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عضویت
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kioomars saliminejad

  • Ebrahim Mirzadegan, Hannaneh Golshahi, Zahra Saffarian, Haleh Edalatkhah, Maryam Darzi, Somayeh Khorasani, Kioomars Saliminejad, Somaieh Kazemnejad *
    Background

    In this study we differentially showed the effects of cell-seeded bilayer scaffold wound dressing in accelerating healing process in diabetic ulcers that still remains as a major clinical challenge. The aim of the study was to compare immunomodulatory and angiogenic activity, and regenerative effect differences between Menstrual blood-derived Stem Cells (MenSCs) and foreskin-derived keratinocytes/fibroblasts.

    Methods

    The streptozotocin-induced diabetic mice model was developed in male C57/BL6 mice. A bilayer scaffold was fabricated by electrospining silk fibroin nanofibers on human Amniotic Membrane (AM). Dermal fibroblasts and keratinocyte isolated from neonatal foreskin and MenSCs were isolated from the menstrual blood of healthy women. The diabetic mice were randomly divided into three groups including no treatment group, fibroblast/keratinocyte-seeded bilayer scaffold group (bSC+FK), and MenSCs-seeded bilayer scaffold group. The healing of full-thickness excisional wounds evaluations in the diabetic mice model in each group were evaluated at 3, 7, and 14 days after treatment.

    Results

    The gross and histological data sets significantly showed wound healing promotion via re-epithelialization and wound contraction along with enhanced regeneration in MenSCs-seeded bilayer scaffold group with the most similarity to adjacent intact tissue. Immunofluorescence staining of mouse skin depicted a descending trend of type III collagen along with the higher expression of involucrin as keratinocyte marker in the MenSCs-seeded bilayer nanofibrous scaffold group in comparison with other treatment groups from day 7 to day 14. Moreover, higher levels of CD31 and von Willebrand factor (VWF), and also a higher ratio of M2/M1 macrophages in association with higher levels of the neural marker were observed in the bSC+MenSCs group in comparison with bSC+FK and no treatment groups.

    Conclusion

    Healing symptoms in wounds dressed with keratinocyte/fibroblast-seeded bilayer scaffold was significantly lower than MenSCs-seeded bilayer scaffold done on impaired diabetic wound chronicity.

    Keywords: Bilayer scaffold, Diabetic wound, Fibroblasts, Keratinocyte, Menstrual blood stemcells
  • Kioomars Saliminejad, Habibollah Mahmoodzadeh, Shahrzad Soleymani Fard, Marjan Yaghmaei, Hamid Reza Khorram Khorshid, Seyed Asadollah Mousavi, Mohammad Vaezi, Seyed Hamidollah Ghaffari*
    Background

     The high mortality rate of Gastric Cancer (GC) is a consequence of delayed diagnosis. The early diagnosis of GC could increase the five-year survival rate among patients. We aimed to find a panel of microRNAs (miRNA) for the detection of GC in the early stages.

    Methods

     In this case-control study, we selected consistently upregulated miRNAs from the results of 12 high-throughput miRNA profiling studies in GC. In the profiling phase, the differential expressions of 13 candidate miRNAs were analyzed by quantitative reverse-transcription PCR (qRT-PCR) in two pooled RNA samples prepared from the plasma of eight GC patients and eight matched controls. In the validation phase, significantly upregulated miRNAs from the profiling phase were further evaluated in the plasma samples of 97 patients with stage I-IV gastric adenocarcinoma and 100 healthy controls.

    Results

     In the profiling phase, six miRNAs (miR-18a, 21, 25, 92a, 125b and 221) were significantly upregulated in the GC patients compared to the controls (p<0.05). However, in the validation phase, only significant up-regulation of miR-18a, 21 and 125b was confirmed (p<0.05). A panel of miR-18a/21/125b was able to detect GC patients with stage I-IV from the controls (p<0.001; AUC=0.92, sensitivity=86%; specificity=85%). In addition, the panel could distinguish the early-stage GC (I+II) from the control group with an AUC of 0.83, a sensitivity of 83%, and a specificity of 75%.

    Conclusion

     A panel of circulating miR18a/21/125b could be suggested as a potential biomarker for the early detection of GC.

    Keywords: Biomarker, Circulating microRNA, Detection, Gastric cancer, Gene expression
  • Kioomars Saliminejad, Shahrzad SoleymaniFard, HamidReza KhorramKhorshid, Marjan Yaghmaie, Habibollah Mahmoodzadeh, SeyedAsadollah Mousavi, and SeyedHamidollah Ghaffari *
    Background

    Most of Gastric Cancer (GC) patients are diagnosed at an advanced stage with poor prognosis. Hypermethylations of several tumor suppressor genes in cell-free DNA of GC patients have been previously reported. In this study, an attempt was made to investigate the methylation status of P16, RASSF1A, RPRM, and RUNX3 and their potentials for early diagnosis of GC.

