Publications by authors named "Hossein Mostafavi"

24 Publications

  • Page 1 of 1

A sham-controlled clinical trial to examine the effect of bilateral tDCS on craving, TNF-α and IL-6 expression levels, and impulsivity of males with opioid use disorder.

J Addict Dis 2021 Mar 15:1-25. Epub 2021 Mar 15.

Faculty of Medicine, Department of Clinical Psychology, Social Determinants of Health Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

Background: Opioid use disorder (OUD) is one of the problems and concerns of all countries in the world. On the other hand, transcranial direct current stimulation (tDCS) has been used as a new therapeutic intervention in various psychiatric disorders.

Objective: This study aimed to investigate the effect of bilateral tDCS on the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), craving and impulsive behaviors of male patients with OUD.

Methods: This is a double-blind sham-controlled clinical trial. Participants were 31 male patients with OUD divided into three groups of left anode/right cathode tDCS, right anode/left cathode tDCS, and sham tDCS. They received active tDCS (2 mA, 20 min), applied over their dorsolateral prefrontal cortex (DLPFC) for 10 consecutive days. Expression levels of IL-6 and TNF-α cytokines were measured using ELISA method, and the Desires for Drug Questionnaire and the Barratt Impulsiveness Scale version 11 were used to assess the craving and impulsivity of subjects, respectively.

Results: Both active and sham tDCS could significantly reduce drug craving in subjects (p < 0.05). Active tDCS over the right/left DLPFC significantly reduced impulsivity and its dimensions (overall, attentional, motor, and nonplanning) compared to the sham tDCS (p < 0.05). It could also reduce the expression levels of IL-6 and TNF-α, but the difference was not statistically significant.

Conclusions: The active tDCS over the right/left DLPFC, as a noninvasive and complementary treatment, can be used along with other common methods for the treatment of patients with OUD. It can improve their cognitive functions by reducing impulsivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10550887.2021.1883208DOI Listing
March 2021

The neuroprotective effect of MicroRNA-149-5p and coenzymeQ10 by reducing levels of inflammatory cytokines and metalloproteinases following focal brain ischemia in rats.

Brain Res Bull 2021 Apr 27;169:205-213. Epub 2021 Jan 27.

Department of Physiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

The increase in some factors following cerebral ischemia, especially Matrix metalloproteinase (MMPs) and inflammatory factors lead to blood-brain barrier (BBB) damages, edema and neuronal death. Previous studies have shown that these molecules are miRNA-149-5p (miR-149) and Coenzyme (Co) Q10 targets. Therefore, in this study, the effect of mimic of miRNA-149-5p (mimic miR) and CoQ10 on the expression of metalloproteinase 1 and 2 and inflammatory cytokines following injury caused by cerebral ischemia is investigated. Cerebral ischemia was modeled by Middle Cerebral Artery Occlusion (MCAO). Male Wistar rats were randomly divided into 6 groups: sham (without surgery and treatment), control (MCAO), negative control (NC): MCAO + scrambled miR, vehicle: MCAO + Ethanole, first treatment: MCAO + mimic miR, second treatment: MCAO + Q10. Each group was divided into 6 subgroups to evaluate neurological defects, the volume of tissue damage using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, blood-brain barrier permeability using cerebral Evans Blue (EB) staining, edema by measuring the percentage of brain water, MMP-2,9 mRNA and miR-149-5p levels using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and the levels of IL-6 and TNF-α proteins using ELISA. The data obtained from this study showed that the use of mimic miR and Q10 increased the level of miR-149, decreased the extent of neurological defects and tissue damage, increased BBB integrity, decreased brain water percentage and also decreased the level of inflammatory cytokines and MMPs. It seems that the use mimic of miRNA-149-5p and Q10 can have a protective effect on the brain by reducing MMPs and inflammatory factors following cerebral ischemia and this could lead to a new treatment strategy to reduce the complications of cerebral ischemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainresbull.2021.01.013DOI Listing
April 2021

Down-regulation of Survivin and Bcl-2 concomitant with the activation of caspase-3 as a mechanism of apoptotic death in KG1a and K562 cells upon exposure to a derivative from ciprofloxacin family.

Toxicol Appl Pharmacol 2020 12 7;409:115331. Epub 2020 Nov 7.

Department of Biology, College of Education, Salahaddin University-Erbil, Erbil, Kurdistan Region, Iraq.

