128 results on '"Majid Kheirollahi"'
Search Results
2. Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis
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Seyedeh Zahra Hosseini Imani, Zohreh Hojati, Sheyda Khalilian, Fariba Dehghanian, Majid Kheirollahi, Mehdi Khorrami, Vahid Shaygannejad, and Omid Mirmosayyeb
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Medicine ,Science - Abstract
Abstract Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Our results showed that the expression level of IL7R was decreased in the sporadic patients in comparison with other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls, and familial group versus FDR was also seen. Our results also represented an increased expression level of RNF213 in familial patients as compared to the control group. The similar RNF213 expression between sporadic and control group, as well as FDR and familial group was also seen. Diagnostic evaluation was performed by receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and Expanded Disability Status Scale (EDSS) with our gene expression levels were also assessed. Overall, decreased expression level of IL7R in the sporadic cases and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. Confirmation of the effects of differential expression of RNF213 gene requires further studies in the wider statistical populations.
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- 2021
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3. Gene expression profiles of YAP1, TAZ, CRB3, and VDR in familial and sporadic multiple sclerosis among an Iranian population
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Sheyda Khalilian, Zohreh Hojati, Fariba Dehghanian, Vahid Shaygannejad, Seyedeh Zahra Hosseini Imani, Majid Kheirollahi, Mehdi Khorrami, and Omid Mirmosayyeb
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Medicine ,Science - Abstract
Abstract Alterations in the regulatory mechanisms that control the process of myelination in the nervous system, may lead to the impaired myelination in the Multiple sclerosis. The Hippo pathway is an important mediator of myelination in the nervous system and might contribute to the pathophysiology of MS. This study examined via qPCR the RNA expression of YAP1, TAZ, and CRB3 as the key effectors of the Hippo pathway and also, VDR in the peripheral blood of 35 sporadic, 37 familial MS patients; and also 34 healthy first-degree relatives of the familial MS patients (HFR) and 40 healthy individuals without a family history of the disease (control). The results showed the increased expression of VDR in the sporadic group, as compared to other groups. There was also an increased expression of TAZ in the familial and HFR groups, as compared to the control group. The familial and sporadic patients displayed a significantly lower level of expression of YAP1 in comparison to the HFR group. The increased expression level in the sporadic patients and control group, as compared to the HFR group, was seen in CRB3. We also assessed different clinical parameters and MRI characteristics of the patients. Overall, these findings suggest that Hippo pathway effectors and also VDR gene may play a potential role in the pathophysiology of the sporadic and familial forms of MS. Confirmation of different gene expression patterns in sporadic and familial MS groups may have obvious implications for the personalization of therapies in the disease.
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- 2021
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4. New Variants in the CDH1 Gene in Iranian Families with Hereditary Diffuse Gastric Cancer
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Majid Kheirollahi, Maryam Saneipour, Mohammad Amin Tabatabaiefar, Mehrdad Zeinalian, Mohammad Minakari, and Abbas Moridnia
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cdh1 gene ,diffuse gastric cancer ,iranian families ,hereditary ,mutation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Hereditary diffuse gastric cancer (HDGC) is a hereditable form of diffuse gastric cancer with very aggressive tumors, poor prognosis, and delayed clinical signs. Method: We assessed 17 probands identified with HDGC upon gastrectomy according to the histopathological criteria confirmed by a pathologist and familial history. We extracted DNA from peripheral blood and formalin fixed paraffin-embedded tissues. DNA sequencing was done following PCR amplification of 16 exons and exon/intron boundaries of the CDH1 gene and exon 2 of CTNNA1 gene. The Multiplex Ligation-dependent Probe Amplification technique was performed on patients with no pathogenic variants in sequencing. Results: Totally, 17 probands comprising seven males and 10 females were assessed. In three patients, we recognized the tumors in the early TNM stage (I, II), while in 14 cases, tumors were observed in the late stages (III, IV). Overall, DNA sequencing of the CDH1 gene identified 16 variants (seven exonic including five new variants and nine intronic containing six new variants). Moreover, Multiplex Ligation-dependent Probe Amplification detected one deletion in exon 1 of two patients. Conclusion: Our results showed that E-cadherin deficiency in HDGC was related to CDH1 gene point mutations and large deletion with high heterogeneity, which should be considered in the diagnosis and treatment of HDGC patients.
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- 2020
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5. Effect of Donepezil and Hyoscyamoside on Improving Spatial Memory in Rats With Alzheimer\'s Disease
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Fatemeh Heidari Soureshjani, Majid Kheirollahi, Parichehreh Yaghmaei, and Fattah Sotoodehnejadnematalahi
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alzheimer’s disease ,hyoscyamoside ,donepezil ,morris water maze ,spatial memory ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background and Aim: Alzheimerchr('39')s Disease (AD) is a neurodegenerative brain disease that gradually destroys memory and cognitive skills. The disease is caused by the formation of beta-amyloid plaques, oxidative stress, dysfunctions in the cholinergic system, neuronal killing inflammation, and ultimately brain atrophy. Donepezil and hyoscyamoside have inhibitory effects on these pathogens; therefore, their impact on the learning process of Alzheimer’s rats in the Morris Water Maze was investigated. Methods & Materials: In the present experimental study, 60 male rats of Wistar breed with approximately 7 weeks age within the control group (rats that received normal water and food), the PBS group (underwent surgery), PBS group (received solvent Aβ), the first Alzheimer›s group (animals that received beta-amyloid by Alzheimer’s surgery, second Alzheimer’s group (after Alzheimer’s surgery, they received 1 cc of normal saline daily, and treatment groups that treated the rats with beta-amyloid after Alzheimer. In the hyoscyamoside group, they received 10 mg/kg daily of hyoscyamoside for 28 days. The donepezil group received it 4 mg/kg daily for 28 days by gavage. The Morris Water Maze test was used to evaluate learning and memory. Data were analyzed by ANOVA statistical analysis and Post Hoc test. Ethical Considerations: The Ethics Committee in Biomedical Research, Islamic Azad University, Science and Research Branch approved the research (Code: IR.IAU.SRB.REC 1397.057) Results: Beta-amyloid injection caused extensive damage to memory. The treatment groups with hyoscyamoside and donepezil spent less time and distance with a significant level (P
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- 2020
6. The Clinical Effectiveness of Preimplantation Genetic Diagnosis for Chromosomal Translocation Carriers: A Meta-analysis
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Manijeh Mahdavi, Seyedeh M. Sharafi, Seyede S. Daniali, Roya Riahi, and Majid Kheirollahi
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pregnancy outcome ,preimplantation genetic diagnosis ,meta-analysis ,translocation ,recurrent miscarriage ,Genetics ,QH426-470 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Published data on the relationship between pregnancy outcomes of preimplantation genetic diagnosis (PGD) in translocation carriers have implicated inconclusive results. To identify potentially eligible reports, an electronic search was conducted in several databases, including PubMed, Scopus, Web of Knowledge, and Cochrane. Pooled odd ratios (ORs) and 95% confidence intervals (Cis) were estimated based on a random-effect model to evaluate the strength of association between PGD and successful pregnancy outcome in translocation carriers. A total of six cohort studies were included in the current study. The meta-analysis of these studies revealed that the PGD method was associated with an increased successful pregnancy outcome of translocation carriers (OR = 8.58; 95%CI: 1.40–52.76). In subgroup analysis, there was no significant association according to the chromosomal translocation carrier origin and the type of translocated chromosomes, as well as country. In developed countries, the pregnancy outcome of PGD was significantly improved in translocation carriers (OR = 21.79; 95%CI: 1.93–245.52). The current meta-analysis demonstrated that the PGD method is associated with successful pregnancy outcome in both types of reciprocal and Robertsonian translocation carriers, especially in developed countries.
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- 2020
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7. Meta-Analysis on the Association of C-Reactive Protein Polymorphisms with Metabolic Syndrome
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Seyedeh Maryam Sharafi, Manijeh Mahdavi, Roya Riahi, Majid Kheirollahi, and Roya Kelishadi
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c-reactive protein ,single-nucleotide polymorphisms (snps) ,metabolic syndrome ,meta-analysis ,Genetics ,QH426-470 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Polymorphisms in the C-reactive protein (CRP) genes might have crucial role in the development of metabolic syndrome (MetS). In the current comprehensive meta-analyses, we aim to provide a quantitative assessment of the association between CRP single-nucleotide polymorphisms (SNPs) and the risk of MetS. An electronic search was performed on several databases. After data extraction, random effect model was used to calculate the pooled odds ratio (OR) and 95% confidence intervals (CIs). Four independent studies including case–control, cohort, and cross-sectional methods were analyzed. Our meta-analysis indicated that CRP polymorphisms are not significantly associated with MetS (OR = 0.92, 95% CI = 0.77–1.10) with significant heterogeneity (I 2 = 55.4%; p-value = 0.008). The subgroup analysis revealed that only GG has significant association with MetS (OR = 0.32, 95% CI = 0.13–0.80, p-value = 0.015) without significant heterogeneity (I 2 = 0%, p-value > 0.05). In conclusion, this meta-analysis provides strong evidence that only some SNPs of CRP gene are associated with the risk for development of MetS; and this relationship does not exist in different ethnic populations.
