Javad Behravan

Mashhad University of Medical Sciences, Mashad, Razavi Khorasan, Iran

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Publications (106)123.44 Total impact


  • No preview · Article · Dec 2015 · Oncology Research and Treatment
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    Full-text · Article · Nov 2015
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    ABSTRACT: Recent in vitro studies showed that sesquiterpene coumarins (SCs) can be used as chemosensitizers. In this study, 14 SCs were isolated and purified from roots of four Ferula species and their structures were elucidated by spectroscopic methods. The purified SCs were evaluated for multidrug resistance (MDR) reversal properties in A2780/RCIS cells (cisplatin-resistant derivatives of the human ovarian carcinoma cell line A2780P). Among the tested compounds, mogoltacin, mogoltadone, farnesiferol A, farnesiferol B, farnesiferol C, lehmferin, conferdione, and samarcandin showed significant MDR reversing effects. The combination of nontoxic concentrations of SCs (20 μM) with cisplatin enhanced cisplatin cytotoxicity on A2780/RCIS cells significantly. Flow cytometric efflux assay confirmed that the intracellular accumulation of 5-carboxyfluorescein diacetate (5-CFDA) was significantly increased in A2780/RCIS cells when treated with SCs. Our findings revealed that conferdione and samarcandin possessed the highest inhibitory effects on multidrug resistance-associated protein 2 pump efflux, and therefore, these compounds could be considered as lead scaffolds for further structure modifications. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · Oct 2015 · Phytotherapy Research
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    ABSTRACT: Background: TNF-α is a pleiotropic cytokine which activates different downstream signaling pathways leading cells to death or survival. In some in vitro examinations, TNF-α treatment demonstrated higher cytotoxic effects on MDR cancer cell lines compared to their parental counterparts. Objective: This study investigated effects of TNF-α in MCF-7 and its mitoxantrone (MX) resistant variant of breast cancer cell line, MCF-7/MX. Moreover, the role of Akt phosphorylation in TNF-α effect was also investigated. Methods: Akt phosphorylation was evaluated using Western blotting and TNF-α effect was examined using cytotoxicity assay following treatment of the cells with TNF-α . Results: TNF-α treatment exerted higher cytotoxic effects on MCF-7/MX compared to MCF-7 cells. Akt phosphorylation was enhanced following TNF-α treatment in MCF-7 cells while it did not change in MCF-7/MX cells. TNF-α treatment along with inhibition of Akt phosphorylation by a chemical inhibitor triciribine, sensitized MCF-7 cells to cytotoxic effects of TNF-α. Moreover, activation of PI3K/Akt pathway by activator peptide 740 Y-P in MCF-7/MX cells enhanced resistance against TNF-α cytotoxicity. Conclusion: Alteration in Akt phosphorylation is involved in the resistance of MCF-7 cells and sensitivity of MCF-7/MX cells to TNF-α -induced cytotoxicity, respectively.
