Evaluation of direct and cell-mediated triple-gene therapy in spinal cord injury in rats

© 2017 Elsevier Inc.Current treatment options for spinal cord injury (SCI) are scarce. One of the most promising innovative approaches include gene-therapy, however no single gene has so far been shown to be of clinical relevance. This study investigates the efficacy of various combinations of vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), angiogenin (ANG) and neuronal cell adhesion molecule (NCAM) in rats. Multiple therapeutic genes were administered intrathecally either via adenoviral vectors or by using genetically modified human umbilical cord blood mononuclear cells (hUCBMCs). Following the induction of SCI, serial assessment of cord regeneration was performed, including morphometric analysis of gray and white matters, electrophysiology and behavioral test. The therapeutic gene combinations VEGF + GDNF + NCAM and VEGF + ANG + NCAM had positive outcomes on spinal cord regeneration, with enhanced recovery seen by the cell-based approach when compared to direct gene therapy. The efficacy of the genes and the delivery methods are discussed in this paper, recommending their potential use in SCI

Analysis of recombinant VEGF gene expression by genetically modified umbilical cord blood mononuclear cells in experiment in vivo

To obtain a significant therapeutic effect transplanted genetically modified cells should have an enhanced ability to survive and active expression of the therapeutic gene. In this paper, by using immunofluorescent staining we investigated the functional activity of the gene-cell formulation designed to deliver a therapeutic gene into the area of regeneration. As a model we used transgenic SOD1-G93A mice with amyotrophic lateral sclerosis phenotype which received xenotransplantation of human umbilical cord blood mononuclear cells, genetically modified with adenoviral expression vector encoding vascular endothelial growth factor (VEGF) and the reporter green fluorescent protein (EGFP). Results of the study allowed to establish not only the duration of survival of transplanted cells, but also the efficiency of expression of recombinant genes in genetically modified cells in vivo. Double immunofluorescent staining with antibodies against human nuclear antigen HNA and VEGF detected HNA+/VEGF+ cells in the terminal stage of disease 15 weeks after transplantation. These data suggest that genetically modified umbilical cord blood mononuclear cells, transplanted into SOD1-G93A transgenic mice, are able to penetrate the blood-brain barrier and migrate into the area of degeneration of nerve tissue and survive from the time of transplantation until the death of animals at the terminal stage of disease. At that time adenoviral expression vector encoding therapeutic gene is functionally active in transplanted cells, and secretory products of recombinant gene act on target cells by a paracrine mechanism

THE DYNAMICS OF THE CLIMATIC CONDITIONS OF THE TEREK-KUMA LOWLAND DURING 120 YEARS

Abstract. Aim. This article is devoted to the analysis of climatic conditions of the territory of the Terek-Kuma Lowland. Data of the last 60 years (1951–2010) are compared with conditions of 1881–1935 (air temperature) and 1898–1948 (precipitation and relative humidity). Determination of tendencies in the age-old range, and for the last 60 years is given.Location. Terek-Kuma Lowland, Eastern Ciscaucasia, Russia.Methods. The following environmental parameters are characterized: the amount of monthly rainfall, average temperatures and humidity, evaporation, moisture ratio and the lack of moisture. Statistical characteristics (mean, variance, coefficient of variation) of annual precipitation, mean annual temperature and humidity, evaporation, lack of moisture are calculated. Separately, the same parameters were calculated for the warm (April – October) and cold (November – March) seasons. Significance of differences between them was assessed by the standard deviation (α) and the coefficient of variation (Cv).Results. Our analysis of the moisture conditions of the Terek-Kuma Lowland in the last 60 years has shown significant changes in key climate indicators in comparison with the corresponding (for the duration of observations) rates in preceding years. The average annual temperature for the period , including for the warm season (April – October), increased by 0.6 °C, annual precipitation decreased respectively by 29.6 and 35.9 mm. Coefficient of humidity (ratio of annual precipitation to evaporation) in the ambient range from 0.11 in 1898–1948 increased to 0.14 in 1951–2010.Conclusions. Aridity of the climate did not increase on this territory. In 1951–2010 coefficient of humidity increased to 0.14, and fits into the range for dry (arid) regions, while in 1898–1948 coefficient of humidity was 0.11 and it was an important characteristic of extra arid (very dry) areas

