emran esmaeilzadeh | AJA University of Medical Sciences (original) (raw)
Papers by emran esmaeilzadeh
Multiple sclerosis and related disorders, Nov 1, 2022
Background Multiple sclerosis is a common auto-immuno-in ammatory diseases of the central nervous... more Background Multiple sclerosis is a common auto-immuno-in ammatory diseases of the central nervous system in adults. There are several underlying mechanisms for pathogenesis of the disease, including in ammation, oligodendrocyte apoptosis, and oxidative stress. Methods We have investigated the mechanism of Shikonin action in C57BL/6 experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Results Our results revealed that EAE induction signi cantly increased the extent of demyelination in the corpus callosum tissues of the animals, while treatment of the mice with Shikonin, signi cantly decreased the extent of demyelination. Real-time PCR based analyzing the brain samples from the EAE mice, revealed a signi cant enhancement in the expression level of TNF-α , IFN-γ and Bax genes as well as a reduction in the expression level of TGF-β and Bcl2. Shikonin treatment signi cantly reduced the expression level of TNF-α , IFN-γ and Bax. On the other hand, the expression levels of TGF-β and Bcl2 as well as the Glutathione peroxidase-1 (GPX-1) enzyme were signi cantly increased following Shikonin treatment. Conclusion This study emphasizes the immune-modulatory, anti-apoptotic, and anti-oxitive effects of Shikonin, which may have an important healing in uence on the severity of EAE.
Clinical Rheumatology, Jun 26, 2021
Systemic lupus erythematosus (SLE) is a multifactorial systemic autoimmune disease, in which gene... more Systemic lupus erythematosus (SLE) is a multifactorial systemic autoimmune disease, in which genetic susceptibility plays a pivotal role. The nucleotide oligomerization domain 2 (NOD2) gene is one of the main regulators of chronic inflammatory conditions and could be involved in SLE pathogenesis. Single nucleotide polymorphisms (SNPs) in miRNA binding sites which are located in 3′UTR of the NOD2 gene could be associated with SLE risk by dysregulation of NOD2 expression. In the present study, we assessed the possible association between SNPs rs3135500 and rs3135499 in the NOD2 gene with SLE risk in the Iranian population. A case–control study using 110 SLE patients and 120 control subjects was undertaken to estimate rs3135500 (G > A) and rs3135499 (A > C) genotypes via real-time PCR high-resolution melting method (HRM). No significant association was observed between allele and genotype frequencies of rs3135500 and rs3135499 polymorphisms and SLE risk in this population (P > 0.05). However, there was an obvious association between rs3135500 (A allele) with laboratory factors that are associated with disease activity (P < 0.05) and some clinical manifestations that are associated with disease severity such as neurological symptoms, skin manifestations, renal involvements, and higher serum concentration of creatinine (P < 0.05). Besides, rs3135499 (C allele) was correlated with renal involvement and also the concentration of creatinine (P < 0.05). Moreover, in the patients group, the risk alleles in these polymorphisms were associated with lower age of onset (P < 0.05). Our results suggest a substantial association between NOD2 polymorphisms with clinicopathological characteristics and SLE disease activity. Key Points • Single nucleotide polymorphisms (SNPs) in miRNA binding sites which are located in 3′UTR of the NOD2 gene could be associated with SLE risk by dysregulation of NOD2 expression. • Our results suggested that two miRSNPs (rs3135500 and rs3135499) in the NOD2 gene were meaningfully correlated with clinicopathological characteristics and disease activity of SLE. Key Points • Single nucleotide polymorphisms (SNPs) in miRNA binding sites which are located in 3′UTR of the NOD2 gene could be associated with SLE risk by dysregulation of NOD2 expression. • Our results suggested that two miRSNPs (rs3135500 and rs3135499) in the NOD2 gene were meaningfully correlated with clinicopathological characteristics and disease activity of SLE.