Ciprofloxacin derivatives belong to a family of antibiotics called fluoroquinolones. Recently, these compounds have been recommended for the treatment of cancer. In the present study, we assessed the cytotoxicity of several new synthetic ciprofloxacin derivatives and the apoptosis-inducing activity of the most efficient derivative in two human myeloid leukemia K562 and KG1-a cell lines. Among the prepared ciprofloxacin derivatives, 1-cyclopropyl-7-(4-(2-((3,7-dimethyloct-6-en-1-yl)oxy)-2-oxoethyl)piperazin-1-yl)-6-fluoro-4-oxo-1,4dihydroquinoline-3-carboxylic acid (4-DMOCP) was more active compound with IC50 of 19.56 and 22.13 μM for K562 and KG1-a, respectively. Apoptotic activity of the 4-DMOCP was examined morphologically through Hoechst 33258 staining, Annexin V/PI double staining, and caspase-3 activity assays. Changes in the expression level of some apoptosis-related genes and protein, including Bcl-2, Bax, Survivin, p53, Caspase-8 and Caspase-9 were evaluated by the real-time quantitative PCR (qRT PCR) and western blotting. The qRT PCR analysis showed that 4-DMOCP induces apoptosis in both cell lines via the down-regulation of Survivin and Bcl2, up-regulation of caspase-8 and -9, as well as a time-dependent increase in the Bax/Bcl2 transcripts. The mRNA level of p53 was also increased in both cell lines. In addition, western blot analysis revealed that treatment with the compound, down-regulated the protein expression levels of Bcl2 and Survivin and up-regulated the protein level of Bax in both cell lines. These findings suggest that these new compounds can be good candidates for the treatment of acute and chronic myeloid leukemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.taap.2020.115331DOI Listing
December 2020

Design, synthesis and evaluation of biological activities of some novel anti-TB agents with bio-reducible functional group.

Bioimpacts 2019 22;9(4):199-209. Epub 2019 May 22.

Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.

With regard to the anti-mycobacterial activity of 2-pyrazinoic acid esters (POEs), recent studies have shown that both pyrazine core and alkyl part of POE interact with the fatty acid synthase type (I) (FAS (I)) precluding a complex formation between NADPH and FAS (I). Considering this interaction at the reductase site of FAS (I) responsible for reduction of β-ketoacyl-CoA to β-hydroxyacyl-CoA, we hypothesized that POE containing a bioreducible center in its alkyl part might show an increased anti-tubercular activity due to the involvement of FAS (I) in extra bio-reduction reaction. Thus, we synthesized novel POEs, confirmed their structures by spectral data, and subsequently evaluated their anti-mycobacterial activity against (Mtb) (H37Rv) strain at 10 μg/mL concentration. Compounds , and showed higher activity with regard to the inhibition of Mtb growth by 45.4, 45.7, and 51.2% respectively. Unexpectedly, the maltol derived POE having the lowest log p value among the POEs indicated the highest anti-mycobacterial growth activity with 56% prevention. Compounds and showed no remarkable cytotoxicity on human macrophages at 10 μg/mL concentration as analyzed by xCELLigence real-time cell analysis. In further experiments, some of the tested POEs, unlike pyrazinamide (PZA), exhibited significant antibacterial and also anti-fungal activities. POEs showed an enhanced bactericidal activity on gram-positive bacteria as shown for , e.g. compound 3b with a MIC value of 125 μg/mL but not as a gram-negative bacteria, except for maltol derived POE () that showed an inverse activity in the susceptibility test. In the anticancer activity test against the human leukemia K562 cell lines using MTT assay, compounds and showed the highest cytotoxic effect with IC50 values of 25±8.0 μΜ and 25±5.0 μΜ, respectively. It was found that the majority of POEs containing a bioreducible center showed higher inhibitory activities on Mtb growth when compared to the similar compounds without a bio-reducible functional group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15171/bi.2019.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879708PMC
May 2019

Trabecular meshwork mesenchymal stem cell transplantation improve motor symptoms of parkinsonian rat model.

Biologicals 2019 Sep 29;61:61-67. Epub 2019 Jun 29.

Department of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran; Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran; Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran; Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran. Electronic address:

Stem cell transplantation is a new therapeutic strategy in the treatment of neurodegenerative disorders such as Parkinson's disease (PD). Therefore, in this study, the therapeutic effects of Trabecular Meshwork Mesenchymal Stem Cells (TM-MSCs) transplantation, as a new source of mesenchymal stem cells, were evaluated in the animal model of PD. After the development and confirmation of hemi-parkinsonian rats by administration of 6-hydroxy dopamine (6-OHDA) and apomorphine-induced rotation test, green fluorescent protein (GFP) labeled TM-MSCs (normal and induced cells) were transplanted in the striatum of rats. Next, the rotation test, rotarod test, open field, passive avoidance memory tests and immunohistochemistry for tyrosine hydroxylase (TH) were done. The results showed that the number of turns significantly decreased and the improvement of motor performance was achieved after cell transplantation. However, there was no significant difference in passive avoidance memory of animals documented by shuttle box test. The number of GFP- labeled cells expressing TH significantly is increased compared to the vehicle group. Collectively, it seems that TM-MSCs and induced TM-MSCs cell transplantation have positive effects on some aspects of the animal model of PD. Other studies may reveal the potentially positive aspects of these cells in the laboratory and clinical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biologicals.2019.06.006DOI Listing
September 2019

Erythropoietin Pretreatment Effect on Blood Glucose and Its Relationship With Inflammatory Factors After Brain Ischemic-Reperfusion Injury in Rats.

