Publications by authors named "Fariba Dehghanian"

24 Publications

  • Page 1 of 1

Quercetin‑conjugated superparamagnetic iron oxide nanoparticles modulate glucose metabolism-related genes and miR-29 family in the hippocampus of diabetic rats.

Sci Rep 2021 Apr 21;11(1):8618. Epub 2021 Apr 21.

Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.

Quercetin (QC) is a dietary bioflavonoid that can be conjugated with nanoparticles to facilitate its brain bioavailability. We previously showed that quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) reduced the level of blood glucose in diabetic rats. Glucose transporters (GLUTs), insulin-like growth factor-1 (IGF-1), and microRNA-29 (miR-29) play a critical role in brain glucose homeostasis. In the current study, we examined the effects of QCSPION on the expression of glucose metabolism-related genes, and the miR-29 family as a candidate regulator of glucose handling in the hippocampus of diabetic rats. Our in silico analyses introduce the miR-29 family as potential regulators of glucose transporters and IGF-1 genes. The expression level of the miR-29 family, IGF-1, GLUT1, GLUT2, GLUT3, and GLUT4 were measured by qPCR. Our results indicate that diabetes significantly results in upregulation of the miR-29 family and downregulation of the GLUT1, 2, 3, 4, and IGF-1 genes. Interestingly, QCSPIONs reduced miR-29 family expression and subsequently enhanced GLUT1, 2, 3, 4, and IGF-1expression. In conclusion, our findings suggest that QCSPION could regulate the expression of the miR-29 family, which in turn increases the expression of glucose transporters and IGF-1, thereby reducing diabetic complications.
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http://dx.doi.org/10.1038/s41598-021-87687-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060416PMC
April 2021

Gene expression profiles of YAP1, TAZ, CRB3, and VDR in familial and sporadic multiple sclerosis among an Iranian population.

Sci Rep 2021 Apr 8;11(1):7713. Epub 2021 Apr 8.

Isfahan Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Alterations in the regulatory mechanisms that control the process of myelination in the nervous system, may lead to the impaired myelination in the Multiple sclerosis. The Hippo pathway is an important mediator of myelination in the nervous system and might contribute to the pathophysiology of MS. This study examined via qPCR the RNA expression of YAP1, TAZ, and CRB3 as the key effectors of the Hippo pathway and also, VDR in the peripheral blood of 35 sporadic, 37 familial MS patients; and also 34 healthy first-degree relatives of the familial MS patients (HFR) and 40 healthy individuals without a family history of the disease (control). The results showed the increased expression of VDR in the sporadic group, as compared to other groups. There was also an increased expression of TAZ in the familial and HFR groups, as compared to the control group. The familial and sporadic patients displayed a significantly lower level of expression of YAP1 in comparison to the HFR group. The increased expression level in the sporadic patients and control group, as compared to the HFR group, was seen in CRB3. We also assessed different clinical parameters and MRI characteristics of the patients. Overall, these findings suggest that Hippo pathway effectors and also VDR gene may play a potential role in the pathophysiology of the sporadic and familial forms of MS. Confirmation of different gene expression patterns in sporadic and familial MS groups may have obvious implications for the personalization of therapies in the disease.
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http://dx.doi.org/10.1038/s41598-021-87131-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032816PMC
April 2021

Effects of quercetin-conjugated with superparamagnetic iron oxide nanoparticles on learning and memory improvement through targeting microRNAs/NF-κB pathway.

Sci Rep 2020 09 15;10(1):15070. Epub 2020 Sep 15.

Department of Plant and Animal Biology, Faculty of Biological Science and Technology, University of Isfahan, HezarJarib Street, 81746-73441, Isfahan, Iran.

Quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) have an ameliorative effect on diabetes-induced memory impairment. The current study aimed to compare the effect of quercetin (QC) and QCSPIONs on inflammation-related microRNAs and NF-κB signaling pathways in the hippocampus of diabetic rats. The expression levels of miR-146a, miR-9, NF-κB, and NF-κB-related downstream genes, including TNF-α, BACE1, AβPP, Bax, and Bcl-2 were measured using quantitative real-time PCR. To determine the NF-κB activity, immunohistochemical expression of NF-κB/p65 phosphorylation was employed. Computer simulated docking analysis also performed to find the QC target proteins involved in the NF-κB pathway. Results indicate that diabetes significantly upregulated the expression levels of miR-146a, miR-9, TNF-α, NF-κB, and subsequently AβPP, BACE1, and Bax. Expression analysis shows that QCSPIONs are more effective than pure QC in reducing the expression of miR-9. Interestingly, QCSPIONs reduce the pathological activity of NF-κB and subsequently normalize BACE1, AβPP, and the ratio of Bax/Bcl-2 expression better than pure QC. Comparative docking analyses also show the stronger binding affinity of QC to IKK and BACE1 proteins compared to specific inhibitors of each protein. In conclusion, our study suggests the potent efficacy of QCSPIONs as a promising drug delivery system in memory improvement through targeting the NF-κB pathway.
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http://dx.doi.org/10.1038/s41598-020-71678-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493930PMC
September 2020

