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Cell Journal [Yakhteh]. 2019; 20 (4): 576-583
in English | IMEMR | ID: emr-199629


Objective: Hemoglobinopathies such as beta-thalassemia and sickle cell disease [SCD] are inherited disorders that are caused by mutations in beta-globin chain. Gamma-globin gene reactivation can ameliorate clinical manifestations of betathalassemia and SCD. Drugs that induce fetal hemoglobin [HbF] can be promising tools for treatment of beta-thalassemia and SCD patients. Recently, it has been shown that Simvastatin [SIM] and Romidepsin [ROM] induce HbF. SIM is a BCL11a inhibitor and ROM is a HDAC inhibitor and both of these drugs are Food and Drug Administration [FDA]-approved for hypercholesterolemia and cutaneous T-cell lymphoma respectively. Our aim was to evaluate the synergistic effects of these drugs in inducing HbF

Materials and Methods: In our experimental study, we isolated CD34+ cells from five cord blood samples that were cultured in erythroid differentiation medium containing ROM and Simvastatin. Then Gamma-globin, BCL11a and HDAC gene expression were evaluated on the 7th and 14th day of erythroid differentiation by real-time polymerase chain reaction [PCR] and immunocytochemistry

Results: Our results showed that combination of SIM and ROM significantly increased Gamma-globin gene expression and inhibit BCL11a and HDAC expression compared to results of using each of them alone. SIM and ROM lead to 3.09- fold increase in HbF production compared to the control group. Also, SIM inhibited BCL11a expression [0.065-fold] and ROM inhibited HDAC1 expression [0.47-fold] as two important inhibitors of HbF production after birth

Conclusion: We propose combination therapy of these drugs may be ameliorate clinical manifestation in beta-thalassemia and SCD with at least side effects and reduce the need for blood transfusion

Cell Journal [Yakhteh]. 2018; 20 (1): 84-89
in English | IMEMR | ID: emr-191500


Objective: Endometriosis is a prevalent gynecologic disease affecting 10% of women in reproductive age. Endometriosis is diagnosed by laparoscopy that was followed by histologic confirmation. Early diagnosis will lead to a more effective treatment with much less morbidity. As miR-31 and miR-145 are shown to be directly or indirectly correlated to biological processes involved in endometriosis, the aim of this study was to examine the association of miR-31 and miR-145 expression in plasma with the presence of endometriosis

Materials and Methods: In this case control study, the plasma samples of 55 patients with endometriosis and 23 women without endometriosis were collected, extracted and analyzed by real time quantitative polymerase chain reaction [qPCR] for the expression of miR-145 and miR-31

Results: Our findings showed that miR-31 expression levels in stage 3 or 4 and stage 1 or 2 were significantly down- regulated [less than 0.01-fold, P<0.05], while the expression level of miR-145 was significantly up-regulated in women with endometriosis in stage 1 or 2

Conclusion: Different cellular biological processes, such as differentiation, proliferation, mitochondrial function, reactive oxygen species [ROS] production, invasion and decidualization, are deregulated in endometriosis. miR-31 and miR-145 are microRNAs [miRNAs] with potential roles, as shown in pathologies like cancers. We found that miR- 31 was under-expressed in patients with endometriosis, while miR-145 was over-expressed in stage 1 or 2, indicating that they were relatively down-regulated in the more severe forms. Our findings suggested that these two miRNAs may be considered as potential biomarkers with probable implications in early diagnosis and even follow-up of patients with endometriosis

Cell Journal [Yakhteh]. 2017; 19 (1): 50-64
in English | IMEMR | ID: emr-185793


Objective: The stem cell theory in the endometriosis provides an advanced avenue of targeting these cells as a novel therapy to eliminate endometriosis. In this regard, studies showed that lovastatin alters the cells from a stem-like state to more differentiated condition and reduces stemness. The aim of this study was to investigate whether lovastatin treatment could influence expression and methylation patterns of genes regulating differentiation of endometrial mesenchymal stem cells [eMSCs] such as BMP2, GATA2 and RUNX2 as well as eMSCs markers

