ORCID Profile
0000-0002-9145-6155
Current Organisation
Macquarie University
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Publisher: Wiley
Date: 17-11-2020
DOI: 10.1002/MRD.23293
Abstract: Failed oocyte activation has been observed in unexplained infertile (UI) and asthenoteratozoospermic (AT) men. The deficiency of phospholipase C-zeta (PLCζ) could be a possible reason for such failures and has not been studied yet. We investigated the expression and localization of PLCζ protein in the sperms of patients with UI and AT conditions. The relationships between PLCζ-related parameters with male age, sperm characteristics, DNA integrity, and cellular maturity were assessed. Semen s les were collected from fertile (n = 40), UI (n = 40), and AT (n = 40) men. Subsequently, semen analysis, DNA fragmentation, hyaluronic acid-binding ability, and PLCζ level along with its distribution were evaluated using computer-assisted sperm analyzer, sperm chromatin structure assay (SCSA), hyaluronic acid-binding assay (HBA), western blot analysis and immunofluorescence microscopy, respectively. Unlike SCSA, the values of HBA, and PLCζ expression were significantly reduced in UI and AT patients compared to fertile men, whereas no significant differences were observed among the experimental groups in terms of PLCζ localization patterns. The regression analysis also showed that HBA is the only variable associated with PLCζ levels. Furthermore, the correlation of male age with PLCζ localization in postacrosomal, equatorial, and acrosomal+postacrosomal+equatorial (A+PA+E) patterns, as well as the relation of normal morphology, with the (A+PA+E) pattern, remained in the regression model. Our findings indicated that reduced PLCζ level along with the increased DNA fragmentation and impaired maturation may be possible etiologies of decreased fertilization in the studied subjects.
Publisher: Knowledge E
Date: 28-04-2019
Abstract: Background: Visceral leishmaniasis (VL) is endemic in the northwest and south of Iran. Untreated cases of VL could cause death. The aim of the present study was to evaluate the diagnostic performance of western blotting to detect a specific immunodominant proteins pattern for Leishmania infantum infection using human sera infected with VL. Methods: We studied a panel of 122 cryopreserved human serum s les from the leishmaniasis Research Laboratory, Tehran University of Medical Sciences, Tehran, Iran from 2010 to 2017. Serum s les were collected from visceral (Group I, n: 43) and cutaneous leishmaniasis (CL) (Group II, n: 8) patients, healthy in iduals from endemic (Group III, n: 13) and non-endemic (Group IV, n: 16) areas for VL, and patients with other infectious diseases (Group V, n: 42). Total antigens were prepared from the Iranian strain of L. infantum promastigote form. Results: In western blotting method, 34 protein bands of 14 to 163 kDa were recognized using the sera of VL patients. The polypeptide fractions with the highest frequency including 29, 51, and 62 kDa fractions were detected using 81.4%, 79%, and 81.4% of the sera, respectively. These bands were not detected using the sera of the negative control. Moreover, 19-23, 27, 31-35, 143-163, and 109 kDa fractions were detected specifically using the sera of the patients with VL. Conclusion: This technique could be a primary step for further exploration of VL immunodominant antigens for cloning (or any technique) further investigations for future planning.