Comparative physiological and proteomic analysis indicates lower shock response to drought stress conditions in a self-pollinating perennial ryegrass.

PLoS One 2020 18;15(6):e0234317. Epub 2020 Jun 18.

Core Facility Proteomics, Center for Biological Systems Analysis (ZBSA), University of Freiburg, Freiburg, Germany.

We investigated the physiological and proteomic changes in the leaves of three Lolium perenne genotypes, one Iranian putative self-pollinating genotype named S10 and two commercial genotypes of Vigor and Speedy, subjected to drought stress conditions. The results of this study indeed showed higher RWC (relative water content), SDW (shoot dry weight), proline, ABA (abscisic acid), nitrogen and amino acid contents, and antioxidant enzymes activities of S10 under drought stress in comparison with the two other genotypes. A total of 915 proteins were identified using liquid chromatography-mass spectrometry (LC/MS) analysis, and the number of differentially abundant proteins between normal and stress conditions was 467, 456, and 99 in Vigor, Speedy, and S10, respectively. Proteins involved in carbon and energy metabolism, photosynthesis, TCA cycle, redox, and transport categories were up-regulated in the two commercial genotypes. We also found that some protein inductions, including those involved in amino acid and ABA metabolisms, aquaporin, HSPs, photorespiration, and increases in the abundance of antioxidant enzymes, are essential responses of the two commercial genotypes to drought stress. In contrast, we observed only slight changes in the protein profile of the S10 genotype under drought stress. Higher homozygosity due to self-pollination in the genetic background of the S10 genotype may have led to a lower variation in response to drought stress conditions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234317PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302502PMC
September 2020

DMLR: A toolkit for investigation of deoxyribozyme-mediated ligation based on real time PCR.

Biochem Biophys Res Commun 2020 04 30;524(2):405-410. Epub 2020 Jan 30.

Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, HezarJarib Street, Isfahan, 81746-73441, Iran.

Deoxyribozymes or DNAzyme are identified as catalytic DNA sequences which catalyze different chemical reactions. Ligating deoxyribozymes catalyze the formation of branched and linear products. Due to the lack of efficient read-out systems, there is no report on in vivo application of ligating deoxyribozymes. To expand the biological application of branched-RNA forming deoxyribozymes, we performed our study in order to suggest a practical toolkit for measurement of in vivo real-time activity of ligating deoxyribozymes. Further in vitro studies were designed to analyze the effects of the location of branch site on reverse transcriptase (RT) interference. With this toolkit even the activity of RT was measured precisely. Our results indicate that the activity of RT enzyme significantly affected by a 17 nt branched adaptor synthesized by 10DM24 ligating deoxyribozyme. The RT stalls at or near the RNA branch point during both initiation and elongation phases. The DNA synthesis is decreased 4.3 and 2.7 fold during initiation and elongation phases respectively. In conclusion, we introduce a general and practical toolkit called "DMLR" which is based on Real-time PCR method. The use of DMLR precisely determines RT behavior when encountered with any backbone modification with the ability of stopping the enzyme activity.
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http://dx.doi.org/10.1016/j.bbrc.2020.01.075DOI Listing
April 2020

Expression Pattern of microRNAs, miR-21, miR-155 and miR-338 in Patients with Type 1 Diabetes.

Arch Med Res 2019 04 24;50(3):79-85. Epub 2019 Jul 24.

Division of Genetics, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran. Electronic address:

Background: Type 1 diabetes (T1D) is a multifactorial disease identified by a deficiency in the production of insulin. MicroRNAs (miRNAs) are identified as important epigenetic regulators in T1D. Many studies highlight the differential expression of these small non-coding molecules in the pathogenesis of T1D.

Aim Of The Study: In the present study, the expression pattern of miR-21, miR-155 and miR-338 were analyzed in the peripheral blood mononuclear cells (PBMCs) of T1D patients compared to healthy controls.