Materials and Methods: In this experimental investigation, MSCs were isolated from endometrial and endometriotic tissues and treated with lovastatin and decitabin. To investigate the osteogenic and adipogenic differentiation of eMSCs treated with the different concentration of lovastatin and decitabin, BMP2, RUNX2 and GATA2 expressions were measured by real-time polymerase chain reaction [PCR]. To determine involvement of DNA methylation in BMP2 and GATA2 gene regulations of eMSCs, we used quantitative Methylation Specific PCR [qMSP] for evaluation of the BMP2 promoter status and differentially methylated region of GATA2 exon 4

Results: In the present study, treatment with lovastatin increased expression of BMP2 and RUNX2 and induced BMP2 promoter demethylation. We also demonstrated that lovastatin treatment down-regulated GATA2 expression via inducing methylation. In addition, the results indicated that CD146 cell marker was decreased to 53% in response to lovastatin treatment compared to untreated group

Conclusion: These findings indicated that lovastatin treatment could increase the differentiation of eMSCs toward osteogenic and adiogenic lineages, while it decreased expression of eMSCs markers and subsequently reduced the stemness

Humans , Women , Endometriosis , Epigenesis, Genetic , Cellular Reprogramming , Bone Morphogenetic Proteins , GATA2 Transcription Factor , Iran
Cell Journal [Yakhteh]. 2015; 17 (1): 71-82
in English | IMEMR | ID: emr-161619


Runt-related transcription factor 2 [RUNX2] and osterix [OSX] as two specific osteoblast transcription factors and distal-less homeobox 5 [DLX5] as a non-specific one are of paramount importance in regulating osteoblast related genes including osteocalcin, bone sialoprotein [BSP], osteopontin and collagen type I?1. The present study sets out to investigate whether epigenetic regulation of these genes is important in osteoblastic differentiation of mesenchymal stem cells [MSCs]. In this experimental study, MSCs were differentiated to osteoblasts under the influence of the osteogenic differentiation medium. DNA and RNA were extracted at days 0, 7, 14 and 21 from MSCs differentiating to osteoblasts. Promoter regions of RUNX2, OSX, DLX5 and BSP were analyzed by methylation-specific PCR [MSP]. Gene expression was analyzed during osteoblastic differentiation by quantitative real-time polymerase chain reaction [PCR]. MSP analysis revealed that promoter methylation status did not change in RUNX2, DLX5 and BSP during MSC osteoblastic differentiation. In contrast, OSX promoter showed a dynamic change in methylation pattern. Moreover, RUNX2, OSX, DLX5 and BSP promoter regions showed three different methylation patterns during MSC differentiation. Gene expression analyses confirmed these results. The results show that in differentiation of MSCs to osteoblasts, epigenetic regulation of OSX may play a leading role

IBJ-Iranian Biomedical Journal. 2015; 19 (1): 23-28
in English | IMEMR | ID: emr-170696


The aim of the current study was to assess the mRNA levels of two mitochondria-related genes,including nuclear-encoded NRF1 [nuclear respiratory factor 1], mitochondrial transcription factor A [TFAM], and mitochondrial-encoded cytochrome c oxidase subunit 1 [MT-CO1] genes in various stages of the human oocyte maturation. Oocytes were obtained from nine infertile women with male factor undergoing in vitro fertilization [IVF]/intra-cytoplasmic sperm injection protocol. Mitochondrial-related mRNA levels were performed by single-cell TaqMan real-time PCR. the expression level of the target genes was low at the germinal vesicle stage [P>0.05]. Although the mRNA level of NRF1gene remained stable in metaphase I, the mRNA level of TFAM and MT-CO1 increased significantly [P<0.05].In metaphase II, the expression level of all genes increasedcompared to metaphase I [P<0.05]. The overexpression levels of NRF1, TFAM, and MT-CO1 genes are related to the oocyte maturation. Therefore, the current study could be used clinically to improve the successrate of IVF.