Publisher: Springer Science and Business Media LLC
Date: 13-03-2017
DOI: 10.1038/SREP44075
Abstract: Glioblastoma (GBM) remains one of the most fatal human malignancies due to its high angiogenic and infiltrative capacities. Even with optimal therapy including surgery, radiotherapy and temozolomide, it is essentially incurable. GBM is among the most neovascularised neoplasms and its malignant progression associates with striking neovascularisation, evidenced by vasoproliferation and endothelial cell hyperplasia. Targeting the pro-angiogenic pathways is therefore a promising anti-glioma strategy. Here we show that tivozanib, a pan-inhibitor of vascular endothelial growth factor (VEGF) receptors, inhibited proliferation of GBM cells through a G2/M cell cycle arrest via inhibition of polo-like kinase 1 (PLK1) signalling pathway and down-modulation of Aurora kinases A and B, cyclin B1 and CDC25C. Moreover, tivozanib decreased adhesive potential of these cells through reduction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Tivozanib diminished GBM cell invasion through impairing the proteolytic cascade of cathepsin B/urokinase-type plasminogen activator (uPA)/matrix metalloproteinase-2 (MMP-2). Combination of tivozanib with EGFR small molecule inhibitor gefitinib synergistically increased sensitivity to gefitinib. Altogether, these findings suggest that VEGFR blockade by tivozanib has potential anti-glioma effects in vitro . Further in vivo studies are warranted to explore the anti-tumour activity of tivozanib in combinatorial approaches in GBM.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2023
Publisher: Wiley
Date: 08-08-2022
Abstract: Fingolimod (FTY720) is an oral drug approved by the Food and Drug Administration (FDA) for management of multiple sclerosis (MS) symptoms, which has also shown beneficial effects against Alzheimer's (AD) and Parkinson's (PD) diseases pathologies. Although an extensive effort has been made to identify mechanisms underpinning its therapeutic effects, much remains unknown. Here, we investigated Fingolimod induced proteome changes in the cerebellum (CB) and frontal cortex (FC) regions of the brain which are known to be severely affected in MS, using a tandem mass tag (TMT) isobaric labeling‐based quantitative mass‐spectrometric approach to investigate the mechanism of action of Fingolimod. This study identified 6749 and 6319 proteins in CB and FC, respectively, and returned 2609 and 3086 differentially expressed proteins in mouse CB and FC, respectively, between Fingolimod treated and control groups. Subsequent bioinformatics analyses indicated a metabolic reprogramming in both brain regions of the Fingolimod treated group, where oxidative phosphorylation was upregulated while glycolysis and pentose phosphate pathway were downregulated. In addition, modulation of neuroinflammation in the Fingolimod treated group was indicated by upregulation of retrograde endocannabinoid signaling and autophagy pathways, and downregulation of neuroinflammation related pathways including neutrophil degranulation and the IL‐12 mediated signaling pathway. Our findings suggest that Fingolimod may exert its protective effects on the brain by inducing metabolic reprogramming and neuroinflammation pathway modulation.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 03-2018
Publisher: Springer Science and Business Media LLC
Date: 17-05-2012
DOI: 10.1007/S00572-012-0445-Z
Abstract: Introduction of exotic plants change soil microbial communities which may have detrimental ecological consequences for ecosystems. In this study, we examined the community structure and species richness of ectomycorrhizal (EcM) fungi associated with exotic pine plantations in relation to adjacent native ectomycorrhizal trees in Iran to elucidate the symbiont exchange between distantly related hosts, i.e. Fagales (Fagaceae and Betulaceae) and Pinaceae. The combination of morphological and molecular identification approaches revealed that 84.6 % of species with more than one occurrence (at least once on pines) were shared with native trees and only 5.9 % were found exclusively on pine root tips. The community ersity of ectomycorrhizal fungi in the pine plantations adjacent to native EcM trees was comparable to their adjacent native trees, but the isolated plantations hosted relatively a species-poor community. Specific mycobionts of conifers were dominant in the isolated plantation while rarely found in the plantations adjacent to native EcM trees. These data demonstrate the importance of habitat isolation and dispersal limitation of EcM fungi in their potential of host range expansion. The great number of shared and possibly compatible symbiotic species between exotic Pinaceae and local Fagales (Fagaceae and Betulaceae) may reflect their evolutionary adaptations and/or ancestral compatibility with one another.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Springer Science and Business Media LLC
Date: 15-09-2013
DOI: 10.1007/S12015-013-9473-0
Abstract: Embryonic stem (ES) cells are considered to exist in a ground state if shielded from differentiation triggers. Here we show that FGF4 and TGFβ signaling pathway inhibitors, designated R2i, not only provide the ground state pluripotency in production and maintenance of naïve ES cells from blastocysts of different mouse strains, but also maintain ES cells with higher genomic integrity following long-term cultivation compared with the chemical inhibition of the FGF4 and GSK3 pathways, known as 2i. Global transcriptome analysis of the ES cells highlights augmented BMP4 signaling pathway. The crucial role of the BMP4 pathway in maintaining the R2i ground state pluripotency is demonstrated by BMP4 receptor suppression, resulting in differentiation and cell death. In conclusion, by inhibiting TGFβ and FGF signaling pathways, we introduce a novel defined approach to efficiently establish the ground state pluripotency.