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- 2020
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8. The impact of maternal predisposing factors on level of maternal serum pregnancy-associated plasma protein A and free subunit human chorionic gonadotropin and nuchal translucency
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Maryam Mirsafaie, Majid Kheirollahi, and Lida Moghaddam-Banaem
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beta subunit ,human chorionic gonadotropin ,maternal age ,maternal weight ,nuchal translucency ,pregnancy-associated plasma protein a ,prenatal screening ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background: This study aimed to investigate the relationship between maternal predisposing factors with the level of maternal serum pregnancy-associated plasma protein A and free subunit human chorionic gonadotropin and nuchal translucency. Materials and Methods: We performed a cross-sectional-analytical study on 762 pregnant women who referred to the Gene Azma Medical Genetics Laboratory in Isfahan for amniocentesis. All pregnant women at high risk of screening in the first trimester of pregnancy for trisomy 21 and other aneuploidy were referred to a gynecologist for amniotic fluid sampling (amniocentesis). Multiple of the means (MoM) of PAPPA ≤0.5, 0.5 ≥ MoM free β-hCG >2.5, and NT ≥3.5 mm were considered abnormal. We used Chi-square method and Mann–Whitney U-test to compare data qualitative and quantitative, respectively. Results: In individuals with less pregnancies and deliveries, the value of abnormal NT was higher (P < 0.01, P < 0.001, respectively). On the other hand, the highest abnormal rate of NT was observed in pregnant women under 35 years (21, 84%, P < 0.012). In addition, abnormal levels of free β-hCG are more common in women < 35 years of age (186, 66.9%, P < 0.02) and female fetuses (171, 58.8%) (P < 0.006). Conclusion: According to the results of this study, it can be said that considering the underlying factors of pregnant mothers in performing tests related to screening in the first trimester of pregnancy can lead to a reduction in false positive rates.
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- 2023
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9. Increased Risk of Multiple Sclerosis in the Presence of a Genetic Variant in 19-Nucleotide Downstream of miR-148a Coding Gene in Isfahan City Population in Iran
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Farzaneh Ahmadi, Maryam Peymani, and Majid Kheirollahi
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mir148a, human ,genetic polymorphism ,multiple sclerosis ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Multiple sclerosis (MS) is a common disease of the central nervous system, and the incidence of this disease in women is twice that of men. Considering the importance of miRNA polymorphisms in the expression and function of mRNAs as well as the risk of disease, this study investigated the association of rs6977848 polymorphism (a genetic variant in 19-nucleotide downstream of miR-148a coding gene) with the risk of MS disease in Isfahan City population in Iran, for the first time. Methods: In this case-control study, a population of 95 healthy individuals and 99 patients were assayed. The genotype of the individuals for the polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). To confirm the results, a number of samples were sequenced. Then, the frequency of genotypes and alleles were evaluated. Findings: Considering the total dominance of T allele, the total TT and TG genotypes significantly increased the susceptibility to MS disease compared with the GG reference genotype [odds ratio (OR) = 2.27, P = 0.043); while considering the genotype GG as reference genotype, there was a significant difference between the TG and the reference genotypes in this population with a risk of disease (P < 0.050). However, no significant difference was observed between genotype TT and GG genotype as reference genotype. Conclusion: Findings indicate that rs6977848 polymorphism in miR-148a coding gene downstream may be effective in influencing the performance of this miRNA as well as its expression level. Moreover, the incidence of the ability of individuals to affect this disease is not significantly related to the incidence of disease in the studied populations.
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- 2019
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10. Methylation and polymorphism in CDH1 gene promoter among patients with diffuse gastric cancer
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Mohadeseh Naghi Vishteh, Mehrdad Zeinalian, Majid Kheirollahi, Amirreza Javadi Mamaghani, Mohammad Ali Zolfaghari, Aliyar Mirzapour, Meisam Barati, and Seyed Javad Seyed Tabaei
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cadherin 1 ,methylation ,polymerase chain reaction ,sequence analysis ,stomach neoplasms ,Medicine - Abstract
Background: The promoter methylation and single nucleotide polymorphisms (SNPs) affect the transcription activity of cancer-related genes in several cancers including diffuse gastric cancer (DGC). Here we aimed to evaluate the promoter methylation status and the rs16260 at the promoter region of the CDH1 gene in DGC. Methods: This case-control study was performed of 48 formalin-fixed paraffin-embedded (FFPE) blocks of DGC patients and 41 fresh frozen tissue samples of healthy individuals. Methylation status was evaluated using methylation-specific polymerase chain reaction (PCR) and the rs16260 at the promoter region of the CDH1 gene was assessed using PCR and sequencing method. Results: The occurrence of methylation at the promoter region of the CDH1 gene in DGC patients was significantly higher than control samples (P < 0.0001). The methylated status was significantly associated with the poor differentiated histological type of DGC (P = 0.0428). The frequency of AC genotype and the A allele in DGC patients was significantly higher than the control subjects (P = 0.006 and 0.003, respectively). Conclusions: Here we showed that methylation at the CDH1 promoter may contribute to the DGC development, and also the AC genotype was associated with the risk of DGC.
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- 2022
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11. Comparative Study on Mutations in CDH1 Gene in Iranian Patients with Hereditary Diffuse Gastric Cancer (HDGC) and Sporadic Diffuse Gastric Cancer (SDGC)
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Abbas Moridnia, Majid Kheirollahi, Mohammad Amin Tabatabaeefar, and Mehrdad Zeinalian
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CDH1 ,Diffuse gastric cancer ,Iran ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Gastric cancer (GC) is the fourth common cancer worldwide and the second cause of mortality among all cancers. Mutations in the CDH1 gene are the most common cause of hereditary diffuse gastric cancer (HDGC) and sporadic diffuse gastric cancer (SDGC). CDH1 gene encode for E-cadherin protein. We compared the nucleotide alterations and copy number variations in CDH1 gene between Iranian patients with HDGC and SDGC. Methods: We evaluated 45 patients including 17 cases with HDGC and 28 cases with SDGC identified according to the histopathological criteria and familial history. DNA extraction was obtained from peripheral blood and formalin-fixed paraffin-embedded (FFPE) tissues. The DNA sequencing was completed using polymerase chain reaction (PCR) amplification of 16 exons of the CDH1 gene. Multiplex ligation-dependent probe amplification (MLPA) method was accomplished on samples with no pathogenic variants in sequencing. Findings: Synonymous substitution of L116L and A692A was detected in patients with HDGC and SDGC; but non-synonymous substitution of D777E, c.889delA, and c.1177delA deletions only detected in patients with HDGC. MLPA results revealed one deletion in exon 1 of CDH1 gene in patients with HDGC and one deletion in exon 2, and one duplication in exon 9 of CDH1 gene in patients with SDGC. Conclusion: According to the results, different variants in CDH1 gene was presented in patients with HDGC and SDGC that emphasis the survey of CDH1 variants and especially detected variants in this study in the diagnosis of diffuse gastric cancer disease.
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- 2017
12. The Effect of Beta Interferon on the Expression of miR-145 in Patients with Multiple Sclerosis
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Naeim Ehtesham, Mohammadreza Sharifi, Fariborz Khorvash, and Majid Kheirollahi
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Interferon beta ,miR-145 expression ,Multiple sclerosis ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: microRNAs are non-coding RNAs that modulate different types of cellular processes like differentiation and cell death. Hitherto several studies have been done to determine the expression profile of microRNAs in patients with multiple sclerosis (MS) to obtain appropriate biomarkers. In previous studies, it was found that miR-145 was over-expressed. This up-regulation was in patients who did not start taking medicine. Therefore, in this study we assessed the effect of beta interferon on the expression of this microRNA in patients with multiple sclerosis. Methods: We evaluated the expression pattern of miR-145 in 15 patients who did not start taking medicine and called treatment naive, in 15 patients who were under treatment and also 15 healthy people using real-time polymerase chain reaction method. Findings: The expression level of miR-145 in treatment naive patients was 3.9 fold of healthy people (P = 0.005), whereas expression level of this microRNA between healthy people and under treatment patients was not significantly different. Conclusion: Down-regulation of miR-145 in under-treatment patients to the extent of healthy people suggests that probably, this microRNA could be used as predictive biomarker.
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- 2016
13. Next-Generation Sequencing and its Applications
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Meysam Mosallayi, Hamed Mirzaei, Miganoosh Simonian, and Majid Kheirollahi
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Sequencing ,Next-generation sequencing ,454 ,Solex ,Sequencing by oligonucleotide ligation and detection (SOLiD) ,Medicine ,Medicine (General) ,R5-920 - Abstract
DNA sequencing is an approach exploited to determine the sequence of a DNA molecule. It includes any method or technology used to identify and determine the order of the four bases of adenine, guanine, cytosine, and thymine in a strand of DNA. DNA sequencing might be used to determine the sequence of individual genes, larger genetic regions, full chromosomes, or entire genomes. Traditional sequencing methods are mainly based on the original Sanger sequencing technique which makes them very expensive and low-throughput; thus, they do not meet the needs of researchers. Consequently, with the considerable advances in molecular biology and the high demand for low-cost sequencing has encouraged the development of high-throughput sequencing (or next-generation sequencing) technologies that parallelize the sequencing process, producing thousands or millions of sequences concurrently. Next-generation sequencing enable us to rapidly sequence a large piece of DNA which could span the whole genome with the latest instruments capable of producing gigabases of data in one isolated sequencing run. Next-generation sequencing platforms have a wide variety of applications, such as whole-genome sequencing, de novo sequencing, RNA sequencing (for applications such as transcriptomics and small RNA analysis), methylation analysis, and protein-nucleic acid interaction analysis.
- Published
- 2016
14. Possible preventive effect of donepezil and hyoscyamoside by reduction of plaque formation and neuroinflammation in Alzheimer's Disease
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Fatemeh Heidari Soureshjani, Majid Kheirollahi, Parichehreh Yaghmaei, and Fattah Sotoodehne jadnematalahi
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alzheimer disease ,amyloid beta-protein ,donepezil ,hyoscyamoside ,neurogenic inflammation ,Medicine - Abstract
Background: Alzheimer disease (AD) is the most common age-dependent dementia. The complex natural accumulation of amyloid beta (Aβ) precursor protein in hippocampus neurons is regarded as the earliest pathological feature of AD, although there are cholinergic assumptions and effective inflammation in AD. In this animal experimental study, we evaluated the preventive effect of hyoscyamoside (Hyo) and donepezil (Dz) on plaque formation and improvement of neurogenic inflammation in AD rats. Methods: Dz was prepared and Hyo (steroidal saponin) was isolated from Hyoscymus niger. Then, Wistar rats divided into five groups including negative and positive controls, AD, Dz, and Hyo treatment groups based on the drug exposure and their behavioral alternation was examined using Morris water maze (MWM) test. Bielschowsky staining was used to detect the nerve fibers. Serum levels of interleukin (IL)-4 and IL-6 were evaluated by ELISA. The RNA expression of cyclin-dependent kinase CDK11-P58 in peripheral blood lymphocytes was performed using quantitative PCR. Results: The MWM test showed significant changes in time the models spent to find the hidden platform. The Hyo treatment group showed a notable speed change (P < 0.01). The histopathological analysis of the hippocampal tissue revealed the inhibition of Aβ formation in the treatment groups. The treatment groups had a significant decline in the serum level of IL-6, and the IL-4 serum level was increased in the Hyo and Dz treated groups. The expression levels of CDK11-P58 was significantly decreased in the treatment groups. Conclusions: In sum, the therapeutic effects of Hyo is comparable with that of Dz in AD rats by suppressing neuroinflammation. Thus, these compounds could be considered as a preventive agent in the AD therapy.
