Publications by authors named "Mir Davood Omrani"

190 Publications

SARS-CoV-2 presented moderately during two episodes of the infection with lack of antibody responses.

Virus Res 2021 Apr 6;299:198421. Epub 2021 Apr 6.

Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

The world has gone through the critical phase of SARS-CoV-2 crisis caused by the new variants of the virus. The globally concerted effort to characterize viral genomic mutations across different clades has revealed several changes in the coding and also non-coding regions which might lead to a violent presentation or re-infection occurrence. Here, we studied a COVID-19 subject who represented the symptoms following the full recovery of the first infection. COVID-19 specific IgM and IgG were evaluated in both steps. The viral samples from oropharyngeal/nasopharyngeal were subjected to RT-PCR and full sequencing was done in both incidences. The sequencing data was fully investigated with the reference sequence of SARS-CoV-2 and the changes were detected. The obtained data is in favor of re-infection with 128 days of interval. SARS-CoV-2 presented more severely in the second episode of the disease and the specific antibodies against COVID-19 were not detectable. Both infections were caused by the same clade 20G, however, the mutation rates were higher in the second incidence including 10 nucleotide substitutions which had rarely been reported before. In the present study, the nucleotide mutations in various regions of the viral genome have been presented. The re-infection could have significant effect on clinical implications as well as vaccination.
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http://dx.doi.org/10.1016/j.virusres.2021.198421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022517PMC
April 2021

Autologous Hematopoietic Stem Cell Transplantation (AHSCT): An Evolving Treatment Avenue in Multiple Sclerosis.

Biologics 2021 2;15:53-59. Epub 2021 Mar 2.

Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Autologous hematopoietic stem cell transplantation (AHSCT) is considered as the novel approach to improve multiple sclerosis (MS) patients with disease-modifying therapies (DMTs)-resistance. The results obtained from different studies indicate that AHSCT increases the life quality of MS patients. Several factors are known to be influenced on the successful rate of AHSCT in patients with MS. The individuals aged <40 years with a short duration of MS disease have been demonstrated to show a better response to AHSCT administration. Furthermore, this treatment approach was more effective in relapsing remitting MS (RRMS) patients than progressive MS (PMS). Different clinical trials revealed that AHSCT with a low density conditioning regimen could be suggested as a suitable candidate approach in the management of MS. Several molecular and cellular mechanisms are known to be involved in the resetting of the immune system following the AHSCT infusion in MS patients. These mechanisms play a role in the depletion of auto-reactive lymphocytes and immune system renewal. In the present review, we discuss different clinical and molecular aspects of AHSCT application in the alleviation of MS symptoms.
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http://dx.doi.org/10.2147/BTT.S267277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936693PMC
March 2021

Altered expression of lncRNAs in autism spectrum disorder.

Metab Brain Dis 2021 Jun 15;36(5):983-990. Epub 2021 Feb 15.

Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs (lncRNAs) have been recognized as an important epigenetic factor in the evolution of neuropsychiatric conditions. We have selected five lncRNAs (DISC2, PRKAR2A-AS1, LOC105375675, LRRC2-AS1, and LOC101928237) to measure their expression in blood samples of children with autism spectrum disorder (ASD) versus children with normal development. Expressions of DISC2, PRKAR2A-AS1 and LOC101928237 have been enhanced in ASD cases compared with healthy children (Posterior Beta = 2.508, P value<0.0001; Posterior Beta = 2.793, P value = 0.014 and Posterior Beta = 1.646, P value <0.0001, respectively). On the other hand, expression of LRRC2-AS1 has been lower in ASD patients compared with controls (Posterior Beta = -3.781, P value<0.0001). Remarkably, expression of DISC2 and PRKAR2A-AS1 have been lower in girls compared with boys (Posterior Beta = -0.982, P value<0.0001 and Posterior Beta = -0.135, P value<0.0001, respectively). In addition, expression of DISC2 has been lower in ASD cases aged more than 6 compared with those aged less than 6 years (Posterior Beta = -0.876, P value = 0.003). DISC2, LOC101928237, LRRC2-AS1, and PRKAR2A-AS1 had the area under curve (AUC) values of 0.76, 0.90, 0.92, and 0.79 in distinguishing between ASD and healthy children. Expression levels of none of DISC2, LOC101928237, LOC105375675, LRRC2-AS1, and PRKAR2A-AS1 were correlated with age of ASD cases or healthy controls. A significant correlation was detected between expressions of DISC2 and PRKAR2A-AS1. There were inverse correlations between the following pairs of lncRNAs: DISC2/LRRC2-AS1, DISC2/LOC101928237, LRRC2-AS1/PRKAR2A-AS1, LOC101928237/LRRC2-AS1, and LOC101928237 /LOC105375675. We conclude that DISC2, LOC101928237, LRRC2-AS1, and PRKAR2A-AS1 might be used as potential markers for this condition.
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http://dx.doi.org/10.1007/s11011-021-00681-zDOI Listing
June 2021

Expression of T helper 1-associated lncRNAs in breast cancer.

Exp Mol Pathol 2021 04 12;119:104619. Epub 2021 Feb 12.

Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Interferon gamma (IFN-gamma)-associated genes participate in the pathobiology of cancer and response of patients to immunotherapeutic modalities. This cytokine is regarded as a hallmark of T helper 1 type responses. In the current study, we estimated expression of this gene and a number of genes/ long non-coding RNAs (IFNG.AS001 and IFNG.AS003, AC007278.2 and AC007278.3 and IL18R1) which are encoded from proximal genomic regions to IFNG in a larger cohort of Iranian patients with breast cancer. Both IFNG.AS001 and IFNG.AS003 were up-regulated in breast cancer tissues compared with nearby non-cancerous tissues (Ratios of Mean Expressions = 5.62 and 5.88, P values = 1.28E-03 and 1.47E-03, respectively). Finally, IL18R1 was over-expressed in breast cancer tissues compared with nearby non-cancerous tissues (Ratio of Mean Expressions = 9.43, P values = 3.14E-03). Expression of AC007278.3 was associated with breast feeding duration (P value = 2.65E-02). Positive significant correlations were detected between expression levels of all genes in both sets of samples. The most robust correlation in the nearby non-cancerous tissues was detected between IFNG-AS003 and AC007278.2 (r = 088, P value = 5.19E-23). In the tumoral tissues, the strongest correlation was found between IFNG-AS001 and IL18R1 (r = 0.86, P value = 3.79E-15). AC007278.3 had the best diagnostic power among the assessed genes (AUC = 0.82). Both AC007278.2 and AC007278.3 were reported to be specific markers for differentiation of tumor tissues from nearby non-cancerous tissues. Combination of expression levels of genes increased specificity, sensitivity and AUC values to 0.97, 0.89 and 0.95, respectively. The current study accentuates the role of IFNG-associated genes in the pathogenesis of breast cancer.
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http://dx.doi.org/10.1016/j.yexmp.2021.104619DOI Listing
April 2021