Methods: The expression levels of miR-21, miR-155 and miR-338 were measured in the PBMCs of 30 T1D patients and 11 healthy controls by real time PCR method. The final results were statistically analyzed and ROC curves were created for miRNAs with significant differential expression.

Results: Both miR-155 (p value: 0.021) and miR-21 (p value: 0.05) were upregulated in the PBMCs of T1D patients compared to healthy controls. There was no significant difference in the expression level of miR-338 between patients and controls. Furthermore, ROC curve analysis was performed for miR-21 (AUC: 0.65) and miR-155 (AUC: 0.73) which suggests the potential role of miR-155 as a biomarker in T1D patients. Using integrative computational analysis, a number of dysregulated miR155-mRNA and miR21-mRNA interactions were also suggested.

Conclusion: Our findings suggest the significant association between the expression levels of miR-21 and miR-155 with T1D. In addition, miR-155 (AUC: 0.73) could be considered as a possible biomarker to track disease in T1D patients.
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http://dx.doi.org/10.1016/j.arcmed.2019.07.002DOI Listing
April 2019

Induction of Tyrosine Hydroxylase Gene Expression in Embryonal Carcinoma Stem Cells Using a Natural Tissue-Specific Inducer.

Dev Neurobiol 2019 06 29;79(6):559-577. Epub 2019 Jun 29.

School of Life Science (LifeNet), Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, 79106, Germany.

A large number of studies have focused on the generation of dopaminergic neurons from pluripotent cells. Differentiation of stem cells into distinct cell types is influenced by tissue-specific microenvironment. Since, central nervous system undergoes further development during postnatal life, in the present study neonatal rat brain tissue extract (NRBE) was applied to direct the differentiation of embryonal carcinoma stem cell line, P19 into dopaminergic (DA) phenotypes. Additionally, a neuroprotective drug, deprenyl was used alone or in combination with the extract. Results from morphological, immunofluorescence, and qPCR analyses showed that during a period of one to three weeks, a large percentage of stem cells were differentiated into neural cells. The results also indicated the greater effect of NRBE on the differentiation of the cells into tyrosine hydroxylase-expressing cells. MS analysis of NRBE showed the enrichment of gene ontology terms related to cell differentiation and neurogenesis. Network analysis of the studied genes and some DA markers resulted in the suggestion of potential regulatory candidates such as AVP, ACHE, LHFPL5, and DLK1 genes. In conclusion, NRBE as a natural native inducer was apparently able to simulate the brain microenvironment and support neural differentiation of P19 cells.
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http://dx.doi.org/10.1002/dneu.22703DOI Listing
June 2019

TGFβ-Signaling and FOXG1-Expression Are a Hallmark of Astrocyte Lineage Diversity in the Murine Ventral and Dorsal Forebrain.

Front Cell Neurosci 2018 28;12:448. Epub 2018 Nov 28.

Department of Molecular Embryology, Institute of Anatomy and Cell Biology, Medical Faculty, University of Freiburg, Freiburg, Germany.

Heterogeneous astrocyte populations are defined by diversity in cellular environment, progenitor identity or function. Yet, little is known about the extent of the heterogeneity and how this diversity is acquired during development. To investigate the impact of TGF (transforming growth factor) β-signaling on astrocyte development in the telencephalon we deleted the TGFBR2 (transforming growth factor beta receptor 2) in early neural progenitor cells in mice using a FOXG1 (forkhead box G1)-driven CRE-recombinase. We used quantitative proteomics to characterize TGFBR2-deficient cells derived from the mouse telencephalon and identified differential protein expression of the astrocyte proteins GFAP (glial fibrillary acidic protein) and MFGE8 (milk fat globule-EGF factor 8). Biochemical and histological investigations revealed distinct populations of astrocytes in the dorsal and ventral telencephalon marked by GFAP or MFGE8 protein expression. The two subtypes differed in their response to TGFβ-signaling. Impaired TGFβ-signaling affected numbers of GFAP astrocytes in the ventral telencephalon. In contrast, TGFβ reduced MFGE8-expression in astrocytes deriving from both regions. Additionally, lineage tracing revealed that both GFAP and MFGE8 astrocyte subtypes derived partly from FOXG1-expressing neural precursor cells.
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http://dx.doi.org/10.3389/fncel.2018.00448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282056PMC
November 2018

Increased expression of microRNAs, miR-20a and miR-326 in PBMCs of patients with type 1 diabetes.

Mol Biol Rep 2018 Dec 7;45(6):1973-1980. Epub 2018 Sep 7.

Division of Genetics, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran.