Publisher: Springer Science and Business Media LLC
Date: 07-08-2013
DOI: 10.1007/S11248-012-9634-Y
Abstract: There are growing numbers of recombinant proteins that have been expressed in milk. Thus one can consider the placement of any gene of interest under the control of the regulatory elements of a milk protein gene in a dairy farm animal. Among the transgene introducing techniques, only nuclear transfer (NT) allows 100 % efficiency and bypasses the mosaicism associated with counterpart techniques. In this study, in an attempt to produce a transgenic goat carrying the human coagulation factor IX (hFIX) transgene, goat fetal fibroblasts were electroporated with a linearized marker-free construct in which the transgene was juxtaposed to β-casein promoter designed to secret the recombinant protein in goat milk. Two different lines of transfected cells were used as donors for NT to enucleated oocytes. Two transgenic goats were liveborn. DNA sequencing of the corresponding transgene locus confirmed authenticity of the cloning procedure and the complementary experiments on the whey demonstrated expression of human factor IX in the milk of transgenic goats. In conclusion, our study has provided the groundwork for a prosperous and promising approach for large-scale production and therapeutic application of hFIX expressed in transgenic goats.
Publisher: American Chemical Society (ACS)
Date: 20-12-2012
DOI: 10.1021/PR300864K
Abstract: The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. This project attempts simultaneously to establish a sound basis for the development of diagnostic, prognostic, therapeutic, and preventive medical applications. In Iran, current efforts focus on mapping the proteome of the human Y chromosome. The male-specific region of the Y chromosome (MSY) is unique in many aspects and comprises 95% of the chromosome's length. The MSY continually retains its haploid state and is full of repeated sequences. It is responsible for important biological roles such as sex determination and male fertility. Here, we present the most recent update of MSY protein-encoding genes and their association with various traits and diseases including sex determination and reversal, spermatogenesis and male infertility, cancers such as prostate cancers, sex-specific effects on the brain and behavior, and graft-versus-host disease. We also present information available from RNA sequencing, protein-protein interaction, post-translational modification of MSY protein-coding genes and their implications in biological systems. An overview of Human Y chromosome Proteome Project is presented and a systematic approach is suggested to ensure that at least one of each predicted protein-coding gene's major representative proteins will be characterized in the context of its major anatomical sites of expression, its abundance, and its functional relevance in a biological and/or medical context. There are many technical and biological issues that will need to be overcome in order to accomplish the full scale mapping.
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.UROLOGY.2012.06.027
Abstract: To compare the sperm protein profile between men with and without varicocele. The present study was designed as a case-control study. The research patients were recruited from the Infertility Unit of the Royan Institute in 2009. We included 20 sperm s les from normozoospermic men without varicocele (control group) and 20 sperm s les from oligozoospermic patients with varicocele, grade 3 (varicocele group) in the present study. The sperm protein profile in the 2 groups was characterized using 2-dimensional gel electrophoresis. Differences in protein expression were established using gel analysis software, and protein identification was performed using mass spectroscopy analysis. In the varicocele group, we noted 15 consistent differences in protein expression (1, spots missing 12, less abundant and 2, more abundant) compared with the control group (P < .01). The findings revealed that heat shock proteins, mitochondrial proteins, and cytoskeleton proteins are the proteins mainly affected by varicocele disease. To our knowledge, the present study is a novel study, with few studies describing the correlation between sperm protein in men with and without varicocele obtained using a 2-dimensional proteomic approach. It could be an important prerequisite to the development of diagnostic tests to predict varicocelectomy outcomes in patients with varicocele and abnormal findings on a spermogram in the clinical environment.
