Electrospun nanofibrous scaffolds in neural tissue engineering provide an alternative approach for neural regeneration. Since the topography of a surface affects the microscopic behaviour of material; the creation of nanoscale surface features, which mimic the natural roughness of live tissue, on polymer surfaces can promote an appropriate cell growth and proliferation. In this research, a unique PLGA nanofibrous structure was fabricated without any post-electrospinning treatment. Scaffolds were prepared in two general groups: cylindrical and ribbon-shaped electrospun fibres, with smooth and rough (porous and grooved) surfaces. The experiments about nerve cell culture have demonstrated that the nanoroughness of PLGA electrospun scaffolds can increase the cell growing rate to 50 % in comparison with smooth and conventional electrospun scaffolds. SEM and AFM images and MTT assay results have shown that the roughened cylindrical scaffolds enhance the nerve growth and proliferation compared to smooth and ribbon-shaped nanofibrous scaffolds. A linear interaction has been found between cell proliferation and surface features. This helps to approximate MTT assay results by roughness parameters.

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Angiogenesis, the development and growth of blood vessels, is a major topic of research which began in 1971 with Folkman's original hypothesis. Different mechanisms of blood vessel growth are sprouting and intussusceptive angiogenesis, vascular mimicry, and blood vessel cooption. Dis-regulated angiogenesis may result in numerous angiogenic diseases and is responsible for solid tumor growth and metastasis. Vascular endothelial cells are generally dormant in adult but in pathological conditions when tumors reach a size of about 0.2-2.0 mm in diameter, they become hypoxic and hindered in tumor growth in the lack of angiogenesis. During angiogenic switch pro-angiogenic factors predominate and result in angiogenesis and tumor progression. Angiogenesis switch leads to the increased production of vascular endothelial growth factor (VEGF) following up-regulation of the hypoxia-inducible transcription factor. The VEGF family comprises from VEGF (VEGF-A), VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PlGF). The VEGF family of receptors consists of three protein-tyrosine kinases. Now, the most conventional approach for controlling tumor angiogenesis is blockade of the vascular endothelial growth factor (VEGF) pathway. The results of preclinical studies, substantial therapeutic effects of VEGF blockers have been stated in various types of human cancers, even in progressive or recurrent cancer cases.

Since spinal cord injury is a complicated problem, neural tissue repair, and regeneration strategies have received a great deal of attention. In this study, a three-dimensional (3D) nanofibrous core-sheath scaffold with nanorough sheath and aligned core were fabricated by a combined electrospinning method with water vortex and two-nozzle system. In vitro and in vivo biological tests were carried out on the poly(lactic-co-glycolic acid) (PLGA) scaffolds. The cell morphology and proliferation evaluation of nerve cells on 3D PLGA scaffolds were studied. Cells were properly orientated along the aligned fiber direction of the scaffold. In animal studies, adult rats received a complete lateral hemisection at the T9-T10 level. Scaffolds were engrafted to bridge 3 mm defects of 10 adult rat spinal cords; 10 rats were used as controls. For 8 weeks, motor and sensory recovery by open field locomotor scale, narrow beam and tail flick tests were assessed. Locomotor and sensory scores of grafted animals were significantly better than the control group. Histological findings demonstrated that the scaffold supports the axonal regeneration of injured spinal cords and regenerating axons were seen to enter the graft and extend along its length.

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer seen in children worldwide and in the Middle East. Although there have been major advances in treatment approaches for childhood ALL, serious toxicities do occur but with significant inter-individual variability. The aim of this study is to measure the frequency of polymorphisms in candidate genes involved in 6-Mercaptopurine (6-MP) disposition in a combined cohort of Middle Eastern Children with ALL, and evaluate whether these polymorphisms predict 6-MP intolerance and toxicity during ALL maintenance therapy. Methods: The study includes children treated for ALL on two treatment protocols from two cohorts; one from Lebanon (N = 136) and another from Kurdistan province of Iran (N = 74). Genotyping for the following six candidate genetic polymorphisms: ITPA 94C > A (rs1127354) and IVS2+21A > C (rs7270101), TPMT*2 238G > C (rs1800462), TPMT*3B 460G > A (rs1800460) and *3C 719A > G (rs1142345), and NUDT15 415C > T (rs116855232) was performed and analyzed in association with 6-MP dose intensity and toxicity. Results: As expected, TPMT and NUDT15 variants were uncommon. As for ITPA , both polymorphisms were more common in the Lebanese as compared to the Kurdish cohort with a minor allele frequency of 0.05 for 94C > A and 0.14 for IVS2+21A > C in the Lebanese only (N = 121), and of 0.01 for either ITPA polymorphism in Kurds. The most significant toxic effects were depicted with the NUDT15 polymorphism with a median 6-MP dose intensity of 33.33%, followed by 46.65% for TPMT*3A polymorphism, followed by 65.33% for two ITPA risk allele carriers and 74% for one ITPA risk allele carriers, in comparison to a median of 100% for the homozygous wild type in the combined cohort (P < 0.001). In addition, the onset of febrile neutropenia was significantly higher in variant allele carriers in the combined cohorts. Conclusions: These data confirm the predictive role of TPMT , NUDT15 , and ITPA in 6-MP intolerance in Middle Eastern children with ALL. Given the relatively high frequency of ITPA variants in our study and their significant association with 6-MP dose intensity, we recommend that physicians consider genotyping for ITPA variants in conjunction with TPMT and NUDT15 prior to 6-MP therapy in these children.