Basic Clin Neurosci 2018 Sep-Oct;9(5):347-356. Epub 2018 Sep 1.

Department of Physiology and Pharmacology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

Introduction: Brain Ichemic-Reperfusion Injury (IRI) activates different pathophysiological processes. It also changes physiological parameters such as Blood Glucose (BG) level. An increase in BG after stroke is associated with poor clinical outcomes. Erythropoietin has been shown to be effective on both reducing inflammation and BG level. Therefore, in this study the erythropoietin pretreatment effect on BG and its relationship with inflammatory markers after brain IRI was investigated.

Methods: Thirty adult male Wistar rats were randomly divided into 5 groups: sham, control and 3 pretreatment groups: single dose, double dose, and triple dose that received 1000 U/kg of erythropoietin before stroke induction in different times intraperitoneally. A rat model of IRI was established by Middle Cerebral Artery Occlusion (MCAO) for 60 minutes. Infarct volume, neurological defects, Interleukin-1α (IL-1α) and IL-6 serum levels were evaluated 24 hours after reperfusion. Also BG was measured after 1, 6, and 24 hours.

Results: Single dose of erythropoietin significantly decreased infarct volume and improved neurological defects which was associated with decreased serum level of IL-1α and IL-6 but higher doses of erythropoietin administration had adverse effects on histological, neurological, and inflammatory results. In addition, erythropoietin significantly increased BG in a dose-dependent manner.

Conclusion: Erythropoietin could reduce brain IRI by reducing inflammation and BG stabilization. The results of the present study demonstrated a relationship between inflammatory factors and hyperglycemia after IRI and suggested that erythropoietin may be useful for preventing brain IRI, but its higher doses should be used with caution due to possible side effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.32598/bcn.9.5.347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360489PMC
September 2018

Differentiation of microfluidic-encapsulated trabecular meshwork mesenchymal stem cells into insulin producing cells and their impact on diabetic rats.

J Cell Physiol 2019 05 14;234(5):6801-6809. Epub 2018 Oct 14.

Department of Medical Biotechnology and Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

Tissue and stem cell encapsulation andtransplantation were considered as promising tools in the treatment of patients with diabetes mellitus. The aim of this study was to evaluate the effect of microfluidic encapsulation on the differentiation of trabecular meshwork mesenchymal stem cells (TM-MSC), into insulin-producing cells (IPCs) both in vitro and in vivo. The presence of differentiated cells in microfibers (three dimensional [3D]) and tissue culture plates (TCPS; two dimensional [2D]) culture was evaluated by detecting mRNA and protein expression of pancreatic islet-specific markers as well as measuring insulin release of cells in response to glucose challenges. Finally, semi-differentiated cells in microfibers (3D) and 2D cultures were used to control the glucose level in diabetic rats. The results of this study showed that MSCs differentiated in alginate microfibers (fabricated by microfluidic device) express more Pdx-1 mRNA (1.938-fold, p-value: 0.0425) and Insulin mRNA (2.841-fold, p-value: 0.0001) compared with those cultured on TCPS. Furthermore, cell encapsulation in microfluidic derived microfibers decreased the level of blood glucose in diabetic rats. The approach used in this study showed the possibility of alginate microfibers as a matrix for differentiation of TM-MSCs (as a new source) into IPCs. In addition, it could minimize different steps in stem cell differentiation, handling, and encapsulation, which lead to loss of an unlimited number of cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.27426DOI Listing
May 2019

Generation of insulin-producing cells from human induced pluripotent stem cells on PLLA/PVA nanofiber scaffold.

Artif Cells Nanomed Biotechnol 2018 27;46(sup1):1062-1069. Epub 2018 Feb 27.

i Department of Physiology, School of Medicine , International Campus, Tehran University of Medical Sciences , Tehran , Iran.