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.JCJD.2014.09.006
Abstract: The stearoyl-CoA desaturase 1 (SCD1), also known as Δ9-desaturase, is a regulatory enzyme in the cellular lipid modification process that has been linked to pancreatic cancer and diabetes. The aim of the present study was to investigate the effect of peroxisome proliferative-activated receptor δ (PPARδ) agonist and ERK1/2- and EGF receptor (EGFR)-dependent pathways on the expression of SCD1 in human pancreatic carcinoma cell line PANC-1. PANC-1 cells cultured in RPMI-1640 were exposed to the commonly used MEK inhibitor PD98059, EGFR-selective inhibitor AG1478, and PPARδ agonist GW0742. Changes in mRNA, protein expression and activity index of SCD1 were then determined using real-time reverse transcription polymerase chain reaction, Western blot and gas liquid chromatography, respectively. The activity index and expression of SCD1 (p<0.01) decreased following treatment with PPARδ agonist at both mRNA and protein levels, whereas significant increases were observed after treatment with MEK or EGFR inhibitor. It was also found that the activity index of SCD1 were lower (p<0.01) in the combined treatment compared to the incubation with either inhibitor alone. PPARδ and MEK/ERK1/2- and EGFR-dependent pathways affect the expression and activity of SCD1 in pancreatic cancer cells. Furthermore, the aforementioned kinase signalling pathways were involved in an inhibitory effect on the expression and activity of SCD1 in these cells, possibly via PPARδ activation.
Publisher: the Pasteur Institute of Iran
Date: 1996
Publisher: MDPI AG
Date: 18-11-2022
Abstract: Neuropeptide Y (NPY), a sympathetic neurotransmitter, is involved in various physiological functions, and its dysregulation is implicated in several neurodegenerative diseases. Glutamate excitotoxicity, endoplasmic reticulum (ER) stress, and oxidative stress are the common mechanisms associated with numerous neurodegenerative illnesses. The present study aimed to elucidate the protective effects of NPY against glutamate toxicity and tunicamycin-induced ER stress in the human neuroblastoma SH-SY5Y cell line. We exposed the SH-SY5Y cells to glutamate and tunicamycin for two different time points and analyzed the protective effects of NPY at different concentrations. The protective effects of NPY treatments were assessed by cell viability assay, and the signalling pathway changes were evaluated by biochemical techniques such as Western blotting and immunofluorescence assays. Our results showed that treatment of SH-SY5Y cells with NPY significantly increased the viability of the cells in both glutamate toxicity and ER stress conditions. NPY treatments significantly attenuated the glutamate-induced pro-apoptotic activation of ERK1/2 and JNK/BAD pathways. The protective effects of NPY were further evident against tunicamycin-induced ER stress. NPY treatments significantly suppressed the ER stress activation by downregulating BiP, phospho-eIF2α, and CHOP expression. In addition, NPY alleviated the Akt/FoxO3a pathway in acute oxidative conditions caused by glutamate and tunicamycin in SH-SY5Y cells. Our results demonstrated that NPY is neuroprotective against glutamate-induced cell toxicity and tunicamycin-induced ER stress through anti-apoptotic actions.
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/607524
Abstract: The Δ6-desaturase (Δ6D), also known as fatty acid desaturase 2, is a regulatory enzyme in de novo fatty acid synthesis, which has been linked to obesity and diabetes. The aim of the present study was to investigate the effect of peroxisome proliferative-activated receptor δ (PPAR δ ) agonist and MEK/ERK1/2-dependent pathway on the expression of Δ6D in human pancreatic carcinoma cell line PANC-1. PANC-1 cells cultured in RPMI-1640 were exposed to the commonly used ERK1/2 pathway inhibitor PD98059 and PPAR δ agonist GW0742. Changes in mRNA and protein expression of Δ6D were then determined using real-time RT-PCR and Western blot, respectively. The expression of Δ6D ( P 0.01 ) increased following treatment with PPAR δ agonist both at mRNA and protein levels, whereas no significant change was observed after treatment with MEK/ERK1/2 pathway inhibitor. It was also found that the increase in the expression of Δ6D in response to GW0742 was significantly inhibited by PD98059 ( %, P 0.05 ) or EGF receptor-selective inhibitor AG1478 ( %, P 0.05 ) pretreatment. PPAR δ and MEK/ERK1/2 signaling pathways affect differentially the expression of Δ6D in pancreatic cancer cells. Furthermore, there may be an inhibitory crosstalk between these two regulatory pathways on the mRNA expression of Δ6D and subsequently on Δ6D protein expression.
