The Effect of Melatonin on Behavioral, Molecular, and Histopathological Changes in Cuprizone Model of Demyelination

Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. The protective effects of melatonin (MLT) on various neurodegenerative diseases, including MS, have been suggested. In the present study, we examined the effect of MLT on demyelination, apoptosis, inflammation, and behavioral dysfunctions in the cuprizone toxic model of demyelination. C57BL/6J mice were fed a chaw containing 0.2 % cuprizone for 5 weeks and received two doses of MLT (50 and 100 mg/kg) intraperitoneally for the last 7 days of cuprizone diet. Administration of MLT improved motor behavior deficits induced by cuprizone diet. MLT dose-dependently decreased the mean number of apoptotic cells via decreasing caspase-3 and Bax as well as increasing Bcl-2 levels. In addition, MLT significantly enhanced nuclear factor-κB activation and decreased heme oxygenase-1 level. However, MLT had no effect on interleukin-6 and myelin protein production. Our data revealed that MLT improved neurological deficits and enhanced cell survival but was not able to initiate myelin production in the cuprizone model of demyelination. These findings may be important for the design of potential MLT therapy in demyelinating disorders, such as MS. © 2015, Springer Science+Business Media New York

Efficient filtration system for paraffin-catalyst slurry separation

The filtration efficiency for separating liquid paraffin (or water) from a slurry consisting of 25 weight% spherical alumina in a Slurry Bubble Column Reactor (SBCR) comprised of a cylindrical tube of 10 cm diameter and 150 cm length was studied. Various differential pressures (ΔP) were applied to two separate tubular sintered metal stainless steel filter elements with nominal pore size of 4 and 16μm. The experimental results disclosed that the rate of filtrations increased on applying higher differential pressure to the filter element. Albeit this phenomenon is limited to moderate ΔPs and for ΔP more than 1 bar is neither harmful nor helpful. The highest filtration rates at ΔPs higher than 1 bar were 170 and 248 ml/minute for 4 and 16μm respectively. Using water as the liquid in slurry the rate of filtration enhanced to 4 folds, and this issue reveals impact of viscosity on filtration efficiency clearly. In all situations, the total amount of particles present in the filtrate part never exceeded a few parts per million (ppm). The statistical analysis of the SEM image of the filtrate indicated that by applying higher pressure difference to the filter element the frequency percent of larger particle size increases. The operation of filter cake removing was performed with back flashing of 300 ml of clean liquid with pressures of 3-5 bar of N2 gas

Design of antisense oligonucleotides against twist1 gene and evaluation of their anti-invasive effects in prostate cancer cell lines

Introduction: Prostate cancer is one of the most common cancers and the second major cause of mortality in men. Different researches have shown that the overexpression of a gene called twist1 leads to initiation of metastasis process in this cancer. TWIST1 protein triggers this process through stimulating the transition pathway of cells from epithelial to mesenchymal tissue.Materials and Methods: In this study, four oligonucleotides of antisense RNA have been designed for twist1 gene, and its anti-metastatic effect was examined in two cell lines PC3 and LNCaP. The antisense oligonucleotides (ASOs) were designed as single strands with a length of 20 nucleotides and chosen from ASOs suggested by Soligo program. The ASOs were synthesized in phosphorothioated form. MTT assay was used for evaluating the ASOs cytotoxicity effect on PC3 and LNCaP cell lines. The cell lines were transfected with 500 nmol of antisense oligonucleotides using cationic polymer turbofect and incubated for 48 hours, and then, their invasive ability were measured by CytoSelect™ Cell Invasion Assay Kit.Results: The anti-invasive effect of ASOs in LNCaP and PC3 had a significant difference. This effect was more significant in LNCaP cell line as compared to PC3. The most anti- invasive effect was observed in LNCaP cell line (50%).Conclusion: According to the results, Antisense oligonucleotides were effective in decreasing the invasion ability of two cell lines PC3 and LNCaP and therfore can be considered as a good candidate for preventing the prostate cancer metastasis.