    No preview · Article · Sep 2015 · Breast disease
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    ABSTRACT: In the present study, fifteen sesquiterpene coumarins were isolated and purified from different Ferula species, and were tested for their MDR reversal properties. Enhancement of doxorubicin cytotoxicity in MCF-7/Adr cells (doxorubicin resistant derivatives of MCF-7 cells overexpressing P-gp), when combined with very non-toxic concentrations of the sesquiterpene coumarins (50μM) including umbelliprenin, farnesiferol B, farnesiferol C and lehmferin, proved significant MDR reversal activity of these coumarins. Flow cytometric efflux assay confirmed that the intracellular accumulation of Rho123 was significantly increased in MCF-7/Adr cells when treated with sesquiterpene coumarins. A deeper insight into the structure-activity relationship of sesquiterpene coumarins revealed that ring-opened drimane-type sesquiterpene coumarins including farnesiferol B, farnesiferol C and lehmferin possessed the best inhibitory effects on P-gp pump efflux and they could be considered as lead scaffolds for further structure modifications. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Apr 2015 · Fitoterapia
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    ABSTRACT: P-glycoprotein (P-gp) is an efflux protein, the overexpression of which has been associated with multidrug resistance in various cancers. Although siRNA delivery to reverse P-gp expression may be promising for sensitizing of tumor cells to cytotoxic drugs, the therapeutic use of siRNA requires effective carriers that can deliver siRNA intracellularly with minimal toxicity on target cells. We investigated a special class of PEGylated lipid-based nanoparticles (NP), named nanolipoparticles (NLPs), for siRNA-mediated P-gp downregulation. NLPs were prepared based on low detergent dialysis method. After characterization, we evaluated the effect of NLPs on siRNA delivery, and P-gp downregulation compared to oligofectamine™ (OFA) in vitro and in vivo. Our results showed a significant decrease in P-gp expression and subsequent enhancement of chemosensitivity to doxorubicin in vitro. Although the effectiveness of NLPs for in vitro siRNA delivery compared to OFA was limited, the results of in vivo studies showed noticeable effectiveness of NLPs for systemic siRNA delivery. siRNA delivery using NLPs could downregulate MDR1 in tumor cells more than 80%, while OFA had a reverse effect on MDR1 expression in vivo. The results indicated that the prepared NLPs could be suitable siRNA delivery systems for tumor therapy.
    Full-text · Article · Apr 2015 · Iranian Journal of Basic Medical Science
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    ABSTRACT: Although cyanoacrylate glues are widely used in medicine, cyanoacrylate based nanocomposites have been recently suggested for dental restorative/filling applications. In the present research, SiO2 nanoparticles were used as filler for development of a novel dental nanocomposite base on alkoxy-ethyl-cyanoacrylate. The nanocomposite samples filled with different levels of nano-sized SiO2 (wt %) were made the mechanical properties were evaluated and comparisons were made with the neat cyanoacrylate. The hardness and wear behavior of the samples were measured using Vickers hardness and pin-on-disk tester, respectively. The wear mechanism of the samples was also evaluated using scanning electron microscopy (SEM). Furthermore, cell biocompatibility of the samples using MTT and LDH assays as well as inflammatory cytokine expression interleukin-6 (IL-6) from L929 cells were investigated. The results showed that an increase in nano-sized SiO2 content improves hardness and wear resistance of the cyanoacrylate based nanocomposites and changes the wear mechanism from adhesive to abrasive. The results of cytotoxicity analysis showed a significant reduction in cell viability and IL-6 produced from the samples-exposed L929 cells compared with untreated control cells. Moreover, increasing in nano SiO2 powder content caused a decrease in the released formaldehyde.
    No preview · Article · Oct 2014 · International Journal of Adhesion and Adhesives
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    ABSTRACT: Abstract Context: Scutellaria lindbergii Rech. f. (Lamiaceae) is an Iranian species of Scutellaria which has been shown to exert antimicrobial, antioxidant and cytotoxic effects. Objective: The protective properties of total methanol extract (TME) of S. lindbergii and its fractions (defatted and CH2Cl2) were investigated against cytotoxic and genotoxic effects of H2O2 in NIH 3T3 cell line as non-malignant cells. Materials and methods: The cells were incubated with different concentrations of S. lindbergii root extracts [TME (15-250 μg ml(-)(1)), defatted fraction (15-500 μg ml(-)(1)) and CH2Cl2 fraction (5-40 μg ml(-)(1))] and toxic concentration of H2O2 (200 µM) at 37 °C for 2 h concurrently and Cell viability was quantitated by MTT assay. The antigenotoxic effect of extracts was investigated using comet assay. The cells were incubated with extracts [TME (25-250 μg ml(-)(1)), defatted fraction (25-500 μg ml(-)(1)) and CH2Cl2 fraction (5-40 μg ml(-)(1))] and H2O2 (25 µM) at 4 °C for 20 min, then the comet assay was performed. DNA damage was expressed as percentage tail DNA. Results: Total methanol extract of S. lindbergii and its fractions had a significant inhibitory effect on DNA damage. The IC50 values of TME, defatted fraction and CH2Cl2 fraction against DNA damage were determined as 48, 138 and 8 μg ml(-)(1), respectively. Conclusion: S. lindbergii extracts can prevent oxidative DNA damage, which is likely due to its flavonoids and phenolic compounds as antioxidant constituents.