Pancreatic tissue engineering as a therapeutic option for restoring and maintenance of damaged pancreas function has a special focus to using synthetic Scaffolds. This study was designed to evaluate pancreatic differentiation of human induced pluripotent stem cells (hiPSCs) on poly-L-lactic acid and polyvinyl alcohol (PLLA/PVA) scaffolds as 3 D matrix. During differentiation process, morphology of cells gradually changed and iPSCs derived insulin producing cells (iPSCs-IPCs) formed spherical shaped cell aggregation that was the typical shape of islets of pancreas. The highly efficient differentiation of iPSCs into a relatively homogeneous population of IPCs was shown by immunostaining. Real-time reverse transcription polymerase chain reaction (RT-PCR) results demonstrated that iPSCs-IPCs expressed pancreas-specific transcription factors (Pdx1, insulin, glucagon and Ngn3). The expressions of these transcription factors in PLLA/PVA scaffold were significantly higher than 2 D groups. Furthermore, we showed that concentration of insulin and C-peptide in PLLA/PVA scaffold and/or 2 D culture in response to various concentrations of glucose increased but the difference between them were not significant. Altogether the current results demonstrated that PLLA/PVA scaffold could provide the microenvironment that promotes the pancreatic differentiation of iPSCs, up-regulate pancreatic-specific transcription factors and improved metabolic activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21691401.2018.1443466DOI Listing
August 2019

Differentiation of conjunctiva mesenchymal stem cells into secreting islet beta cells on plasma treated electrospun nanofibrous scaffold.

Artif Cells Nanomed Biotechnol 2018 14;46(sup1):178-187. Epub 2017 Dec 14.

b Department of Medical Biotechnology and Nanotechnology, School of Medicine , Zanjan University of Medical Sciences , Zanjan , Iran.

Transplantation of stem cells using biocompatible nanofibrous scaffolds is a promising therapeutic method for treating Diabetic Mellitus. The aim of this study was to derive insulin-producing cells (IPCs) from conjunctiva-derived mesenchymal stem cell (CJMSCs) and to compare the functionality of differentiated IPCs in a three-dimensional (3D) culture with 2D. Furthermore, the effects of hydrophobicity of scaffold on IPCs differentiation were examined. Scanning electron microscopy (SEM), quantitative real times PCR (qPCR), Immunostaining and flow cytometry were used to analyze fabricated scaffold and the presence of IPCs. Functional maturity of differentiated cells was determined by measuring insulin release and the creation of IPCs was confirmed via gene and protein expression. In this study, the induced CJMSCs were morphologically similar to pancreatic islet-like cells. The expression of the islet-associated genes (glucagon, insulin and Pdx-1) and the insulin release (2.5-fold) in 3D-cultured cells was significantly higher than the 2D. The expression of IPCs genes was significantly higher in CJMSCs differentiated on plasma-treated nanofibers compared to those on untreated scaffolds. In conclusion, the results show that CJMSCs might be a new source for Diabetic Mellitus therapy and the nanofibrous scaffold could be used as a potential cell carrier for islet tissue engineering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21691401.2017.1416391DOI Listing
August 2019

Differentiation of mesenchymal stem cells -derived trabecular meshwork into dopaminergic neuron-like cells on nanofibrous scaffolds.

Biologicals 2017 Nov 21;50:49-54. Epub 2017 Sep 21.

Department of Medical Biotechnology and Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran; Cancer and Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran. Electronic address:

Parkinson's disease (PD) is a neurodegenerative disorder of the brain which is produced by the damage to dopaminergic neurons. Stem cell transplantation with a nanofibrous scaffold is one of the encouraging strategies for Parkinson's disease therapy. In this study, human mesenchymal stem cells (MSCs) from eye trabecular meshwork (TM) were differentiated into dopaminergic neurons on nanofibrous scaffold. After Trabecular meshwork biopsy, MSCs were isolated, cultivated on Poly-l-Lactide Acid (PLLA) nanofibrous scaffold (fabricated by electrospinning methods) and treated with medium containing DMEM supplemented with RA, IBMX and forskolin for 7 days. Scanning electron microscopy imaging, qPCR and immunostaining were used to analyze differentiated TM-MSCs on scaffold and their expression of dopaminergic-specific markers such as TH and Nurr-1. qPCR analysis revealed the expression of dopaminergic neuron genes such as TH, Nurr-1 on fibrous scaffold as well as TCPS. Immunostaining revealed that the differentiated TM-MSCs on TCPS and Scaffold not only express TH and Nurr-1 genes, but also express TH protein. In conclusion, the results indicate that TM-MSCs might be a suitable source for cell transplantation therapy. In addition the nanofibrous scaffold reported herein could be used as a potential cell carrier for the central system diseases such as PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biologicals.2017.09.002DOI Listing
November 2017

A new fish-based multi-metric assessment index for cyprinid streams in the Iranian Caspian Sea Basin.

Limnologica 2015 Mar;51:37-52

Department of Water, Atmosphere and Environment, Institute of Hydrobiology and Aquatic Ecosystem Management, BOKU University of Natural Resources and Life Sciences, Vienna, Austria.