Modares Journal of Medical Sciences. 2014; 17 (2): 13-25
in Persian | IMEMR | ID: emr-167799


Bipolar I disorder is a common disorder with a complex etiology. A genetic approach is gaining increasing importance in this disorder. The dysbindin gene, located at 6p22.3 is considered a susceptibility gene for schizophrenia. Certain genotypes of dysbindin are thought to be associated with other psychoses such as bipolar disorders. This study intends to assess the association in previously implicated dysbindin genotypes and haplotypes with bipolar I disorder in an Iranian population. We genotyped four previously reported SNPs: rs2619522, rs1018381, 2743852 and rs2619538. Their haplotypes were analyzed in a population of 124 patients that consisted of 44 confirmed bipolar I disorder patients and 80 control subjects. We used multiple allele-specific PCR method for genotyping, which was verified by direct sequencing. In concordance with previous reports in other populations our findings showed no association between the single SNPs and bipolar I disorder. Furthermore, none of the alleles showed a significant association with the disorder. In contrast to previous reports, haplotype analysis did not reveal any statistically significant associations with bipolar I disorder. Considering reports of previous studies regarding the implication of these dysbindin genotypes in bipolar I disorder, it is probable that allelic heterogeneity along with lack of an established causal variant in the dysbindin gene can be main factors for this discordance. With regards to ethnicities in other studies, population variation can also be considered an important factor in the observed variation

Humans , Male , Female , Genotype , Genetic Association Studies , Membrane Proteins/physiology , Alleles , Polymerase Chain Reaction , Dystrophin-Associated Proteins/genetics
Modares Journal of Medical Sciences, Pathobiology. 2014; 16 (4): 39-46
in Persian | IMEMR | ID: emr-147037


A recent field of research in epigenetics is DNA methylation which involves the CpG island in the genome that subsequently controls transcription and translation of targeted genes. In the hepatitis B virus [HBV] genome, there are three CpG islands which tend to be methylated. The aim of the current study is to determine the methylation pattern of the HBV X gene in chronically infected HBV patients. Study participants comprised 45 chronically infected HBV patients. According to the presence of the HBeAg, patients were divided into two groups, HBeAg positive [n=24] and HBeAg negative [n=21]. Initially, viral DNA was treated with natrium bisulfate. Then, analysis was performed with two sets of methylated and non-methylated primers by the MSP method. The overall methylation rate in serum samples of hepatitis B infected patients was 35.5%; the rate in the HBeAg positive patients was 20.8%, whereas it was 52.3% in HBeAg negative patients. There was a significantly higher rate of methylation in serum samples of HBeAg negative patients compared to HBeAg positive patients [student's t-test; P=0.02]. Methylation of HBV can be used as a new mechanism to control the progression of viral infection. This methodology can be useful for determining the characteristics of clinical stages of this infection

Neurology Asia ; : 83-86, 2013.
Article in English | WPRIM | ID: wpr-628588


Multiple sclerosis (MS) is a chronic infl ammatory demyelinating disease of the central nervous system. Interleukin-2 (IL-2) is identifi ed as the crucial and main immunoregulatory cytokines. Previously, we showed signifi cant association between -330 T/T IL-2 genotype and relapsing remitting MS among Iranian population. In this study we investigated 100 relapsing remitting, 30 secondary progressive MS and 125 healthy controls to compare the relapsing remitting and secondary progressive course MS in association to -330 IL-2 polymorphism. Our results showed that the -330 T/T IL-2 genotype was signifi cantly more frequent in relapsing remitting and secondary progressive MS than controls. The signifi cant increased frequency of -330 T/T IL-2 genotype in secondary progressive than relapsing remitting MS, imply -330 T/T IL-2 genotype can cause higher susceptibility to secondary progressive MS than relapsing remitting.

Cell Journal [Yakhteh]. 2013; 15 (2): 124-129
in English | IMEMR | ID: emr-127535


