Boron neutron capture therapy (BNCT) is a targeted therapy based on a selective damage to cancer cells due to the interaction between boron-10 isotope and neutron. Reactor-based BNCT has been found to be effective in the treatment of high-grade gliomas. It is believed that compact accelerator-based neutron sources will ensure widespread adoption of the technique in clinical practice. New accelerator-based neutron sources are being actively developed all over the world. At the Institute of Nuclear Physics (Russia), the accelerator-based neutron source was developed for pre-clinical studies of BNCT.Purpose: to determine the cytopathic effects of accelerator-based BNCT on the human U87-glioblastoma cell line and to select a concentration of boron drugs that do not have a toxic effect on the cells before irradiation in vitro.Material and Methods. To assess the cytopathic effects (MTT test and colony-forming assay) of various concentrations of boron-containing drugs, U87 cells were incubated with boronophenylalanine (BPA) and sodium borocaptate (BSH) for 1, 2 and 10 days. The effect of BNCT on the U87 cell line was determined using colony-forming assay.Results. The MTT test showed a decrease in cell survival at a boron-10 isotope concentration of 160 μg/ml after 48 hours and 640 μg/ml after 24 hours of incubation for BPA. The cytopathic effects for sodium BSH appeared at a boron concentration of 80 µg / ml after 48 hours of incubation, and survival fraction of cells was reduced to 89 % compared to the control. According to the colonyforming assay, the cytotoxic effects of BSH and BPA at a boron concentration of 40 µg/ml in the medium were 79.6 and 84 %, respectively. The proportions of surviving cells were 18 ± 2 % and 13 ± 2 % after epithermal neutron irradiation in the presence of boronophenylalanine and in the presence of sodium borocaptate, respectively. Cell death without boron drugs occurred due to the neutron elastic scattering, nuclear reactions of thermal neutron capture by hydrogen and nitrogen, and accompanying gamma radiation.Conclusion. The study clearly showed a decrease in the proportion of surviving U87 cells after accelerator-based BNCT in the presence of 10B-enriched BSH and BPA.

Autophagy is a dynamic cellular process involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. It is particularly important in neurons, which do not have a proliferative option for cellular repair. Autophagy has been shown to be suppressed in the striatum of a transgenic mouse model of Parkinson’s disease. Cystatin C is one of the potent regulators of autophagy. Changes in the expression and secretion of cystatin C in the brain have been shown in amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s diseases, and in some animal models of neurodegeneration, thus proving a protective function of cystatin C. It has been suggested that cystatin C plays the primary role in amyloidogenesis and shows promise as a therapeutic agent for neurodegenerative diseases (Alzheimer’s and Parkinson’s diseases). Cystatin C colocalizes with the amyloid β-protein in the brain during Alzheimer’s disease. Controlled expression of a cystatin C peptide has been proposed as a new approach to therapy for Alzheimer’s disease. In Parkinson’s disease, serum cystatin C levels can predict disease severity and cognitive dysfunction, although the exact involvement of cystatin C remains unclear. The aim: to study the role of cystatin C in neurodegeneration and evaluate the results in relation to the mechanism of autophagy. In our study on humans, a higher concentration of cystatin C was noted in cerebrospinal fluid than in serum; much lower concentrations were observed in other biological fluids (intraocular fluid, bile, and sweat). In elderly persons (61–80 years old compared to practically healthy people at 40–60 years of age), we revealed increased cystatin C levels both in serum and intraocular fluid. In an experiment on C57Bl/6J mice, cystatin C concentration was significantly higher in brain tissue than in the liver and spleen: an indication of an important function of this cysteine protease inhibitor in the brain. Using a transgenic mouse model of Parkinson’s disease (5 months old), we demonstrated a significant increase in osmotic susceptibility of brain lysosomes, depending on autophagy, while in a murine model of Alzheimer’s disease, this parameter did not differ from that in the appropriate control.