Type 1 diabetes (T1D) is an autoimmune disorder which is characterized by autoimmune attack on β cells of pancreas and lack of insulin. The involvement of microRNAs (miRNAs) in the development of immune system and their differential expression in various autoimmune diseases including T1D have been well established. In this study, the association between expression levels of miR-20a, miR-326 and T1D were evaluated. The expression levels of miR-20a and miR-326 were measured in the PBMCs of 21 T1D patients and 16 healthy controls using qPCR method. In silico analysis was also performed on targetome of miR-20a and miR-326. Both miR-20a (p value: 0.015) and miR-326 (p value: 0.005) were upregulated in the PBMCs of T1D patients compared to healthy controls. Furthermore, different dysregulated miR326-mRNA and miR20a-mRNA interactions were also suggested using integrative computational analysis. The expression level of miR-20a and miR-326 indicates significant association with T1D which suggests the possible regulatory effects of these non-coding RNAs in T1D.
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http://dx.doi.org/10.1007/s11033-018-4352-zDOI Listing
December 2018

Reconstruction of the genome-scale co-expression network for the Hippo signaling pathway in colorectal cancer.

Comput Biol Med 2018 08 26;99:76-84. Epub 2018 May 26.

Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. Electronic address:

The Hippo signaling pathway (HSP) has been identified as an essential and complex signaling pathway for tumor suppression that coordinates proliferation, differentiation, cell death, cell growth and stemness. In the present study, we conducted a genome-scale co-expression analysis to reconstruct the HSP in colorectal cancer (CRC). Five key modules were detected through network clustering, and a detailed discussion of two modules containing respectively 18 and 13 over and down-regulated members of HSP was provided. Our results suggest new potential regulatory factors in the HSP. The detected modules also suggest novel genes contributing to CRC. Moreover, differential expression analysis confirmed the differential expression pattern of HSP members and new suggested regulatory factors between tumor and normal samples. These findings can further reveal the importance of HSP in CRC.
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http://dx.doi.org/10.1016/j.compbiomed.2018.05.023DOI Listing
August 2018

Network-based expression analyses and experimental validations revealed high co-expression between Yap1 and stem cell markers compared to differentiated cells.

Genomics 2019 07 22;111(4):831-839. Epub 2018 May 22.

Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. Electronic address:

The Hippo signaling pathway is identified as a potential regulatory pathway which plays critical roles in differentiation and stem cell self-renewal. Yap1 is a primary transcriptional effector of this pathway. The importance of Yap1 in embryonic stem cells (ESCs) and differentiation procedure remains a challenging question, since two different observations have been reported. To answer this question we used co-expression network and differential co-expression analyses followed by experimental validations. Our results indicate that Yap1 is highly co-expressed with stem cell markers in ESCs but not in differentiated cells (DCs). The significant Yap1 down-regulation and also translocation of Yap1 into the cytoplasm during P19 differentiation was also detected. Moreover, our results suggest the E2f7, Lin28a and Dppa4 genes as possible regulatory nuclear factors of Hippo pathway in stem cells. The present findings are actively consistent with studies that suggested Yap1 as an essential factor for stem cell self-renewal.
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http://dx.doi.org/10.1016/j.ygeno.2018.05.007DOI Listing
July 2019

Exploring the crizotinib resistance mechanism of NSCLC with the L1196M mutation using molecular dynamics simulation.

J Mol Model 2017 Oct 24;23(11):323. Epub 2017 Oct 24.

Division of Genetics, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Islamic Republic of Iran.

Crizotinib is an anticancer tyrosine kinase inhibitor that is approved for use as a first-line treatment for some non-small-cell lung cancers. L1196M is the most frequently observed mutation in NSCLC patients. This mutation, known as the gatekeeper mutation in the ALK kinase domain, confers resistance to crizotinib by sterically blocking the binding of the drug. However, the molecular mechanism of crizotinib resistance caused by the L1196M mutation is still unclear. Molecular dynamics simulation was therefore utilized in this study to investigate the mechanism by which the L1196M mutation may affect crizotinib resistance. Our results suggest that larger fluctuations in some important regions of the mutant complex compared to the wild-type complex may contribute to the resistance of the mutant complex to crizotinib. Also, mutation-induced alterations to the secondary structure of the complex as well as unstable hydrogen-bonding patterns in the A-loop and P-loop regions decrease the total binding energy of the complex. This study therefore provides a molecular explanation for the resistance to crizotinib caused by the L1196M mutation, which could aid the design of more efficient and selective drugs.
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http://dx.doi.org/10.1007/s00894-017-3495-5DOI Listing
October 2017

F1174V mutation alters the ALK active conformation in response to Crizotinib in NSCLC: Insight from molecular simulations.