Lupus, May 6, 2021
Objective Nod-like receptor pyrin domain containing 3 ( NLRP3) gene encodes an intracellular rece... more Objective Nod-like receptor pyrin domain containing 3 ( NLRP3) gene encodes an intracellular receptor whose dysregulation in systemic lupus erythematosus (SLE) has been reported in multiple studies. Activation of NLRP3 inflammasome leads to the induction of inflammatory response via cleaving and producing of specific cytokines. In the present study, we assessed the possible association between three functional polymorphisms in this gene and SLE risk in the Iranian population. These variants include two gain of function (rs4612666 and rs10754558) and one loss of function (rs6672995) which are correlated with modulation of expression of NLRP3. Methods A case-control study involving 110 SLE patients and 116 control subjects was undertaken to estimate the frequency of rs4612666, rs10754558, and rs6672995 genotypes using real-time PCR high resolution melting method (HRM). Results Our findings revealed significant associations between GG genotype and G allele of rs10754558 with increased risk of SLE (OR for GG genotype= 2.82; 95%CI [1.45–5.46]/OR for G allele= 1.97; 95%CI [1.36–2.87]). Although, no significant associations were recognized between allele and genotype frequencies of rs4612666 and rs6672995 polymorphisms with SLE risk ( P > 0.05). Also, our analysis revealed that the C allele in rs4612666 and G allele in rs10754558 was correlated with the severity of disease activity (P < 0.001). Moreover, these common variants were associated with lower age of onset and some clinical symptoms in the patient group, such as skin manifestation, neurological symptom and, renal involvement (P < 0.05). Conclusion This study demonstrates a substantial association between NLRP3 polymorphisms with increased risk, clinical symptoms, and the severity of disease activity of SLE.
Lupus, Jan 24, 2022
Background Signal transducer and activator of transcription 3 (STAT3) is a major regulator of imm... more Background Signal transducer and activator of transcription 3 (STAT3) is a major regulator of immune response and chronic inflammatory conditions acting through regulation of B cells, T-helper 17 (Th17) cells, and IL-17 production. Previous studies have demonstrated that dysregulation of STAT3 is crucial for SLE pathogenesis and disease severity. It is believed that single nucleotide polymorphisms (SNPs) located at the 3′-UTR sequence of the target genes could dysregulate their expression by disrupting the binding site of miRNAs. In the present study, we assessed the possible association between rs1053005 and rs1053023 SNPs at miRNA binding sites in the STAT3 gene and the risk of SLE in the Iranian population for the first time. Methods 112 SLE cases and 120 healthy controls were genotyped for rs1053005 (A>G) and rs1053023 (A>G) polymorphisms in STAT3 using real-time PCR high resolution melting method (HRM). Results Our results revealed substantial associations between GG genotype and G allele of rs1053023 with enhanced risk of SLE (OR for GG genotype= 3.13; 95%CI [1.61–6.1], OR for G allele = 2.22; 95%CI [1.51–3.25]). However, no important correlations have been found between rs1053005 polymorphism and SLE susceptibility in this population ( p>0.05). Moreover, stratification analysis showed that these polymorphisms are correlated with parameters indicating disease activity and more severe course of the disease. These factors include some laboratory test results and clinical manifestations such as renal involvements. Conclusion The current study suggests a significant association between STAT3 polymorphisms and augmented risk of SLE, clinical symptoms, disease activity, and severity.
Iranian Journal of Pharmaceutical Research, 2020
The present study was designed to primarily examine the therapeutic potential of the herbal extra... more The present study was designed to primarily examine the therapeutic potential of the herbal extract of Melilotus Officinalis for the treatment of multiple sclerosis in the experimental autoimmune encephalomyelitis (EAE) model of the disease. The animal model was induced in C57BL/6 female mice, and then the herbal extract was intraperitoneally administered for a total of 21 days after the first day of post-immunization. The phenotypic signs, a gene expression profile of inflammatory cytokines, antioxidant state, and pathological hallmarks of the disease in the corpus callosum were evaluated. The prophylactic administration of Melilotus Officinalis attenuates the clinical signs of the disease. It significantly declined the gene expression of proinflammatory cytokines like IL-6, TNF-α, and IFN-γ. This herbal extract also surged the gene expression, as an anti-inflammatory cytokine. The gene expression of Glutathione peroxidase and Catalase (antioxidant enzymes) was meaningfully higher in the treatment group. Pathological evaluation of corpus callosum cross-sections by Luxol Fast Blue staining revealed preserved myelin sheath in the treated group compared to the EAE mice. The results of our assay confirmed that immunomodulatory and antioxidant features of the herbal extract of Melilotus Officinalis ameliorated the EAE severity. This study finding disclosed the therapeutic efficiency of this compound in MS treatment.