    Methods

    Methylation status of the four tumor suppressor genes in 96 plasma samples from histopathologically confirmed gastric adenocarcinoma patients (Stage I-IV) and 88 healthy controls was determined using methylation-specific PCR method. Receiver operating characteristic curve analysis was performed and Area Under the Curve (AUC) was calculated. Two tailed p<0.05 were considered statistically significant.

    Results

    Methylated P16, RASSF1A, RPRM, and RUNX3 were significantly higher in the GC patients (41.7, 33.3, 66.7, and 58.3%) compared to the controls (15.9, 0.0, 6.8, and 4.5%), respectively (p<0.001). Stratification of patients showed that RPRM (AUC: 0.70, Sensitivity: 0.47, Specificity: 0.93, and p<0.001) and RUNX3 (AUC: 0.77, Sensitivity: 0.59, Specificity: 0.95, and p<0.001) had the highest performances in detection of early-stage (I+II) GC. The combined methylation of RPRM and RUNX3 in detection of early-stage GC had a higher AUC of 0.88 (SE=0.042; 95% CI:0.793–0.957; p<0.001), higher sensitivity of 0.82 and reduced specificity of 0.89.

    Conclusion

    Methylation analysis of RPRM and RUNX3 in circulating cell free-DNA of plasma could be suggested as a potential biomarker for detection of GC in early-stages.

    Keywords: Biomarkers, Cell-free DNA, Gastric cancer, DNA methylation
  • Shahrzad Soleymani Fard, Masoud Sotoudeh, Kioomars Saliminejad, Mansour Yazdanbod, Habibollah Mahmoodzadeh, Shaghayegh Kouchaki, Marjan Yaghmaie, Seyed Asadollah Mousavi, Reza Malekzadeh, Kamran Alimoghaddam *, Seyed Hamidollah Ghaffari
    Background

    Zinc-finger Enhancer Binding protein (ZEB1) acts as a transcription factor to promote cancer progression through regulating Epithelial to Mesenchymal Transition (EMT). It is well-known that ZEB1 mRNA expression is directly induced by both Estrogen Receptor (ER) and Progesterone Receptor (PR). Moreover, Androgen Receptor (AR) and PR could bind to the same regulatory element. Since it has been shown that AR overexpresses in Gastric Cancer (GC) as a male-predominant tumor, the goal of this study was to evaluate whether AR could regulate ZEB1 expression in GC.

    Methods

    The expression profile of ZEB1 in 60 fresh GC and adjacent non-tumor tissues and 50 normal gastric specimens was assessed by qRT-PCR, and the association of ZEB1 expression with clinicopathological features was investigated. Furthermore, possible correlation between ZEB1 and AR was evaluated to elucidate a novel prognostic marker using Kaplan-Meier method and Cox regression model. Finally, molecular interaction of ZEB1 and AR was assessed using a potent AR antagonist in GC cells.

    Results

    Among GC patients, 70.2% (40/57) overexpressed ZEB1 and 64.91% (37/57) overexpressed AR relative to normal gastric tissues. ZEB1 overexpression was significantly correlated with the AR overexpression in GC patients. Moreover, ZEB1 overexpression was remarkably associated with lower overall survival; however, it was not an independent prognostic factor. Evidence shows that simultaneous evaluation of ZEB1 and AR expression could independently predict survival of GC patients (HR= 2.193, p=0.047).

    Conclusion

    These findings have clinical importance suggesting simultaneous evaluation of ZEB1 and AR expression as a potential prognostic marker. Moreover, AR may regulate ZEB1 expression in GC cells proposing a possible promising targeted therapy for GC patients.