Multiple sclerosis [MS] is a chronic autoimmune disease due to demyelination of the central nervous system. It is believed that cytokines are involved in the pathogenesis of MS. The interleukin-2 [IL2] gene is powerful functional candidate that is involved in immune regulation and operation. In this study, for the first time, we investigated the effect of -475 A/T and -631 G/A IL2 polymorphisms on MS disease in Iranian patients. In this case-control study, 100 MS patients [mean age: 32.95 +/- 6.51 years, age range: 20-42 years] selected according to McDonald criteria, and 100 ethnically, sex and age matched healthy controls [mean age: 29 +/- 7.8 years, age range: 20-52 years] with no personal or family history of autoimmune diseases were studied. The restriction fragment length polymorphism-polymerase chain reaction [RFLP-PCR] method was applied to define different alleles and genotypes of IL2 promoter single nucleotide polymorphism -475 A/T as well as -631 G/A among individuals. chi [2] was calculated and Fisher's exact test was applied to analyze the obtained data. The value of p <0.05 was considered significantly. Evaluation of the -475 IL2 revealed that T allele and A/T genotype are present in 2% and 4% of MS patients, respectively, whereas T allele was absent in control samples. The comparison between alleles and genotypes in MS patients and healthy controls was not significant [p=0.1]. For the -631 position, 1% and 2% of MS patients carried A allele and A/G heterozygote genotypes, respectively. All control samples had G allele and G/G genotype. The differences between patients and controls were not significant [p=0.4]. Moreover, our results showed a very low frequency of T at -475 and A at -631 IL2 position in each of the two groups. Both -475 and -631 IL2 polymorphisms were higher in MS patients as compared to controls, but the frequency differences were not significant. Based on these data, it is suggested that the -475 and -631 IL2 polymorphisms as functional promoter position may be involved in IL2 expression and regulation. To find out the exact effect of the mentioned SNPs on susceptibility to MS, study on a larger sample size is suggested

Humans , Female , Male , Interleukin-2 , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Case-Control Studies
Cell Journal [Yakhteh]. 2012; 14 (2): 90-97
in English | IMEMR | ID: emr-155395


Mechanism of zoledronic acid on osteoblastic differentiation of mesenchymal stem cells [MSCs] has not fully understood. With the knowledge of some drugs mechanism that alter methylation pattern of some genes, the present research sets out to evaluate osterix [OSX] promoter methylation pattern during zoledronic acid-induced osteoblastic differentiation of MSCs. In this experimental study, MSCs were isolated from human bone marrow. For osteogenic differentiation, MSCs were pulse treated with 5 micro M Zoledronic acid for 3 hours and incubated after a medium change in osteogenic differentiation medium for 3 weeks. DNA and RNA were extracted on days 0, 7, 14 and 21 of MSCs differentiating to osteoblast. After cDNA synthesis, OSX expression was evaluated by RT-PCR and quantitative Real-Time PCR. After multiplicity of infection [MOI] treatment, gene specific methylation of OSX was analyzed by methylation specific PCR [MSP]. The mRNA expression of OSX was increased in osteoblast differentiated cells induced by zoledronic acid, especially on days 14 and 21 of differentiation [p<0.05], but expression of OSX didn't change in undifferentiated MSCs. MSP revealed that, on day 0, undifferentiated MSCs are totally methylated. But, on day 7 of differentiation, MSCs treated by zoledronic acid were totally unmethylated. OSX promoter remained unmethylated, afterwards. MSP revealed that OSX had a dynamic pattern in methylation, while MSCs gradually differentiated to osteoblasts. Our finding showed that promoter region of OSX is hypomethylated independently from zoledronic acid treatment during osteoblastic differentiation. This knowledge is important to understand drug mechanisms and can be useful for developing new therapies to combat against bone diseases

Humans , Mesenchymal Stem Cells , Transcription Factors , Diphosphonates/pharmacokinetics , Bone Marrow , Promoter Regions, Genetic , Methylation
Cell Journal [Yakhteh]. 2012; 14 (2): 102-109
in English | IMEMR | ID: emr-155397