DYNAMICS OF ENVIRONMENTAL FACTORS AND REALIZATION OF THE POTENTIAL PRODUCTIVITY OF ECOSYSTEMS WITH MEADOW-CHESTNUT SOILS IN THE TEREK-KUMA PERI-CASPIAN LOWLAND

The aim is to reveal theoretically possible productivity of pasture phytocenosis on meadow-chestnut soils in protected area of Terek-Kuma Lowland.Methods. To determine the dynamics of the basic physical and chemical properties of soil, evaporation, humidity coefficient (HC) of the area, the productivity of phytocenoses and utilization factors of photosynthetically active radiation (PAR).Results. Highly productive ephemeral synusia (5 q/ha of air-dry weight) is formed in years with precipitation of 80-85 mm during April - May at a relative humidity of 70-73%, with evaporation of 130-140 mm, humidity coefficient of 0.30, and integral of moisture of 29.8. Decreasing precipitation amount in the same period to 25-26 mm, the relative humidity to 61%, humidity coefficient to 0.06, evaporation to 200-202mm form an integral of aridity of 37.3, where the 0- 24 cm Cl ion content in the soil increase to 5.56 mgEq/100g, the yield of a biomass is reduced to 1.0 q/ha. Increase of 102 mm in rainfall in July – August period results in humidity coefficient increase - 0.21, decrease of Cl- content in horizons of А+В to 1.40 mg-eq./100g. Productivity of grasses and saltwort increases to 21.1q/ha. The utilization factor of PAR by phytocenosis makes up 0,023-0,033 (21.4% share of ephemera, herbs and saltwort make up 78.6%) and had little effect on productivity of phytocenosis.Main conclusion. The formation of a biomass in the meadow-chestnut soil is the result of the combined effects of the amount of rainfall, evaporation, humidity coefficient, the degree and the chemistry of soil salinity. Were calculated multiple regression equations expressing the relationship between these factors

THE DYNAMICS OF THE CLIMATIC CONDITIONS OF THE TEREK-KUMA LOWLAND DURING 120 YEARS

Abstract. Aim. This article is devoted to the analysis of climatic conditions of the territory of the Terek-Kuma Lowland. Data of the last 60 years (1951–2010) are compared with conditions of 1881–1935 (air temperature) and 1898–1948 (precipitation and relative humidity). Determination of tendencies in the age-old range, and for the last 60 years is given.Location. Terek-Kuma Lowland, Eastern Ciscaucasia, Russia.Methods. The following environmental parameters are characterized: the amount of monthly rainfall, average temperatures and humidity, evaporation, moisture ratio and the lack of moisture. Statistical characteristics (mean, variance, coefficient of variation) of annual precipitation, mean annual temperature and humidity, evaporation, lack of moisture are calculated. Separately, the same parameters were calculated for the warm (April – October) and cold (November – March) seasons. Significance of differences between them was assessed by the standard deviation (α) and the coefficient of variation (Cv).Results. Our analysis of the moisture conditions of the Terek-Kuma Lowland in the last 60 years has shown significant changes in key climate indicators in comparison with the corresponding (for the duration of observations) rates in preceding years. The average annual temperature for the period , including for the warm season (April – October), increased by 0.6 °C, annual precipitation decreased respectively by 29.6 and 35.9 mm. Coefficient of humidity (ratio of annual precipitation to evaporation) in the ambient range from 0.11 in 1898–1948 increased to 0.14 in 1951–2010.Conclusions. Aridity of the climate did not increase on this territory. In 1951–2010 coefficient of humidity increased to 0.14, and fits into the range for dry (arid) regions, while in 1898–1948 coefficient of humidity was 0.11 and it was an important characteristic of extra arid (very dry) areas.</p