    Keywords: Androgen receptor, Enzalutamide, Gastric cancer, Prognostic marker, Targetedtherapy, ZEB1
  • Zohreh Heidary, Majid Zaki Dizaji, Kioomars Saliminejad, Hamid Reza Khorramkhorshid *
    Background
    The purpose of this study was to analyze the expression level of CRISP2, CATSPER1, PATE1 and SEMG1 genes in the sperm of men with asthenozoospermia (AZS). AZS is a cause of infertility in men in which the motility of the sperm is reduced. So far, a few genes have been associated with AZS; however, in most of the cases, its molecular etiology is unclear.
    Methods
    A total of 35 subjects with idiopathic AZS and 35 fertile and healthy men as control were included. In study after total RNA extraction and cDNA synthesis, relative quantification was performed. B2M was used as the normalizer gene and fold change was calculated by 2−ΔΔCt</sup>method. Mann-Whitney test was used to compare the expression levels between the case and control groups with significance level of p<0.05.
    Results
    Our results showed that CRISP2 (p=0.03) and SEMG1 (p=0.03) were significantly down- and up-regulated in AZS men respectively compared to the controls. But CATSPER1 and PATE1 did not show significant changes.
    Conclusion
    Down-regulation of CRISP2 and up-regulation of SEMG1 were associated with AZS, which could be suggested as the potential candidate genes for the development of a diagnostic marker or potentially for more studies for treatment of AZS.
    Keywords: Asthenozoospermia, CATSPER1, CRISP2, Gene expression, Male infertility, PATE1, Real-time PCR, SEMG1, Sperm motility
  • Homa Farrokhi Karibozorg, Nahid Masoudian, Kioomars Saliminejad, Asghar Ebadifar, Koorosh Kamali, Hamid Reza Khorram Khorshid *
    Background
    Nonsyndromic cleft lip and/or palate (NSCL/P) is the most common orofacial birth defect, often attributed to ethnic and environmental differences. Up to now, linkage analyses and genome-wide association studies have identified several genomic susceptibility regions for NSCL/P. The WNT genes including WNT3 are strong candidates for NSCL/P, since they are involved in regulating mid-face development and upper lip fusion. This study tested association of the WNT3 polymorphisms, rs3809857 G/T and rs9890413 G/A, with the risk of NSCL/P in a population of Iranian infants.
    Methods
    The allelic and genotypic frequencies for each participant were determined in 113 unrelated Iranian subjects with NSCL/P and 220 control subjects using PCR and restriction fragment length polymorphism (RFLP) methods. A p-value of 0.05 was considered statistically significant.
    Results
    The WNT3 rs3809857 GT genotype was significantly lower (p=0.039, OR=0.55, 95% CI=0.30-0.97) in the NSCL/P (21.2%) than the control group (30.42%). For the WNT3 rs9890413 G/A polymorphism, neither genotype nor allele frequencies were significantly different between the case and control groups.
    Conclusion
    Our results indicated that the WNT3 rs3809857 GT genotype may have a protective effect against NSCL/P in Iranian population.
    Keywords: Genome wide association study, Cleft lip, palate, Polymorphism, WNT3
  • Diman Fayez, Kioomars Saliminejad, Shiva Irani, Koorosh Kamali, Toktam Memariani, Hamid Reza Khorram Khorshid *
    Background
    Human arylamine N-acetyltransferase 2 (NAT2) gene has a key role in xenobiotic metabolism through the conjugation of acetyl group to xenobiotic substances. NAT2 has been suggested as a susceptibility factor in endometriosis; however, the results of studies have been controversial. In this study, the association of NAT2 polymorphisms with susceptibility to endometriosis was evaluated in an Iranian population.
    Methods
    This is an association study and totally 141 women with diagnosis of endometriosis and 158 healthy women as control group were analyzed for NAT2 gene polymorphisms (C481T, A803G, G857A and G590A) by PCR-RFLP methods.
    Results
    The 590 GA genotype was significantly lower (p=0.001; OR=0.42, 95% CI: 0.25-0.71) in the patients (38.3%) than the control group (55.1%). The 590A allele was significantly lower (p=0.033; OR=0.69, 95% CI: 0.49-0.79) in the patients (31.2%) compared with the controls (39.6%). Analysis of haplotypes showed that NAT2 481C, 803A, 590A, 587A combination was significantly different between the case and control women (p= 0.029; OR=3.11, 95% CI: 1.13-8.52).
    Conclusion
    The NAT2 G590A SNP may be associated with susceptibility to endometriosis and the 590A allele may have a protective role in development of endometriosis. The NAT2 481C, 803A, 590A, 587A haplotype was associated with a higher risk of endometriosis in Iranian population.
    Keywords: Endometriosis, Genome wide association study, NAT2, Polymorphism
  • Niloofar Bazazzadegan, Marzieh Dehghan Shasaltaneh, Kioomars Saliminejad, Koorosh Kamali, Mehdi Banan, Reza Nazari, Gholam Hossein Riazi, Hamid Reza Khorram Khorshid
    Purpose
    Alzheimer’s disease (AD) is pathologically defined by the presence of amyloid plaques and tangles in the brain, therefore, any drug or compound with potential effect on lowering amyloid plaques, could be noticed for AD management especially in the primary phases of the disease. Ectoine constitutes a group of small molecule chaperones (SMCs). SMCs inhibit proteins and other changeable macromolecular structures misfolding from environmental stresses. Ectoine has been reported successfully prohibit insulin amyloid formation in vitro.
    Methods
    We selected eight genes, DAXX, NFκβ, VEGF, PSEN1, MTAP2, SYP, MAPK3 and TNFα genes which had previously showed significant differential expression in Alzheimer human brain and STZ- rat model. We considered the neuroprotective efficacy by comparing the expression of candidate genes levels in the hippocampus of rat model of Sopradic Alzheimer’s disease (SAD), using qPCR in compound-treated and control groups as well as therapeutic effects at learning and memory levels by using Morris Water Maze (MWM) test.
    Results