Breast Cancer is the most common cancer in Iranian women. Breast tumors are classified based on the estrogen receptor alpha [ER alpha] expression status into ER negative and ER positive tumors. ER negative tumors tend to have worse prognosis and less likely to respond to endocrine therapy. Aberrant methylation of gene promoter is one of the mechanisms for gene silencing in breast tumors. Because of its reversible nature, promoter methylation is a good target for new therapeutic strategies. We aimed to evaluate the frequency of this epigenetic event in ER alpha gene and its association to clinicopathological features in Iranian breast cancer patients. In this case control study the patient series consisted of 100 sporadic primary breast cancer cases [51 ER negative and 49 ER positive tumors]. None of the participants had chemo or radiotherapy before surgery. In breast tumors ER alpha promoter methylation were assessed with methylation specific polymerase chain reaction [MSP]. Data was collected on clinicopathological features of the patients. Correlation between ER alpha methylation and clinicopathological characteristics of the patients was investigated by Pearson Chi-Square and Fisher's exact test. ER alpha methylation was detected in 98% of ER negative and 65% of ER positive breast tumors. A strong correlation was found between ER alpha methylation and ER negativity in tumors [p<0.0001]. Also, ER alpha methylation has associated to progesterone receptor negativity [p<0.008] and double receptor negative status [p<0.0001] in breast tumors. ER alpha methylation occurs with high frequency in the breast tumors of Iranian breast cancer patients and may play a considerable role in pathogenesis of ER alpha negative tumors as a poor prognosis and more aggressive category. The reversible nature of DNA methylation may provide new therapeutic possibilities in ER negative breast tumors

Humans , Female , Estrogen Receptor alpha , Receptors, Estrogen , Promoter Regions, Genetic , Methylation , Case-Control Studies
Modares Journal of Medical Sciences. 2011; 14 (3): 1-14
in Persian | IMEMR | ID: emr-162835


Estrogen receptor alpha protein status is determined by routine immunohistochemistry analysis in all malignant breast tumors. This assay has its limitations. RNA based techniques are potential complements for immunohistochemistry but it must be noticed that gene silencing may occur at different levels from RNA to protein. The aim of this study was the comparison of the results from these two assays and characterizing the tumors subgroup in which gene expression occurs at RNA level but the target protein is absent. 92 primary breast tumors including their clinical and IHC results were collected before treatment. Estrogen receptor gene expression of tumors was studied by Reverse Transcription Polymerase Chain Reaction [RT PCR]. In this assay, GAPDH was used as a reference gene. 36.6% of tumors with negative estrogen receptor protein showed gene expression at mRNA level. In this subgroup most of the patient were older than 50 years and in stages 3 or 4 of breast cancer and had poor prognosis according to Nottingham prognostic index. Most cases of the perineural invasion have been seen in this subgroup. It seems that RT-PCR assay would enable us to recognize a subgroup of breast tumors with poor prognosis which expresses RNA but not protein

Modares Journal of Medical Sciences. 2011; 14 (3): 61-68
in Persian | IMEMR | ID: emr-162841


Low density Lipo-protein Receptor-related Protein [LRP] is the most important cholesterol receptor in neurons. It serves as a receptor for APOE protein which is the most important risk factor for Alzheimer's Disease. LRP also contributes to the ligation of lipoproteins with APOE in neurons. Association between LRP C766T and Alzheimer's disease in Iranian patients with late onset Alzheimer's disease [LOAD] was investigated in this research. 100 patients with LOAD were selected based on DSM-IV-TR and NINCDS-ADRDA diagnostic criteria and 100 normal controls without any personal and family history of Alzheimer's disease or dementia were included in this case-control study. AD patients and control subjects were matched for age and sex. PCR-RFLP was set up to detect LRP C766T polymorphism. LRP C/C genotype and C allele distribution were more frequent in AD patients than in control subjects. However, this difference was not statistically significant. When association between LRP C/C genotype and AD was categorized by the gender, in both genders, there was not any significant correlation. Our findings indicate that 766C allele of LRP gene could not significantly alter the risk of developing late-onset Alzheimer's disease in Iranian patients. Analysis of other genetic factors and environmental factors are promoted in Iranian population

AJMB-Avicenna Journal of Medical Biotechnology. 2011; 3 (2): 61-66
in English | IMEMR | ID: emr-124073