Publisher: Wiley
Date: 15-12-2023
Publisher: Informa UK Limited
Date: 07-07-2020
DOI: 10.1080/09603123.2020.1789947
Abstract: The association between Cadmium and the risk of preterm birth (PTB) has remained controversial. A number of studies found a positive correlation between maternal Cd exposure and PTB however, there are conflicting reports about this correlation. Therefore, herein we performed this meta-analysis to examine the association between maternal Cd exposure and the risk of PTB.A systematic search was conducted through PubMed, Scopus, Embase and OpenGrey from inception to May 2020 to find all eligible studies. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to examine this correlation. A random-effects model was applied in this meta-analysis due to significant statistical heterogeneity among included studies.Overall, 10 eligible studies met the inclusion criteria and were included in our analysis, and results of the present meta-analysis indicated that maternal cadmium exposure is associated with the risk of PTB (OR = 1.32 95% CI = 1.08-1.61).This meta-analysis suggests that maternal Cd exposure might be associated with the risk of PTB. Yet, large prospective studies from different ethnic populations which consider other influencing parameters are still required to confirm this finding.
Publisher: Springer Science and Business Media LLC
Date: 06-10-2021
Publisher: American Chemical Society (ACS)
Date: 13-09-2017
DOI: 10.1021/ACS.JPROTEOME.7B00391
Abstract: Despite evidence for sex-specific cardiovascular physiology and pathophysiology, the biological basis for this dimorphism remains to be explored. Apart from hormonal factors, gender-related characteristics may reside in the function of sex chromosomes during cardiac development. In this study, we investigated the differential expression of the male-specific region of the Y chromosome (MSY) genes and their X counterparts during cardiac differentiation of human embryonic stem cells (hESC). We observed alterations in mRNA and protein levels of TBL1Y, PCDH11Y, ZFY, KDM5D, USP9Y, RPS4Y1, DDX3Y, PRY, XKRY, BCORP1, RBMY, HSFY, and UTY, which accompanied changes in intracellular localization. Of them, the abundance of a Y chromosome missing protein, TBL1Y, showed a significant increase during differentiation while the expression level of its X counterpart decreased. Consistently, reducing TBL1Y cellular level using siRNA approach influenced cardiac differentiation by reducing its efficacy as well as increasing the probability of impaired contractions. TBL1Y knockdown may have negatively impacted cardiogenesis by CtBP stabilization. Furthermore, we presented compelling experimental evidence to distinguish TBL1Y from TBL1X, its highly similar X chromosome homologue, and proposed reclassification of TBL1Y as "found missing protein" (PE1). Our results demonstrated that MSY proteins may play an important role in cardiac development.
Publisher: Springer Science and Business Media LLC
Date: 06-04-2017
DOI: 10.1038/SREP45954
Abstract: Epithelial ovarian cancer (EOC) is the most fatal gynaecological malignancy. Despite initial therapeutic response, the majority of advanced-stage patients relapse and succumb to chemoresistant disease. Overcoming drug resistance is the key to successful treatment of EOC. Members of vascular endothelial growth factor (VEGF) family are overexpressed in EOC and play key roles in its malignant progression though their contribution in development of the chemoresistant disease remains elusive. Here we show that expression of the VEGF family is higher in therapy-resistant EOC cells compared to sensitive ones. Overexpression of VEGFR2 correlated with resistance to cisplatin and combination with VEGFR2-inhibitor apatinib synergistically increased cisplatin sensitivity. Tivozanib, a pan-inhibitor of VEGF receptors, reduced proliferation of the chemoresistant EOC cells through induction of G2/M cell cycle arrest and apoptotic cell death. Tivozanib decreased invasive potential of these cells, concomitant with reduction of intercellular adhesion molecule-1 (ICAM-1) and diminishing the enzymatic activity of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-2 (MMP-2). Moreover, tivozanib synergistically enhanced anti-tumour effects of EGFR-directed therapies including erlotinib. These findings suggest that the VEGF pathway has potential as a therapeutic target in therapy-resistant EOC and VEGFR blockade by tivozanib may yield stronger anti-tumour efficacy and circumvent resistance to EGFR-directed therapies.
Publisher: Medknow
Date: 02-10-2024
Location: Iran (Islamic Republic of)
No related grants have been discovered for shahab mirshahvaladi.