    Our results showed significant down-regulation of Syp, Mapk3 and Tnfα and up-regulation of Vegf in rat’s hippocampus after treatment with ectoine comparing to the STZ-induced group. In MWM, there was no significant change in swimming distance and time for finding the hidden platform in treated comparing to STZ-induced group. In addition, it wasn’t seen significant change in compound-treated comparing to STZ-induced and control groups in memory level.
    Conclusion
    It seems this compound may have significant effect on expression level of some AD- related genes but not on clinical levels.
    Keywords: Sporadic Alzheimer disease, Ectoine, Gene expression, Morris Water Maze test, STZ, rat model
  • Niloofar Bazazzadegan, Marzieh Dehghan Shasaltaneh, Kioomars Saliminejad, Koorosh Kamali, Mehdi Banan, Hamid Reza Khorram Khorshid *
    Purpose
    Sporadic Alzheimer’s disease (AD) accounts for over 95% of cases. Possible mechanisms of AD such as inflammation and oxidative stresses in the brain motivate researchers to follow many therapies which would be effective, especially in the early stages of the disease. IMOD, the herbal extract of R. Canina, T. Vulgare and U. Dioica plant species enriched with selenium, has anti-inflammatory, immunoregulatory and protective effects against oxidative stress.
    Methods
    In this study three AD-related genes, DAXX, NFκβ and VEGF, were chosen as candidate to investigate the neuroprotective effect of the extract by comparing their expression levels in the hippocampus of rat model of sporadic AD, using qPCR in the herbal-treated and control groups. The therapeutic effects on learning and memory levels were evaluated by Morris Water Maze (MWM) test.
    Results
    Gene expression results were indicative of significant up-regulation of Vegf in rat’s hippocampus after treatment with the herbal extract comparing to model group (P-value= 0.001). The MWM results showed significant changes in path length and time for finding the hidden platform in all groups during test and the same change in the treated comparing to the control group in memory level.
    Conclusion
    It could be concluded that the herbal extract may have significant effect on gene expression but not on behavioral level.
    Short
    Keywords: Alzheimer's disease, Gene expression, Herbal extract, Rat model
  • Niloofar Bazazzadegan, Marzieh Dehghan Shasaltaneh, Kioomars Saliminejad, Koorosh Kamali, Mehdi Banan, Hamid Reza Khorram Khorshid*
    Background
    Possible mechanisms of Alzheimer Disease (AD) such as inflammation and oxidative stresses in the brain led us to investigate potential AD therapeutics of Melilotus officinalis, an herbal extract, with possible role as an anti-inflammatory and anti-oxidant agent. Among different genes which had important role in Sporadic AD (SAD), three genes including DAXX, NFkB and VEGF have shown significant statistical diversity in the brains of Alzheimer patients.
    Methods
    These genes were chosen to be investigated for neuroprotective effects of the extract by comparing the expression level in the hippocampus of Sporadic AD (SAD) rat model using quantitative polymerase chain reaction (qPCR) in the treated and untreated groups. In addition, therapeutic effects at the behavioral, learning and memory level by Morris Water Maze (MWM) test were investigated.
    Results
    The results represented significant decreased expression in Daxx, Nfkb and Vegf genes in the SAD rat’s model treated with the herbal extract compared to the Streptozotocin-induced (STZ-induced) rats. Furthermore, no significant changes were seen in swimming distance and time for finding the hidden platform in the herbal-treated compared to the STZ-induced group. In memory level, no significant changes were observed among treated and untreated groups.
    Conclusion
    It seems that the herbal extract may have significant effect on Alzheimer-related gene expression changes but not on clinical levels.
    Keywords: Alzheimer disease, Gene expression, Herbal medicine
  • Neuroprotective Effects of Herbal Extract (R. Canina, T. Vulgare and U. Dioica) on Rat Model of Sporadic Alzheimer's Disease
    Parvaneh Daneshmand, Kioomars Saliminejad, Marzieh Dehghan Shasaltaneh, Koorosh Kamali, Gholam Hossein Riazi, Reza Nazari, Pedram Azimzadeh, Hamid Reza Khorram Khorshid
    Sporadic Alzheimer’s disease (SAD) is affected by genetic risk factors, aging and oxidative stresses. The herbal extract of R. canina, T. vulgare and U. dioica has a beneficial role in aging, as an anti-inflammatory and anti-oxidative agent. We investigate the neuroprotective effects of this herbal extract in the rat model of SAD.
    The rats were divided into control, sham, model, herbal extract -treated and ethanol-treated groups. Drug interventions were started on the 21st day after modeling and each treatment group was given the drugs by intraperitoneal (I.P.) for 21 days. The expression levels of the five important genes for pathogenesis of SAD including Syp, Psen1, Mapk3, Map2 and Tnf-α were measured by qPCR between the hippocampus of SAD model which were treated by this herbal extract and control groups. The Morris Water Maze was adapted to test spatial learning and memory ability of the rats.
    Treatment of the rat model of SAD with herbal extract induced a significant change in expression of Syp (P=0.001) and Psen1 (P=0.029). In Morris Water Maze, significant disturbed changes in spatial learning that was seen in the rat model group were improved in herbal-treated group.
    This herbal extract could have anti-dementia properties and improve spatial learning and memory in SAD model rats.
    Keywords: Sporadic Alzheimer's disease, Herbal Extract, Gene Expression, Morris Water Maze Test
  • Study the effect of SemililTM on expression of Daxx, Nfkb and Vegf genes in the streptozotocin-rat model of sporadic Alzheimer's disease
    Niloofar Bazazzadegan, Marzieh Dehghan Shasaltaneh, Kioomars Saliminejad, Parvaneh Daneshmand, Koorosh Kamali, Mehdi Banan, Hamid Reza Khorram Khorshid