Cancer genetics, Nov 1, 2019
Single nucleotide polymorphisms (SNPs) in the recognition sites of microRNAs (miRNAs), located at... more Single nucleotide polymorphisms (SNPs) in the recognition sites of microRNAs (miRNAs), located at 3 untranslated region (UTR) of mRNAs, interfere with posttranslational gene regulation. Deregulation of genes may contribute to some disease susceptibility including colorectal cancer (CRC). In the present study, in a case-control setup, 167 CRC patients and 161 control subjects were studied for allele and genotype frequency of rs10889677 polymorphism in miRNAs Let-7e and Let-7f binding sites at 3 UTR of IL23R gene using PCR-RFLP assay. Also, related articles were retrieved from MEDLINE, Cochrane review, Google Scholar and Scopus databases for meta-analysis study. According to our results, AA genotype of SNP rs10889677 was significantly correlated with increased risk of CRC (OR = 3.10; 95% CI [1.86-5.18]; P: < 0.001). In a meta-analysis on 10 risk estimates for the CC versus AA genotype, we found an inverse association between CC SNPs and risk of all cancer (OR = 0.59; 95% CI [0.49-0.71]; P < 0.001). In conclusion, our results demonstrate that rs10889677 polymorphism is significantly associated with CRC risk.
CEN Case Reports, Mar 1, 2023
Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microang... more Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia caused by small vessel thrombosis, thrombocytopenia, and renal failure. The common cause of aHUS is a dysregulation in the alternative complement pathway. Mutations in none complement genes such as diacylglycerol kinase epsilon (DGKE) can also result in this syndrome. Case presentation: Here, we report on a 19-year-old female with the clinical diagnosis of aHUS, who has unaffected consanguineous parents and an older sibling who was deceased from aHUS when she was seven months old. We performed whole exome sequencing (WES) followed by evaluation of detected variants for functional significance, using several online prediction tools. Next, in order to confirm the detected pathogenic variant in proband and segregation analysis in her family, Sanger sequencing was done. The novel variant was analyzed in terms of its impact on the protein 3-dimensional structure by computational structural modeling. The results revealed that the proband carried a novel homozygous missense variant in DGKE located in exon 6 of the gene (NM_003647.3, c.942C > G [p.Asn314Lys]), and in silico analysis anticipated it as damaging. Protein computational study confirmed the influence of potential pathogenic variant on structural stability and protein function. Conclusion: We suggest that some variations in the catalytic domain of DGKE like p.Asn314Lys which can cause alterations in secondary and 3-D structure of protein, might lead to aHUS.
Journal of Pharmacy and Pharmacology, Sep 6, 2020
Background Multiple sclerosis is a common auto-immuno-in ammatory diseases of the central nervous... more Background Multiple sclerosis is a common auto-immuno-in ammatory diseases of the central nervous system in adults. There are several underlying mechanisms for pathogenesis of the disease, including in ammation, oligodendrocyte apoptosis, and oxidative stress. Methods We have investigated the mechanism of Shikonin action in C57BL/6 experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Results Our results revealed that EAE induction signi cantly increased the extent of demyelination in the corpus callosum tissues of the animals, while treatment of the mice with Shikonin, signi cantly decreased the extent of demyelination. Real-time PCR based analyzing the brain samples from the EAE mice, revealed a signi cant enhancement in the expression level of TNF-α , IFN-γ and Bax genes as well as a reduction in the expression level of TGF-β and Bcl2. Shikonin treatment signi cantly reduced the expression level of TNF-α , IFN-γ and Bax. On the other hand, the expression levels of TGF-β and Bcl2 as well as the Glutathione peroxidase-1 (GPX-1) enzyme were signi cantly increased following Shikonin treatment. Conclusion This study emphasizes the immune-modulatory, anti-apoptotic, and anti-oxitive effects of Shikonin, which may have an important healing in uence on the severity of EAE.
Molecular Biology Reports, Nov 1, 2020
Deregulation of microRNAs, as key elements in colorectal cancer (CRC) pathogenesis, is correlated... more Deregulation of microRNAs, as key elements in colorectal cancer (CRC) pathogenesis, is correlated with various stages of this cancer. miR-196 is involved in the initiation and progression of a verity of malignances, especially CRC. miR-196 in CRC cells could target different types of genes with oncogenic and/or tumor suppressor function such as HOX genes, GATA6, SOCS1, SOCS3, ANXA1, DFFA, PDCD4, ZG16 and ING5. Therefore, these genes could be up or down-regulated in cells and subsequently change the capacity of CRC cells in terms of tumor development, progression and, response to therapy. Comprehension of miR-196-associated aberrations underlying the CRC pathogenesis might introduce promising targets for therapy. Additionally, it seems that miR-196 expression profiling, especially circulatory exosomal miR-196, might be useful for diagnosis and prognosis determination of the CRC patients. In this review, at first, we summarize the roles of miR-196 in different types of cancers. After that, a detailed discussion about this miRNA and also their targets in CRC pathogenesis, progression, and response to treatment are represented. Moreover, we highlight the potential utilization of miR-196 and its targets as therapeutic targets and novel biomarkers in early detection and prediction of prognosis in CRC patients.
