 specific to rat complement C3 component and similar to antibody hC34 was demonstrated to be pharmacologically active in model of closed craniocerebral injury (data of functional and histological studies). The results of this study indicate the humanized antibody hc34 to be promising for treatment of central nervous system pathologies and of other diseases associated with complement hyperactivation.

The radioprotective efficacy of recombinant flagellin (FL) and interleukin-1 beta (IL-1) administered in combinations for preventive or therapeutic purposes was studied in experiments on white mongrel mice. The drugs were administered i.p. at doses of 1 mg/kg (FL) and 50 μg/kg (IL-1β). Simultaneous administration of the drugs in the early stages before irradiation was shown to be most efficacious in terms of 30-day survival of mice exposed to x-rays at a dose of 7.5 Gy (100% survival of mice vs. 53% survival in the control group, p < 0.01). Sequential administration of FL before exposure and IL-1β after exposure increased survival of the mice by 40% ( p < 0.05). The results indicated that combined use of biotechnological drugs for radioprotection was promising.

В настоящей работе исследована противоопухолевая активность активированного рекомбинантного антимюллерова гормона (рАМГ) человека в отношении клеток линий NBL-7 и OVCAR3. Показано, что гормон, содержащийся в высокоочищенных препаратах, обладает не только способностью к связыванию c рекомбинантным рецептором II типа (MISRII), но и цитотоксическим эффектом в отношении клеток, экспрессирующих MISRII. Полученные данные могут лечь в основу разработки первого отечественного противоопухолевого лекарственного средства на основе активированного рАМГ.

Multiple sclerosis is a chronic disease of the CNS that affects people of working age, in which the targets of aggressive immune cells become the myelin and myeline producing cells, as well as neurons. It is assumed that a predisposition to MS is forming in childhood, due to common infections. In this paper the experimental allergic encephalomyelitis (EAE) was examined in rats administered IL-1beta at different periods of the early postnatal ontogenesis. EAE was induced in rats at the age of 3 months by single subcutaneous immunization with a homologous homogenate of spinal cord in complete Freund's adjuvant. The number of sick animals were evaluated, as well as the severity of the disease and its duration. It was shown that in rats after administration of IL-1beta on 1st and on 4th week of life EAE is more severe than corresponding control groups of rats. Discusses the damaging or protective effects of injections of IL-1beta during different periods of early postnatal ontogenesis, role of stress reactivity and communication with the "hygiene hypothesis".

Hypotheses relating to the developmental nature of cognitive impairments in schizophrenia and other neuropathologies propose that the development of stable cognitive deficit involves important roles for hypoxia, trauma, and infections operating during the prenatal and early postnatal periods. These pathological states are accompanied by increases in the production of proinflammatory cytokine interleukin-1β (IL-1β) in cells of the nervous and immune systems. We report here studies of the characteristics of the expression of the Fgf1 and Timp1 genes, which are involved in regulating the cerebral mechanisms of neuroplasticity, in cells of the medial prefrontal cortex and the dorsal and ventral areas of the hippocampus in adult rats given IL-1β during early postnatal ontogeny. Experiments were performed in standard conditions and on acquisition of a conditioned active avoidance reflex. Learning impairments in experimental animals were accompanied by decreased production of FGF-2 mRNA in cells of the medial prefrontal cortex and ventral hippocampus. There were no differences between groups in conditions without cognitive loading.

The actions of chronic i.p. administration of the proinflammatory cytokine interleukin-1β (IL-1β) on exploratory behavior and spatial memory were studied in rats. IL-1β was given at the weakly pyrogenic dose of 0.5 μg/kg daily for 14 days (starting seven days before and continuing through seven days of behavioral testing). Behavior was analyzed 23.5 h after sequential injections of cytokine. A battery of tests was used, including the open field test (on three sequential days), exploration of novel objects, and the Morris water maze. Experimental animals showed a significant decrease in motor activity, a minor increase in anxiety, and suppression of exploratory behavior. Impairments to spatial memory were not seen.

The spectral luminescence properties of aqueous solutions of the Hsp70 protein are studied, the dependence of the luminescence spectrum on the excitation wavelength is revealed, and the temperature dependence of luminescence intensity of tyrosine and tryptophan residues in the temperature interval of 20–80° C is analyzed. The luminescence method is used to determine temperature interval (42–57° C) in which protein melting takes place. An increase in the fluorescence quantum yield of tryptophan and the bathochromic shift of the emission spectrum of denatured Hsp70 prove that transition takes place of tryptophanyls to the surface of the protein molecule.

Исследованы спектрально-люминесцентные свойства водных растворов белка БТШ70, показана зависимость спектра испускания люминесценции от длины волны возбуждения, исследована зави- симость интенсивности люминесценции тирозиновых и триптофановых остатков от температуры в диапазоне от 20 до 80°С. Люминесцентным методом определен температурный интервал (42-57°С), в котором происходит плавление белка. Увеличение квантового выхода флуоресценции триптофа- на и батохромный сдвиг спектра испускания денатурированной формы БТШ70 свидетельствуют о выходе триптофанилов на поверхность молекулы белка.