    Full-text · Article · Sep 2014 · Drug and Chemical Toxicology
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    ABSTRACT: Elevated expression of the drug efflux transporter ABCG2 seems to correlate with multidrug resistance of cancer cells. Specific COX-2 inhibitor celecoxib has been shown to enhance the sensitivity of cancer cells to anticancer drugs. To clarify whether ABCG2 inhibition is involved in the sensitizing effect of celecoxib, we investigated whether the expression of ABCG2 in breast cancer cell lines, could be modulated by celecoxib. The expression of the multidrug resistant gene (ABCG2) at mRNA and protein level was detected by real-time quantitative reverse transcription-polymerase chain reaction and flow cytometry analysis, respectively. Among three human breast cancer cell lines ABCG2 and COX-2 were highly expressed in MCF7-MX and MDA-MB-231 cells, respectively. The COX-2 inhibitor celecoxib up-regulated the expression of ABCG2 mRNA in MCF-7 and MCF7-MX cells, which was accompanied by increased ABCG2 protein expression. While celecoxib was able to block the 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated increase in COX-2 expression in MDA-MB-231 cells, it increased the expression of ABCG2 up to 4.27 times to the control level at mRNA level and with less intensity at protein level. Our findings provide evidence that celecoxib up-regulates ABCG2 expression in human breast cancer cells and proposed that ABCG2 is not involved in chemosensitizing effects of celecoxib.
    Full-text · Article · Sep 2014 · Iranian journal of pharmaceutical research (IJPR)
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    ABSTRACT: Objective: Ferula szowitsiana has been widely used for medicinal purposes around the world. The anti-oxidant effect of F. szowitsiana had been proved. The current study aims to determine the protective effects of galbanic acid, a sesquiterpene coumarin from F. szowitsiana, against hydrogen peroxide (H2O2) - induced oxidative DNA damage in human lymphocytes. Materials and Methods: Human lymphocytes were incubated with H2O2 (0, 25, 50, 100, and 200 µM), galbanic acid (200 and 400 µM) and a combination of galbanic acid (200 and 400 µM) and H2O2 (25 µM) at 4 C for 30 minutes. Solvents of galbanic acid without H2O2 were used as negative controls. Results: The findings of this study demonstrated that H2O2 exposure leads to a significant concentration-dependent increase in DNA damage. Galbanic acid did not cause DNA damage compared with the control cells. Data showed that galbanic acid does not have a protective effect against H2O2-induced oxidative DNA damage in human lymphocytes. Conclusion: According to the results, it is concluded that the capability of F. szowitsiana in reducing reactive oxygen species and the anti-inflammatory property of its methanolic extract may be due to its other ingredients.
    Full-text · Article · Sep 2014 · Avicenna Journal of Phytomedicine
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    ABSTRACT: Objective: To investigate the insecticidal activity of the essential oil of Thymus transcaspicus (T. transcaspicus) against Anopheles stephensi (An. stephensi). Methods: An. stephensi were exposed to 31, 63, 125 and 250 μg/L of essential oil of T. transcaspicus for 24 h. Results: The most toxicity was observed at 250 μg/L of essential oil with the LC50 values of 134.1 μg/L after 24 h. Conclusions: The essential oil of T. transcaspicus exhibited strong insecticidal activity against An. stephensi which can be attributed to its constituent especially carvacrol and thymol phenols.