MicroRNAs [miRNAs] are a class of small non coding regulatory RNAs that have key functions in multiple cell processes. Deregulation of these tiny miRNAs are involved in various human diseases. MiR-155 is one of the multifunctional miRNA that its over-expression has been found to be associated with different kinds of cancer such as leukemia, breast and colon cancers. It is thought that deregulation and over-expression of this microRNA may be associated with PC12 cell proliferation. So, the aim of this study was to investigate the role of miR-155 expression on PC12 cell growth. For this reason, PC12 cells were cultured and transfected by 3 different concentration [25, 50 and 75 nmol] of either LNA anti-miR-155 or scramble antisense in 24-well plate. Then, total RNA was extracted from transfected cells. miRNA cDNAs were synthesized from isolated total RNA. In the second step, miR-155 expression level was analyzed using the quantitative real-time polymerase chain reaction [QRT-PCR]. MTT test was performed to evaluate cell viability. In the next step, apoptosis assay was assessed to investigate anti miR-155 effect on PC12 cells death. Obtained results were analyzed with t-test. MTT test revealed that cell viability of transfected cells with 75 nM of anti-miR- 155 to be reduced by half of the control and scramble groups [0.5 vs. 0.97 and 0.94]. Our data suggest that miR-155 over-expression is associated with PC12 cell growth. So, miR-155 down regulation by anti-miR-155 could open up new ways to restrain brain tumor growth, as anti-miR-155 causes PC12 cells to repress

Humans , Animals , PC12 Cells , MicroRNAs , Cell Line , Down-Regulation , Cell Proliferation
Yakhteh Medical Journal. 2011; 13 (1): 11-18
in English | IMEMR | ID: emr-129891


Osteoblasts arise from multipotent mesenchymal stem cells [MSCs] present in the bone marrow stroma and undergo further differentiation to osteocytes or bone cells. Many factors such as proteins present in the Wnt signaling pathway affect osteoblast differentiation. ROR2 is an orphan tyrosine kinase receptor that acts as a co-receptor in the non-canonical Wnt signaling pathway. However, ROR2 has been shown to be regulated by both canonical and non-canonical Wnt signaling pathways, ROR2 expression increases during differentiation of MSCs to osteoblasts and then decreases as cells differentiate to osteocytes. On the other hand, research has shown that ROR2 changes MSC fate towards osteoblasts by inducing osteogenic transcription factor OSTERIX. Here we speculated whether ROR2 gene expression regulation during osteoblastogenesis is epigenetically determined. MSCs from bone marrow were isolated, expanded and characterized in vitro according to standard procedures. ROR2 promoter methylation status was determined using methylation specific PCR in a multipotent state and during differentiation to osteoblasts. We determined that the demethylation process in ROR2 promoter occurs during the differentiation process. The process of demethylation begins at day 8 and continues until 21 days of differentiation. This result is in concordance with previous works on the role of ROR2 on osteoblast differentiation, which have shown an upregulation of ROR2 expression during this process

Humans , Mesenchymal Stem Cells , Cell Differentiation , Methylation , In Vitro Techniques
Modares Journal of Medical Sciences, Pathobiology. 2011; 14 (1): 49-57
in Persian | IMEMR | ID: emr-136892


In this study quantitative expression of MDR1 and hOCT1 genes in CML patients and normal people were measured using Real-Time PCR. To study quantitative expression of these genes by real-time PCR, mastermix with syber green was used. Peripheral blood samples from 30 CML patients and 27 normal persons were harvested. Real-time PCR results were analyzed with relative quantification method. This study showed that in the patients group who were under treatment with Imatib, MDR1 gene expression was increased which was statistically significant. This increase has a direct relation with disease progress. Gene expression in AP and BP patients was also higher than CP patients. In contrast, hOCT1 expression in patients group in comparison with normal group was not statistically significant. MDR1 increase in leukemic cell membrane results in the reduction of intra-cellular drug concentration. Thus, optimal concentration of drug for inhibition of BCR-ABL tyrosine kinase is not achieved which culminated in disease progression to AP and BP phases. Moreover changes in hOCT1 gene expression as an influx transporter of Imatib could affect intracellular concentration of drug and finally determine therapy outcome. However, in this study hOCT1 gene expression was variable and was not statistically significant

Modares Journal of Medical Sciences, Pathobiology. 2011; 14 (1): 59-69
in Persian | IMEMR | ID: emr-136893