J Mol Graph Model 2017 08 8;75:287-293. Epub 2017 Jun 8.

Division of Genetics, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Islamic Republic of Iran. Electronic address:

Crizotinib is an efficient antineoplastic drug for treatment of non-small cell lung carcinoma (NSCLC), which is identified as an anaplastic lymphoma kinase (ALK) inhibitor. F1174V is a recently identified acquired point mutation relating to the Crizotinib resistance in NSCLC patients. The mechanism of Crizotinib resistance relating to F1174V mutation as a non-active site mutation remains unclear. In this study, the molecular dynamic simulation was used to investigate the possible mechanisms by which F1174V mutation may affect the structure and activity of ALK kinase domain. The results suggested that F1174V mutation could cause two important secondary structure alterations, which led to the local conformational change in ALK kinase domain. This causes more positive free energy in the mutant complex in comparison with the wild-type one. In addition, our structural analyses illustrated that F1174V mutation could result in some important interactions, which represent the key characteristics of the ALK active conformation. This study provided a molecular mechanism for ALK Crizotinib resistance caused by F1174V mutation,which could facilitate designing more efficient drugs.
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http://dx.doi.org/10.1016/j.jmgm.2017.06.010DOI Listing
August 2017

Neuronal Activity, TGFβ-Signaling and Unpredictable Chronic Stress Modulate Transcription of Gadd45 Family Members and DNA Methylation in the Hippocampus.

Cereb Cortex 2017 08;27(8):4166-4181

Department of Molecular Embryology, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.

Neuronal activity is altered in several neurological and psychiatric diseases. Upon depolarization not only neurotransmitters are released but also cytokines and other activators of signaling cascades. Unraveling their complex implication in transcriptional control in receiving cells will contribute to understand specific central nervous system (CNS) pathologies and will be of therapeutically interest. In this study we depolarized mature hippocampal neurons in vitro using KCl and revealed increased release not only of brain-derived neurotrophic factor (BDNF) but also of transforming growth factor beta (TGFB). Neuronal activity together with BDNF and TGFB controls transcription of DNA modifying enzymes specifically members of the DNA-damage-inducible (Gadd) family, Gadd45a, Gadd45b, and Gadd45g. MeDIP followed by massive parallel sequencing and transcriptome analyses revealed less DNA methylation upon KCl treatment. Psychiatric disorder-related genes, namely Tshz1, Foxn3, Jarid2, Per1, Map3k5, and Arc are transcriptionally activated and demethylated upon neuronal activation. To analyze whether misexpression of Gadd45 family members are associated with psychiatric diseases, we applied unpredictable chronic mild stress (UCMS) as established model for depression to mice. UCMS led to reduced expression of Gadd45 family members. Taken together, our data demonstrate that Gadd45 family members are new putative targets for UCMS treatments.
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http://dx.doi.org/10.1093/cercor/bhx095DOI Listing
August 2017

Association between polymorphisms of exon 12 and exon 24 of JHDM2A gene and male infertility.

Int J Reprod Biomed 2016 Jun;14(6):389-96

Division of Genetics, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran.

Background: Some dynamic changes occurs during spermatogenesis such as histone removal and its replacement with transition nuclear protein and protamine. These proteins are required for packing and condensation of sperm chromatin. JHDM2A is a histone demethylase that directly binds to promoter regions of Tnp1 and Prm1 genes and controls their expression by removing H3K9 at their promoters.

Objective: The association between polymorphisms of exon 12 and exon 24 in JHDM2A gene and male infertility were evaluated for the first time.

Materials And Methods: In this experimental study, 400 infertile men (oligospermia and azoospermia) and normal healthy fathers were evaluated (n=200). Single Strand Conformation Polymorphism (SSCP-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods were used for screening any polymorphisms that are exist in exon 12 and exon 24.

Results: Exon 24 PCR products were analyzed by RFLP but no polymorphism was found in this exon at the restriction site of EcoRV enzyme. Our monitoring along the whole nucleotides of exon 12 and exon 24 were continued using SSCP method, but we found no change along these exons.

Conclusion: Generally, this study evaluated the association between polymorphisms in exon 12 and exon 24 of JHDM2A gene and male infertility which suggests that polymorphisms of these exons may not be associated with the risk of male infertility.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971551PMC
June 2016

Association between Serum Paraoxonase 1 Activities (PONase/AREase) and L55M Polymorphism in Risk of Female Infertility.