    Full-text · Article · Jul 2014 · Asian Pacific Journal of Tropical Biomedicine
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    ABSTRACT: Background: Despite the wide range of investigations on the therapeutic potentials of herbal extracts in cancer cell lines, there is not usually enough data on their probable effects on normal cells. Recently, both anti-tumoral and anti-oxidant properties of Scutellaria litwinowii extracts have been reported on different cancer cell lines. In the present study, the possible protective effects of S. litwinowii root extracts against cytotoxicity and DNA damage induced by hydrogen peroxide (H2O2) on normal cells were investigated using MTT and Comet assays, respectively. Methods: A method of sequential extraction with solvents of different polarities was used to generate methanolic, de-fatted, and dichloromethane fractions. Both MTT and Comet assays were performed here to assess, respectively, changes in cell viability and levels of DNA damage from H2O2. In a pre-treatment regimen, test materials were applied to the cells prior to H2O2 treatment, while in a co-treatment protocol, cells were treated simultaneously with H2O2 and extracts. Results: In the co-treatment studies, only methanolic extract at 1,000 μg/mL (p<0.001) imparted a significant protective effect as shown in the MTT assay. Pre-treatment of cells for 24 h with different concentrations of the test materials did not lead to any significant protection. Results from the Comet assays in the co-treatment studies suggested a significant (p<0.01) protective effect of the test materials against DNA damage caused by H2O2. However, in the pre-treatment studies, only methanolic extract at ≥500 μg/mL showed a protective effect (p<0.01). Conclusions: Considering the probable high levels of phenolic and flavonoid compounds in the methanolic extract, these compounds may impart the noted protective effects of the S. litwinowii root through the scavenging of free radicals.
    No preview · Article · Apr 2014 · Journal of Complementary and Integrative Medicine
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    ABSTRACT: Background: Rosemary (Rosmarinus officinalis) possesses various pharmacological properties such as antioxidant, anti-tumorigenesis and anti-mutagenesis activities. In this study, we investigated the possible protective effects of ethanol and aqueous extracts of rosemary on human lymphocyte DNA damage induced by H2O2. The extent of DNA lesions was measured using comet assay. Methods: Blood samples were taken from healthy volunteers and lymphocytes were isolated. The lymphocytes were then incubated in aqueous and ethanol extract of rosemary (0.05, 0.1, 0.5, 1 and 2.5 mg/mL) and H2O2 (50, 100 and 200 mM). Lymphocytes were also incubated with a combination of H2O2 (100 mM) with either 1 or 2.5 mg/mL of both extracts for 30 min at 4°C. Results: Our findings showed that H2O2 treatment led to a significant concentrate-dependent DNA damage in human lymphocyte when compared to respective controls (p<0.001). The DNA damage which was initially occurred as the result of 100 µM H2O2 (Percentage tail DNA 55.1%) was inhibited due to the ethanol extract of rosemary at the doses tested (percentage tail DNA 4.7% and 4.03%). However, the aqueous extract has no effects on H2O2 genotoxicity. Conclusions: We suggest that antioxidant constituents in ethanol extract of rosemary can prevent human lymphocytes oxidative DNA damage which is due to its free radical scavenging activity.
    Full-text · Article · Feb 2014 · Journal of Complementary and Integrative Medicine
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    ABSTRACT: Abstract The antigenotoxic activity of glucosamine (GlcN) and N-acetylglucosamine (GlcNAc) in human peripheral lymphocytes exposed to oxidative stress was investigated. Human lymphocytes were treated with different concentrations of these aminosugars (0, 2.5, 5, 10, 20 and 40 mM) and 25 µM H2O2 simultaneously and evaluated by single cell gel electrophoresis technique (Comet assay). The single cells were analyzed using "TriTek Cometscore version 1.5" software and the data were presented as % DNA in tail. Both GlcN and GlcNAc at examined concentrations (2.5, 5, 10, 20 and 40 mM) did not reveal any genotoxicity compared to the vehicle control (PBS). Glucosamine at all concentrations (2.5, 5, 10, 20 and 40 mM) showed a significant protective activity (% DNA in tail ranging from 16.07 ± 0.85 to 5.47 ± 0.26, p < 0.001) against H2O2 induced DNA damage (% DNA in tail = 38 ± 0.65) while its N-acetylated analog only indicated a slight DNA protection at concentration of 40 mM (% DNA in tail = 33.4 ± 1.17, p < 0.01). We concluded that GlcN at tested concentrations exhibited potent antigenotoxic effect and its protection activity might be related to the presence of 2-NH2 moiety in its chemical backbone.