A major issue for water resource management is the assessment of environmental degradation of lotic ecosystems. The overall aim of this study is to develop a multi-metric fish index for the cyprinid streams of the Caspian Sea Basin (MMICS) in Iran. As species diversity and composition as well as population structure in the studied streams are different to other regions, there is a substantial need to develop a new fish index. We sampled fish and environmental data of 102 sites in medium sized streams. We analysed human pressures at different spatial scales and determined applicable fish metrics showing a response to human pressures. In total, five structural and functional types of metrics (i.e. biodiversity, habitat, reproduction, trophic level and water quality sensitivity) were considered. In addition, we used 29 criteria describing major anthropogenic human pressures at sampling sites and generated a regional pressure index (RPI) that accounted for potential effects of multiple human pressures. For the MMICS development, we first defined reference sites (least disturbed) and secondly quantified differences of fish metrics between reference and impaired sites. We used a Generalised Linear Model (GLM) to describe metric responses to natural environmental differences in least disturbed conditions. By including impaired sites, the residual distributions of these models described the response range of each metric to human pressures, independently of natural environmental influence. Finally, seven fish metrics showed the best ability to discriminate between impaired and reference sites. The multi-metric fish index performed well in discriminating human pressure classes, giving a significant negative linear response to a gradient of the RPI. These methods can be used for further development of a standardised monitoring tool to assess the ecological status and trends in biological condition for streams of the whole country, considering its complex and diverse geology and climate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.limno.2014.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418740PMC
March 2015

Regulation of connexin 43 and microRNA expression via β2-adrenoceptor signaling in 1321N1 astrocytoma cells.

Mol Med Rep 2015 Aug 14;12(2):1941-50. Epub 2015 Apr 14.

Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran 1417743371, Iran.

Connexin 43 (Cx43) is the main gap junction protein in astrocytes and exerts the same effects on growth inhibition in astrocytoma and glioma as microRNA-146a (miR-146a) in glioma. β2-adrenergic receptor (AR) signaling modulates Cx43 expression in myocytes via components downstream of protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac). However, it remains to be elucidated how expression of Cx43 is modulated in astrocytes. In the present study, 1321N1 astrocytoma cells were treated with β2-AR signaling agents in order to evaluate the expression of Cx43 and miRNAs. RNA and protein were extracted from the cells for use in reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The results revealed that clenbuterol increased miR-146a level and upregulated Cx43 expression via cAMP/PKA at the mRNA and protein level. Pre-inhibition of adenyl cyclase decreased expression of Cx43 and miR-146a. PKA activation and overexpression of miR-146a in A-1321N1 cells increased the expression of Cx43. β2-AR stimulation and 6Bnz, a PKA activator, suppressed oncomiRs miR-155 and miR-27a, while 8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate, an Epac activator, increased their levels. The current findings demonstrated that β2-AR signaling has growth inhibitory effects via modulation of the cAMP/PKA pathway in A-1321N1 cells through increasing the expression level of Cx43 and miR-146a as well as decreasing miR-155 and miR-27a levels. Thus, stimulation of the β2-AR and PKA signaling pathway may be a useful approach for astrocytoma therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2015.3609DOI Listing
August 2015

cAMP-Epac Pathway Stimulation Modulate Connexin-43 and MicroRNA-21 Expression in Glioma Cells.

Basic Clin Neurosci 2015 Jan;6(1):52-7

Neuroscience Institute, Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran.; Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: Malignant astrocytic gliomas are the most common and lethal brain malignancies due to their refractory to the current therapies. Nowadays, molecular targeted therapy has attracted great attention in treatment of glioma. Connexin 43 (Cx43) and micro ribonucleic acid-21(miR-21) are among molecules that are involved in glioma development and progression. These molecules showed potential to be as target molecules with regard to glioma. Some studies have reported that cyclic adenosine monophosphate (cAMP) signaling could be effective on Cx43 and miR-21 in tissues other than in brain. We investigate possible relationship between β-adrenergic receptor and its newly described downstream, exchange protein directly activated by cAMP (Epac) signaling pathway and expression of Cx43 and miR-21 in low (1321N1) and high grade (U87MG) glioma cell lines.

Methods: We treated cells with β-adrenergic agonist and Epac activator with and without adenyl cyclase inhibitor. Cx43 and miR-21 expression were measured with real-time PCR.

Results: Our data showed that in 1321N1 cells, β-adrenergic-Epac pathway stimulation up and down-regulated Cx43 and miR-21 expression respectively. Whereas, in U87MG cells these interventions had no effect on Cx43 and miR-21 expression.

Discussion: These findings demonstrate that low grade astrocytoma cells have better response to our pharmacological interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741269PMC
January 2015

Fluoxetin upregulates connexin 43 expression in astrocyte.