Preclinical studies and clinical trials with mesenchymal stem cell for demyelinating diseases: A systematic review.

Curr Stem Cell Res Ther 2021 Feb 8. Epub 2021 Feb 8.

Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran. Iran.

Aim: Different studies have been performed to investigate the stem cell administration as promising tool for recovery of injured tissue in Multiple Sclerosis (MS), the most common demyelinating disease.

Methods: In the present systematic review, the electronic databases of PubMed and ScienceDirect were searched to screen English language studies published until April 2020.

Results: The results obtained from experimental autoimmune encephalomyelitis (EAE) animals revealed that modified mesenchymal stem cells (MSCs) transplantation was associated with remyelination, inflammation suppression and oligodendrocyte precursor cells regeneration. Clinical trials indicated that 70% of the patients with MS showed disease stabilization following MSCs administration.

Conclusion: Although MSC therapy has showed to be effective in the improvement of some patients with MS, designing of larger placebo-controlled clinical trials with MSCs expressing immune-regulators or MSCs-exosomes may provide the novel viewpoint in the treatment of MS.
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http://dx.doi.org/10.2174/1574888X16666210208162318DOI Listing
February 2021

Investigating the CYP2B6 rs3745274 and rs3211371 polymorphisms in Methadone-Responder and Non-Responder Addicts in Iran.

Iran Biomed J 2021 02 6;25(3):220-5. Epub 2021 Feb 6.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Methadone therapy is a major protocol in opioid addiction cases in many health care systems. Population-based studies have shown that in addicted people, the genetic profile affects their response to methadone therapy. Therefore, this study designed to examine the frequency of two SNPs of the CYP2B6 gene (rs3745274 and rs3211371) in addicted cases in two methadone-responders and methadone non-responders groups.

Methods: A total of 199 opioid-addicted individuals and 117 unaffected control subjects were genotyped for rs3745274 and rs3211371 polymorphisms of the CYP2B6 gene using the tetra-primer amplification refractory mutation system-polymerase chain reaction.

Results: Results of this study revealed the significant association of rs3745274 GG (p < 0.001; OR = 0.027; 95% CI = 0.14-0.49) and GT (p < 0.001; OR = 4.04; 95% CI = 2.26-7.21) genotypes with the risk of addiction in methadone-responders. Also, a significant association between rs3745274 GG (p < 0.001; OR = 0.28; 95% CI = 0.15-0.51) and GT (p < 0.001; OR = 5.1; 95% CI = 2.8-5.28) genotypes and addiction relapse was found in methadone non-responders.

Conclusion: Based on our findings, we can conclude that rs3745274 variant of CYP2B6 gene could serve as a potential biomarker, to evaluate the prognosis of addicted people fate under treatment with methadone.
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http://dx.doi.org/10.29252/ibj.25.3.220DOI Listing
February 2021

Expression of BDNF-Associated lncRNAs in Treatment-Resistant Schizophrenia Patients.

J Mol Neurosci 2021 Jan 5. Epub 2021 Jan 5.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs (lncRNAs) play a decisive role in the development of the central nervous system and modulation, differentiation, and function of neurons. Thus, any abnormal pattern of expression of these transcripts might alter normal development leading to neuropsychiatric disorders. In this regard, transcripts of brain-derived neurotrophic factor (BDNF) and four BDNF-associated lncRNAs (BDNF-AS, MIR137HG, MIAT, and PNKY) were evaluated in the peripheral blood of schizophrenia (SCZ) patients as well as normal subjects. The results indicated that the relative expression (RE) of PNKY was higher in SCZ patients as compared with controls (posterior beta of RE = 2.605, P value = 0.006) and in female patients compared with female controls (posterior beta of RE = 2.831, P value < 0.0001). BDNF expression was also higher in SCZ patients when compared with controls (posterior beta of RE = 0.64, P value < 0.036). Finally, a correlation was detected between the disease status and gender in terms of BDNF-AS expression (P value = 0.026). An inverse correlation was also found between levels of PNKY and age in the control group (r = - 0.30, P value < 0.0001). Expressions of BDNF and all lncRNAs were correlated with each other in both patients and controls. PNKY had the best diagnostic power among all assessed genes in the identification of disease status (area under curve = 0.78). BDNF, BDNF-AS, MIR137HG, and MIAT genes could discriminate SCZ patients from normal subjects with diagnostic power of 71%, 72%, 67%, and 68%, respectively. The current investigation suggests the possibility of the application of transcript levels of lncRNAs as an SCZ diagnostic marker. However, it warrants further studies in larger sample sizes.
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http://dx.doi.org/10.1007/s12031-020-01772-9DOI Listing
January 2021

Clinical and Genetic Characteristics of Splicing Variant in CYP27A1 in an Iranian Family with Cerebrotendinous Xanthomatosis.

Iran Biomed J 2021 03 1;25(2):132-9. Epub 2021 Mar 1.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Cerebrotendinous xanthomatosis (CTX) is a rare congenital lipid-storage disorder, leading to a progressive multisystem disease. CTX with autosomal recessive inheritance is caused by a defect in the CYP27A1 gene. Chronic diarrhea, tendon xanthomas, neurologic impairment, and bilateral cataracts are common symptoms of the disease.