THEORETICALLY POSSIBLE AND PRACTICALLY RELIZABLE PRODUCTIVITY OF THE LIGHT-CHESTNUT SOILS OF THE NORTHERN WEST PRECASPIAN REGION ACORDING TO THE MOISTURE AND SOLINITY (ON EXAMPLE OF KOCHUBEY BIOSPHERE STATION OF PIBR DNC RAS)

Abstract. The article presents the productivity data, the species composition and utilization rates phytocenoses FAR depending on theintegrals of dryness and moisture climate volatility, coefficient of moisture and dynamics of harmful salts in the soil according to years and seasons of the year.Methods.The studies were conducted on light-chestnut carbonate saline soil of Kochubey biosphere stations on the territory of the Terek- Kuma Lowland Precaspianregion in 2011–2013. The calculation of the use of FAR was conducted using the formula A.A. Nichiporovich to determine the theoretically possible yield of plants. Klimatogrammy during these years has been compiled by the method Walter. Stocks above and below ground plant matter into account by the method of A.A.Titlyanova.The names of species given by S.K. Cherepanov.Results. According to the results of our observations, the most important for achieving high productivity ephemeral synusia under these conditions include precipitation for April and May. Between the amount of rainfall in April and May and the productivity of abovegroundphytomass ofephemera direct correlation exists, which in 2011 had a strong, and in the next two years-the average severity. In 2012 the volatility increased, KU fell in 5 times. Such weather conditions contributed to the rise of water-soluble salts to the upper soil horizons and substantial change in species composition phytocenoses. The content Cl- in the layer 0–20 cm over the same period 2011 increased in 3.9 times, SO4--- 1.7 in times. If in 2011 the stepen soil salinity in the layer 0–35 cm characterized as weak, in 2012 the average at the same chloride- sulphate type of salinity. Obviously , an increase in the content of Cl- - ions and its relationship to the S04-- contributed to a dramatic increase in productivity and thistle herbs in 2012. Luxuriant growth of Salsola iberica Sennen et Pau particularly stood.Thus, the formation of a biomass and species composition in the Terek-Kuma Lowland Precaspian is the result of the cumulative effects of different environmental factors, the main ones are: precipitation, air temperature, its relative humidity, evaporation, moisture ratio and the degree of soil salinity and chemistry. These dependencies are expressed by the following multiple regression equation. Depending on climatic conditions, the pasture use phytocoenoses 0,20–0,57 % FAR. Win ephemera and ephemeroids of this amount is an average over years of research about 20 %, the remaining 80%-grasses and thistle, the majority of which occur in Salsola iberica Sennen et Pau, bad eating animals and less valuable as fodder representative thistle. Main conclusion.Our results suggest that, in the context of the Terek-Kuma Lowland there are two peaks of productivity of phytocenoses: first one of ephemeras andephemeroids is in mid-May to early July, the second one of grasses and thistleis in the second half of September. The main factors to achieve high productivity ephemeras and ephemeroids on light-chestnut soil of the North- West Precaspian are about 80–85 mm rainfall during April – May, with average daily air temperature 15–16 °C, its relative humidity 70–73 %, volatility of 130–140 mm, KU 0.30, chloride-sulphate type of salinity in the layer of a low degree of 0–35 cm. In years with heavy rainfall in July and August (102 mm), despite an increase in average daily air temperature to 25–26 °C and volatility to 275mm, a relatively high KU (0.21), the content of Cl-in the layer 0–20 cm reduced 1,40 mg-ekv./100 g, ratio Cl-:SO4-- to 0,59–0,84 and productivity grasses and Salsola iberica Sennen et Pauincreased. The FAR utilization reaches 0.57, of which the biomass of grasses and Salsola iberica Sennenet Pau falls 87.6 % (2012).The task of future research is to determine its phitomeliorative role: removal of salt-forming ions from the soil and itsfurther redistribution in ecosystem, considering the nature of movement on the territory of Salsola iberica Sennen et Pau