Avicenna J Med Biotechnol 2015 Oct-Dec;7(4):173-8

Genetics Division, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran.

Background: The risk of developing female infertility has been associated with gene polymorphisms that decrease the activity of enzymes involved in systemic Oxidative Stress (OS). In this study, PON1 L55M polymorphism for association with susceptibility to infertility was investigated among Iranian female population.

Methods: Samples from 120 Iranian females [20 endometriosis; 30 Polycystic Ovary Syndrome (PCO); 70 controls] were analyzed and PCR-RFLP assay was used to determine the PON1 rs854560 (L55M) frequencies. The paraoxonase (PONase) and arilesterase (AREase) activities of PON1 enzyme were also assessed in order to investigate the association between serum PON1 activities, female infertility, and PON1 L55M polymorphism.

Results: The women with a MM genotype (p=0.021; OR=2.55) showed more possibilities of experiencing infertility than those with a LM genotype (p=0.039; OR=1.91). According to LSD test, endometriosis subjects had significantly lower paraoxonase enzyme activity compared to control group (p=0.0024; CI=95%). No significant difference was found in women with PCOS for both PONase and AREase activity in comparison with control group (p=0.469; CI=95%). Furthermore, PON1 activities were the highest in LL genotype followed by LM and then MM genotype (MM
Conclusion: PON1 L55M polymorphism may be associated with serum PON1 activity and the risk of developing female infertility.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629460PMC
November 2015

Multiplex PCR based screening for micro/partial deletions in the AZF region of Y-chromosome in severe oligozoospermic and azoospermic infertile men in Iran.

Iran J Reprod Med 2015 Sep;13(9):563-70

Division of Genetics, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran.

Background: Infertility is a health problem which affects about 10-20% of married couples. Male factor infertility is involved approximately 50% of infertile couples. Most of male infertility is regarding to deletions in the male-specific region of the Y chromosome.

Objective: In this study, the occurrence of deletions in the AZF region and association between infertility and paternal age were investigated in Iranian men population.

Materials And Methods: To assess the occurrence of Y chromosomal microdeletions and partial deletions of the AZF region, 100 infertile men and 100 controls with normal spermatogenesis were analyzed. AZFa, AZFb, AZFc and partial deletions within the AZFc region were analyzed using multiplex PCR method. Finally, the association between paternal age and male infertility was evaluated.

Results: No AZFa, AZFb or AZFc deletions were found in the control group. Seven infertile men had deletions as the following: one AZFb, five AZFc, and one AZFab. Partial deletions of AZFc (gr/gr) in 9 of the 100 infertile men (9/100, 9%) and 1 partial AZFc deletions (gr/gr) in the control group (1/100, 1%) were observed. In addition, five b2/b3 deletions in five azoospermic subjects (5/100, 5%) and 2 partial AZFc deletions (b2/b3) in the control group (2/100, 2%) were identified. Moreover, the risk of male infertility was influenced by the paternal age.

Conclusion: The results of this study suggested that the frequency of Y chromosome AZF microdeletions increased in subjects with severe spermatogenic failure and gr/gr deletion associated with spermatogenic failure.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637124PMC
September 2015

Molecular dynamics study of biodegradation of azo dyes via their interactions with AzrC azoreductase.

J Biomol Struct Dyn 2016 1;34(3):453-62. Epub 2015 Sep 1.

d Department of Chemistry , Isfahan University of Technology , Isfahan 84156-83111 , Iran.

Azo dyes are one of the most important class of dyes, which have been widely used in industries. Because of the environmental pollution of azo dyes, many studies have been performed to study their biodegradation using bacterial systems. In present work, the AzrC of mesophilic gram-positive Bacillus sp. B29 has been considered to study its interaction with five common azo dyes (orange G, acid red 88, Sudan I, orange I, and methyl red). The molecular dynamics simulations have been employed to study the interaction between AzrC and azo dyes. The trajectory was confirmed using root mean square deviation and the root mean square fluctuation analyses. Then, the hydrogen bond and alanine scanning analyses were performed to reveal active site residues. Phe105 (A), Phe125 (B), Phe172 (B), and Pro132 (B) have been found as the most important hydrophobic residues whereas Asn104 (A), Tyr127 (B), and Asn187 (A) have key role in making hydrogen bond. The results of molecular mechanics Poisson-Boltzmann surface area and molecular mechanics generalized Born surface area calculations proved that the hydrophobic azo dyes like Acid red 88 binds more tightly to the AzrC protein. The calculated data suggested MR A 121 (B) I as a potential candidate for improving the AzrC-MR interactions.
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http://dx.doi.org/10.1080/07391102.2015.1039585DOI Listing
December 2016

A novel recombinant AzrC protein proposed by molecular docking and in silico analyses to improve azo dye's binding affinity.