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- 2021
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15. Variants in Human Prostacyclin Receptor Gene in Patients with Migraine Headache
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Fariborz Khorvash, Majid Kheirollahi, Mohammad Kazemi, Gilda Amini, Mehdi Khorrami, Maryam Mirsafaie, and Mohammad Reza Mohammadi
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Iranian Patients ,Migraine ,Prostaglandin I2 receptor Gene ,Variants ,Psychiatry ,RC435-571 - Abstract
Objective: Prostaglandin I2 receptor plays a major physiologic role in the relaxation of arterial smooth muscle and vasodilation and possibly during migraine attacks. Therefore, in this study, the coding and noncoding exons and exon-intron boundaries of Prostaglandin I2 receptor gene were examined in patients with migraine headache and healthy controls and the potential effects of identified single nucleotide variations were evaluated using direct PCR-sequencing and in silico analysis. Method: In this study, the peripheral blood samples of 50 patients and 50 controls were examined to find any mutation in coding and noncoding exons and exon-intron boundaries of PTGIR gene. DNA was extracted and all the samples were amplified by polymerase chain reaction (PCR) and sequenced. Results: In this study, the patients had a mean age of 35.235 ± 10.99 years (range, 9–60 yrs.), and female to male ratio was 4:1 in this group. The controls had a mean age of 35.058 ± 11.116 years (range, 8–59 yrs.), and female to male ratio was 3.7:1.3 in this group. Two patients had mutations in exon 2. The first mutation was located in exon 2 (at amino acid position 251) of PTGIR gene at nucleotide position c.866A > T, a synonymous variant described previously in the database. The second mutation was located in exon 2 c.867G > A, which is a missense variant. Sequence analysis revealed high occurrence of previously reported intronic variants mostly in a homozygous statue. Conclusion: The data supported the hypothesis that mutations in PTGIR gene, particularly the mutation we described, should be considered even in cases of migraine. The presence of this mutation in patients with family history raises important issues regarding genetic counselling.
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- 2018
16. The Role of Transcription Factors in Regulating the Development and Differentiation of Neural Retina Cells
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Razeih Heidari, Fatemeh Nazemroaya, and Majid Kheirollahi
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Transcription factor ,Neural retina ,Retinal progenitor cells ,Medicine ,Medicine (General) ,R5-920 - Abstract
Neural retina is the part of the diencephalon and because of the relatively simple structure in known as a suitable model for studying the molecular mechanisms of the central nervous system. Visual perception is the result of the function of six types of neurons organized in the structure of the neural retina. Neural retina develops via the proliferation of a common precursor cell in the inner layer of the optic cup. Retinal progenitor cell acquires the competent to differentiate into different cell fates by different factors in a time-dependent and protected manner in the mammals. Destruction and loss of these cells in the retina occurs in various retinal diseases and impairs the process of human vision. Lack of reconstruction of damaged nerve cells in the retina of mammals, including humans is a noted problem; and in recent decades, a wide range of research in the eye field allocated the possibility of replacing the retinal cells and many efforts is made to treat these diseases. Study and identifying the transcription factors involved in neuronal differentiation can provide a useful tool for gene therapy aiming to regenerate retinal neurons in the near future.
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- 2015
17. TERRA و بیماریهای انسانی مرتبط با آن
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Sepideh Dashti and Majid Kheirollahi
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Telomere ,Telomeric repeat-containing RNA (TERRA) ,Telomere maintenance mechanisms ,Genomic instability ,Telomere syndrome ,Cancer ,Medicine ,Medicine (General) ,R5-920 - Abstract
تلومرها، انتهای فیزیکی کروموزومهای خطی را تشکیل میدهند و عملکرد آنها به منظور نگهداری پایداری کروموزومی ضروری میباشد. در صورت از دست رفتن عملکرد تلومرها، ظرفیت همانندسازی سلولی کاهش مییابد و در نهایت، منجر به پیری سلولی و بیماریهای مرتبط با نقص در احیای اندام و بازسازی بافت (سندرمهای تلومر) میگردد. از سوی دیگر، سرطانها نیز میتوانند در نتیجهی ناپایداریهای ژنومی ناشی از اختلال در عملکرد تلومر ایجاد شوند. تاکنون دو نوع مکانیسمهای نگهداری طول تلومر (TMM یا Telomere maintenance mechanism) شناسایی شدهاند که شامل تلومراز و ALT (Alternative lengthening of telomeres) میباشد. در نئوپلازیها، مکانیسمهای نگهداری طول تلومر (TMM) میتوانند به پیشبینی بیماری کمک نمایند و احتمال میرود در آینده باعث درمان مستقیم شوند. در طی مطالعات اخیر، مشخص شد که تلومرهای یوکاریوتی رونویسی میشوند و به رونوشت آنها TERRA (Telomeric repeat-containing RNA) میگویند. به طور کلی، افزایش میزان رونویسی از TERRA با کوتاه شدن طول تلومر مرتبط میباشد و در عملکرد تلومر تأثیرگذار است. در این مقاله، به طور خلاصه اصول کلی بیماریهای مرتبط با اختلال در عملکرد تلومر بررسی شده است. به علاوه، در مورد ارتباطات شناخته شده بین رونوشت تلومر (TERRA) و بیماریها بحث شده است. در نهایت، پتانسیل TERRA در رویکردهای درمانی بیماریهای مرتبط با نقص در عملکرد تلومر مورد بررسی قرار گرفته است.
- Published
- 2015
18. Retinal Cell Regeneration by Stem Cells
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Fatemeh Nazem-Roaya, Razieh Heidari, and Majid Kheirollahi
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Stem cell ,Retina ,Eye ,Medicine ,Medicine (General) ,R5-920 - Abstract
A number of different cellular sources of neural stem cells have been identified. These sources include stem cells at the retinal margin, pigmented cells in the ciliary body and iris, non-pigmented cells in the ciliary body and Müller glia within the retina and also embryo and adult neural stem cells (NSCs). In the present review, we discuss the combinations of growth factors that are capable of stimulating the proliferation and making of neurons from stem cells, neural progenitors, non-neural epithelial cells, and postmitotic support cells.
- Published
- 2015
19. بیان miR-148a در تومورهای مننژیومای انسانی
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Mahdiyeh Moodi and Majid Kheirollahi
- Subjects
Meningioma ,miR-148a expression ,Real-time polymerase chain reaction ,Medicine ,Medicine (General) ,R5-920 - Abstract
مقدمه: تومورهای مننژیوما از شایعترین تومورهای مغزی هستند که از لایهی مننژ منشأ میگیرند. اگرچه درصد زیادی از انواع مننژیوما خوش خیم هستند و شمار معدودی از تغییرات ژنتیک دارند، با این حال موقعیت داخل جمجمهای آنها اغلب منجر به پیامدهای جدی و مرگبار میشود. به دنبال کشف نقش پروتئین Phosphatase and tensin homolog (PTEN)، به عنوان یک مهارکنندهی تومور در مننژیوما که یکی از اهداف miR-148a میباشد و از آن جایی که این میکروRNA در بررسی نمونههای تومور مغزی با تکنیک Microarray افزایش بیان نشان داده بود، در این مطالعه به ارزیابی الگوی بیان این میکروRNA در مننژیوما پرداختیم. روشها: ما الگوی بیان miR-148a را بین 25 نمونهی بافتی مننژیوما و چهار نمونهی طبیعی با استفاده از تکنیک Real-time polymerase chain reaction بررسی کردیم. یافتهها: سطح بیان miR-148a بین نمونههای بافتی مننژیوما و نمونهی طبیعی تفاوت معنیداری نشان داد (05/0 > P). نتیجهگیری: از آن جایی که تفاوت معنیداری در بیان miR-148a با بافت طبیعی وجود دارد، با انجام بررسیهای بیشتر شاید بتوان miR-148a را به عنوان یک نشانگر در تومورهای مننژیوما مطرح نمود.