    Sporadic Alzheimer’s disease (SAD) is a multi-factorial disease caused by genetic, epigenetic, environmental and metabolic factors. Current understandings of the possible mechanisms of AD such as inflammation and oxidative stresses in the brain have led us to investigation of potential AD therapeutics. Currently herbal medicines with fewer side effects comparing to other chemical medicine are in the point of attention. SemililTM is a herbal extract with possible role as an anti-inflammatory and anti-oxidant agent that can improve the blood circulation, lymphedema and immune system functions. Among genes that have been implicated in SAD, three genes including Daxx, Nfkb and Vegf have shown significant statistical diversity in Alzheimer human brain as apoptosis mediator, pro-inflammatory transcription factor and key factor in orchestrating angiogenesis respectively. With this knowledge these genes have been chosen in our study to be investigated for neuroprotective effect of Semilil. This study was performed by comparing the expression level of the mentioned genes in the hippocampus of SAD rat model using qPCR method in treated and untreated groups. The therapeutic effect of this extract was studied at the behavioral, learning and memory level using Morris Water Maze (MWM) test as well. Five rat groups (control, sham, SAD model, herbal extract treated and ethanol treated) were used for the study. Drug interventions were started on the 21st day after modeling and each treatment group received the drug by intra-peritoneal route for 21 days. Gene expressions were measured using qPCR technique among groups. MWM was applied to determine the spatial learning and memory ability of the rats. All genes showed lower expression in SAD rat’s model comparing to control group but only Nfkb gene showed higher expression in SAD rat’s model treated with herbal extract. Two other genes did not show any expression change between the studied groups. In MWM, the significant changes in spatial learning that had been observed in rat’s model group did not show any alteration in the herbal-treated group.