Gene 2015 Sep 28;569(2):233-8. Epub 2015 May 28.

Department of Agronomy and Plant Breeding, Razi University, Kermanshah, Iran; Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Azo dyes are broadly used in different industries through their chemical stability and ease of synthesis. These dyes are usually identified as critical environmental pollutants and many attentions were performed to degradation of azo dyes using biological systems. In this study, the interactions of an azoreductase from mesophilic gram-positive Bacillus sp. B29, AzrC, with four common azo dyes (orange I, orange II, orange G and acid red 88) were investigated. Fifteen points, double, triple and quadruple mutant forms of AzrC were made using Molegro Virtual Docker 6.0 in order to improve the binding affinity of azo dyes to AzrC. The impact of 15 different mutations on azo dye affinity potency of AzrC was computationally analyzed using AzrC-azo dye molecular docking, and each interaction was scored based on AutoDock 4.2 free binding energy. Our results have indicated that Asn 104 (A), Asn 187 (B), and Tyr 151 (A) make stable hydrogen bond between AzrC and azo dyes. The hydrophobic amino acids like Phe105 (A), Phe 125 (B), and Phe 172 (B) in wild type form make hydrophobic interactions. In addition, the presence of more hydrophobic residues F60 (B), I119 (B), I121 (B) and F132 (B) in mutant forms made more powerful hydrophobic pocket in the active site. In conclusion, recombinant AzrC with quadruple mutations was suggested in order to increase the biodegradation capacity of AzrC through improving its affinity to four studied azo dyes. This study would be promising for future experimental analyses in order to produce recombinant form of AzrC.
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http://dx.doi.org/10.1016/j.gene.2015.05.063DOI Listing
September 2015

Enhanced expression of bioactive recombinant VEGF-111 with insertion of intronic sequence in mammalian cell lines.

Appl Biochem Biotechnol 2015 Apr 18;175(8):3737-49. Epub 2015 Feb 18.

Division of Genetics, Biology Department, Faculty of Sciences, University of Isfahan, Isfahan, Iran,

Among all VEGF-A isoforms, VEGF-111 is particularly important in molecular biology research owing to its potent angiogenic properties and its remarkable resistance to proteolysis. These features make it a potential candidate for therapeutic use in ischemic diseases. VEGF-111 is not expressed in normal cells, but expression is induced by UV-B irradiation and exposure to genotoxic agents. Here, to increase expression at the transcriptional and translational levels, we synthesized and cloned recombinant VEGF-111 cDNA. Two fragments encoding exons 1-4 and intron 4/5 plus exon 8a were amplified and cloned into the pBud.CE4.1 vector using a class IIs restriction enzyme-based method. The expression of VEGF-111 in CHO-dhfr - and HEK 293 cell lines was evaluated with real-time PCR, dot blotting, and ELISA. VEGF expression was increased about 10- and 18-fold in transfected CHO-dhfr - and HEK 293 cells, respectively. Dot blotting and ELISA confirmed successful production of VEGF-111 in both cell lines.
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http://dx.doi.org/10.1007/s12010-015-1541-2DOI Listing
April 2015

New Insights into VEGF-A Alternative Splicing: Key Regulatory Switching in the Pathological Process.

Avicenna J Med Biotechnol 2014 Oct;6(4):192-9

Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran.

Vascular endothelial growth factor (VEGF-A) is one of the most important regulatory factors in pathological and physiological angiogenesis. Alternative splicing is a complicated molecular process in VEGF-A gene expression which adds complexity to VEGF-A biology. Among all VEGF-A exons, alternative splicing of exon 8 is the key determinant of isoform switching from pro-angio-genic VEGF-xxx to anti-angiogenic VEGF-xxxb. This is known as a key molecular switching in many pathological situations. In fact, the balance between VEGF-xxx and VEGF-xxxb isoforms is a critical controlling switch in both conditions of health and disease. Here, the properties of VEGF-xxx and VEGF-xxxb isoforms were discussed and their regulatory mechanism and their roles in certain pathological processes were evaluated. In summary, it was suggested that C-terminal VEGF-A alternative splicing can provide a new treatment opportunity in angiogenic diseases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224658PMC
October 2014

Comparative insight into expression of recombinant human VEGF111b, a newly identified anti-angiogenic isoform, in eukaryotic cell lines.