- Published
- 2015
20. بیان پروانسولین انسانی در گیاه با استفاده از ناقل pVUT (Plasmid Viral University of Tehran)
- Author
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Mahnaz Kheirollahi, Ali Akbar Shahnejat-Bushehri, Majid Kheirollahi, Fariba Abooei-Mehrizi, and Hooshang Alizadeh
- Subjects
Human proinsulin gene ,Transient expression ,Cowpea Mosaic Virus-Hyper Translatable (CPMV-HT) expression system ,Transgenic plant tissue ,Medicine ,Medicine (General) ,R5-920 - Abstract
مقدمه: انسولین هورمون پروتئینی است که توسط سلولهای بتای پانکراس ترشح میشود. به علت معایب تولید پروتئینهای نوترکیب در میکروارگانیسمها، هزینه به نسبت بالا، امکان آلودگی با پروتئینهای سمی و مراحل هزینهبر خالصسازی، تولید پروتئینهای نوترکیب در گیاهان امری قابل بررسی است. توسعهی سیستم بیان گذرا بر پایهی نوع حذف شدهی RNA-2 ویروس موزائیک لوبیا چشم بلبلی (Cowpea Mosaic Virus-Hyper Translatable یا CPMV-HT)، امکان تولید سریع و سطوح بالای پروتئینها را بدون استفاده از همانندسازی ویروسی فراهم کرده است. روشها: در این مطالعه، سازههای pBI121-Proinsulin-Zera (pBI-ProZ) در بر دارندهی توالی ژن پروانسولین انسانی و Zera (دومین انتهای N غنی از پرولین گاما- زئین ذرت) و pCAMBIA1304-Proinsulin-Extensin (pCAMBIA-ProE) در بر دارندهی سیستم بیانی CPMV-HT، به منظور بهبود ترجمهی ژن پروانسولین انسانی و توالی سیگنال پپتید اکستنسین هویج ساخته شد. این دو سازه، به واسطهی باکتری Agrobacterium tumefaciens pv. C58، به صورت بیان گذرا به گیاهان کاهو و یونجه انتقال داده شدند. تحلیل آماری این پژوهش بر پایهی آزمایش فاکتوریل، در قالب طرح بهکلی تصادفی بر روی غلظت پروانسولین تولیدی در هر گرم برگ تراریخت صورت گرفت. بیان ژن پروانسولین در بافت گیاهی تراریخت در سطح رونویسی، با استفاده از واکنش Reverse transcription polymerase chain reaction (RT-PCR) و در سطح ترجمه، با استفاده از آزمون لکهگذاری نقطهای و Enzyme-linked immunosorbent assay (ELISA) مورد تأیید قرار گرفت. یافتهها: میزان پروانسولین فعال تولیدی با سازههای pCAMBIA-ProE و pBI-ProZ، در برگهای یونجه تراریخت، به ترتیب 82/6 و 32/4 نانوگرم در هر گرم برگ تر و در برگهای کاهوی تراریخت، به ترتیب 6/6 و 8/3 نانوگرم در هر گرم برگ تر بود. نتیجهگیری: طبق نتایج به دست آمده از این تحقیق، میزان بیان پروتئین پروانسولین در سازهی pCAMBIA-ProE در بر دارندهی خصوصیات سیستم بیانی CPMV-HT، بیشتر از سازهی pBI-ProZ بود.
- Published
- 2015
21. Expression of TERRA in Different Grades of Astrocytoma
- Author
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Sepideh Dashti, Saeideh Ashouri, and Majid Kheirollahi
- Subjects
Expression ,TERRA ,Telomere ,Astrocytoma ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Brain tumors include burden of mortality from cancers. High grades of brain tumors are more aggressive and have poor prognosis. Introduction telomeres are the ends of linear chromosomes that serve as a protective cap to avoid permanent proliferation arrest, termed replicative senescence. In vertebrates, telomeres consist of tandem repeats of TTAGGG hexanucleotide sequences. In spite of heterochromatin structure of telomeres, they are transcribed into a non-coding RNA called telomeric repeat-containing RNA or TERRA which acts as a natural inhibitor of telomerase activity. Considering astrocytoma, as one of the most common tumors of the central nervous system (CNS), and a very poor prognosis tumor, the aim of this study was to evaluate the TERRA expression level in astrocytoma tumors and nontumoral controls. Furthermore, expression levels of TERRA were compared between different grades of astrocytoma. Methods: The mRNA of 26 brain tumor samples and 4 samples as nontumoral controls were extracted and cDNA was synthesized. Then, real-time reverse transcription polymerase chain reaction (SYBR Green kit) for quantitation of total TERRA levels was developed. Findings: We demonstrated the correlation between total TERRA levels of expression with different grades of astrocytoma. High grades (III and IV) of astrocytoma tumors had lower mean of ∆Ct than low grades (II) and down-regulation for TERRA mRNA was 4.377-fold (P = 0.036). Additionally, measurement of TERRA expression in astrocytoma showed 4.969-fold less compared to levels of TERRA expression in nontumoral controls (P = 0.029). Conclusion: According to our study, TERRA may be prognostic marker in astrocytoma tumors.
- Published
- 2015
22. Report a Novel Mutation in Human Prostacyclin Receptor Gene in patient affected with Migraine
- Author
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Majid Kheirollahi, Mohammad Reza Pourreza, Fariborz Khorvash, Mohammad Kazemi, and Gilda Amini
- Subjects
Migraine ,Mutation ,Prostacyclin Receptor Gene ,Psychiatry ,RC435-571 - Abstract
Objective: The human prostacyclin receptor gene (PTGIR) encodes the human prostacyclin (PGI2) receptor. PTGIR is a part of vasodilator system during the migraine attacks and probably has an important role in the mechanism of this disease. Materials and Methods: We used direct PCR and sequencing to determine the any variants in PTGIR gene. A blood sample was collected from the patients and genomic DNA was extracted. Polymerase chain reaction was carried out on extracted DNA. The PCR products were then sequenced using a cycle sequencing kit, on an automated DNA sequencing machine. Results: In reviewing of familial and clinopathological of these two patients, both patients have migraines with visual aura and their mothers also are suffering from migraines. Their parents had been married strangers. Direct sequencing analysis of exon 2 of the PTGIR gene showing the presence of two mutations in two patients. These mutations were heterozygote that made the following changes; g.1626T>A, c.754T>A, cDNA.867T>A, and p.S252T for the first mutation and c.753C>T, cDNA866C>T, g.1625C>T, p.C251C for the second mutation. The first mutation alters the amino acid and is a novel mutation. The second change is a conservative mutation that have already been reported. Conclusion: The prediction results predicted the variant would negatively affect the protein’s function and seems to be disease causing. Although functional analysis is required to confirm the association between the variant and the disease.
- Published
- 2017
23. miRNA, Biogenesis and Mechanisms of Regulations
- Author
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Naeim Ehtesham, Mahdiyeh Modi, and Majid Kheirollahi
- Subjects
miRNA ,Biogenesis ,Regulations mechanism ,Medicine ,Medicine (General) ,R5-920 - Abstract
miRNAs(microRNAs) were discovered in 1993 in Caenorhabditis elegans as one of the most important gene expression regulatory factors. This regulatory role includes many of the important intracellular processes like genesis, differentiation, proliferation and apoptosis. miRNAs are among mRNAs and like them are transcribed by RNA polymerase II and then cap and polyA tail are added to them. The resulted pri-miRNA converts to mature miRNA by two sequential trimming reactions. miRNAs exerts their regulatory effects by translation repression, translation activation and mRNA degradation. miRNAshave an important role in regulation of immune and nervous systems and disorder in their expression can lead to separate disease in both systems.
- Published
- 2014
24. Detection of Mutation in Exons 3 and 8 of SLC3A1 and Exons 4 and 10 of SLC7A9 Genes in Patients with Cystinuria in Iran
- Author
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Leila Koulivand, Mehrdad Mohammadi, Rasoul Salehi, Behrouz Ezatpour, and Majid Kheirollahi
- Subjects
Cystinuria ,Mutation ,Iran ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Cystinuria, one of the first diagnosed inborn errors of metabolism, recognized by hyperexcretion of cystine, lysine, ornithine and arginine into the urine. So far, two genes associated with cystinuria have been identified: SLC3A1 (2p16.3) that encodes the heavy subunit rBAT of the renal b0,+ transporter and SLC7A9 (19q13.1), which encodes the light subunit b0,+AT. Patients with type A cystinuria have two SLC3A1 mutations, whereas patients with type B have two SLC7A9 mutations and finally patients with type AB have one mutation in each gene. Considering the population-specific distribution of mutations in disease, limited studies on the genetic bases of the cystinuria have been done in Middle East. This research presents the results of mutation analysis on patients with cystinuria in Iran. Methods: Thirty unrelated patients with cystinuria operated to remove kidney stones were screened by urologist .The patients were analyzed for mutation using amplification refractory mutation system (ARMS) and polymerase chain reaction-Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) methods. Findings: We found some variations including missense mutations, polymorphism and intron variant, but the most frequent mutations, M467T and also T216M and R333W, were not detected in our patients. Conclusion: Our research may confirm the ethnic distribution of mutations in cystinuria and this study can expand our concept of the genetic basis of cystinuria in Iranian patients.
- Published
- 2014
25. Evaluation of Measuring Radiation-Induced Apoptosis in Human T-Lymphocytes by Flow Cytometry as a Biological Dosimetry System
- Author
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Mohammad Bagher Tavakkoli, Majid Kheirollahi, Ali Kiani, Mohammad Kazemi, Leili Mohebat, Shagayegh Haghjooy Javanmard, and Mahnaz Roayaei
- Subjects
Apoptosis ,Flowcytometry ,T-cells ,Lymphocyte ,Biological dosimetry ,Radiation Apoptosis ,Radiation ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: In events such as a nuclear explosion or leakage of radioactive material from nuclear power dungeons or other events in nuclear medicine departments in hospitals, many people accidentally receive an unspecified amount of ionizing radiation. First step to treat is evaluation of radiation dose received by the victims. In such situation and in radiotherapy program, dosimetry is used for evaluation of treatment planning. Some measurable biological indexes used for evaluation of dose of radiation. Some measurable biological indexes can be used in biological dosimetry to measure the radiation dose and estimate the radiation effect. Methods: In this study, the test for biological dosimetry based on apoptosis induced by gamma radiation in peripheral blood T-lymphocytes was performed in 16 volunteers. The blood lymphocytes were isolated and cultured in RPMI (Roswell Park Memorial Institute) 1640 medium and then, were placed in 5% CO2 atmosphere at 37°C. Then, the samples were prepared from the culture medium and radiated with different doses of gamma radiation. Sample transferred to incubator again to measure their apoptosis. Radiation-induced apoptosis in the cell population was measured by flow cytometry using Annexin V + fluorescein isothiocyanate (FITC) and prodidium iodide (PI) stains. Findings: Radiation induced apoptosis was measureable with enough precision. But measured apoptosis depended on delay time after irradiation and protocole of flow cytometry. Conclusion: The results of this study show that it is possible to use radiation for measuring apoptosis as a biological dosimeter in a short time after radiation exposure in the events such as a nuclear explosion or leakage of radioactive material.