Basic Clin Neurosci 2014 ;5(1):74-9

Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran ; Division of Neuroscience, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran ; Neuroscience Institute, Brain and Spinal cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: Recent studies have shown that astrocytes play major roles in normal and disease condition of the central nervous system including multiple sclerosis (MS). Molecular target therapy studies in MS have revealed that connexin-43 (Cx43) and Aquaporin-4 (AQP4) contents of astrocytes undergo expression alteration. Fluoxetine had some effects in MS patients unrelated to its known antidepressant effects. Some of fluoxetine effects were attributed to its capability of cAMP signaling pathway stimulation. This study aimed to investigate possible acute effects of fluoxetine on Cx43 and AQP4 expression in astrocyte.

Methods: Astrocytoma cells were treated for 24 hours with fluoxetine (10 and 20 µg/ml) with or without adenyl cyclase (AC) and protein kinase A (PKA) inhibition. Cx43 expression at both mRNA and protein levels and AQP4 expression at mRNA level were evaluated.

Results: Acquired results showed that fluoxetine with and without AC and PKA inhibition resulted in Cx43 up-regulation both in mRNA and protein levels, whereas AQP4 expression have not changed.

Discussion: In conclusion, data showed that fluoxetine alone and in the absence of serotonin acutely up-regulated Cx43 expression in astrocytes that can be assumed in molecular target therapy of MS patients. It seems that cAMP involvement in fluoxetine effects need more researches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202606PMC
December 2014

BDNF modifies hippocampal KCC2 and NKCC1 expression in a temporal lobe epilepsy model.

Acta Neurobiol Exp (Wars) 2014 ;74(3):276-87

Department of Neuroscience, School of Advanced Technologies in Medicine,

Excitatory GABA actions, induced by altered expression of chloride transporters (KCC2/NKCC1), can contribute to seizure generation in temporal lobe epilepsy. In the present study, we evaluated whether BDNF administration can affect KCC2/NKCC1 expression, ictogenesis and behavioral alterations in this paradigm. Status epilepticus was induced in male rats with pilocarpine, followed by a treatment of either a single high dose or multiple injections of BDNF during the latent phase of temporal lobe epilepsy. Chloride transporters expression, spontaneous recurrent seizures, and hyperexcitability post-seizural behaviors were evaluated after treatment. NKCC1 protein expression was markedly upregulated, whereas that of KCC2 was significantly downregulated in epileptic hippocampi compared to intact controls. Application of BDNF (both single high dose and multiple injections) increased KCC2 expression in epileptic hippocampi, while NKCC1 expression was downregulated exclusively by the single high dose injection of BDNF. Development of spontaneous recurrent seizures was delayed but not prevented by the treatment, and hyperexcitability behaviors were ameliorated for a short period of time. To prevent GABA-A mediated depolarization and design appropriate treatment strategies for temporal lobe epilepsy, chloride transporters can be considered as a target. Future studies are warranted to investigate any possible therapeutic effects of BDNF via altering chloride transporters expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2015

Selective β2 adrenergic agonist increases Cx43 and miR-451 expression via cAMP-Epac.

Mol Med Rep 2014 Jun 8;9(6):2405-10. Epub 2014 Apr 8.

Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran 1417755469, Iran.

It has been demonstrated that connexin 43 (Cx43) and microRNAs have significant roles in glioma. Cyclic adenosine monophosphate (cAMP) is suggested to be a regulator of connexins and microRNAs. However, it remains elusive whether cAMP and exchange protein directly activated by cAMP (Epac2), have a regulatory effect on Cx43 and microRNA-451 (miR-451) in astrocytoma cells. We treated 1321N1 astrocytoma cells with a selective β2 adrenergic agonist and a selective Epac activator with and without adenyl cyclase and protein kinase A inhibition. Cx43 and miR-451 expression were measured. Next, we evaluated the effect of miR-451 overexpression on Cx43 expression. Cell proliferation was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results demonstrated that cAMP-Epac2 increased Cx43 and miR-451 expression. However, the alteration of miR-451 expression required a higher dose of drugs. Overexpression of miR-451 had no significant effect on Cx43 expression. The MTT assay showed that cAMP-Epac stimulation and miR-451 overexpression had a synergic inhibitory effect on cell proliferation. These findings may expand our understanding of the molecular biology of glioma and provide new potential therapeutic targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2014.2120DOI Listing
June 2014

Predicting presence and absence of trout () in Iran.

Limnologica 2014 Mar;46:1-8

Department of Water, Atmosphere and Environment, Institute of Hydrobiology and Aquatic Ecosystem Management, BOKU University of Natural Resources and Life Sciences, Vienna, Austria.