Methods: Three affected siblings with an initial diagnosis of non-syndromic intellectual disability were recruited for further molecular investigations. To identify the possible genetic cause(s), whole exome sequencing was performed on the proband. Sanger sequencing was applied to confirm the final variant. The clinical and molecular genetic features of the three siblings from the new CTX family and other patients with the same mutations, as previously reported, were analyzed. The CYP27A1 gene was also studied for the number of pathogenic variants and their location.

Results: We found a homozygous splicing mutation, NM_000784: exon6: c.1184+1G>A, in CYP27A1 gene, which was confirmed by Sanger sequencing. Among the detected pathogenic variants, the splice site mutation had the highest prevalence, and the mutations were mostly found in exon 4.

Conclusion: This study is the first to report the c.1184+1G>A mutation in Iran. Our findings highlight the other feature of the disease, which is the lack of relationship between phenotype and genotype. Due to nonspecific symptoms and delay in diagnosis, CYP27A1 genetic analysis should be the definitive method for CTX diagnosis.
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http://dx.doi.org/10.29252/ibj.25.2.132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921520PMC
March 2021

Opposite trends of GAS6 and GAS6-AS expressions in breast cancer tissues.

Exp Mol Pathol 2021 02 24;118:104600. Epub 2020 Dec 24.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Growth arrest-specific gene 6 (GAS6) is a growth factor-like cytokine whose function is related with vitamin K. This protein interacts with receptor tyrosine kinase proteins such as Tyro3, Axl, and TAM Receptor family, therefore affecting the tumorigenic processes via different mechanisms. GAS6-antisense 1 (GAS6-AS1) is a long non-coding RNAs (lncRNAs) that is transcribed from a genomic regions nearby GAS6. This lncRNA is also implicated in the pathobiology of cancer. We intended to judge the role of GAS6 and GAS6-AS1 in the pathogenesis of breast cancer through appraisal of their expression levels in breast cancer tissues and their paired neighboring non-cancerous samples. Expression of GAS6 was up-regulated in breast cancer tissues compared with neighboring tissues (Ratio of Mean Expressions = 2.18, P value = 4.98E-02). On the other hand, expression of GAS6-AS1 was down-regulated in breast tumor tissues compared with controls (Ratio of Mean Expressions = 0.37, P value = 4.26E-03). There were substantial correlations between expression levels GAS6 and GAS6-AS1 in non-cancerous tissues (r = 0.74, P value = 1.47e-13) and cancer tissues (r = 0.85, P value = 2.28e-20). Expression of GAS6-AS was associated with progesterone receptor status (P value = 1.36E-02). However, expressions of this gene and the sense transcript were not linked with any other clinical or demographic variable. Taken together, GAS6 and GAS6-AS1 might partake in the development of breast cancer.
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http://dx.doi.org/10.1016/j.yexmp.2020.104600DOI Listing
February 2021

A Single Nucleotide Polymorphism Within Molybdenum Cofactor Sulfurase Gene Is Associated With Neuropsychiatric Conditions.

Front Mol Biosci 2020 24;7:540375. Epub 2020 Sep 24.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Molybdenum cofactor sulfurase (MOCOS) is an enzyme participating in purine metabolism. The aim of current study was to evaluate the role of a single nucleotide polymorphism (SNP) in the coding gene (rs594445) in mood disorders and methamphetamine addiction.

Methods: This SNP was genotyped in 200 persons with methamphetamine addiction, 85 patients with bipolar disorder 1 (BP1), 78 patients with BP2, 33 patients with major depressive disorder (MDD) and 200 age-/sex-matched normal subjects using the tetra-primer amplification-refractory mutation system (ARMS)-PCR technique.

Results: The rs594445 was associated with methamphetamine addiction in co-dominant model [A/A vs C/C: OR (95% CI) = 0.466 (0.252-0.864), -value = 0.014; C/A vs C/C: OR (95% CI) = 0.641 (0.418-0.981), -value = 0.04]. This SNP was also associated with this trait in dominant model [OR (95% CI) = 0.591 (0.398-0.879), -value = 0.009]. The A allele of rs594445 had a protective role against methamphetamine addiction [A vs C: OR (95% CI) = 0.645 (0.48-0.866), -value = 0.004]. The rs594445 was associated with BP1 in co-dominant model [C/A vs C/C: OR (95% CI) = 0.423 (0.230-0.778), -value = 0.005]. However, the associations were insignificant in other inheritance models.

Conclusion: Finally, there were no significant associations between the mentioned SNP and risk of BP2 or MDD in any inheritance model. The present project highlights the role rs594445 in two psychiatric conditions and implies the presence of common genetic factors for these disorders.
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http://dx.doi.org/10.3389/fmolb.2020.540375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542180PMC
September 2020

Non-coding RNAs and type 2 diabetes mellitus.

Arch Physiol Biochem 2020 Nov 6:1-10. Epub 2020 Nov 6.

Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Type 2 diabetes mellitus (T2DM) is a worldwide disease with rapidly increasing prevalence. This complex disorder caused by interplay between genetic predisposition factors, early developmental elements, diet and inactive lifestyle. Several researches have shown impact of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the pathogenesis of this disorder. Several miRNAs such as miR-126, miR-222-3p, miR-182, let-7b-5p, and miR-1-3p have been down-regulated in different biological sources of patients with T2DM. Some other miRNAs including miR-21, miR-30d, miR-148a-3p, miR-146b and miR-486 have the opposite trends. In addition, a number of lncRNAs such as LY86-AS, HCG27_201, VIM-AS1, CTBP1-AS2, CASC2, GAS5, LINC-PINT, and MALAT1 have been altered in the peripheral blood, serum samples or tissues obtained from patients with T2DM. Taken together, both miRNAs and lncRNAs contribute to the development of T2DM and might be applied as markers or therapeutic molecules for this disorder.
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http://dx.doi.org/10.1080/13813455.2020.1843498DOI Listing
November 2020

The genetic basis for the inverse relationship between rheumatoid arthritis and schizophrenia.

