Polymerization of new aniline derivatives: synthesis,characterization and application as sensors

This work is focused on modifying aniline monomers with various characteristics that allows one to study the effect of the substituent on the respective polymer. A series of new polyaniline (PANI) derivatives based on an ortho-substituted aniline derivative, 2-(1-methylbut-2-en-1-yl)aniline, were synthesized and characterized. The structures and composition of the polymers that we synthesized were confirmed by elemental analysis, proton nuclear magnetic resonance (¹H NMR) spectroscopy, carbon nuclear magnetic resonance (¹³C NMR) spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), and ultraviolet-visible spectroscopy (UV). Characterization by FT-IR and UV-visible spectroscopy techniques indicated that the polymers exist in protonated emeraldine forms. Scanning electron microscope (SEM) results revealed that the surface morphology of the resulting polymers changed from a heterogeneous hierarchical to spherical structure upon changing the substituent in the aniline monomers. The polymers are soluble in common organic solvents, so they can be used to make films. The electrical properties of the polymers were studied and their high sensitivity to moisture and ammonia was demonstrated. The results of the studies showed the prospects of using thin polymer films in the design of chemical sensors. The impact of the substituent on the polymer characteristics is rationalized in terms of steric and electronic effects.

This work is focused on modifying aniline monomers with various characteristics that allows one to study the effect of the substituent on the respective polymer.     

Gene-modified leucoconcentrate for personalized ex vivo gene therapy in a mini pig model of moderate spinal cord injury

We previously demonstrated that gene-modified umbilical cord blood mononuclear cells overexpressing a combination of recombinant neurotrophic factors are a promising therapeutic approach for cell-mediated gene therapy for neurodegenerative diseases, neurotrauma, and stroke. In this study, using a mini pig model of spinal cord injury, we proposed for the first time the use of gene-modified leucoconcentrate prepared from peripheral blood in the plastic blood bag for personalized ex vivo gene therapy. Leucoconcentrate obtained from mini pig peripheral blood was transduced with a chimeric adenoviral vector(Ad5/35 F) that carried an enhanced green fluorescent protein(EGFP) reporter gene in the plastic blood bag. The day after blood donation, the mini pigs were subjected to moderate SCI and four hours post-surgery they were intravenously autoinfused with gene-modified leucoconcentrate. A week after gene-modified leucoconcentrate therapy, fluorescent microscopy revealed EGFP-expressing leucocytes in spinal cord at the site of contusion injury. In the spleen the groups of EGFP-positive cells located in the lymphoid follicles were observed. In vitro flow cytometry and fluorescent microscopy studies of the gene-modified leucoconcentrate samples also confirmed the production of EGFP by leucocytes. Thus, the efficacy of leucocytes transduction in the plastic blood bag and their migratory potential suggest their use for temporary production of recombinant biologically active molecules to correct certain pathological conditions. This paper presents a proof-of-concept of simple, safe and effective approach for personalized ex vivo gene therapy based on gene-modified leucoconcentrate autoinfusion. The animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee(approval No. 5) on May 27, 2014.     

Combination of epidural electrical stimulation with ex vivo triple gene therapy for spinal cord injury:a proof of principle study

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.     

Application of neurotrophic and proangiogenic factors as therapy after peripheral nervous system injury

The intrinsic ability of peripheral nerves to regenerate after injury is extremely limited,especially in case of severe injury.This often leads to poor motor function and permanent disability.Existing approaches for the treatment of injured nerves do not provide appropriate conditions to support survival and growth of nerve cells.This drawback can be compensated by the use of gene therapy and cell therapy-based drugs that locally provide an increase in the key regulators of nerve growth,including neurotrophic factors and extracellular matrix proteins.Each growth factor plays its own specific angiotrophic or neurotrophic role.Currently,growth factors are widely studied as accelerators of nerve regeneration.Particularly noteworthy is synergy between various growth factors,that is essential for both angiogenesis and neurogenesis.Fibroblast growth factor 2 and vascular endothelial growth factor are widely known for their proangiogenic effects.At the same time,fibroblast growth factor 2 and vascular endothelial growth factor stimulate neural cell growth and play an important role in neurodegenerative diseases of the peripheral nervous system.Taken together,their neurotrophic and angiogenic properties have positive effect on the regeneration process.In this review we provide an in-depth overview of the role of fibroblast growth factor 2 and vascular endothelial growth factor in the regeneration of peripheral nerves,thus demonstrating their neurotherapeutic efficacy in improving neuron survival in the peripheral nervous system.     

Photoconductivity of Thin Films Obtained from a New Type of Polyindole

The optoelectronic properties of a new poly(2-ethyl-3-methylindole) (MPIn) are discussed in this paper. The absorption and photoluminescence spectra were studied. The electronic spectrum of MPIn showed a single absorption maximum at 269 nm that is characteristic of the entire series of polyindoles. The fluorescence spectra show that the emission peaks of the test sample are centered around 520 nm. The photoconductivity of thin film samples of MPIn polyindole was studied by measuring the current-voltage characteristics under ultraviolet radiation with a wavelength of 350 nm. Samples of phototransistors were obtained, where thin films of MPIn polyindole were used as a transport layer, and their characteristics were measured and analyzed. The value of the quantum efficiency and the values of the mobility of charge carriers in thin polyindole films were estimated.