Species distribution modelling, as a central issue in freshwater ecology, is an important tool for conservation and management of aquatic ecosystems. The brown trout () is a sensitive species which reacts to habitat changes induced by human impacts. Therefore, the identification of suitable habitats is essential. This study explores the potential distribution of brown trout by a species distribution modelling approach for Iran. Furthermore, modelling results are compared to the distribution described in the literature. Areas outside the currently known distribution which may offer potential habitats for brown trout are identified. The species distribution modelling was based on five different modelling techniques: Generalised Linear Model, Generalised Additive Model, Generalised Boosting Model, Classification Tree Analysis and Random Forests, which are finally summarised in an ensemble forecasting approach. We considered four environmental descriptors at the local scale (slope, bankfull width, wetted width, and elevation) and three climatic parameters (mean air temperature, range of air temperature and annual precipitation) which were extracted on three different spatial extents (1/5/10 km). The performance of all models was excellent (≥0.8) according to the TSS (True Skill Statistic) criterion. Slope, mean and range of air temperature were the most important variables in predicting brown trout occurrence. Presented results deepen the knowledge about distribution patterns of brown trout in Iran. Moreover, this study gives a basic background for the future development of assessment methods for riverine ecosystems in Iran.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.limno.2013.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974070PMC
March 2014

The ecological associations of surface-dwelling lizards in Qom Province in the Northwest of Central Plateau of Iran.

PLoS One 2013 13;8(12):e83890. Epub 2013 Dec 13.

Department of the Environmental Sciences, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran.

We used pitfall trapping to investigate the effects of elevation, plant density and soil structure on species diversity and the impact of these habitat factors on lizard habitat selectivity in the Qom Province in the Central Plateau of Iran. From a total of 12 1-ha plots, we captured 363 individuals of 15 species of lizards (six species of Lacertidae, five species of Agamidae, two species of Gekkonidae, one species of Varanidae and one species of Scincidae). A generalized linear model (GLM) determined that elevation was the most important factor impacting species diversity. The highest species diversity was at the intermediate elevation (1289 m). Abundance of 6 out of 15 species showed strong relationships with some habitat factors. These relationships were demonstrated by habitat selectivity index (Ivlev's index). Our result supports other surveys that showed that elevation plays an important role in determining lizard species diversity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083890PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862808PMC
September 2014

Bumetanide reduces seizure frequency in patients with temporal lobe epilepsy.

Epilepsia 2013 Jan 12;54(1):e9-12. Epub 2012 Oct 12.

Cellular and Molecular Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Alterations in the balance of K-Na-2Cl cotransporter (NKCC1) and Na-Cl cotransporter (KCC2) activity may cause depolarizing effect of γ-aminobutyric Acid (GABA), and contribute to epileptogenesis in human temporal lobe epilepsy. NKCC1 facilitates accumulation of chloride inside neurons and favors depolarizing responses to GABA. In the current pilot study we provide the first documented look at efficacy of bumetanide, a specific NKCC1 antagonist, on reduction of seizure frequency in adult patients with temporal lobe epilepsy. According to our results, seizure frequency was reduced considerably in these patients. Furthermore, epileptiform discharges decreased in two of our patients. If the efficacy of bumetanide is proven in large scale studies, it can be used as a supplemental therapy in temporal lobe epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1528-1167.2012.03654.xDOI Listing
January 2013

Vegetation mapping of the Mond Protected Area of Bushehr Province (south-west Iran).

J Integr Plant Biol 2009 Mar;51(3):251-60

Department of Biodiversity and Ecosystems Management, Environmental Sciences Research Institute, Shahid Beheshti University, Tehran, Iran.

Arid regions of the world occupy up to 35% of the earth's surface, the basis of various definitions of climatic conditions, vegetation types or potential for food production. Due to their high ecological value, monitoring of arid regions is necessary and modern vegetation studies can help in the conservation and management of these areas. The use of remote sensing for mapping of desert vegetation is difficult due to mixing of the spectral reflectance of bright desert soils with the weak spectral response of sparse vegetation. We studied the vegetation types in the semiarid to arid region of Mond Protected Area, south-west Iran, based on unsupervised classification of the Spot XS bands and then produced updated maps. Sixteen map units covering 12 vegetation types were recognized in the area based on both field works and satellite mapping. Halocnemum strobilaceum and Suaeda fruticosa vegetation types were the dominant types and Ephedra foliata, Salicornia europaea-Suaeda heterophylla vegetation types were the smallest. Vegetation coverage decreased sharply with the increase in salinity towards the coastal areas of the Persian Gulf. The highest vegetation coverage belonged to the riparian vegetation along the Mond River, which represents the northern boundary of the protected area. The location of vegetation types was studied on the separate soil and habitat diversity maps of the study area, which helped in final refinements of the vegetation map produced.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1744-7909.2008.00712.xDOI Listing
March 2009

An Iranian herbal-marine medicine, MS14, ameliorates experimental allergic encephalomyelitis.

Phytother Res 2008 Aug;22(8):1083-6

National Research Institute for Genetic Engineering and Biotechnology, Tehran, Iran.