    Full-text · Article · Jan 2014 · Drug and Chemical Toxicology
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    ABSTRACT: Histopathological evaluation and grading of meningioma give important prognostic information. We evaluated retrospectively monotonous sheeting, necrosis, hypercellularity, nuclear pleomorphism, small cell changes, brain invasion, mitosis, mast cells, psammoma bodies, MIB-1 labeling index (MIB-1 LI) and histological grade of 230 primary meningioma tumors according to the latest World Health Organization (WHO) classification. To reveal any possible association between clinical features and promoter hypermethylation of O(6)-methylguanine-DNA methyltransferase (MGMT) as an important epigenetic modification in many human cancers, we also evaluated the methylation status of MGMT in meningiomas by a SYBR-green-based real-time PCR method. There was a female predominance (2.38 to 1) in the meningiomas. The mean age of the patients was 49.9 ± 12.6 years (range 16 to 78 years). Transitional meningiomas were the most common subtype of the meningiomas (35.21%, n = 81). Most of the meningiomas were located in the falx and parasagital area. There was a significant correlation between histopathological features of malignancy. These features were observed more frequently and with statistical relation to grade II rather than grade I. Mast cells, psammoma bodies and nuclear pleomorphism had poor associations (P > 0.05). When we re-evaluated the tumor grading, 31 patients with grade I meningiomas were upgraded to grade II. None of the meningiomas tested by MSQP were methylated in MGMT promoter sequence. High MIB-1 LI could be indicative for higher grade of meningioma. Continuous revision of the classification system is needed to improve the accuracy of prognostic judgments in meningioma. The data confirm that there is no rationale to test meningiomas for MGMT methylation status.
    No preview · Article · Jan 2014 · Gene
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    ABSTRACT: Abstract The antigenotoxic effects of umbelliferone (UMB), herniarin (HER) and 7-isopentenyloxy coumarin (7-IP), common natural dietary coumarins, were evaluated on the human lymphocyte DNA damage using single-cell gel electrophoresis. H2O2-induced DNA break was measured based on the percentage of DNA in tail, and the antigenotoxic effects of the tested compounds were compared with that of ascorbic acid (10, 25, 50, 100 and 200 μM). UMB, HER and 7-IP did not show any genotoxicity, as compared to phosphate-buffered saline. Treatment with UMB, HER and 7-IP led to a significant reduction in the percentage of DNA in tail induced by H2O2 (p < 0.001) at all concentrations. The presence of prenyl moiety in the chemical structure of 7-IP may contribute to its better antigenotoxic property, compared to UMB. The results of this study showed that 7-IP possessed the best antigenotoxic activity among the tested compounds.
    Full-text · Article · Oct 2013 · Drug and Chemical Toxicology
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    ABSTRACT: The composition and antimicrobial activity of the essential oil of Pistacia vera L., grown in Iran, was studied. The oil was obtained from the resin and analyzed by GC-MS. Twenty compounds, accounting for 99.5 % of the total components, were identified. The main constituents were α-pinene, β-pinene , and α-thujene. The antimicrobial effects of the essential oil of Pistacia vera L. gum and its major constituents ((+)α-pinene, (-)α-pinene, (-)β-pinene, (-)α-thujene and α, β-thujene) were investigated. Antibacterial assays were performed using broth microdilution assays to determine the minimum inhibitory concentrations (MICs) against two Gram positive bacteria (Staphylococcus aureus, Bacillus subtilis) and three Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiela pneumoniae). The antifungal activity against Candida albicans was determined by the agar dilution method. The essential oil of Pistacia vera L. gum exhibited strong inhibitory effects against Gram positive bacteria and C. albicans. Moreover, The results indicated that (-)β-pinene had the most inhibitory effects against Gram positive bacteria and C. albicans while α, β-thujene was more active against Gram negative bacteria.
