ABSTRACT
It has been found that the development of schizophrenia and some other psychiatric disorders is related to defects in the normal functioning of Disrupted-In-Schizophrenia 1 (DISC1). It is a large-sized protein containing 855 residues and acts as an active hub at the core of many interactions with various proteins. On the other hand, NudE Neurodevelopment Protein 1 Like 1 (Ndel1) plays a role in nervous system development via interaction with the DISC1. It was shown that some point mutations on DISC1 have clinical implications. In line with these reports, here we have used the NMR structure of the wild-type (WT) C-terminal tail of DISC1 in complex with the N-terminal fragment of Ndel1, and have constructed the three-dimensional structures of L62Q and L29Q mutants, as the pathologic variants of the complex. The time-dependent interaction of DISC1 with Ndel1 in the WT complex and mutants was simulated by performing molecular dynamics (MD) simulation using programs in the GROMACS package. It was found that the flexibility of residues in some regions of the protein chains increases, and secondary structural changes from ordered toward unordered one leads to destabilizing of the complex in mutants. Destabilization of the complex upon substitution of Leu by Gln was also confirmed by analysis of the contact map plot.Communicated by Ramaswamy H. Sarma.
Subject(s)
Carrier Proteins , Nerve Tissue Proteins , Humans , Nerve Tissue Proteins/chemistry , Carrier Proteins/chemistry , Point Mutation , Molecular Dynamics SimulationABSTRACT
Nervous inflammation is an important component of the pathogenesis of neurodegenerative diseases including chronic diabetic neuropathic pain. In order to obtain a decrease in the progression of diabetic neuronal damage, it may be necessary to examine therapeutic options that involve antioxidants and anti-inflammatory agents. The aim of this study was to investigate the attenuation of inflammatory factors with endurance training in the spinal cord of rats with neuropathic pain. Thirty-two 8-week-old male Wistar rats (with a weight range of 204 ± 11.3 g) were randomly divided into 4 groups (n = 8), including (1) diabetic neuropathy (50 mg/kg streptozotocin intraperitoneal injection), (2) diabetic neuropathy training (30 minutes of endurance training at 15 meters per minute, 5 days a week for 6 weeks), (3) healthy training, and (4) healthy control. After confirmation of diabetic neuropathy by behavioral tests, training protocol and supplementation were performed. The NLRP3, P38 MAPK, TNF-α, and IL-1ß gene expressions were measured by a real-time technique in the spinal cord tissue. One-way analysis of variance and Tukey's post hoc test were used for statistical analysis. Endurance training reduced the sensitivity of the nervous system to thermal hyperalgesia and mechanical allodynia; also, compared to the diabetic neuropathy group, the gene expressions of NLTP3, P38 MAPK, TNF-α, and IL-1ß were significantly reduced by endurance training (P < 0.05). Endurance training modulates NLRP3, P38 MAPK, and TNF-α, IL-1ß gene expressions and improves the sensitivity of nociceptors to pain factors. Accordingly, it is recommended to use endurance training to reduce neuropathic pain for diabetics.
Subject(s)
Diabetes Mellitus , Diabetic Neuropathies , Endurance Training , Neuralgia , Animals , Biomarkers/metabolism , Diabetic Neuropathies/drug therapy , Diabetic Neuropathies/metabolism , Diabetic Neuropathies/pathology , Humans , Hyperalgesia/metabolism , Hyperalgesia/pathology , Male , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Neuralgia/drug therapy , Neuralgia/metabolism , Rats , Rats, Wistar , Spinal Cord , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/therapeutic use , p38 Mitogen-Activated Protein Kinases/metabolism , p38 Mitogen-Activated Protein Kinases/therapeutic useABSTRACT
Carbon-doped titanium dioxide photocatalyst with improved performance in visible light was prepared via the typical sol-gel method. Microcrystalline cellulose (MCC) was used as carbon elements source. The prepared pure and carbon-doped TiO2 samples were calcined at 400-650°C in air and the effect of annealing temperature on the stability of carbon ions was investigated. EDX analysis showed the presence of 5.66â wt.% carbon atoms in TiO2 nanoparticles formed on MCC, which was attributed to the doping of carbon atoms in TiO2 lattice. Carbon doping was also confirmed by Raman spectroscopy. According to the UV-VIS DRS analysis, the band gap of TiO2 particles decreased from 2.96 to 2.71â eV in pure and carbon-doped TiO2, respectively. Therefore the visible light absorbance increased to 15.05% compared to 0% absorbance in pure TiO2. The heat treatment of carbon-doped TiO2 nanostructures showed that carbon element could escape from the O-Ti-O lattice at temperatures higher than 600°C. According to the SEM images, synthesis of TiO2 in presence of MCC also limited the growth of TiO2 nanoparticles and controlled the morphology and aggregation of nanoparticles. Carbon doping improved the photocatalytic performance of TiO2 photocatalyst compared to the pure nanoparticles in degradation of methylene blue in the aqueous phase. Carbon-doped TiO2 attained the efficiency of 56.25%, 51.18% and 62.95% under UV, visible and solar lights, respectively, compared to 28.43%, 6.36% and 33.65% related to the pure TiO2.