    Keywords: SAD, Herbal Extract, Gene expression profile, MWM
  • Parvaneh Daneshmand, Kioomars Saliminejad, Marzieh Dehghan Shasaltaneh, Koorosh Kamali, Gholam Hossein Riazi, Reza Nazari, Pedram Azimzadeh, Hamid Reza Khorram Khorshid*
    Background
    Sporadic Alzheimer’s Disease (SAD) is caused by genetic risk factors, aging and oxidative stresses. The herbal extract of Rosa canina (R. canina), Tanacetum vulgare (T. vulgare) and Urtica dioica (U. dioica) has a beneficial role in aging, as an anti-inflammatory and anti-oxidative agent. In this study, the neuroprotective effects of this herbal extract in the rat model of SAD was investigated.
    Methods
    The rats were divided into control, sham, model, herbal extract -treated and ethanol-treated groups. Drug interventions were started on the 21st day after modeling and each treatment group was given the drugs by intraperitoneal (I.P.) route for 21 days. The expression levels of the five important genes for pathogenesis of SAD including Syp, Psen1, Mapk3, Map2 and Tnf-α were measured by qPCR between the hippocampi of SAD model which were treated by this herbal extract and control groups. The Morris Water Maze was adapted to test spatial learning and memory ability of the rats.
    Results
    Treatment of the rat model of SAD with herbal extract induced a significant change in expression of Syp (p=0.001) and Psen1 (p=0.029). In Morris Water Maze, significant changes in spatial learning seen in the rat model group were improved in herbal-treated group.
    Conclusion
    This herbal extract could have anti-dementia properties and improve spatial learning and memory in SAD rat model.
    Keywords: Alzheimer disease, Gene expression, Herbal extract
  • مینا حسنی، کیومرث سلیمی نژاد، مسعود حیدری زاده، کوروش کمالی، تکتم معماریانی، حمیدرضا خرم خورشید*
    مقدمه

    اندومتریوز تحت تاثیر دو عامل ژنتیک و محیط قرار دارد. ارتباط پلی مورفیسم های ژن های گلوتاتیون S-ترانسفراز (GSTs) با بیماری اندومتریوز مورد مطالعه پژوهشگران قرار گرفته است؛ با این وجود نتایج آن ها با هم همخوانی ندارد.