- Published
- 2014
26. Comparison of Inserted Mouse IP-10 Gene Copy Number in Helper-Dependent and Independent System Based on PiggyBac Transposition in Human Embryonic Kidney Cells
- Author
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Hadi Mirzapour, Arezo Karamzade, Hossein Khanahmad, Rasoul Salehi, and Majid Kheirollahi
- Subjects
Piggybac transposon ,Gene therapy ,Recombinant protein ,Transgene copy number ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: A major bottleneck in the production of recombinant proteins in conventional linear method is the heterogeneity in number of transgene copies in the genome of the host cell that lead to variable levels of transgene expression. Aside from the low efficiency of the random integration, other phenomena such as positional effect contribute to low efficiency of transgene expression. PiggyBac is a class of DNA transposons which can transpose through “cut and paste” mechanism in host genome. Some specific characteristic of this transposon makes it promise vector in gene transfer studies. High capacity of transgene transposition and flexibility in molecular engineering of transposase are characteristics of PiggyBac transposons that are important in recombinant protein and gene therapy approaches. The aim of this study was estimation of transgene copy number based on helper-dependent and independent PiggyBac transposition system in human embryonic kidney (HEK) cells. Methods: Plasmid containing interferon gamma inducible protein 10 (IP-10) coding sequence flanked by PiggyBac terminal repeat element and plasmid containing transposase system and a unit plasmid containing both transposae and IP-10 coding sequence were used for generating recombinant cells in helper-dependent and independent system, respectively. Human embryonic kidney cells were transfected by each group. After clonal selection, absolute quantitative real-time polymerase chain reaction was used for estimation of transgene copy number. Findings: Estimation of IP-10 copy number has revealed 5 and 2 copies per cell in helper-independent and dependent system, respectively. Conclusion: Here, we report activity of PiggyBac transposition in human embryonic kidney cell line. PiggyBac helper-independent and dependent system was used for generation of stable cell line producing mouse IP-10 protein and our data confirmed permanent expression of this transgene with the mean of about 5 transgene copies per each cell.
- Published
- 2014
27. Telomerase and Therapy of Brain Tumors
- Author
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Majid Kheirollahi, Roya Khajeh-Goodari, and Reza Ghavimi
- Subjects
Telomerase ,Therapy ,Brain tumors ,Medicine ,Medicine (General) ,R5-920 - Abstract
Telomere is a special structure protects the ends of human chromosomes to degrade. Telomere becomes shorter after each cycle of cell division. However, telomerase is an enzyme activated in cancer cells and germ lines rebuild telomere. However, apparently there is no correlation between telomere length and telomerase activity. The enzymatic activity of telomerase correlates with tumor malignancy. In general, telomerase activity and histological grade are too closely correlated and the results of studies indicate that telomerase activity may be an important malignancy marker in brain tumors. As a conclusion, we can say that activity of telomerase should be considered as a prognostic biological marker of response to treatment.
- Published
- 2014
28. مروری بر اسید نوکلئیک پپتیدی: ساختار، خصوصیات و کاربردها
- Author
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Aref Farrokhifard and Majid Kheirollahi
- Subjects
Peptide Nucleic Acids ,Structure ,Biochemical properties ,Biomedical applications ,Medicine ,Medicine (General) ,R5-920 - Abstract
چندین دهه است که موضوع آنالوگهای اسیدهای نوکلئیک توجه برخی دانشمندان علم بیولوژی را به خود معطوف نموده است. برخی از این مولکولهای صناعی به عنوان ابزارهای قدرتمندی در بیولوژی مولکولی و بیوتکنولوژی، مورد توجه ویژه قرار گرفتهاند. چهار دستهی عمدهی این آنالوگهای صناعی عبارت از زنونوکلئیک اسید (XNA یا Xeno nucleic acid)، مورفولینو (Morpholino) و اسید نوکلئیک قفل شده (LNA یا Locked nucleic acid) و نوکلئیک اسید پپتیدی (PNA یاPeptide nucleic acid) که دستهی چهارم این آنالوگها بود و در این میان، جایگاه برجستهای دارد. PNA، پلیمری است از واحدهای ان-آمینو اتیل گلایسین که به هر یک از این واحدها بازهای پورین/ پیریمیدین اتصال یافته است. این پلیمر، خصوصیات پپتیدها و اسیدهای نوکلئیک را توأمان دارد و قادر است به طور اختصاصی به نوکلئیک اسیدهای طبیعی یا PNAهای دیگر، هیبرید شود که این ویژگی و دیگر خصوصیات ویژهی این مولکول باعث به کارگیری آن در بسیاری از روشهای بیولوژی مولکولی در زمینهی تشخیص و درمان بیماریها شده است. در این مقاله، ساختار، خصوصیات بیوشیمیایی و کاربردهای زیست پزشکی PNA شرح داده میشود.
- Published
- 2014
29. Genetics Aspects of Male Infertility
- Author
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Arezoo Karamzade, Hadi Mirzapour, and Majid Kheirollahi
- Subjects
Infertility ,Spermatogenesis ,Chromosome abnormality ,Epigenetics ,Medicine ,Medicine (General) ,R5-920 - Abstract
Infertility is one of the most common reproductive disorders occurring in approximately 15% of the couples. Male factor accounts for about half of these cases. The causes of reproductive defects in infertile men are multifactorial and many environmental and genetic factors affect male infertility. Genetics factors cause an account for 10-15% of male infertility, including chromosomal aberrations and single gene mutations. The current review will focus on genetics aspect of male infertility, including chromosomal disorder, single gene mutation and polymorphism, role of mitochondrial DNA and microRNA. We also take a look at last reported new genes causes of infertility.
- Published
- 2013
30. ایجاد بانک تومور و چالشهای آن
- Author
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Majid Kheirollahi, Zahra Khalaj, Fatemeh Nazem-Roaia, Sepideh Dashti, Fariborz Khorvash, and Mohammad Kazemi
- Subjects
Tumor bank ,Challenges ,Cancer ,Biomarker ,Medicine ,Medicine (General) ,R5-920 - Abstract
سرطان یک اختلال چند عاملی میباشد که بررسی آنها نیازمند انجام مطالعات همه جانبه بر روی سلولها، DNA، RNA و پروتئینهای تومور میباشد. این نوع از مطالعات به نام Omics میباشند که شامل ژنومیکس و پروتئومیکس هستند. بانک تومور یک واژه است که به طور معمول برای جمعآوری، ذخیرهسازی و استفاده از بافت تازه در مقاصد تحقیقات زیست پزشکی سرطان استفاده میشود. اکثر بانکهای تومور به جمعآوری نمونههایی از بافت تومور میپردازند که نیازی به آن برای تشخیصهای پاتولوژیک بعد از جراحی و برداشتن تومور نیست. این بافت اغلب به منظور یخ بستن به سرعت در نیتروژن مایع قرار داده میشود یا این که ممکن است در محلولهای ثابتکننده نگهداری شود. اکثر مراکز سرطان دارای بانک توموری هستند که ذخیرهسازی نمونههای توموری از بیمار و بافت سالم مجاور آن را انجام میدهند. تغییر در روشهای تشخیص و شناسایی بیومارکرها نیازمند دسترسی به تعداد کافی از نمونهها دارد و فراهم نمودن یک بانک از تومورها یک قدم ضروری در این مورد است. سالیانه، دهها و شاید صدها عمل جراحی در کشور ما انجام میشود که گنج بزرگی از سلولهای سرطانی است و میتوان با جمعآوری آنها یک بانک تومور ایجاد نمود.