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Introduction. Boron neutron capture therapy (bnct) is a promising method for treating tumors, in particular, infiltrative malignant tumors, due to the selective destruction of tumor cells without damaging the surrounding normal tissues. This type of therapy is based on nuclear reaction of neutron capture by stable 10b isotope. For the successful implementation of bnct, boron delivery drugs that must be selectively accumulated in malignant cells in a sufficient amount, and a neutron source with the energy required for the neutron capture reaction are needed. At the budker institute of nuclear physics, the accelerator-based neutron source was designed with flux parameters allowing studies on bnct to be conducted.Objective: to assess the effect of bnct on tumor and normal cell lines using borphenylalanine (bpa), borcaptate (bsh) and liposomal borcaptat as boron delivery drugs.Materials and methods. Human cell cultures: glioblastoma (u87), colorectal human adenocarcinoma (sw-620), human melanoma (sk-mel28) and primary embryonic cell lines were irradiated with a neutron flux at the presence of bpa, bsh and liposomal bsh with a concentration of 10b 40 μg/ml. The short-term cytotoxic effect of irradiation was evaluated using trypan blue. Cell survival 96 hours after irradiation was determined using mtt test, and survival fraction was evaluated using the clonogenic test.Results. Early cytotoxic effects of irradiation were not observed for all 4 cell lines. According to mtt and clonogenic tests, the most pronounced effect of bnct was noticed for sw-620 and u87 lines, regardless of boron delivery drug used. For sk-mel28 line, the best effect was achieved after irradiation with liposomal borocaptate. For the primary transplanted embryonic line, high toxicity was revealed when bnct was performed with borphenylalanine and borcaptate.Conclusion. The data obtained indicate that the accelerator-based bnct using boron delivery drugs, such as borphenylalanine, borcaptate and liposomal borcaptat, has a positive effect on tumor lines of glioblastoma, colorectal adenocarcinoma and melanoma.

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Here, to study the relationship between anxiety levels with changes in the neurometabolic profile in the hippocampus and amygdala, an experimental predator stress model was reproduced in which Sprague-Dawley rats were exposed to cat urine for 10 minutes on a daily basis for 10 days. At the time of presentation of the stimulus, an online survey of behavioral reactions was conducted. Fear, aggressiveness, avoidance of stimulus and grooming were recorded. Fourteen days after the completion of the last stress exposure, the total level of anxiety was determined in the test of the“cross maze”. Using the method of in vivo NMR spectroscopy, the content of neurometabolites was determined in the hippocampus and in the amygdala. According to the peculiarities of behavioral reactions to a stressor, animals were retrospectively divided into two phenotypes. The first phenotype used a passive behavioral strategy, and the second phenotype was active. In animals of the first phenotype, the indicators of anxiety behavior remained at the control level. In animals of the second phenotype, a decrease in anxiety was observed. Animals of the second phenotype showed elevated levels of lactate in the hippocampus compared to animals of the first phenotype, and the lowest N-acetylaspartate levels significantly differed from those in the control and the first phenotype animals. In the amygdala, in animals of the second phenotype, the content of taurine is sharply reduced in comparison with those in the control and the animals of the first phenotype. Thus, the results obtained indicate a relationship of post-stress changes in anxiety, with the peculiarities of the behavioral reactions presented at the moment of the immediate action of the stressor. Among the hippocampal and amygdala neurometabolites, the most informative for the characterization of the anxiolytic action of the predator stress are identified.

The purpose of the study was to analyze the antitumor effects of the extract of mycelium from Duddingtonia flagrans (strain F-882) on xenografts of human C33a cervical cancer cells.Material and Methods. To evaluate the antitumor effect, we used the absolute values of xenograft volumes and calculated the tumor growth inhibition and the index of tumor growth.Results. At the first stage of the experiment, a 4-week subcutaneous injection of the water extract of F-882 resulted in an almost twofold slowdown in xenograft growth, with the tumor growth inhibition value of 50.6 %. In the second stage of the experiment, a 2.5-week subcutaneous injection followed by a 1.5-week intratumoral injection of F-882 also caused the tumor growth inhibition. After completing F-882 injections, the effect of tumor growth inhibition continued for 2.5 weeks and the tumor growth inhibition value was 58.7 %.Conclusion. The mycelium extract F-882 was shown to have an antitumor effect on subcutaneous xenografts of human C33a cervical carcinoma cells.

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