Zoledronic acid as a main treatment for osteoporosis has an important role in differentiation of mesenchymal stem cells. However, mechanism of osteoblastic differentiation induction by zoledronic acid is not well understood until now. In this research we evaluate zoledronic acid effect on methylation status of RUNX2 and DLX5 promoters. After isolation and expansion of hMSCs from BM, they were pulse treated with 5 micro M ZA for 3h, and incubated in osteogenic differentiation medium for 3 weeks. DNA was extracted after first, second and third weeks of culture and also from undifferentiated MSCs. After SBS treatment, gene specific methylation analysis for RUNX2 and DLX5 were carried out by MSP using methylated and unmethylated primers. In the genes RUNX2 and DLX5, M and U primers of MSP amplified promoter regions of undifferentiated and osteoblastic differentiated MSCs. Therefore, methylation status in RUNX2 and DLX5 promoters present incomplete methylation. Methyltion patterns of RUNX2 and DLX5 don't change during zoledronic acid osteoblastic differentiation of MSCs. Our findings show that zoledronic acid does not induce osteoblastic differentiation via epigenetic mechanisms. Therefore, zoledronic acid can induce osteoblastic differentiation in a manner independent from DNA epigenetic changes

Yakhteh Medical Journal. 2010; 12 (2): 241-248
in Persian, English | IMEMR | ID: emr-98595


Chronic myeloid leukemia [CML] develops when a hematopoietic stem cell acquires the BCR/ABL fusion gene. This causes these transformed hematopoietic cells to have a greater than normal proliferation rate. Scientists attempt to improve the CML treatment process by silencing the BCR/ABL oncogene. In this work, we used morpholino antisense oligos to silence the BCR/ABL oncogene. In this study, the K562 was used as a BCR/ABL fusion-gene positive cell line and the Jurkat cell line as a control. We explored the inhibiting capacity of morpholino antisense oligos in the the expression of the BCR/ABL oncogene and studied their p210 BCR/ABL suppression, inhibition of cell proliferation and stimulation of apoptosis in the K562 cells after 24 and 48 hours. Endo-Porter was used for delivery of morpholino antisense oligos into cell cytosols. Meanwhile, flow cytometric analysis was performed in order to determine the appropriate concentration of morpholino antisense oligos. Prolonged exposure of the K562 cell line to the morpholino antisense oligos targeted against the BCR-ABL gene showed proliferation inhibition as its main feature. After western blotting, we found that complete silencing of BCR/ABL was achieved, but flow cytometric analysis showed no broad apoptosis. The results indicate that the Morpholino antisense oligo is able to inhibit p210 BCR/ABL; however, it cannot induce broad apoptosis due to co-silencing of BCR

Cell Line , Gene Silencing , Genes, abl , Oligonucleotides, Antisense
Genetics in the 3rd Millennium. 2010; 7 (4): 1864-1867
in Persian | IMEMR | ID: emr-104787


With 1 million new cases causing 375000 deaths worldwide per year, breast cancer is the leading cause of cancer death in women in both developing and developed countries. Recent findings indicate epigenetic modifications as key factors in breast carcinogenesis. Epigenetic refers to the cellular information of transcription memory which is transmitted through cell divisions but is not sequence based. Epigenetic is the connecting circle of the genotype and the environment. Which connect the inheritable gene transcription pattern and phenotype of a cell. DNA promoter methylation and chromatin remodeling are two main mechanisms of epigenetic modifications which are emerging as targets for breast cancer detection, prognosis and treatment. Because of their potential for reversal, epigenetic alterations are considered to be promising in caner treatment and epidrug production. Therapeutics that target methylation and histone modifications in breast cancer already exist. Advances in epidrugs are likely to play important role in future of cancer treatment

Genetics in the 3rd Millennium. 2010; 8 (2): 2054-2057
in Persian | IMEMR | ID: emr-104798


Tay-Sachs disease is a rare autosomal recessive disorder of sphingolipid metabolism, caused by deficiency of enzyme beta hexosaminidase A, that leads to accumulation of GM2 ganglioside in cellular lysosomes. Clinical findings are progressive weakness, gradual loss of aquired neuromotor skills, and deterioration of intelligence from about 3 to 6 months of age, as well as seizure attacks and blindness. There is also evidence on progressive neurodegeneration. In most of the patients bilateral cherry red spot were reported on funduscopy. In this report, we present two patients with Tay-Sachs disease, which are confirmed by enzyme assay. In both of them beta hexosaminidase A activity were strongly decreased