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| 1 | Combination of epidural electrical stimulation with ex vivo triple gene therapy for spinal cord injury:a proof of principle study显示文摘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. | Filip Olegovich Fadeev Farid Vagizovich Bashirov Vahe Arshaluysovich Markosyan Andrey Alexandrovich Izmailov Tatyana Vyacheslavovna Povysheva Mikhail Evgenyevich Sokolov Maxim Sergeevich Kuznetsov Anton Alexandrovich Eremeev Ilnur Ildusovich Salafutdinov Albert Anatolyevich Rizvanov Hyun Joon Lee Rustem Robertovich Islamov | 2021 | Neural Regeneration Research2021，16，3： | 4 |
| 2 | On application of euler’s differential method to a continued fraction depending on parameter显示文摘 | Bashirov A E Belaghi M J S | 2014 | Indian J of Pure and Applied Mathematics2014，45，3： | 1 |
| 3 | Exploiting colored Petri nets to decide on permutation admissibility显示文摘 | Bashirov R Kordon F Lort H | 2009 | Acta Informatiea2009，46，： | 1 |
| 4 | On concepts of controllability for deterministic and stochastic systems显示文摘 | Bashirov A E Mahmudov N I | 1999 | SlAM J Contro Optim1999，37，： | 1 |
| 5 | A randomized controlled study evaluating the effects of the temperature of insufflated CO2 on core body temperature and blood gases ( an experimental study) 显示文摘 | Bashirov E Cetiner S Emre M | 2007 | Surg Endosc2007，，： | 1 |
| 6 | Surgical creation of a reservoir-colostomy with reflex evacuation 显示文摘 | Zherlov GK Bashirov SR Krasnopemv AV | 2002 | Acta Chdalugosl2002，49，2： | 1 |
| 7 | A randomized controlled study evaluating the effects of the temperature of insuffiated CO2 on core body temperature and blood gases (an experimental study) 显示文摘 | Bashirov E Cetiner S Emre M | 2007 | Surg Endosc2007，21，10： | 1 |
| 8 | Quantum real-space transfer in a heterostructure over- grown on the cleaved edge of a superlattice显示文摘 | Gribnikov Z S Vagidov N Z Bashirov R R | 2003 | J Appl Pys2003，93，1： | 1 |
| 9 | Biostable electrospun microfibrous scaffolds mitigate hypertrophic scar contraction in an immune-competent murine model显示文摘 | Elizabeth R. Lorden Kyle J. Miller Mohamed M. Ibrahim Latif Bashirov Ellen Hammett Syandan Chakraborty Carlos Quiles-Torres M. Angelica Selim Kam W. Leong Howard Levinson | 2015 | Acta Biomaterialia2015，，： | 1 |
| 10 | Molecular and cellular changes in the post-traumatic spinal cord remodeling after autoinfusion of a genetically-enriched leucoconcentrate in a mini-pig model显示文摘Post-traumatic spinal cord remodeling includes both degenerating and regenerating processes,which affect the potency of the functional recovery after spinal cord injury(SCI).Gene therapy for spinal cord injury is proposed as a promising therapeutic strategy to induce positive changes in remodeling of the affected neural tissue.In our previous studies for delivering the therapeutic genes at the site of spinal cord injury,we developed a new approach using an autologous leucoconcentrate transduced ex vivo with chimeric adenoviruses(Ad5/35)carrying recombinant cDNA.In the present study,the efficacy of the intravenous infusion of an autologous genetically-enriched leucoconcentrate simultaneously producing recombinant vascular endothelial growth factor(VEGF),glial cell line-derived neurotrophic factor(GDNF),and neural cell adhesion molecule(NCAM)was evaluated with regard to the molecular and cellular changes in remodeling of the spinal cord tissue at the site of damage in a model of mini-pigs with moderate spinal cord injury.Experimental animals were randomly divided into two groups of 4 pigs each:the therapeutic(infused with the leucoconcentrate simultaneously transduced with a combination of the three chimeric adenoviral vectors Ad5/35‐VEGF165,Ad5/35‐GDNF,and Ad5/35‐NCAM1)and control groups(infused with intact leucoconcentrate).The morphometric and immunofluorescence analysis of the spinal cord regeneration in the rostral and caudal segments according to the epicenter of the injury in the treated animals compared to the control mini-pigs showed:(1)higher sparing of the grey matter and increased survivability of the spinal cord cells(lower number of Caspase-3-positive cells and decreased expression of Hsp27);(2)recovery of synaptophysin expression;(3)prevention of astrogliosis(lower area of glial fibrillary acidic protein-positive astrocytes and ionized calcium binding adaptor molecule 1-positive microglial cells);(4)higher growth rates of regeneratingβIII-tubulin-positive axons accompanied by a higher number of oligodendrocyte transcription factor 2-positive oligodendroglial cells in the lateral corticospinal tract region.These results revealed the efficacy of intravenous infusion of the autologous genetically-enriched leucoconcentrate producing recombinant VEGF,GDNF,and NCAM in the acute phase of spinal cord injury on the positive changes in the post-traumatic remodeling nervous tissue at the site of direct injury.Our data provide a solid platform for a new ex vivo gene therapy for spinal cord injury and will facilitate further translation of regenerative therapies in clinical neurology. | Maria Aleksandrovna Davleeva Ravil Rasimovich Garifulin Farid Vagizovich Bashirov Andrei Aleksandrovich Izmailov Leniz Faritovich Nurullin Ilnur Ildusovich Salafutdinov Dilara Zilbarovna Gatina Dmitrij Nikolaevich Shcherbinin Andrei Aleksandrovich Lysenko Irina Leonidovna Tutykhina Maksim Mikhailovich Shmarov Rustem Robertovich Islamov | 2023 | Neural Regeneration Research2023，18，7： | 1 |
| 11 | Surgical creationof a reservoir - colostomy with reflex evacuation 显示文摘 | Zherlov GK Bashirov SR Krasnopemv AV | 2002 | ActaChdalugosl2002，49，2： | 1 |
| 12 | A Randomized Con-trolled Study Evaluating the Effects of the Temperature ofInsufflated C02 on Core Body Temperature and Blood Gases(An Experimental Study)显示文摘 | Bashirov E Cetiner S Emre M | 2007 | Surg Endosc2007，21，10： | 1 |
| 13 | On path dependent loss and switch crosstalk reduction in optical networks显示文摘 | Bashirov R Karanfiller T | 2010 | Information Sciences2010，180，6： | 1 |
| 14 | Effects of Nonparabolicity on Electron Thermopower of Size-Quantized Semiconductor Films显示文摘thermopower 上的精力乐队的 nonparabolicity 的效果,在里面飞机有效质量和费密精力在使量子化尺寸的半导体电影被调查在一强壮当时非使量子化的磁场。我们作为厚度,集中和 nonparabolicity 参数的函数获得这些数量的表达式。nonparabolicity 的影响为退化、非退化的电子气体被学习,并且 nonparabolicity 改变厚度的特性和 thermopower 的集中依赖,这被显示出,在里面飞机有效质量和费密精力。而且,这些数量的大小显著地在 nano 电影在强壮的 nonparabolicity 的情况中关于 nonparabolicity 参数增加。集中依赖也被学习,并且集中什么时候减少,被显示出 thermopower 增加。这些结果与试验性的数据一致。 | BAHSHELI Guliyev AKBAR Barati Chiyaneh NOVRUZ Bashirov GENBER Kerimli | 2015 | Chinese Physics Letters2015，32，7： | 0 |
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