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

Studing the Acclimation of Bromus Tomentellus in Esfahan Province

Bromus tomentellus is one of the drought resistant species that has a relatively well developed in Esfahan province, therefore, in the present study some of the important factors that influence the distribution of this species are studied. In this study, 17 climatic variables from 43 synoptic and climatology stations were selected within and adjacent areas of Esfahan province which the stations managed by Weather Organization of Iran. To reduce the number of variables and determining effective factor was used factor analysis using by principal components analysis with varimax rotation, then the average factor scores in the habitat of this species and the areas without it were calculated and the spatial distribution of the factor scores were plotted in Surfer ver8. The results of the factor analysis identified three factors of precipitation, temperature and wind and sunshine hours. These factors are included 69.70%, 11.98% and 10.14%, respectively and 92% of the total variance of the data. Also, the results showed that both precipitation and cooling temperature are the important factors to presence of these species as dominant and following species and wind and sunshine hours has the least effect on it. Generally, the climate vegetative of Bromus tomentellus can be named in Isfahan province, semi-steppe vegetation region in Fereidan, Freydoonshahr, Semirom, Golpayegan, Khonsar, Meimeh up around the Shahreza and alpine steppe of Natanz and Kashan

The Impact of Climatic Factors on Distribution of Taverniera glabra in Iran by Multivariate Statistical Analysis Methods

To study the effect of climatic factors on Taverniera glabra species distribution in Iran rangelands, climatic variables were selected and factors affecting species distribution were evaluated using factor analysis. Then a spatial distribution map was prepared for all these factors throughout Iran. Factor analysis showed that 9 factors included: temperature, relative humidity, winter precipitation and summer precipitation, partly cloudy days, average wind speed, thunder and snowy days with eigenvalues greater than 1, explained 29.71, 22.32, 9.58, 7.52, 6.80, 6.22, 4.25, 3.69, 2.22 percent of variance, respectively and 92.35% of total variance. Finally, the climatic factors of temperature, relative humidity, average wind speed and thunderstorm were identified as the most important factors affecting distribution of vegetation types which Taverniera glabra are dominant species. Furthermore temperature, summer precipitation, average wind speed and thunderstorm factors affecting on distribution of vegetation types in which Taverniera glabra are accompanied species. The results showed that these climatic factors caused distribution of Taverniera glabra in the South East of Iran

PEGylated superparamagnetic iron oxide nanoparticles (SPIONs) ameliorate learning and memory deficit in a rat model of Alzheimer's disease: Potential participation of STIMs

The amyloid-beta (Aβ) fibrillation process seems to execute a principal role in the neuropathology of Alzheimer's disease (AD). Accordingly, novel therapeutic plans have concentrated on the inhibition or degradation of Aβ oligomers and fibrils. Biocompatible nanoparticles (NPs), e.g., gold and iron oxide NPs, take a unique capacity in redirecting Aβ fibrillation kinetics; nevertheless, their impacts on AD-related memory impairment have not been adequately evaluated in vivo. Here, we examined the effect of commercial PEGylated superparamagnetic iron oxide nanoparticles (SPIONs) on the learning and memory of an AD-animal model. The outcomes demonstrated the dose-dependent effect of SPIONs on Aβ fibrillation and learning and memory processes. In vitro and in vivo findings revealed that Low doses of SPIONs inhibited Aβ aggregation and ameliorated learning and memory deficit in the AD model, respectively. Enhanced level of hippocampal proteins, including brain-derived neurotrophic factor, BDNF, phosphorylated-cAMP response element-binding protein, p-CREB, and stromal interaction molecules, e.g., STIM1 and STIM2, were also observed. However, at high doses, SPIONs did not improve the detrimental impacts of Aβ fibrillation on spatial memory and hippocampal proteins expression. Overall, we revealed the potential capacity of SPIONs on retrieval of behavioral and molecular manifestations of AD in vivo, which needs further investigations to determine the mechanistic effect of SPIONs in the AD conundrum

Neuroprotective effect of exogenous melatonin on the noradrenergic neurons of adult male rats� locus coeruleus nucleus following REM sleep deprivation

Melatonin is primarily secreted by the pineal gland in dark. In addition to its role as an internal sleep facilitator, melatonin acts as an antioxidant, anti-inflammatory and neuroprotective agents. melatonin has been introduced as a therapeutic strategy for sleep disorders. Hence, in the present study, we studied the neuroprotective effects of pre- and post-treatment of melatonin in locus coeruleus nucleus (LC) of rapid eye movement (REM) sleep deprived (REM-SD) male adult rats. Adult male rats of control, sham and trial groups were used Exogenous melatonin (ExMe) was intraperitoneally injected in two forms of pre and post treatment. The protein level of cleaved caspase-3, the number and density of tyrosine hydroxylase (TH) positive neurons and the microglia population in LC were studied by western blot and immunohistochemistry respectively. Morphological changes of LC nucleus and its neurons were also studied by using stereological analysis. The number of neurons and volume of LC was reserved in animals that had received post-RSD ExMe. Apoptosis significantly was decreased comparing to RSD and Pre-RSD animals. Melatonin post-treatment of RSD rats also decreased cleavage of caspase-3 and increased reduced glutathione content in LC. Moreover, immunohistochemistry analysis showed an increase in the number of TH positive neurons and a decrease in microglia migration. Based on our findings antioxidant properties of exogenous melatonin could play a critical role in certain types of sleep disorders. © 201

Impact of Gold Nanoparticles on Amyloid β-Induced Alzheimer's Disease in a Rat Animal Model: Involvement of STIM Proteins

Alzheimer's disease (AD) is the most common type of neurodegenerative amyloid disorder causing progressive cognitive decline and memory loss. A considerable number of therapies for AD rely on inhibition/delay/dissociation of amyloid beta (Aβ) oligomers and fibrils. In this case, nanoparticles (NPs) demonstrated substantial effects on the Aβ fibrillation process; however, their effects on progressive cognitive decline and memory have been poorly investigated in vivo. In this study, acquisition and retention of spatial learning and memory are studied in a rat animal model of AD after intrahippocampal (IH) and intraperitoneal (IP) injections of a model NP, i.e., gold NPs (AuNPs). The outcomes revealed that the AuNPs could improve the acquisition and retention of spatial learning and memory in Aβ treated rats as indicated by decreased time (Aβ: 39.60 ± 3.23 s vs Aβ+AuNPs: 25.78 ± 2.80 s) and distance (Aβ: 917.98 ± 50.81 cm vs Aβ+AuNPs: 589.09 ± 65.96 cm) of finding the hidden platform during training days and by increased time spent in the target quadrant (Aβ: 19.40 ± 0.98 s vs Aβ+AuNPs: 29.36 ± 1.14 s) in the probe test in Morris water maze (MWM). Expression of brain-derived neurotrophic factor, BDNF, cAMP response element binding protein, CREB, and stromal interaction molecules, e.g., STIM1 and STIM2 was also increased, supporting improved neural survival. Our outcomes may pave a way for mechanistic insights toward the role of NPs on retrieval of the deteriorated behavioral functions in brain tissue after AD outbreak