- Published
- 2013
31. The Role of Telomere in Cell; Telomere Dysfunction and Tumorigenesis
- Author
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Majid Kheirollahi, Mahsa Kolahdouz, Fatemeh Ahangari, Leila Koulivand, and Fariborz Khorvash
- Subjects
Medicine ,Medicine (General) ,R5-920 - Abstract
Telomeres consist of repetitive DNA sequences and a variety of non-nucleosomal proteins which are essential to survive chromosome. Telomeres protect the ends of chromosomes, but can also inhibit the expression of nearby genes, called telomere position effect. The telomeric cap is a dynamic structure between a fully capped closed and a partially uncapped or open conformation. The protection of chromosome termini from being sensed by the cell as broken DNA is an important function of the telomeres as the capping function. Functional telomeres have a special role in response to DNA damage. The presence of telomere and the length of telomere are two important determinants for binding of chromosomes to the nuclear envelope in meiosis. Future studies about the characteristics of epigenetic factors in telomere length will lead to a better understanding of telomere regulation and its role in human cancers. It seems that telomere dysfunction, rather than telomere length alone, may create insights not only into the pathogenesis, but could also have significant impact on the diagnosis of cancer. Keywords: Role, Telomere, Tumorigenesis, Telomere dysfunction
- Published
- 2013
32. Telomere Structure and Its Role in DNA Damage and Genetic Disorders
- Author
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Majid Kheirollahi and Leila Koulivand
- Subjects
Medicine ,Medicine (General) ,R5-920 - Abstract
Telomeres are special structures at the ends of chromosomes, especially in eukaryotes, that include repetitive sequences of deoxyribonucleic acid (DNA) and non-nucleosomal proteins. These structures are essential to protect chromosomes from recombination and degradation. Telomeres are gene-poor repetitive sequences, but they are close to the more gene-rich subtelomeric regions. Proteins associated with telomeres are able to interact directly with the TTAGGG repeats and also can bind to other factors to form large protein complexes. These proteins are involved in DNA repair and telomere stability. Therefore, defects in the synthesis of these proteins could induce imperfections in telomere maintenance and DNA repair; and accordingly, should cause a number of genetic syndromes. Keywords: Telomere, DNA damage, Genetic diseases
- Published
- 2012
33. The MTHFR C677T polymorphism influences the efficacy of folic acid supplementation on the nerve conduction studies in patients with diabetic polyneuropathy; A randomized, double blind, placebo-controlled study
- Author
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Tayebeh Mottaghi, Fariborz Khorvash, Majid Kheirollahi, Mohammadreza Maracy, and Gholamreza Askari
- Subjects
diabetic polyneuropathy ,folic acid ,methylenetetrahydrofolate reductase ,Medicine - Abstract
Background: Among patients with diabetic polyneuropathy, the status of folic acid, homocysteine, and nerve conduction studies (NCS) variations has been associated with methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms. The objective of the present study is to assess B9 vitamin supplementation associated with MTHRF C677T polymorphism can be effective on NCS variations in patients. Materials and Methods: This study is a randomized, double-blind, placebo-controlled study. Patients were randomly allocated to either intervention (1 mg of folic acid, n = 40) or placebo (n = 40) groups based on parallel group design. Blood samples were taken to determine the serum levels of folic acid and homocysteine. The NCS data were collected for the assessment of diabetic neuropathy. Genotyping was performed for C677T polymorphism of the MTHFR gene. Results: Four months after intervention, patients significantly observed change of serum folic acid and homocysteine levels based on C677T genotypes in the MTHFR gene. The amplitude of sensory peroneal nerve between intervention and placebo groups with CC genotype was significantly different (2.8 ± 1.6 vs. 1.9 ± 1.1). However, peak latency and amplitude of sensory sural nerve between CC (3.8 ± 1.8 vs. 4.0 ± 1.5 for peak latency and 3.5 ± 1.0 vs. 2.5 ± 1.0 for amplitude; and CT + TT genotypes (3.7 ± 1.7 vs. 3.9 ± 1.3 for peak latency and 3.2 ± 1.0 vs. 2.3 ± 1.1 for amplitude) were significant. Furthermore, significant difference for variables of motor tibial nerve and motor peroneal nerve amplitude was observed in different groups of MTHFR C677T genotypes (5.4 ± 2.9 vs. 4.6 ± 3.2 for onset-latency of tibial nerve between CC genotype; 4.8 ± 2.8 vs. 4.6 ± 3.2 for onset-latency of tibial nerve between CT + TT genotype; 0.6 ± 0.2 vs. 0.3 ± 0.1 for amplitude of tibial nerve between CC genotype; 0.5 ± 0.3 vs. 0.3 ± 0.2 for amplitude of tibial nerve between CT + TT genotype; 26.0 ± 13.3 vs. 23.2 ± 13.4 for velocity of tibial nerve between CC genotype; 26.0 ± 13.7 vs. 23.1 ± 9.6 for velocity of tibial nerve between CT + TT genotype; 1.6 ± 1.0 vs. 0.9 ± 0.7 for amplitude of peroneal nerve between CC genotype; 1.4 ± 0.7 vs. 0.9 ± 0.5 for amplitude of peroneal nerve between CT + TT genotype). Conclusion: The study determined that MTHFR C677T polymorphism effects the efficacy of folic acid supplementation on serum folic acid, homocysteine levels and some NCS parameters in diabetic polyneuropathy patients.
- Published
- 2019
- Full Text
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34. Targeting MCF-7 Cell Line by Listeriolysin O Pore Forming Toxin Fusion with AHNP Targeted Peptide
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Gholamreza Fotoohi-Ardakani, Majid Kheirollahi, Hossein Zarei Jaliani, Mohadese Noorian, and Hossein Ansariniyia
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Breast cancer ,listeriolysin O ,quick-change polymerase chain reaction ,tumor-targeting peptide ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background: Tumor-targeting peptides are attracting subjects in cancer therapy. These peptides, which are widely studied, deliver therapeutic agents to the specific sites of tumors. In this study, we produced a new form of recombinant listeriolysin O (LLO) with genetically fused Anti-HER2/neu peptide (AHNP) sequence adding to its C-terminal end. The aim of the study was to engineer this pore-forming toxin to make it much more specific to tumor cells. Materials and Method and Results: Two forms of the toxin (with and without peptide) were subcloned into a bacterial expression plasmid. Subcloning was performed using a polymerase chain reaction (PCR) product as a megaprimer in a quick-change PCR to introduce the whole insert gene into the expression plasmid. After expression of two recombinant forms of LLO in BL21 DE3 cells, purification was performed using Ni-NTA affinity column. MDA-MB-231 and MCF-7 cell lines (as negative and positive controls, respectively) were treated with both LLO toxins to evaluate their cytotoxicity and specificity. The IC50 of LLO on MDA-MB-231 and MCF-7 cells was 21 and 5 ng/ml, respectively. In addition, IC50 for the fusion AHNP-LLO toxin was 140 and 60 ng/ml, respectively. It was found that the cytotoxicity of the new engineered AHNP-LLO toxin has decreased by about 9x compared to the wild-type toxin and the specificity of the AHNP-LLO toxin has been also reduced. Conclusions: Results show that the C-terminal of the LLO should not be modified and it seems that N-terminal of the toxin should be preferred for engineering and adding peptide modules.
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- 2019
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35. Evaluation of miR-362 Expression in Astrocytoma of Human Brain Tumors
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Majid Kheirollahi, Mahdiye Moodi, Saeideh Ashouri, Parvaneh Nikpour, and Mohammad Kazemi
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Astrocytoma ,brain tumors ,expression ,miR-362 ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background: Patients affected by gliomas have a poor prognosis. Astrocytoma is a subtype of glioma. Identification of biomarkers could be an effective way to an early diagnosis of tumor or to distinguish more aggressive tumors that need more intensive therapy. In this study, we investigated whether the expression of miR-362 was increased or decreased in patients with different grades of astrocytoma. Materials and Methods: miR-362 expression was compared in 25 patients with astrocytoma with that of 4 normal nonneoplastic brain tissues. Results: In all tumor tissues, the expression of miR-362 was significantly decreased relative to its expression in normal brain tissues. However, there was no significant difference between miR-362 expressions in high and low grades of astrocytoma. Conclusions: In conclusion, miR-362 showed a down-regulation pattern in astrocytoma tissues that was different from the pattern obtained from previously published microarray studies.
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- 2017
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36. Report of SLC3A1/rBAT gene mutations in Iranian cystinuria patients: A direct sequencing study
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Samaneh Markazi, Majid Kheirollahi, Abbas Doosti, and Mehrdad Mohammadi
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Aminoaciduria ,cystinuria ,rBAT ,SLC3A1 ,transport ,Medicine - Abstract
Background: Considering a few studies on the genetic basis of the cystinuria in the Middle East and the population-specific distribution of mutations in the SLC3A1, we tried to find genetic variants in three exons (1, 3, and 8) of SLC3A1. Materials and Methods: In this study, exons 1, 3, and 8 of SLC3A1 gene of 25 unrelated cystinuria patients searched for genetic variations by polymerase chain reaction and sequencing. Results: There were five different variations in our studied population. We found one mutation in the SLC3A1 gene including missense variant M467K and identified three polymorphisms: nonsynonymous variant G38G, c. 610 + 169C>T and c. 610 + 147C>G within the SLC3A1 gene, and one new variant. Conclusion: Our results confirm that cystinuria is a heterogeneous disorder at the molecular level and more studies are needed to identify the distribution and frequency of mutations causing cystinuria in the Iranian population.
- Published
- 2017
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37. Simple and Easy to Perform Preimplantation Genetic Diagnosis for β-thalassemia Major Using Combination of Conventional and Fluorescent Polymerase Chain Reaction
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Rasoul Salehi, Sharifeh Khosravi, Mansour Salehi, Majid Kheirollahi, and Hossein Khanahmad
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β-thalassemia ,nested fluorescent polymerase chain reaction ,polymorphic markers ,preimplantation genetic diagnosis ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background: Thalassemias are the most common monogenic disorders in many countries throughout the world. The best practice to control the prevalence of the disease is prenatal diagnosis (PND) services. Extensive practicing of PND proved effective in reducing new cases but on the other side of this success high abortion rate is hided, which ethically unfair and for many couples, especially with a previous experience of a therapeutic abortion, or moral concerns, is not a suitable choice. Preimplantation genetic diagnosis (PGD) is a strong alternative to conventional PND. At present PGD is the only abortion free fetal diagnostic process. Considering the fact that there are more than 6000 single gene disorders affecting approximately 1 in 300 live-births, the medical need for PGD services is significant. Materials and Methods: In the present study development of a PGD protocol for a thalassemia trait couple using nested multiplex fluorescent polymerase chain reaction (PCR) for the combination of polymorphic linked short tandem repeat (STR) markers and thalassemia mutations is described. Restriction fragment length polymorphism used to discriminate between wild and mutated alleles. Results: In PGD clinical cycle, paternal and maternal alleles for D11S988 and D11S1338 STR markers were segregated as it was expected. PCR product for IVSII-1 mutation was subsequently digested with BtscI restriction enzyme to differentiate normal allele from the mutant allele. The mother's mutation, being a comparatively large deletion, was detectable through size differences on agarose gel. Conclusion: The optimized single cell protocol developed and evaluated in this study is a feasible approach for preimplantation diagnosis of β-thalassemia in our patients.
