Despite emerging contemporary biotechnological methods such as gene- and stem cell-based therapy, there are no clinically established therapeutic strategies for neural regeneration after spinal cord injury. Our previous studies have demonstrated that transplantation of genetically engineered human umbilical cord blood mononuclear cells producing three recombinant therapeutic molecules, including vascular endothelial growth factor (VEGF), glial cell-line derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) can improve morpho-functional recovery of injured spinal cord in rats and mini-pigs. To investigate the efficacy of human umbilical cord blood mononuclear cells-mediated triple-gene therapy combined with epidural electrical stimulation in the treatment of spinal cord injury, in this study, rats with moderate spinal cord contusion injury were intrathecally infused with human umbilical cord blood mononuclear cells expressing recombinant genes VEGF165, GDNF, NCAM1 at 4 hours after spinal cord injury. Three days after injury, epidural stimulations were given simultaneously above the lesion site at C5 (to stimulate the cervical network related to forelimb functions) and below the lesion site at L2 (to activate the central pattern generators) every other day for 4 weeks. Rats subjected to the combined treatment showed a limited functional improvement of the knee joint, high preservation of muscle fiber area in tibialis anterior muscle and increased H/M ratio in gastrocnemius muscle 30 days after spinal cord injury. However, beneficial cellular outcomes such as reduced apoptosis and increased sparing of the gray and white matters, and enhanced expression of heat shock and synaptic proteins were found in rats with spinal cord injury subjected to the combined epidural electrical stimulation with gene therapy. This study presents the first proof of principle study of combination of the multisite epidural electrical stimulation with ex vivo triple gene therapy ( VEGF , GDNF and NCAM ) for treatment of spinal cord injury in rat models. The animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee (approval No. 2.20.02.18) on February 20, 2018.
One of the most important sectors of the economy in Russia is industry. In this regard, the state seeks to stimulate the development of innovations in this area. Over the past few years, many industrial sectors in Russia have been in a crisis situation, which is caused by several factors: a decrease in the level of real investment, a decrease in the solvent demand of enterprises-customers and public consumers, and the introduction of financial and economic sanctions in 2014 against Russia by the United States and the European Union countries, as well as the effect of other macroeconomic factors independent of the activities of industrial enterprises. This study aims to identify the main trends in the development of industrial production in Russia in recent years, and an explanation of its causes. This topic is relevant in connection with the foregoing and may be of interest to academic economists studying industry development trends in developing countries. The aim of the study is to analyze the state of industry in Russia from 2015 to 2018 during the period of sanction pressure on the industrial and financial sectors of the Russian economy. Having examined the latest data on the results of the activity of Russian industry as a whole, one can note positive trends in the development of industrial production in Russia despite a number of negative internal and external factors. It is concluded that today, for Russia, the strategic tasks in industrial policy are reduced to overcoming technological backwardness and carrying out technological modernization of industries based on the use of innovative achievements, as well as import substitution for the sectors of the economy that are sensitive to foreign sanctions.
Today we have an inadequate set of methods for treating spinal cord injuries. Gene therapy (direct or cell-mediated) is one of the most promising approache for successfully solving this problem. The present study focused on evaluating the therapeutic efficacy of genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG), and the neuronal cell adhesion molecule (NCAM) in the model of contusion injury in rats. The therapeutic genes in two combinations (VEGF + GDNF + NCAM and VEGF + ANG + NCAM) either were administered intrathecally, with the help of adenoviral vectors, or on cellular carriers - genetically modified mononuclear cells of human umbilical cord blood. On 30 day after a spinal cord injury, the safety of the myelin fibers of the white matter and the kinematics of the left hindlimb joints in experimental animals were analyzed. Both therapeutic combinations of genes have shown a positive effect on the conduction pathways and kinematics of the joints.
Aim. To determine the level of gene expression of the serotonergic neurotransmission system (Slc6a4, Tph2, Htr1b, Htr2a) in the cervical and lumbar enlargement of the spinal cord for mice after 30-day microgravity exposure simulation by using the antiorthostatic unloading model by Morey-Holton et al. and a subsequent 7-dayrecovery period. Methods. The experimental animals were divided into three groups: Unloading group with mice undergoes hindlimb-unloading procedure for 30 days (n=5); Recovery group with mice undergoes hindlimb-unloading procedure for 30 days, followed by readaptation within 7 days (n=5); Control group with mice kept at standard vivarium conditions (n=5). The expression level of genes encoding synaptic proteins in the central nervous system was estimated by a real-time polymerase chain reaction. Results. There were no statistically significant differences between the studied groups regarding the Tph2, Htr1b, and Htr2a expressions in the cervical and lumbar enlargement of the spinal cord. Compared to the Control group, a statistically significant increase (6.3 times) in the level of Slc6a4 expression in the lumbar spinal cord was revealed after microgravity exposure simulation (Unloading group), followed by a 3-fold decrease during the readaptation period (Recovery group ). Conclusion. The expression level of the Slc6a4 gene, which encodes carrier protein involved in the function of serotonergic synapses, may indicate the potential involvement of this neurotransmitter system in the pathogenesis of movement disorders after microgravity exposure simulation on earth.
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