    Full-text · Article · Mar 2013 · Journal of essential oil-bearing plants JEOP
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    ABSTRACT: In this study, a methanolic extract and an essential oil of Artemisia kopetdaghensis were tested for possible Cytotoxic activity using potato disk assay. Seven concentration of methanolic extract and four concentration of the essential oil were applied on potato discs. The methanolic extract and essential oil of A. kopetdaghensis exhibited tumor growth induction at different concentrations but at concentration equal to 0.01 % (v/v) the essential oil of A. kopetdaghensis exhibited tumor growth inhibition (52 %). A dose activity relationship between methanolic extract and essential oil concentration with tumor growth on potato discs was observed.
    No preview · Article · Mar 2013 · Journal of essential oil-bearing plants JEOP
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    ABSTRACT: The cytotoxic and anti-fungal activities of Artemisia turanica essential oil were investigated. Also the composition of the essential oil of the plant was determined. For cytotoxic activity tests, a potato disc tumor inhibition method was exploited. For antifungal activity tests, a poisoned food technique against standard strains of Trichophyton rubrum, Trichoderma reesei, Microsporum gypseum and Aspergillus niger was adopted. The essential oils of A. turanica exhibited tumor growth inhibition (100 % ) inhibition at concentrations equal to 0.02 % (w/v) and higher. Thirteen components were identified in the essential oil of Artemisia turania. The main compounds consisted of 1,8-cineol (40.9 %), cis-verbenyl actate (19.0 %) and camphor (11.0 %). A dose activity relationship between the essential oil concentrations with inhibition of tumor growth on potato discs, and between the essential oil concentrations with antifungal activities was observed.
    Full-text · Article · Mar 2013 · Journal of essential oil-bearing plants JEOP
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    ABSTRACT: The essential oil components of Ziziphora clinopodioides Lam. from Iran were isolated via hydrodistillation and analyzed by GC-MS. Twenty seven components were identified in the essential oil of the plant. The main compounds consisted of pulegone (44.5 %), terpineol (14.5%) methyl acetate (10.9%), iso-neomenthol (7.1%) and 1, 8-cineole (4.1%). Antifungal and antimicrobial acitivities of different concentrations of the essential oil of Ziziphora clinopodioides Lam. was also evaluated. The antifungal tests were conducted by a poisoned food technique against the filamentous fungi (Aspergillus niger, Trichophyton rubrum, Trichoderma reesei and Microsporum gypseum). antimicrobial tests were carried out against four Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Klebsiella pneumonia) and one Gram positive pathogen (Staphyloccocus aureus) using a microdilution assay. The essential oil was found to be fungicidal at >1 μl/ml against T. rubrum and M. gypseum. The minimum inhibitory concentration of the oil against Escherichia coli, Staphyloccocus aureus, Pseudomonas aeruginosa, Salmonella typhi and Kleb-siella pneumonia were found to be 0.003, 0.033, 0.033, 0.067 and 0.067 % (v/v) respectively.
    Full-text · Article · Mar 2013 · Journal of essential oil-bearing plants JEOP

Publication Stats

855 Citations
123.44 Total Impact Points

Institutions

  • 2004-2015
    • Mashhad University of Medical Sciences
      • • Biotechnology Research Center
      • • Department of Pharmacognosy
      • • Faculty of Pharmacy
      • • Pharmaceutical Research Center
      • • Department of Biotechnology
      Mashad, Razavi Khorasan, Iran
  • 2013
    • Agricultural Biotechnology Research Institute of Iran
      Leredi, Alborz, Iran
  • 2011
    • Islamic Azad University Shiraz branch
      • Faculty of Sciences
      Chimaz, Fārs, Iran
  • 2010
    • Avicenna Research Institute
      Teheran, Tehrān, Iran
  • 2006-2008
    • University of Toronto
      Toronto, Ontario, Canada