Statistical-Synoptic Analysis of April 2019 Heavy Rainfall in Doroud-Boroujerd Basin

The occurrence of catastrophic floods in March-April 2019 in Lorestan province was a clear example of heavy rains that caused very heavy damage to agricultural, urban, transportation, and communications infrastructure.  The purpose of this study is to investigate the March-April 2019 rainfall in the Droud-Borujerd catchment area in terms of statistical, synoptic, and dynamic characteristics. In this regard, from the data related to the daily station rainfall in March-April 2019 of Boroujerd and Doroud synoptic stations, NOAA climate Synoptic factor data for the 25th March and 2nd April 2019, and upper atmospheric data from the University of Wyoming database for the mentioned days of April 2019. The results of statistical analysis showed that the occurrence of rainfall in April 2019 was one of the heavy rains that in the first wave (25th March) 2019 was 15% of the total annual rainfall and in the second wave (2nd April 2019) 20% of the total annual rainfall was recorded. Analysis of synoptic patterns of these heavy rainfall events showed that a similar synoptic pattern produced these two waves of heavy rainfall in the region. On both days, the presence of a strong trough a height of 5500 and 5550 geopotential meters, on the east of the Mediterranean Sea that the western region of Iran located in the front of this trough, lead to heavy rainfall. In these two days, the omega index had reached a significant critical value (-0.2). Moisture injection in the study area was done by the interaction of two cyclonic systems (east of the Mediterranean Sea) and anti-cyclone (on the Gulf of Aden) and the source of moisture supply was the Mediterranean Sea, the Red Sea, and the Persian Gulf, respectively. High atmospheric instability indices did not confirm the existence of very severe instability in the region. Moderate instability in the lower levels of the atmosphere, which could not be extended to the upper level (Skew-T diagram), indicated that a global synoptic system was involved in the whole region and no local convection factor played a role

Targeting enteroviral 2A protease by a 16-mer synthetic peptide: Inhibition of 2Apro-induced apoptosis in a stable Tet-on HeLa cell line

AbstractEnteroviridae such as coxsackievirus are important infectious agents causing viral heart diseases. Viral protease 2A (2Apro) initiates the virus life cycle, and is an excellent target for developing antiviral drugs. Here, to evaluate the validity of the 2Apro as a proper therapeutic target, and based on the existing information and molecular dynamics, a 16-mer peptide was designed to specifically target the active site of protease 2Apro in order to block the activity of CVB3 2Apro. We showed that the peptide could compete with endogenous substrate in a concentration-dependent manner. Further, we established a HeLa cell line that expressed 2Apro. Expression of 2Apro resulted in significant morphological alteration and eventual cell death. Western blot and viability assay showed that the 16-mer peptide (200 μg/ml) could significantly block 2Apro activity and its cytotoxic effect. Future modification of the 16-mer peptide can improve its affinity for 2Apro and therefore develop effective antiviral drug

Inhibition study on insulin fibrillation and cytotoxicity by paclitaxel

Alzheimer, a neurodegenerative disease, and a large variety of pathologic conditions are associated with a form of protein aggregation known as amyloid fibrils. Since fibrils and prefibrillar intermediates are cytotoxic, numerous attempts have been made to inhibit fibrillation process as a therapeutic strategy. Peptides, surfactants and aromatic small molecules have been used as fibrillation inhibitors. Here we studied the effects of paclitaxel, a polyphenol with a high tendency for interaction with proteins, on fibrillation of insulin as a model protein. The effects of paclitaxel on insulin fibrillation were determined by Thioflavin T fluorescence, Congo red absorbance, circular dichroism and atomic force microscopy. These studies indicated that paclitaxel considerably hindered nucleation, and therefore, fibrillation of insulin in a dose-dependant manner. The isothermal titration calorimetry studies showed that the interaction between paclitaxel and insulin was spontaneous. In addition, the van der Waal's interactions and hydrogen bonds were prominent forces contributing to this interaction. Computational results using molecular dynamic simulations and docking studies revealed that paclitaxel diminished the polarity of insulin dimer and electrostatic interactions by increasing the hydrophobicity of its dimer state. Furthermore, paclitaxel reduced disrupting effects of insulin fibrils on PC12 cell's neurite outgrowth and complexity, and enhanced their survival. © 2014 The Authors 2014