Mol Genet Genomic Med 2020 11 23;8(11):e1483. Epub 2020 Sep 23.

Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Introduction: Rheumatoid arthritis is a common autoimmune disease and schizophrenia is a relatively common and debilitating neurological disorder. There are several common features between rheumatoid arthritis and schizophrenia. The inverse relationship between rheumatoid arthritis and schizophrenia has been replicated in several studies. Despite evidence for an inverse epidemiological relationship and negative correlations for risk between rheumatoid arthritis and schizophrenia, there are no biological data that directly support this inverse relationship.

Materials And Methods': We meta-analyzed the genome-wide association studies to investigate the shared association loci between rheumatoid arthritis and schizophrenia at the genome-wide scale. Rheumatoid arthritis- and schizophrenia-associated loci in most recent genome-wide association studies of rheumatoid arthritis and schizophrenia were tested. Genetic risk score analysis was also conducted to investigate the collective contribution of schizophrenia risk loci to rheumatoid arthritis risk.

Results: Rheumatoid arthritis and schizophrenia meta-genome-wide association study showed a significant peak at the major histocompatibility complex locus on chromosome 6 in both rheumatoid arthritis-schizophrenia meta-genome-wide association study and inverted meta-genome-wide association study datasets. Testing rheumatoid arthritis- and schizophrenia-associated loci outside the human leukocyte antigen region showed no association with both rheumatoid arthritis and schizophrenia at a genome-wide level of significance. Weighted genetic risk scores showed no evidence for a statistically significant association between rheumatoid arthritis and schizophrenia.

Conclusion: The finding of our study is consistent with the role of the major histocompatibility complex locus in the genetic correlation between rheumatoid arthritis and schizophrenia, and suggests that either schizophrenia has an autoimmune basis and/or rheumatoid arthritis has an active neurological component.
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http://dx.doi.org/10.1002/mgg3.1483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667353PMC
November 2020

Expression Analysis of Long Non-coding RNA Lnc-DC in HLA-DRB1*15:01-Negative Patients with Multiple Sclerosis: A Probable Cause for Gender Differences in Multiple Sclerosis Susceptibility?

J Mol Neurosci 2021 Apr 19;71(4):821-825. Epub 2020 Sep 19.

Molecular Medicine Department, Biotechnology Research Center, Pasteure Institute of Iran, Tehran, Iran.

Multiple sclerosis is a disease that affects male and female patients differently. Several studies have been performed to explain the gender differences in MS susceptibility, but the genetic causes underlying gender differences remain unknown. The association between multiple sclerosis and the HLA-DRB1*15:01 haplotype has been confirmed to be female-specific. We hypothesized other immunological components such as lnc-DC may be gender-specific among multiple sclerosis patients, especially when MS patients are negative for the HLA-DRB1*15:01 allele. Therefore, the current study, considering the results of previous studies, aimed to evaluate the expression level of the lnc-DC gene in HLA-DRB1*15:01-negative female patients with relapsing remitting MS (RRMS). A total of 50 MS female patients and 50 female healthy controls were enrolled in this observational case-control study. HLA-DRB1*15:01, as a critical risk factor for MS, was ruled out in all patients. The peripheral blood mononuclear cells were obtained from all patients and total RNA was isolated and cDNA synthesis was carried out. The gene expression of lnc-DC was evaluated by real-time quantitative PCR. Our results have shown that lnc-DC expression level was significantly higher in total MS female patients compared with female controls (P = 0.0044). In addition, the correlation between lnc-DC with disease duration, EDSS, and age at onset did not reach a statistical significance in our study (r = 0.0336, P = 0.817; r = 0.0914, P = 0.5278 and r = 0.0743, P = 0.6083, respectively). Our results give further evidence that lnc-DC may play a gender-dependent role in MS pathogenesis.
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http://dx.doi.org/10.1007/s12031-020-01704-7DOI Listing
April 2021

Peripheral Blood Mononuclear Cells Expression Levels of miR-196a and miR-100 in Coronary Artery Disease Patients.

Immunol Invest 2020 Sep 15:1-11. Epub 2020 Sep 15.

Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

As a chronic inflammatory disease, coronary artery disease (CAD) is a common cause of death worldwide. Dysregulation of microRNA expression levels in peripheral blood mononuclear cells (PBMCs) may contribute to CAD and serve as a potential diagnostic biomarker. Here, we evaluated PBMC expression of two CAD-related inflammatory miRNAs, miR-196a and miR-100, in PBMCs of CAD patients with significant stenosis (CAD, n: 72), patients with insignificant coronary stenosis (ICAD, n: 30), and controls (n: 74) and checked whether they can segregate study groups. MiRNA expression was evaluated using the standard stem-loop RT-qPCR method. MiR-196a expression was downregulated in ICAD compared to CADs and healthy groups. MiR100 expression levels were not different between groups. The receiver operating characteristic (ROC) curve analysis acquainted that miR-196a expression levels in PBMC could segregate CAD individuals or any of its clinical manifestations (i.e. unstable angina, stable angina, acute myocardial infarction) from ICADs. In conclusion, this study reported a distinct miR-196a expression pattern in PBMCs of all patient groups and recommended a biomarker potential for miR-196a in discriminating ICADs from CADs or healthy controls.
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http://dx.doi.org/10.1080/08820139.2020.1791177DOI Listing
September 2020

Peripheral Blood Mononuclear Cells Expression Levels of miR-196a and miR-100 in Coronary Artery Disease Patients.

Immunol Invest 2020 Sep 15:1-11. Epub 2020 Sep 15.

Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

As a chronic inflammatory disease, coronary artery disease (CAD) is a common cause of death worldwide. Dysregulation of microRNA expression levels in peripheral blood mononuclear cells (PBMCs) may contribute to CAD and serve as a potential diagnostic biomarker. Here, we evaluated PBMC expression of two CAD-related inflammatory miRNAs, miR-196a and miR-100, in PBMCs of CAD patients with significant stenosis (CAD, n: 72), patients with insignificant coronary stenosis (ICAD, n: 30), and controls (n: 74) and checked whether they can segregate study groups. MiRNA expression was evaluated using the standard stem-loop RT-qPCR method. MiR-196a expression was downregulated in ICAD compared to CADs and healthy groups. MiR100 expression levels were not different between groups. The receiver operating characteristic (ROC) curve analysis acquainted that miR-196a expression levels in PBMC could segregate CAD individuals or any of its clinical manifestations (i.e. unstable angina, stable angina, acute myocardial infarction) from ICADs. In conclusion, this study reported a distinct miR-196a expression pattern in PBMCs of all patient groups and recommended a biomarker potential for miR-196a in discriminating ICADs from CADs or healthy controls.
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http://dx.doi.org/10.1080/08820139.2020.1791177DOI Listing
September 2020

Expression profile of microRNAs in bladder cancer and their application as biomarkers.

Biomed Pharmacother 2020 Nov 2;131:110703. Epub 2020 Sep 2.

Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Bladder cancer (BC) comprises 3% of all cancers and is particularly common in the developed countries. Early diagnosis is an important necessity in improvement of BC prognosis, as patients' outcome is significantly different between muscle invasive BC (MIBC) and non-muscle invasive BC cases. This cancer is resulted from an intricate interaction between genetic and environmental factors. Recent studies have identified microRNAs (miRNAs) as potential modulators of carcinogenic potential of BC cells. These small transcripts regulate expression of target genes mostly through binding with their 3' untranslated regions. Expression of several oncomiRs has been increased in BC tissues, peripheral blood or urine samples of these patients. These miRNAs promote oncogenic potential of BC through modulation of epithelial-mesenchymal transition or PI3K/AKT, JAK/STAT and NF-κB/Snail signaling pathways. Besides, a number of tumor suppressive miRNAs have been down-regulated in BC samples leading to enhanced proliferation, invasiveness and metastasis of these cells. TGFβ1, Akt, MAPK, MET/SMAD3/SNAIL, MAPK1/Slug/vimentin and Wnt7a/β-catenin pathways and axes are among molecular targets of these miRNAs. Aberrant expressions of miRNAs in biofluids of patients with BC have potentiated them as molecular markers for prediction of disease course. In the current review, we provided a summary of studies which reported aberrant expression of miRNAs and their implications in the diagnosis or prognosis of patients with BC.
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http://dx.doi.org/10.1016/j.biopha.2020.110703DOI Listing
November 2020

Expression Analysis of GDNF/RET Signaling Pathway in Human AD-MSCs Grown in HEK 293 Conditioned Medium (HEK293-CM).

Cell Biochem Biophys 2020 Dec 14;78(4):531-539. Epub 2020 Aug 14.

Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Mesenchymal stem cells have been considered as the suitable source for the repair of kidney lesions. The study and identification of novel approaches could improve the efficiency of these cells in the recovery of kidney. In the present study, the effect of HEK 293 conditioned medium (HEK293-CM) was evaluated on the expression of GDNF/RET signaling pathway and their downstream genes in the human adipose-derived mesenchymal stem cells (AD-MSCs). For this purpose, the human AD-MSCs were cultured in the medium containing HEK293-CM. After the RNA extraction and cDNA synthesis, the expression level of GFRA1, GDNF, SPRY1, ETV4, ETV5, and CRLF1 genes were determined by SYBR Green Real time PCR. The obtained results indicated that the GDNF and GFRA1 expression enhanced in the AD-MSCs following treatment with 10% HEK293-CM-5%FBS as compared to the untreated AD-MSCs. These results were consistent with the decreased expression of SPRY1. The significant increased expression of ETV4, ETV5, and CRLF1 genes also showed that HEK293-CM activated the GDNF/RET signaling pathway in the AD-MSCs (P < 0.05). The obtained data suggested that the treatment with HEK293-CM activated the GDNF/RET signaling pathway in the human AD-MSCs.
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http://dx.doi.org/10.1007/s12013-020-00936-zDOI Listing
December 2020

TINCR: An lncRNA with dual functions in the carcinogenesis process.

Noncoding RNA Res 2020 Sep 9;5(3):109-115. Epub 2020 Jul 9.

Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs (lncRNAs) have prominent roles in the pathogenesis of human cancers. Several studies have shown oncogenic or tumor suppressor roles of lncRNAs in different human tissues. Thus, these transcripts have been regarded as putative targets in treatment of cancer. The lncRNA terminal differentiation-induced non-coding RNA (TINCR) has an especial position in this regard, as it exerts different opposite roles in the pathogenesis of different human cancers. While it is up-regulated in gastric, esophageal, bladder and breast cancer; it is down-regulated in glioma, retinoblastoma and prostate cancer. Notably, data regarding expression profile of this lncRNA in a number of human cancers such as colon cancer, squamous cell carcinoma, non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC) are controversial. Expression level of this lncRNA has been associated with clinical outcome in patients with gastric cancer, colorectal cancer, NSCLC and head and neck squamous cell carcinoma. Moreover, Kaplan-Meier analyses have shown correlation between expression levels of TINCR and patients survival in patients with lung cancer and HCC. A number of cellular pathways such as Wnt/β-catenin, ERK1/2-SP3 and MAPK signaling pathways have been identified as targets of this lncRNA in different cancers. Moreover, the rs8113645, rs2288947 and rs8105637 within this lncRNA have been associated with risk of gastric and colorectal cancer. In conclusion, although the role of TINCR in the carcinogenesis is essential, based on the conflicting data regarding the direction of effect of this lncRNA, therapeutic targeting of this lncRNA is a complicated issue which should be considered in a tissue-specific or even individualized manner.
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http://dx.doi.org/10.1016/j.ncrna.2020.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358216PMC
September 2020

Dysregulation of NF-κB-Associated lncRNAs in Multiple Sclerosis Patients.