Gene 2014 Dec 5;553(1):57-62. Epub 2014 Oct 5.

Division of Genetics, Biology Department, Faculty of Sciences, University of Isfahan, Isfahan, Iran. Electronic address:

VEGF-A is a critical growth factor in tumor growth and progression. Two families of VEGF-A isoforms are produced through alternative splicing including VEGFxxx pro-angiogenic and VEGFxxxb anti-angiogenic isoforms. VEGF111b is a new member of the VEGFxxxb family that is induced by mitomycin C and doesn't express in normal conditions. The potent anti-angiogenic properties of VEGF-111b and its remarkable resistance to proteolysis make it an interesting alternative candidate for therapeutic use in all types of cancers. Here, the recombinant VEGF-111b cDNA with insertion of intronic sequence was constructed by using a class IIs restriction enzyme-based method. The recombinant pBud-VEGF111b was transfected into CHO dhfr(-) and HEK 293 cell lines which are currently the standard hosts for the production of candidate therapeutic proteins. Then, the VEGF-111b expression was evaluated in two cell lines using the Real-time PCR. The production of VEGF-111b protein was also investigated here by dot blotting. The VEGF expression was increased about 109 and 185-folds in transfected CHO-dhfr(-) and HEK 293 cells, respectively, in comparison with the un-transfected cells. Dot blotting approach confirmed that both cell lines have successfully produced the VEGF-111b protein.
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http://dx.doi.org/10.1016/j.gene.2014.10.002DOI Listing
December 2014

Association between XPD (Lys751G1n) Polymorphism and Lung Cancer Risk: A Population-Based Study in Iran.

Cell J 2014 4;16(3):309-14. Epub 2014 Oct 4.

Genetics Division, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran.

Objective: People are usually susceptible to carcinogenic aromatic amines, present in cigarrette smoke and polluted environment, which can cause DNA damage. Therefore, maintenance of genomic DNA integrity is a direct result of proper function of DNA repair enzymes. Polymorphic diversity could affect the function of repair enzymes and thus augment the risk of different cancers. Xeroderma pigmentosum group D (XPD) gene encodes one of the most prominent repair enzymes and the polymorphisms of this gene are thought to be of importance in lung cancer risk. This gene encodes the helicase, which is a component of transcription factor IIH and an important part of the nucleotide excision repair system. Studies reveal that individuals with Lys751Gln polymorphism of XPD gene have a low repairing capacity to delete the damages of ultraviolet light among other XPD polymorphisms.

Materials And Methods: In this case-control study, first Lys751Gln polymorphism was genotyped, then its association with lung cancer risk was analyzed. Genomic DNA was extracted from the whole blood sample of 640 individuals from Iran (352 healthy individuals and 288 patients). Allele frequencies and heterozygosity of Lys751Gln polymorphism were determined using polymerase chain reaction-restriction fragment length polymorphism method.

Results: According to statistical analyses, lung cancer risk in individuals with Lys751Gln polymorphism (Odd Ratio=1.8, 95% Confidence Interval 0.848-3.819) is approximately twice as high as that of Lys/Lys genotype, however 751Gln/Gln genotype did not relate to lung cancer risk (Odd Ratio=0.7, 95% Confidence Interval 0/307-1/595).

Conclusion: This study suggests that heterozygous polymorphism (Lys/Gln) increases the sensitivity of lung cancer risk, while homozygous polymorphism (Lys/Lys) probably decreases its risk and C allele frequency shows no remarkable increase in the patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204198PMC
December 2014

The molecular study of IFNβ pleiotropic roles in MS treatment.

Iran J Neurol 2013 ;12(4):149-56

MSc Student, Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran.

Multiple sclerosis (MS) is one of the most important autoimmune diseases recognized by demyelination and axonal lesion. It is the most common cause of disability in the young population. Various immunomodulatory and immunosuppressive therapies, including different formulations of interferon beta (IFNβ), glatiramer acetate (GA), mitoxantrone, and natalizumab are available for this disease. However, interferon has been the best prescribed. Although the precise mechanism of IFNβ is unclear, many studies indicate some potential mechanism including blocking T cells activation, controlling pro- and anti-inflammatory cytokine secretion, preventing activated immune cell migration through BBB, and inducing repair activity of damaged nerve cells by differentiating neural stem cells into oligodendrocytes. These molecular mechanisms have significant roles in IFNβ therapy. More researches are required in order for us to comprehend the mechanism of action of IFNβ, and improve and develop drugs for more efficient MS treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829308PMC
June 2014