    هدف

    در این بررسی ما ارتباط بین ژنوتیپ های نول در ژن های GSTM1 و GSTT1 و همچنین GSTP1 313 A/G را با بیماری اندومتریوز در جمعیت ایرانی مورد مطالعه قرار دادیم.

    مواد و روش ها

    در این بررسی مورد-شاهد در مجموع 151 زن مبتلا به اندومتریوز و 156 زن سالم به عنوان گروه کنترل وارد شدند. بررسی ژنوتیپ ها با استفاده از multiplex PCR و PCR-RFLP انجام شد.

    نتایج

    فراوانی ژنوتیپ نول GSTM1 به طور معنی داری (0/027=p) در گروه مورد (7/3%) نسبت به گروه کنترل (1/3%) بالاتر بود. اختلاف معنی داری بین فراوانی ژنوتیپ های GSTT1 در بین گروهای مورد و شاهد مشاهده نشد. ژنوتیپ GSTP1 313 AG به طور معنی داری (0/048=p) در گروه مورد (1/33%) نسبت به شاهد (44/4%) پایین تر بود.

    نتیجه گیری

    نتایج ما نشان داد که پلی مورفیسم های GSTM1 و GSTP1 با احتمال ابتلا به اندومتریوز در زنان ایرانی مرتبط می باشد.

    کلید واژگان: اندومتریوز، مطالعه Association، GSTM1، GSTT1، GSTP1، پلی مورفیسم
    Mina Hassani, Kioomars Saliminejad, Masood Heidarizadeh, Koorosh Kamali, Ph.D., Toktam Memariani, Hamid Reza Khorram Khorshid, Ph.D
    Background

    Endometriosis influenced by both genetic and environmental factors. Associations of glutathione S-transferases (GSTs) genes polymorphisms in endometriosis have been investigated by various researchers; however, the results are not consistent.

    Objective

    We examined the associations of GSTM1 and GSTT1 null genotypes and GSTP1 313 A/G polymorphisms with endometriosis in an Iranian population.

    Materials And Methods

    In this case-control study, 151 women with diagnosis of endometriosis and 156 normal healthy women as control group were included. The genotyping was determined using multiplex PCR and PCR- RFLP methods.

    Results

    The GSTM1 null genotype was significantly higher (p=0.027) in the cases (7.3%) than the control group (1.3%). There was no significant difference between the frequency of GSTT1 genotypes between the cases and controls. The GSTP1 313 AG genotype was significantly lower (p=0.048) in the case (33.1%) than the control group (44.4%).

    Conclusion

    Our results showed that GSTM1 and GSTP1 polymorphisms may be associated with susceptibility of endometriosis in Iranian women.