- Published
- 2017
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38. Assessment Effects of Resveratrol on Human Telomerase Reverse Transcriptase Messenger Ribonucleic Acid Transcript in Human Glioblastoma
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Azin Mirzazadeh, Majid Kheirollahi, Ehsan Farashahi, Fatemeh Sadeghian-Nodoushan, Mohammad Hasan Sheikhha, and Behrouz Aflatoonian
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Glioblastoma ,human telomerase reverse transcriptase messenger ribonucleic acid ,resveratrol ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background: Glioblastoma (GBM) is the most common and aggressive brain tumor, which has a poor prognosis despite the advent of different therapeutic strategies. There are numerous molecular biomarkers to contribute diagnosis, prognosis, and prediction of response to the current therapy in GBM. One of the most important markers that are potentially valuable is immortalization-specific or immortalization-associated marker named “hTERT messenger ribonucleic acid (mRNA)” the key subunit of telomerase enzyme, which is expressed in more than 85% of cancer cells, in spite of the majority of normal somatic cells. In this study, we investigated the effects of resveratrol (RSV) on this mRNA marker level, leading to cancer progression. Materials and Methods: U-87MG cell line was obtained from Pasteur Institute of Iran and treated with various concentrations of 0– 160 μg/mL of RSV and at different time points (24, 48, and 72 h). To evaluate viability of U-87MG cells, standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed. Real-time polymerase chain reaction (RT-PCR) was used for comparative and quantitative assessment of human telomerase reverse transcriptase (hTERT) mRNA copy number versus control– untreated group. Results: The results of our investigation suggested that RSV effectively inhibited cell growth and caused cell death in dose-dependent (P < 0.05) and not in time-dependent manner (P > 0.05), in vitro. Interestingly, quantitative RT-PCR analysis demonstrated that at half inhibition concentration, RSV dramatically decreased mRNA expression of hTERT, the catalytic subunit of telomerase enzyme, which leads to prevention of cell division and tumor progression. Conclusion: With regard to downregulation of this immortalization-associated marker, RSV may potentially be used as a therapeutic agent against GBM.
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- 2017
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39. Comparison of the Frequency of Y-short Tandem Repeats Markers between Sadat and Non-Sadat Populations in Isfahan Province of Iran
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Reihaneh Seyedebrahimi, Ebrahim Esfandiari, Bahman Rashidi, Rasoul Salehi, Ali Gholami Dahghi, Shahriar Dabiri, and Majid Kheirollahi
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Sadat ,short tandem repeat ,Y chromosome ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background: Y chromosome is one of the two sex chromosomes and is male specific. Due to limited genetic exchange, the main part of that is passed virtually unchanged from one generation to next generation. The short tandem repeats (STRs) are almost constant on chromosomes that make them as an appropriate factor for use in population genetic studies. In this study, we used the STRs of Y chromosome markers in Sadat families and comparison with other families was investigated. Materials and Methods: In this study, sampling was done from fifty unrelated males of Sadat families and fifty unrelated males of non-Sadat families. After the extraction of DNA from blood samples and primer design, polymerase chain reaction (PCR) was performed for each primer pairs separately. The PCR products were run on agarose gel that followed by running on polyacrylamide gel for better resolution. In addition, some sequenced samples were used as identified markers to determine the length of other alleles in polyacrylamide gel. Results: The survey of six STR in two case and control groups was carried out, and analysis revealed that the frequency of some alleles is different in case group compared to control group. Allele frequency of the markers DYS392, DYS393, DYS19, DYS390, DYS388, and DYS437 on the Y chromosome in Sadat families was quite different in comparison with other families. Conclusions: The reason for these differences in allele frequencies of the Sadat family in comparison with other families is having a common ancestor.
- Published
- 2017
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40. Genetic analysis of Iranian family with hereditary cardiac arrhythmias by next generation sequencing
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Marzieh Asadi, Roger Foo, Mohammad Reza Samienasab, Ahmad Reza Salehi, Majid Kheirollahi, Hossein Khanahmad, and Rasoul Salehi
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Atrioventricular block ,congenital long QT syndrome ,hereditary cardiac arrhythmias ,next generation sequencing ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background: Cardiac arrhythmias are responsible for several cases of syncope and sudden cardiac death annually worldwide. Due to overlapping clinical symptoms in some cardiac arrhythmias genetic studies would help to confirm the primary clinical diagnosis made on the basis of solely clinical findings. In addition clinical management of the patient, family screening and provide appropriate counseling and risk assessment for the family members are other advantages of genetic study. Materials and Methods: Totally nine patients from a family included in this study. The primary diagnosis on the basis of clinical findings was second-degree atrioventricular (AV) block for this family. Mutation in SCN5A gene is frequently reported for second-degree AV block and hence the gene was analyzed using whole gene sequencing but no mutation was detected. Subsequently, the samples were subjected to customized Ampliseq 77 gene panel using next generation sequencing to detect the underlying molecular defects. Results: We found c. 5570T>A missense mutation in ANK2 gene for this family. Based on the Online Mendelian Inheritance in Man, ANK2 gene and the mutation detected correspond to long QT syndrome type 4. Conclusion: This mutation, although already known in other populations, but is reported for the first time in Iranian patients with cardiac arrhythmias. As the case with this family, genetic analysis of patients with cardiac arrhythmias would be helpful in reassessment of clinical diagnosis and therefore would help for patients' management and in some cases re-evaluation of ongoing treatment may be needed.
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- 2016
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41. Effect of teicoplanin on the expression of c-myc and c-fos proto-oncogenes in MCF-7 breast cancer cell line
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Saeideh Ashouri, Maryam Hosseindokht Khujin, Mohammad Kazemi, and Majid Kheirollahi
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Breast cancer ,c-fos ,c-myc ,MCF-7 ,teicoplanin ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background: Teicoplanin is a member of vancomycin-ristocetin family of glycopeptide antibiotics. It mediated wound healing by increasing neovascularization possibly through activation of MAP kinase signaling pathway. The aim of this study is an evaluation of c-myc and c-fos genes expression after treatment of cells by teicoplanin and determines whether this glycopeptide antibiotic exerts its proliferation effects by influencing the expression of these genes. Hence, this study was designed to elucidate one possible mechanism underlying teicoplanin effects on cell proliferation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Materials and Methods: Breast cancer cell line, MCF-7, was cultured, and three different concentrations of teicoplanin were added to the plates. We measured the cell proliferation rate by MTT assay. After cell harvesting, total RNA was extracted to synthesize single-stranded cDNA. Real-time polymerase chain reaction was performed, and the data were analyzed. Results: It was observed that the level of c-fos and c-myc genes' expressions was decreased at all three different concentrations of teicoplanin. Conclusion: it could be concluded that although teicoplanin is considered as an enhancing cell growth and proliferation, but probably its effect is not through MAP kinase signaling pathway or perhaps even has inhibitory effect on the expression of some genes such as c-myc and c-fos in this pathway. Hence, the mechanism of action of teicoplanin for increasing cell propagation, through cell signaling pathways or chromosomal abnormalities, remains unclear, and further studies should be conducted.
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- 2016
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42. Existence of mutations in the homeodomain-encoding region of NKX2.5 gene in Iranian patients with tetralogy of Fallot
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Majid Kheirollahi, Fereshteh Khosravi, Saeideh Ashouri, and Alireza Ahmadi
- Subjects
Cardiac defect ,Iranian patient ,NKX2.5 gene ,tetralogy of Fallot (TOF) ,Medicine - Abstract
Background: Tetralogy of Fallot (TOF), the most common cyanotic heart defect and one of the most common congenital heart diseases, occurs mostly sporadically and nonsyndromically. The underlying molecular genetic mechanism is not known. Therefore, the existence of mutations in the homeodomain-encoding region of NKX2.5 gene in Iranian patients with tetralogy of Fallot is evaluated. Materials and Methods: In the present study, we analyzed the peripheral blood samples of27 patients in order to find any mutation in the 180 bp homeodomain-encoding region of NKX2.5 gene, which is known to be involved in heart development and diseases. DNA was extracted and all the samples were amplified by polymerase chain reaction (PCR) and sequenced. Results: Twenty-seven patients were included in the study. Twenty-five of them were infants and children (6 days to 11 years of age), one was a teenager (14-years of age), and another was a 33-year-old man [mean ± standard deviation (SD): 5.80 ± 3.90 years]. Thirteen patents were males (mean ± SD: 6.587077 ± 5.02 years) and 14 were females (mean ± SD: 5.0726 ± 2.81 years). One synonymous variant, i.e., c.543G>A was identified in one patient. Conclusion: Mutations in the homeodomain-encoding region of NKX2.5 gene may not have an outstanding role in etiology of tetralogy of Fallot patients in Iran.
- Published
- 2016
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43. Expression of prostaglandin I2 (prostacyclin) receptor in blood of migraine patients: A potential biomarker
- Author
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Majid Kheirollahi, Mohammad Kazemi, Gilda Amini, Fariborz Khorvash, Fatemeh Ahangari, Mahsa Kolahdouz, and Leila Koulivand
- Subjects
Biomarker ,expression ,migraine ,prostaglandin I2 ,receptor ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background: Migraine is the most common chronic neurological disorders that may be associated with vasodilatation. According to the role of prostaglandin I2 (prostacyclin) receptor (PTGIR) in migraine as a receptor, which acts in vasodilatation, we decided to study the changes of PTGIR expression in migraine patients in relation to a suitable control group. Materials and Methods: Extracted mRNA from lymphocytes of 50 cases and 50 controls was used to synthesize cDNA. Real-time polymerase chain reaction was performed, and the data were analyzed. Our results show that PTGIR mRNA expression in cases was significantly higher than the control group (P = 0.010). Results: In conclusion, mRNA expression of PTGIR in the blood of people with migraines could be considered as a biomarker. Conclusion: In addition, repression of PTGIR gene expression by methods such as using siRNA is probably suitable for therapy of migraine patients.
- Published
- 2015
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44. Annexin V FITC conjugated as a radiation toxicity indicator in lymphocytes following radiation overexposure in radiotherapy programs
- Author
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Mohammad Bagher Tavakoli, Majid Kheirollahi, Ali Kiani, Mohammad Kazemi, Shaghayegh Haghjooy Javanmard, and Leili Mohebat
- Subjects
Annexin V ,apoptosis ,flow cytometry ,phosphatidylserine ,radiotherapy ,toxicity ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background: Following human radiation exposure in hospital or accidents, dose assessments are of prime importance in radiation accidents. These issues are of continuing importance with respect to socioeconomic policy relating to the industrial and medical uses of ionizing radiation, and also for risk assessment among people who are occupationally exposed to low and/or high linear energy transfer (LET) radiation, such as astronauts, pilots, stewardesses, nuclear power plant workers, and victims of radiation accidents. Materials and Methods: In this study, an assay for assessing radiation dose based on the induction of apoptosis in human T-lymphocytes was done to examine T-lymphocyte cells isolated from the fresh blood of 16volunteers, cultured and exposed to gamma rays. Radiation-induced apoptosis (RIA) was assessed by flow cytometric identification of cells displaying apoptosis-associated DNA condensation. Results: Dose-response experiments showed that at 2Gy dose level of radiotherapy programs, the RIA frequency was significantly above control. Apoptotic levels significantly depend on the dose of radiation rather than the donor. Conclusion: The results demonstrate the potential use of this assay as a biological indicator of radiation toxicity, optimizing patient dose in radiotherapy and biological dosimetry process.