Multiple sclerosis is an inflammatory and demyelinating disease of the central nervous system which mainly affects young adults. To overcome wide spectrum troublesome symptoms of multiple sclerosis which affects the quality of life both in patients and their families, new drugs and remedies have been examined and offered. The preclinical beneficial effects of different medicines have mostly been examined in an animal model of multiple sclerosis called experimental allergic encephalomyelitis (EAE). In this study we have tested a traditionally used natural (herbal-marine) product called MS(14) in EAE mice. EAE mice were fed with MS(14) containing diet (30%) on the immunization day and monitored for 20 days. The results show that while clinical scores and therefore severity of the disease was progressive in normal-fed EAE mice, the disease was slowed down in MS(14)-fed EAE mice. Moreover, while there were moderate to severe neuropathological changes in normal fed mice, milder changes were seen in MS(14) fed mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ptr.2459DOI Listing
August 2008

Immunomodulating and anticancer agents in the realm of macromycetes fungi (macrofungi).

Int Immunopharmacol 2007 Jun 14;7(6):701-24. Epub 2007 Feb 14.

Plant Protection Department, Faculty of Agriculture, Tehran University, Karaj, Iran.

Nowadays macrofungi are distinguished as important natural resources of immunomodulating and anticancer agents and with regard to the increase in diseases involving immune dysfunction, cancer, autoimmune conditions in recent years, applying such immunomodulator agents especially with the natural original is vital. These compounds belong mainly to polysaccharides especially beta-d-glucan derivates, glycopeptide/protein complexes (polysaccharide-peptide/protein complexes), proteoglycans, proteins and triterpenoids. Among polysaccharides, beta(1-->3)-d-glucans and their peptide/protein derivates and among proteins, fungal immunomodulatory proteins (Fips) have more important role in immunomodulating and antitumor activities. Immunomodulating and antitumor activity of these metabolites related to their effects to act of immune effecter cells such as hematpoietic stem cells, lymphocytes, macrophages, T cells, dendritic cells (DCs), and natural killer (NK) cells involved in the innate and adaptive immunity, resulting in the production of biologic response modifiers. In this review we have introduced the medicinal mushrooms' metabolites with immunomoduling and antitumor activities according to immunological evidences and then demonstrated their effects on innate and adaptive immunity and also the mechanisms of activation of immune responses and signaling cascade. In addition, their molecular structure and their relation to these activities have been shown. The important instances of these metabolites along with their immunomodulating and/or antitumor activities isolated from putative medicinal mushrooms are also introduced.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2007.01.008DOI Listing
June 2007

Induction of experimental allergic encephalomyelitis in C57/BL6 Mice: an animal model for multiple sclerosis.

Iran J Allergy Asthma Immunol 2005 Sep;4(3):113-7

The National Research Centre for Genetic Engineering and Biotechnology, Tehran, Iran.

Basic research on the autoimmune disease multiple sclerosis has been performed mainly on its animal model namely experimental allergic encephalomyelitis. There are many different approaches established to get this model. Despite the existence of many references in literature in this regard, we have been faced with many difficulties generating the model suitable for studying different therapies. After a long time of challenging to get a reliable and replicable method, we came up with the following major points: First, the key element for getting a maximum number of sick animals at a defined time is to consider the most appropriate animal body weight (19-20 gr). Even though the age of immunized animals (6-8 week old) is highlighted in literature, we found out that body weight is of a greater importance. Secondly, because the only available susceptible mice strain in Iran is C57/BL6, the choice of peptide for immunization would be myelin oligodendrocyte glycoprotein (35-55 sequence of this peptide 200 mg/animal). Finally, pertussis toxin which is a costly reagent plays a key role in stimulating the immune response. Altogether, we recommend that considering the above mentioned tricks and tracks, one would definitely be able to generate a chronic progressive type of model, for basic research on therapies of multiple sclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/04.03/ijaai.113117DOI Listing
September 2005

Functional and structural characterization of a novel member of the natriuretic family of peptides from the venom of Pseudocerastes persicus.

FEBS Lett 2004 Jan;557(1-3):104-8

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

A novel peptide, PNP (Pseudocerastes persicus natriuretic peptide), was isolated from the venom of the Iranian viper P. persicus. Amino acid sequencing revealed that the 37-residue peptide belongs to the family of natriuretic peptides. The physiological effects of intra-venously PNP infused into anesthetized rats on urine flow, sodium excretion and blood pressure were comparable to those of atrial natriuretic peptide (ANP). In PC12 cells that were treated with either PNP, ANP, or C-type natriuretic peptide, PNP induced a similar cGMP response as ANP. Since PC12 cells only express the natriuretic peptide receptor (NPR)-A receptor we conclude that PNP binds to the NPR-A receptor. The solution conformation of PNP was characterized using (1)H nuclear magnetic resonance spectroscopy and indicates a high degree of conformational flexibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0014-5793(03)01455-8DOI Listing
January 2004