    Keywords: Endometriosis, Association study, GSTM1, GSTT1, GSTP1, Polymorphism
  • Asghar Ebadifar, Roya Hamedi, Hamid Reza Khorram Khorshid, Kioomars Saliminejad, Koorosh Kamali, Fatemeh Aghakhani Moghadam, Nazanin Esmaeili Anvar, Nazila Ameli
    Background
    Cleft lip with or without cleft palate (CL/P) is one of the most common congenital anomalies and the etiology of orofacial clefts is multifactorial. Transforming growth factor alpha (TGFA) is expressed at the medial edge epithelium of fusing palatal shelves during craniofacial development. In this study, the association of two important TGFA gene polymorphisms, BamHI (rs11466297) and RsaI (rs3732248), with CL/P was evaluated in an Iranian population.
    Methods
    The frequencies of BamHI and RsaI variations were determined in 105 unrelated Iranian subjects with nonsyndromic CL/P and 218 control subjects using PCR and RFLP methods, and the results were compared with healthy controls. A p-value of <0.05 was considered statistically significant.
    Results
    The BamHI AC genotype was significantly higher (p=0.016) in the patients (12.4%) than the control group (5.0%). The BamHI C allele was significantly higher (p=0.001; OR=3.4, 95% CI: 1.6-7.4) in the cases (8.0%) compared with the control group (2.5%).
    Conclusion
    Our study showed that there was an association between the TGFA BamHI variation and nonsyndromic CL/P in Iranian population.
    Keywords: Association Study, Cleft lip, palate, Polymorphism, Transforming Growth Factor Alpha
  • Ehsan Hejazi, Javad Nasrollahzadeh, Ramina Fatemi, Leila Barzegar-Yar Mohamadi, Kioomars Saliminejad, Zohre Amiri, Masoud Kimiagar, Mohammad Houshyari, Maryam Tavakoli, Farah Idali
    Background
    Emergence of drug resistance has brought major problems in chemotherapy. Using nutrients in combination with chemotherapy could be beneficial forimprovement of sensitivity of tumors to drug resistance. Soybean-derived isoflavones have been suggested as chemopreventive agents for certain types of cancer, particularlybreast cancer. In this study, the synergistic effects of soy isoflavone extract in combination with docetaxel in murine 4T1 breast tumor model were investigated.
    Methods
    In this study, mice were divided into 4 groups (15 mice per group) of control, the dietary Soy Isoflavone Extract (SIE, 100 mg/kg diet), the Docetaxel (DOCE, 10 mg/kg) injection and the combination of dietary soy isoflavone extract and intravenousdocetaxel injection (DOCE+SIE). After 3 injections of docetaxel (once a week), 7 mice were sacrificed to analyze MKI67 gene and protein expressions and the rest weremonitored for diet consumption, tumor growth and survival rates.
    Results
    In DOCE+SIE group, diet consumption was significantly higher than DOCE group. While lifespan showed a trend towards improvement in DOCE+SIE group, nosignificant difference was observed among the 4 studied groups. Tumor volume was not significantly affected in treated groups. A lower but not significant MKI67 protein expression was detected in western blot in DOCE+SIE group. The mRNA expression was not significantly different among groups.
    Conclusion
    The results suggest that the combination of soy isoflavone as an adjunct to docetaxel chemotherapy can be effective in improving diet consumption in breast cancer.
    Keywords: Breast cancer, Docetaxel, Soy isoflavone extract
  • Khorram Hamid Reza Khorshid, Elnaz Gozalpour, Kioomars Saliminejad, Masood Karimloo, Mina Ohadi, Koorosh Kamali
    Background
    Late-onset Alzheimer''s disease (AD), a genetically heterogeneous neurodegenerative disorder, is the most common form of dementia in people over 65 years old. The role of vitamin D in neuropsychiatric and neurodegenerative disorders such as AD has been supported by epidemiologic investigations and animal models, as well. We examined the association of the vitamin D receptor (VDR) gene polymorphisms and late-onset AD in an Iranian population.
    Methods
    This study was performed in Tehran, Iran from 2007 to 2008. Totally, 145 AD patients and 162 age-matched unrelated healthy controls were included. The genotype and allele frequencies for the VDR polymorphisms, ApaI (G>T; rs7975232) and TaqI (C>T; rs731236), were determined in the case and control subjects PCR-RFLP analysis. Logistic regression analysis was performed to assess the effect of mutant genotype or allele in the study groups.
    Results
    The statistical analyses showed significant differences neither in genotype nor in allele frequencies of the ApaI and TaqI polymorphisms between the case and control groups.
    Conclusion
    It seems that the ApaI and TaqI polymorphisms are not associated with the risk of late-onset AD in Iranian population.
    Keywords: Alzheimer's Disease_Vitamin D Receptor_Polymorphism_Association Study_PCR_RFLP_Iran
  • Fereshteh Ashtari, Kioomars Saliminejad, Koorosh Kamali, Zhamak Pahlevanzadeh
    Background
    Familial Idiopathic Basal Ganglia Calcification (IBGC) is a rare neurodegenerative disorder which is usually transmitted as an autosomal dominant trait. IBGC is genetically heterogeneous and SLC20A2, on chromosome 8p21.1–8q11.23, is the first gene found in IBGC-affected patients with varied ancestry. On the other hand, several candidate genes for IBGC on chromosome 2q37, including the SPP2 gene, may play a role in inhibiting calcification.
    Methods
    Totally, 22 members of a three generational Iranian family affected by IBGC, with an autosomal dominant pattern of inheritance were included in this study. DNA was extracted from the whole blood using standard salting out method. To find a mutation responsible for IBGC, we sequenced the coding region of SLC20A2 as well as promoter and coding region of SPP2 in the index subject of IBGC-affected family.
    Results
    Pathogenic mutation was found neither in SLC20A2 nor in SPP2.
    Conclusion
    Our results strengthen genetic heterogeneity of this condition. Additional mutation studies are necessary to find a gene or genes responsible for IBGC in this affected family.
    Keywords: Familial Idiopathic Basal Ganglia Calcification, Mutation, SLC20A2 protein, SPP2 protein
  • Saman Mohammad Zahery, Kioomars Saliminejad, Hamid Reza Khorram Khorshid, Ali Ahani
    Background
    Retinoblastoma is the most common intraocular tumor in childhood and mutation in the RB1 gene will trigger the tumorigenesis. So far, a wide range of the mutations along the length of RB1 gene have been reported. However, some could not be detected by common detection methods. In such condition, linkage analysis using microsatellite markers is suggested to trace unknown RB1 mutations in the affected family. The aim of the present study was to evaluate the heterozygosity rates and genotyping of three microsatellite markers near or inside of the RB1 gene.
    Methods
    Totally, 120 unrelated healthy people from Fardis, Karaj, Iran were recruited and from each participant genomic DNA was extracted from 5 ml of peripheral blood. Three microsatellite markers D13S153, D13S156 and D13S128 located within or adjacent to the RB1 gene were selected for linkage analysis. The reliability of microsatellite markers and linkage analysis were investigated in 10 members of 2 families with familial retinoblastoma.
    Results
    Our results showed that heterozygosity rates for the three markers D13S153, D13S156 and D13S128 were 74, 70 and 78%, respectively. On the other hand, 2 and 36 out of 120 people were homozygote and heterozygous for all loci, respectively.
    Conclusion
    Given the heterozygosity rates, it may be concluded that all microsatellite markers D13S153, D13S156 and D13S128 are informative and have a high rate of heterozygosity and sensitivity. Therefore, tracing the unknown RB1 mutated alleles using linkage analysis in Iranian family with familial retinoblastoma could be recommended by means of these three microsatellite markers.
    Keywords: Genetic markers, Genotyping techniques, Iran, Retinoblastoma
  • تکتم معماریانی، کیومرث سلیمی نژاد، کوروش کمالی، عادل شروین، بهرخ مهاجر، محمد مهدی آخوندی، حمیدرضا خرم خورشید
    زمینه و هدف
    رگزایی یا رشد و نمو عروق جدید از عروق موجود، یک فرایند فیزیولوژیک لازم برای ترمیم بافت است که در فرایندهای پاتولوژیک مثل بدخیمی ها و اندومتریوز نیز بسیار تاثیر گذار است. فاکتور رشد اندوتلیال عروقی (VEGF)، واسطه اصلی رگزایی و نفوذپذیری عروقی است که در بروز بیماری اندومتریوز نقش مهمی ایفا می کند. هدف از این مطالعه بررسی ارتباط بین پلی مورفیسم (G
    روش بررسی
    این مطالعه بر روی 105 بیمار با تشخیص قطعی اندومتریوز به کمک لاپاروسکوپی و 150 خانم که عدم وجود بیماری در آنها به کمک لاپاروسکوپی تایید شد، به عنوان گروه کنترل انجام شد. DNA با روش استاندارد salting out از خون محیطی استخراج و سپس ژنوتیپ و فراوانی اللی پلی مورفیسم (G p به عنوان سطح معنی داری در نظر گرفته شد.
    نتایج
    در گروه بیماران وقوع پلی مورفیسم هموزیگوت G/G VEGF به میزان 3/41%، هتروزیگوت C/G به میزان 2/46% و پلی مورفیسم هموزیگوت C/C به میزان 5/12% مشاهده شد. از طرف دیگر در گروه شاهد 32% ژنوتیپ هموزیگوت G/G، 3/53% ژنوتیپ هتروزیگوت و 7/14% ژنوتیپ هموزیگوت C/C را نشان دادند. در این مطالعه اختلاف معنی داری بین سه ژنوتیپ و فراوانی اللی پلی مورفیسم (G
    نتیجه گیری
    بر خلاف مطالعات قبلی در این بررسی ارتباط معنی داری بین پلی مورفیسم (G
    کلید واژگان: اندومتریوز، رگزایی، فاکتور رشد اندوتلیال عروقی، پلی مورفیسم، کنترل، شاهد، ناباروری زنان
    Taktom Memariani, Kioomars Salimi Nejad, Kourosh Kamali, Adel Shervin, Behrokh Mohajer-Maghari, Mohammad Mehdi Akhondi, Hamid Reza Khorram Khorshid
    Introduction
    Angiogenesis, growth of new blood vessels from pre-existing vessels, is a crucial physiological process for tissue regeneration. This state is also seen in pathological processes such as malignancies and endometriosis. Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and vascular permeability which is known to play an important role in the development of endometriosis. The aim of this study was to investigate the relationship between 405 G>C VEGF polymorphism and endometriosis in an Iranian population.
    Materials And Methods
    The study population was comprised of 105 women with and 150 women without laparoscopic evidence of endometriosis. Genomic DNA from blood cells was extracted using salting out method. Genotype and allele frequency of 405 G>C polymorphism was compared between women with endometriosis and the controls using PCR-RFLP. Statistical analysis was performed using SPSS 13.0 software. Chi-squared test and odds ratio plus 95% confidence interval were determined. A p-value less than 0.05 was considered statistically significant.
    Results
    While the 405 VEGF genotype frequencies in the case group were 41.3% G/G, 46.2% C/G and .5 C/C, they were 32% GG, S.3 GC and 14.7% CC in the control group. The distribution of three genotypes and allele frequencies of 405 G>C VEGF polymorphism between the case and control groups did not demonstrate any significant difference.
    Conclusion
    In contrast to previous studies, no significant correlation was found between 405 G>C VEGF polymorphism and endometriosis. Since this was the first study in an Iranian population, further investigation with bigger sample sizes may be indicated to be able to generalize the findings.
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