J Mol Neurosci 2021 Jan 29;71(1):80-88. Epub 2020 Jun 29.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs (lncRNAs) have been reported to participate in the pathogenesis of several complex disorders such as immune-related disorders. Multiple sclerosis (MS) as an inflammatory disorder of the central nervous system has been associated with aberrant expression of several lncRNAs. In the current study, we assessed expression of NF-κB-, autophagy-, and obesity-associated lncRNAs/genes and two inflammatory cytokines in the peripheral blood of MS patients and healthy controls. LNC-MKI67IP was down-regulated in total MS patients compared with total controls (P value < 0.0001). However, when comparing its expression in a gender-based manner, no significant difference was found between patients and controls. Expression of HNF1A-AS1 was significantly lower in total MS patients and patients of both sexes when compared with the matched controls (P value < 0.0001; P value = 0.03; P value = 0.004, respectively). Expression of LINC00305 had a similar pattern to HNF1A-AS1 (P value < 0.0001; P value = 0.005; P value < 0.0001, respectively). Expressions of other assessed NF-κB associated lncRNAs were not different between cases and controls. Expression of IL-1B was significantly lower in total MS patients compared with total controls (P value < 0.0001). Such decreased expression was detected in female patients compared with female controls as well (P value < 0.0001). Expression of IL-6 was not different between cases and controls. Expression of CEBPA was higher in total MS patients compared with controls (P value = 0.047). However, when dividing study participants into male and female subgroups, no significant difference was detected between cases and gender-matched controls. There were no significant difference in the expression of any assessed autophagy-associated lncRNAs between cases and controls. ATG5, CEBPA, HNF1A-AS1, IL-1B, LINC00305, and LNC-MKI67IP could differentiate disease status with diagnostic power values of 0.781, 0.582, 0.744, 0.76, 0.926, and 0.703, respectively. Expression levels of ADINR and CHAST were correlated with age of MS patients and disease duration, respectively (r = 0.33, P < 0.0001; r = 0.34, P < 0.0001, respectively). The present study highlighted the role of a number lncRNAs in the pathogenesis of MS and supported the previous data regarding aberrant expression of these transcripts in this immune-related disorder.
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http://dx.doi.org/10.1007/s12031-020-01628-2DOI Listing
January 2021

Downregulation of Cancer-Associated lncRNAs in Peripheral Blood of Multiple Sclerosis Patients.

J Mol Neurosci 2020 Oct 23;70(10):1533-1540. Epub 2020 Jun 23.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Recent studies have shown contribution of long non-coding RNAs (lncRNAs) in the pathogenesis of immune-related disorders including multiple sclerosis (MS). Based on the role of these transcripts in the regulation of immune response, peripheral levels of lncRNAs can reflect the level of immune activation. In the present study, we quantified expression of four lncRNAs namely SPRY4-IT1, HOXA-AS2, LINC-ROR, and MEG3 in venous blood of MS patients and controls using quantitative real-time PCR method. Relative expressions of SPRY4-IT1, HOXA-AS2, LINC-ROR, and MEG3 were significantly lower in female MS patients compared with female healthy subjects. For MEG3, this pattern of expression was also observed in male subjects. However, for other lncRNAs, no significant difference was detected between male patients and male controls. Expression of HOXA-AS2 was correlated with progression index (r = 0.36, P < 0.001). Besides, there was a significant correlation between expression of this lncRNA and expression of LINC-ROR in MS patients (r = 0.44, P < 0.0001). There was no other correlation between expression of lncRNAs and clinical data in MS patients. In control group, expressions of none of lncRNAs were correlated with age of persons. Notably, significant correlations were demonstrated between expression levels of all lncRNAs in healthy subjects with r values ranging from 0.23 to 0.42. The current investigation shows dysregulation of lncRNAs in MS patients in a sex-specific manner and warrants further studies to unravel the clinical and therapeutic implications of such dysregulation.
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http://dx.doi.org/10.1007/s12031-020-01646-0DOI Listing
October 2020

Association study of a single nucleotide polymorphism in brain cytoplasmic 200 long-noncoding RNA and psychiatric disorders.

Metab Brain Dis 2020 10 1;35(7):1095-1100. Epub 2020 Jun 1.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The Brain cytoplasmic 200 RNA (BC200 RNA) is neuron-specific lncRNA with putative roles in normal aging and in the pathogenesis of Alzheimer's disease. Its role in the neuron plasticity has also been documented. In the current study, we genotyped a single nucleotide polymorphism (SNP) within this lncRNA (rs4404327) in a population of Iranian patients with diverse neuropsychiatric conditions including substance addiction (n = 315), attention deficit hyperactive disorder (ADHD) (n = 53), bipolar 1 (BP1) (n = 131), bipolar 2 (BP2) (n = 68), major depressive disorder (MDD) (n = 56) and schizophrenia (SCZ) (n = 177) as well as age-/ sex-matched healthy controls. This SNP was associated with ADHD in co-dominant model (C/T vs. C/C) (OR (95% CI) = 3.7 (1.96-10), P value = 0.000193), dominant model (C/T + T/T vs. C/C) (OR (95% CI) = 4.43(2.02-9.72), P value = 1.37E-04) and multiplicative model (C vs. T) (OR (95% CI) = 3.20(1.64-6.25), P value = 4.316269E-04). Moreover, this SNP was associated with risk of BP1 in dominant model (OR (95% CI) = 1.67(1.08-2.62), P value = 0.02) and multiplicative model (OR (95% CI) = 1.51 (1.04-2.21), P value = 0.028). After correction for multiple comparisons (6 cohorts × 4 models), associations remained significant in ADHD but not in BP1. No other significant association was detected. The current project showed association between a certain SNP within BC200 RNA and ADHD. Further studies are required to assess these associations in larger cohorts of patients and find the underlying mechanism for this observation.
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http://dx.doi.org/10.1007/s11011-020-00582-7DOI Listing
October 2020

Effects of host genetic variations on response to, susceptibility and severity of respiratory infections.

Biomed Pharmacother 2020 Aug 29;128:110296. Epub 2020 May 29.

Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland. Electronic address:

The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global crisis, necessitating the identification of genetic factors that modulate the risk of disorder or its severity. The current data about the role of genetic risk factors in determination of rate of SARS-CoV-2 infection in each ethnic group and the severity of disorder is limited. Moreover, several confounding parameters such as the number of tests performed in each country, the structure of the population especially the age distribution, the presence of risk factors for respiratory disorders such as smoking and other environmental factors might be involved in the variability in disease course or prevalence of infection among different ethnic groups. However, assessment of the role of genetic variants in determination of the course of other respiratory infections might help in recognition of possible candidate for further analysis in patients affected with SARS-CoV-2. In the current review, we summarize the data showing the association between genomic variants and risk of acute respiratory distress syndrome, respiratory infections or severity of these conditions with an especial focus on the SARS-CoV-2.
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http://dx.doi.org/10.1016/j.biopha.2020.110296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258806PMC
August 2020

Effects of host genetic variations on response to, susceptibility and severity of respiratory infections.

Biomed Pharmacother 2020 Aug 29;128:110296. Epub 2020 May 29.

Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland. Electronic address:

The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global crisis, necessitating the identification of genetic factors that modulate the risk of disorder or its severity. The current data about the role of genetic risk factors in determination of rate of SARS-CoV-2 infection in each ethnic group and the severity of disorder is limited. Moreover, several confounding parameters such as the number of tests performed in each country, the structure of the population especially the age distribution, the presence of risk factors for respiratory disorders such as smoking and other environmental factors might be involved in the variability in disease course or prevalence of infection among different ethnic groups. However, assessment of the role of genetic variants in determination of the course of other respiratory infections might help in recognition of possible candidate for further analysis in patients affected with SARS-CoV-2. In the current review, we summarize the data showing the association between genomic variants and risk of acute respiratory distress syndrome, respiratory infections or severity of these conditions with an especial focus on the SARS-CoV-2.
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http://dx.doi.org/10.1016/j.biopha.2020.110296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258806PMC
August 2020

Angiotensin converting enzyme: A review on expression profile and its association with human disorders with special focus on SARS-CoV-2 infection.

Vascul Pharmacol 2020 07 11;130:106680. Epub 2020 May 11.

Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland. Electronic address:

Angiotensin-converting enzyme (ACE) and its homologue, ACE2, have been mostly associated with hypertensive disorder. However, recent pandemia of SARS-CoV-2 has put these proteins at the center of attention, as this virus has been shown to exploit ACE2 protein to enter cells. Clear difference in the response of affected patients to this virus has urged researchers to find the molecular basis and pathophysiology of the cell response to this virus. Different levels of expression and function of ACE proteins, underlying disorders, consumption of certain medications and the existence of certain genomic variants within ACE genes are possible explanations for the observed difference in the response of individuals to the SARS-CoV-2 infection. In the current review, we discuss the putative mechanisms for this observation.
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http://dx.doi.org/10.1016/j.vph.2020.106680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211701PMC
July 2020

Poly-phosphate increases SMC differentiation of mesenchymal stem cells on PLGA-polyurethane nanofibrous scaffold.

Cell Tissue Bank 2020 Sep 9;21(3):495-505. Epub 2020 May 9.

Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The use of bioactive scaffolds in tissue engineering has a significant effect on the damaged tissue healing by an increase in speed and quality of the process. Herein, electrospinning was applied to fabricate composite nanofibrous scaffolds by Poly lactic-co-glycolic acid (PLGA) and Polyurethane (PU) with and without poly-phosphate (poly-P). Scaffolds were characterized morphologically by scanning electron microscope (SEM), and their biocompatibility was also investigated by SEM, protein adsorption, cell attachment and survival assays. The applicability of the scaffolds for bladder tissue engineering was also evaluated by culturing mesenchymal stem cells (MSCs) on the scaffolds and their differentiation into smooth muscle cell (SMC) was studied at the gene and protein levels. The results demonstrated that scaffold biocompatibility was increased significantly by loading poly-P. SMC related gene and protein expression level in MSCs cultured on poly-P-loaded scaffold was also increased significantly compared to those cells cultured on empty scaffold. It can be concluded that poly-P hasn't also increased scaffold biocompatibility, but also SMC differentiation potential of MSCs was also increased while cultured on the poly-P containing scaffold compared to the empty scaffold. Taken together, our study showed that PLGA-PU-poly-P alone and in combination with MSCs has a promising potential for support urinary bladder smooth muscle tissue engineering.
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http://dx.doi.org/10.1007/s10561-020-09836-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223593PMC
September 2020

Correlation of and Expressions with Proliferation Potential of Early and Late Culture of Human Peripheral Blood Mesenchymal Stem Cells.

Cell J 2021 Jan 22;22(4):431-436. Epub 2020 Apr 22.

Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objective: In the recent years, mesenchymal stem cells (MSCs) were considered as the suitable source of cells for transplantation into the damaged tissues in regenerative medicine. There was low number of these cells in different organs and this characteristic was the main drawback to use them in treatment of diseases. Cellular senescence of the stem cells has been demonstrated to be dependent to the telomerase activity. The aim of present experimental study was to evaluate correlation of the expression of telomerase components and WNT signaling pathway in MSCs derived from human peripheral blood (PB-MSCs).

Materials And Methods: In this experimental study, following the isolation of MSCs from peripheral blood mononuclear cells, RNA was extracted from these cells in the early culture (8-9 days) and late culture (14-17 days). Then, expression of and was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) based on SYBR Green.

Results: Our data indicated that there was a significantly reduced expression of in the late culture of human MSCs derived from peripheral blood (P<0.05). Although a negative correlation was observed between and expression levels in the early culture of MSCs, spearman analysis showed that there was no significant correlation between the expression of telomerase components ( and ) and WNT signaling pathway (P>0.05).

Conclusion: The obtained results suggested that WNT signaling pathway likely plays a minor role in the maintenance of telomere length and proliferation potential of MSCs.
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http://dx.doi.org/10.22074/cellj.2021.6920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211286PMC
January 2021

Efficient smooth muscle cell differentiation of iPS cells on curcumin-incorporated chitosan/collagen/polyvinyl-alcohol nanofibers.

In Vitro Cell Dev Biol Anim 2020 Apr 19;56(4):313-321. Epub 2020 Apr 19.

Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Bladder dysfunction is one of the most common diseases that occur for a number of reasons and the current treatment modalities do not improve much in its recovery process. Tissue engineering in the last two decades has given great hope for the treatment of these disorders. In this study, a composite nanofibrous scaffold was fabricated from chitosan, collagen, and polyvinyl-alcohol polymer blend while curcumin incorporated in scaffold fibers. The scaffold supportive functions from smooth muscle cell differentiation were studied when human-induced pluripotent stem cells were cultured on the scaffolds under differentiation medium. Biocompatibility of the fabricated scaffold increased significantly by incorporating curcumin in the scaffold fibers, where protein adsorption, cell attachment, and viability were increased in the nanofiber/curcumin group compared with the other groups. In addition, the expression level of smooth muscle cell-related genes, including alpha-smooth muscle actin (αSMA), smooth muscle 22 alpha (SM-22a), Caldesmon1, and Calponin1in the stem cells upregulated while cultured in the presence of curcumin, but this increase was significantly improved while cells cultured on the nanofibers/curcumin. In addition, αSMA protein in the cells cultured on the nanofibers/curcumin expressed significantly higher than those cells cultured on the nanofibers without curcumin. It can be concluded that smooth muscle cell differentiation of the induced pluripotent stem cells promoted by curcumin and this promotion was synergistically improved while curcumin incorporated in the nanofibers. Graphical abstract.
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http://dx.doi.org/10.1007/s11626-020-00445-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223336PMC
April 2020

Gastric Cancer MicroRNAs Meta-signature.

Int J Mol Cell Med 2019 24;8(2):94-102. Epub 2019 Aug 24.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Gastric cancer (GC) is one of the most common types of cancer and the second leading cause of cancer-associated mortalityIdentification of novel biomarkers is critical to prolonging patient survival. MicroRNAs (miRNAs) proved to play diverse roles in the physiological and pathological state in cancers including GC. Herein we aimed at performing a meta-analysis on miRNA profiling studies that used microarray platforms. Relevant studies were retrieved from PubMed and GEO databases. We used the robust rank aggregation to perform the meta-analysis. Moreover, for meta-signature miRNAs target genes, we performed pathway enrichment and GO molecular function enrichment analysis. A total of 19 upregulated miRNAs and seven downregulated miRNAs in GC samples were identified. However, only three upregulated and one downregulated miRNA reached statistical significance after multiple test correction. Here we showed that hsa-miR-21-5p, hsa-miR-93-5p, hsa-miR-25-3p, and hsa-miR-375 are differentially expressed in GC samples.
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http://dx.doi.org/10.22088/IJMCM.BUMS.8.2.94DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081082PMC
August 2019

Application of Artificial Neural Network for Prediction of Risk of Multiple Sclerosis Based on Single Nucleotide Polymorphism Genotypes.

J Mol Neurosci 2020 Jul 9;70(7):1081-1087. Epub 2020 Mar 9.

Student of Dentistry, Dental School, Shahid Beheshti University of Medical Science, Tehran, Iran.

The artificial neural network (ANN) is a sort of machine learning method which has been used in determination of risk of human disorders. In the current investigation, we have created an ANN and trained it based on the genetic data of 401 multiple sclerosis (MS) patients and 390 healthy subjects. Single nucleotide polymorphisms (SNPs) within ANRIL (rs1333045, rs1333048, rs4977574 and rs10757278), EVI5 (rs6680578, rs10735781 and rs11810217), ACE (rs4359 and rs1799752), MALAT1 (rs619586 and rs3200401), GAS5 (rs2067079 and rs6790), H19 (rs2839698 and rs217727), NINJ2 (rs11833579 and rs3809263), GRM7 (rs6782011 and rs779867), VLA4 (rs1143676), CBLB (rs12487066) and VEGFA (rs3025039 and rs2071559) had been genotyped in all individuals. We used "Keras" package for generation and training the ANN model. The k-folds cross-validation strategy was applied to confirm model generalization and overfit prevention. The locally interpretable model-agnostic explanation (LIME) was applied to explain model predictions at the data sample level. The TT genotype of the GAS5 rs2067079 had the most protective effect against MS, while the DD genotype of the ACE rs1799752 was the most prominent risk genotype. The accuracy, sensitivity and specificity values of the model were 64.73%, 64.95% and 64.49% respectively. The ROC AUC value was 69.67%. The current study is a preliminary study to appraise the application of ANN for prediction of risk of MS based on genomic data.
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http://dx.doi.org/10.1007/s12031-020-01514-xDOI Listing
July 2020

Associations Between Genomic Variants in lncRNA-TRPM2-AS and lncRNA-HNF1A-AS1 Genes and Risk of Multiple Sclerosis.

J Mol Neurosci 2020 Jul 26;70(7):1050-1055. Epub 2020 Feb 26.

Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Multiple sclerosis (MS) is a complex genetic trait characterized by demyelination of central nervous system (CNS), inflammation, and progressive neurological dysfunction. There is evidenced that autophagy and stress mechanisms are tightly linked with MS. Previous studies have demonstrated that LncRNAs TRPM2-AS and HNF1A-AS1 are involved in oxidative stress and autophagy, respectively. In the current study, we investigated the association of TRPM2-AS and HNF1A-AS1 single nucleotide polymorphisms (SNPs) with MS risk in 300 Iranian patients and 300 healthy controls. Our results have shown that T allele of the rs933151 was statistically significant underrepresented in MS patients compared with healthy subjects (OR (95% CI) = 0.696 (0.532-0.911), P = 0.005). This SNP was associated with lower MS risk in codominant and dominant models (OR (95% CI) = 0.68 (0.48-0.96), P value = 0.032; OR (95% CI) = 0.65 (0.47-0.91), P value = 0.012, respectively). The rs7953249 was not associated with MS susceptibility in any inheritance models (P values of 0.73, 0.46, 0.61, and 0.71 for codominant, dominant, recessive, and overdominant models, respectively). Present study highlighted a novel association at the TRPM2-AS gene (SNP rs933151) with MS susceptibility.
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http://dx.doi.org/10.1007/s12031-020-01504-zDOI Listing
July 2020