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- 2015
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45. Brain tumors: Special characters for research and banking
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Majid Kheirollahi, Sepideh Dashti, Zahra Khalaj, Fatemeh Nazemroaia, and Parvin Mahzouni
- Subjects
Banking ,brain ,tumor ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
A brain tumor is an intracranial neoplasm within the brain or in the central spinal canal. Primary malignant brain tumors affect about 200,000 people worldwide every year. Brain cells have special characters. Due to the specific properties of brain tumors, including epidemiology, growth, and division, investigation of brain tumors and the interpretation of results is not simple. Research to identify the genetic alterations of human tumors improves our knowledge of tumor biology, genetic interactions, progression, and preclinical therapeutic assessment. Obtaining data for prevention, diagnosis, and therapy requires sufficient samples, and brain tumors have a wide range. As a result, establishing the bank of brain tumors is very important and essential.
- Published
- 2015
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46. A Novel Biallelic Variant in CDH23 Gene in a Family with Atypical USH1D Manifestation: A Literature Review and Investigation of Genotype-Phenotype Correlation
- Author
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Erfan Khorram, Omid Iravani, Mehdi Khorrami, Masoomeh Amini, Sara Jahanian, Mohammad Hossein Nilforoush, Seyyed Reza Mousavi, Mahsa Ehsanifard, and Majid Kheirollahi
- Subjects
Speech and Hearing ,Otorhinolaryngology ,Physiology ,Sensory Systems - Abstract
Introduction: Usher syndrome (USH) is an autosomal recessive disorder that predominantly affects hearing, vision, and, in some cases, vestibular function. USH, according to the onset age, severity, and progression of symptoms, is categorized into four main types. In addition, there are a significant number of reports that patients’ manifestations deviate from canonical phenotypic criteria of main types of USH, which are named atypical USH. CDH23 is the second most common USH gene in which its defects result in USH1D, non-syndromic autosomal recessive deafness-12 (DFNB12), and in a few cases, atypical USH1D. While some studies have suggested that missense and truncating damaging variants in the CDH23 gene cause DFNB12 and USH1D, respectively, no genotype-phenotype correlation for atypical USH1D has been established. Methods: Using whole-exome sequencing, we studied an Iranian family with two affected siblings who manifested congenital bilateral hearing loss, late-onset nyctalopia, retinitis pigmentosa, and normal vestibular function, indicating that their clinical symptoms are consistent with USH2. Results: Whole-exome data analysis revealed a novel bi-allelic nonsense variant (c.6562G>T; p.Glu2188Ter) in the CDH23 gene, which was confirmed by Sanger sequencing. Surprisingly, CDH23 is a member of the USH1 genes; therefore, our patients suffered from atypical USH1D. Also, by conducting a literature review, we provided a clinical and mutational profile of all reported patients with atypical manifestations or those who refuted the claimed genotype-phenotype correlation. Conclusion: By reporting a novel damaging variant, we expand the mutational spectrum of the CDH23 gene that leads to atypical USH1D. Also, reviewing the literature shows that, contrary to previous claims, different genotypes occur in the CDH23 gene allelic disorders, and there is no clear-cut genotype-phenotype correlation.
- Published
- 2023
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47. Griscelli syndrome type 1: a novel pathogenic variant, and review of literature
- Author
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Erfan Khorram, Mohammad Amin Tabatabaiefar, Omid Yaghini, Mehdi Khorrami, Vida Yazdani, Fatemeh Fakhr, Masoomeh Amini, and Majid Kheirollahi
- Subjects
Genetics ,General Medicine ,Molecular Biology - Published
- 2023
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48. A Chronic Autochthonous Fifth Clade Case of Candida auris Otomycosis in Iran
- Author
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Majid Kheirollahi, Hossein Mirhendi, Jacques F. Meis, Mahboobeh Madani, Hamid Badali, Hamed Fakhim, Fatemeh Safari, and Amir-Abbas Kargoshaie
- Subjects
Antifungal Agents ,SARS-CoV-2 ,Hospitalized patients ,Veterinary (miscellaneous) ,Nosocomial pathogens ,Candidiasis ,Otomycosis ,COVID-19 ,Candida auris ,Iran ,Biology ,medicine.disease ,Applied Microbiology and Biotechnology ,Microbiology ,High morbidity ,medicine ,Humans ,Colonization ,Clade ,Agronomy and Crop Science ,Genotyping ,Candida - Abstract
Candida auris, a multidrug-resistant nosocomial pathogen, has emerged globally with high morbidity and mortality among immunocompromised individuals and COVID19 hospitalized patients. Five major clades of C. auris have been previously described. The fifth clade is exclusively found in Iran where C. auris isolates are genetically distinct from other clades by > 200,000 single-nucleotide polymorphisms. The origin of C. auris remains unclear, and limited clinical data are available at present regarding clade V infection or colonization. Herein, another case of otomycosis in Iran caused by an isolate of C. auris belonging to the fifth clade is reported. Genotyping revealed that the obtained C. auris isolate from Isfahan clustered with earlier clade V isolates from Babol, cities around 600 km separated, which indicates that C. auris clade V is established in Iran. C. auris is thought to exist more commonly in Iran, given that limited diagnostic capacity in the country has probably curbed the identification of more C. auris cases. Therefore, surveillance of the environment, patients and healthcare facilities in different geographical regions in Iran is urgently required.
- Published
- 2021
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49. Anterior cruciate ligament injury and its postoperative outcomes are not associated with polymorphism in COL1A1 rs1107946 (G/T): a case–control study in the Middle East elite athletes
- Author
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Majid Kheirollahi, SM Javad Mortazavi, Peyman Mirghaderi, Hossein Akbari-Aghdam, and Maryam Salimi
- Subjects
Male ,Collagen Type I, alpha 1 Chain ,Athletes ,Anterior Cruciate Ligament Injuries ,Case-Control Studies ,Humans ,Orthopedics and Sports Medicine ,Surgery ,Polymorphism, Single Nucleotide - Abstract
Background It is unclear what role COL1A1 polymorphisms play in anterior cruciate ligament (ACL) injury pathophysiology. The present study investigated the relationship between COL1A1-1997 guanine (G)/thymine (T) (rs1107946) polymorphism and ACL injury. Moreover, the possible effect of this polymorphism on the postoperative outcomes of ACL reconstruction surgery was evaluated. Methods This prospective case–control study was performed on 200 young professional men with an ACL tear who underwent arthroscopic ACL reconstruction surgery. Moreover, 200 healthy athletes without a history of tendon or ligament injury who were matched with the case group were selected as the control group. DNA was extracted from the leukocytes of participants, and the desired allele was genotyped. Clinical outcomes were collected for the case group before and one year after surgery. Results The genotype distribution was in accordance with the Hardy–Weinberg principle. In the ACL injury group, the G allele frequency was non-significantly higher than the healthy controls, with an odds ratio [95% CI] of 1.08 [0.79–1.47] (P = 64). We did not find a significant difference between the genotype of individuals—GG, GT, and TT—in the case and control groups (P > 0.05). Clinical outcomes of the ACL tear group were significantly improved in terms of preoperative values. However, none of them were significantly different between the three genotypes (GG, GT, and TT). Conclusion According to the findings of the present investigation, single-nucleotide polymorphism (SNP) at COL1A1 rs1107946 (G/T) was not a predisposing genetic factor for ACL injury in a young professional male athlete population in the Middle East. Furthermore, patients' responses to treatment were not different between distinct genotypes. Level of evidence III.
- Published
- 2022
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50. Molecular investigation of the incidence of Candida auris infections at selected hospitals in Iran
- Author
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Fatemeh Safari, Mahboobeh Madani, Majid Kheirollahi, and Hossein Mirhendi
- Subjects
Antifungal Agents ,Incidence ,Dermatology ,General Medicine ,Saccharomyces cerevisiae ,Microbial Sensitivity Tests ,Candida auris ,Iran ,Real-Time Polymerase Chain Reaction ,Hospitals ,Infectious Diseases ,Humans ,Candidiasis, Invasive ,Candida - Abstract
The accurate occurrence rate of C. auris infections is still not clear, mainly due to the defects in detection and identification tools routinely used. In this study, we used conventional PCR and real-time PCR assays for sensitive and specific detection/identification of C. auris from either yeast isolates or clinical specimens collected from various patients in different parts of Iran. Our survey is the first large-scale study rating the incidence of C. auris infections in Iran.A total of 439 yeast isolates and 590 clinical specimens were screened by specific C. auris-PCR, targeting the ITS region. The validity of positive samples was assessed by sequencing.Four out of 590 clinical specimens (0.68%) were positive by conventional PCR, while in real-time PCR performed on 100 clinical samples, including those four samples positive in conventional samples, 6 samples were positive. A complete agreement of the identification of positive cases with sequencing results was documented. Among 439 culture isolates, none was positive for C. auris. After following up and resampling of the patients with positive PCR, only one specimen showed positive culture for C. auris, which was confirmed by sequencing.C. auris is not a common cause of systemic or superficial fungal infections in Iran, and a few detected positive cases can be considered as a commensal, coloniser or infecting yeast which may potentially emerge in some clinical and therapeutical conditions. Mycological and phenotypical assays are not sensitive approaches for isolation/identification of C. auris, unless a specific and sensitive molecular-based method is applied.
- Published
- 2022
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