Clinical Rheumatology, Jul 20, 2022
Journal of Human Hypertension, Aug 20, 2018
The multifactorial basis of preeclampsia (PE) implies that there are several genes and risk facto... more The multifactorial basis of preeclampsia (PE) implies that there are several genes and risk factors that are important in the development of the disease. Therefore, the exact etiology and pathogenesis of preeclampsia remains unclear. It is suggested that inappropriate regulation of the renin-angiotensin system (RAS) is a risk factor for hypertension during pregnancy. The angiotensin I-converting enzyme (ACE) serum level, a key component of the RAS, affects the blood pressure. It is hypothesized that the ACE gene polymorphisms contribute to preeclampsia development. In a case-control study containing 296 subjects (165 PE patients and 131 normotensive controls), we aimed to examine the association of the ACE gene I/D and rs4343 polymorphisms with preeclampsia in Iranian women. Genotyping for rs4343 and ACE I/D polymorphisms was performed by using TP-ARMS-PCR and conventional PCR, respectively. The rs4343 G allele frequency was higher in the case group (OR = 1.90, 95% CI, 1.37-2.65; P = 0.0001). Besides, a significant difference was detected for the genotype frequencies between the studied groups under dominant (OR = 3.94, 95% CI, 2.05-7.56; P < 0.0001) and recessive (OR = 2.21, 95% CI, 1.22-4.01; P = 0.009) inheritance models. For the I/D polymorphism, no significant differences were detected in the genotype and allele frequencies or any of the inheritance models between PE patients and controls. To verify the current results and validate the significance of the studied genetic variations, additional studies in diverse ethnic populations are required.
Iranian journal of public health, Sep 5, 2021
Background: Human Leukocyte Antigen (HLA) system composed of a group of related proteins with imp... more Background: Human Leukocyte Antigen (HLA) system composed of a group of related proteins with important functions in the immune system. Several studies have reported that there is a significant association between specific HLA alleles and the susceptibility to different infectious diseases. This study aimed to detect the specific HLA alleles that cause higher susceptibility to COVID-19, we analyzed the HLA allele frequency distribution in Iranian patients with a severe form of COVID-19. Methods: Overall, 48 severe cases of COVID-19 that were hospitalized and required intensive care unit (ICU) admission between Oct and Dec 2020 were included in this study. Genomic DNA was extracted from the peripheral blood samples and HLA typing (Locus A, B, and DR) was performed for the patients. Results: After analyzing and comparing the results with a reference group of 500 Iranian individuals, a significant association was found for HLA-B*38, HLA-A*68, HLA-A*24, and HLA-DRB1*01. Conclusion: These results may be valuable for studying the potential association of specific HLA alleles with susceptibility to COVID-19 and mortality due to the disease.
Arak Medical University Journal, Dec 1, 2020
Background and Aim Since late 2019, with the emergence of a new type of coronavirus that causes a... more Background and Aim Since late 2019, with the emergence of a new type of coronavirus that causes a new respiratory disease called COVID-19, there have been many concerns about the spread of this disease and how to deal with it. Due to the ability of the virus to be transmitted rapidly, diagnosing the infected individuals in the early stages for isolating them is critical. This study aims to evaluate the reliability of Computed Tomography (CT) scan in diagnosing COVID-19. Methods & Materials Participants were 212 patients admitted to hospital with confirmed diagnosis of CO-VID-19. Demographic information, medical history, symptoms, and the chest CT scan results were collected and analyzed. Finally, the power of CT scans in the diagnosis of this disease was compared with the Real-Time Polymerase Chain Reaction (RT-PCR) molecular test. Ethical Considerations This study received ethical approval from the ethics committee of AJA University of Medical Sciences (Code: IR.AJAUMS.REC.1399.091). Results The sensitivity of CT scan in the diagnosis of COVID-19 was relatively high, but its false-positive results were also high. Conclusion CT scan is a relatively sensitive method for diagnosing COVID-19, but caution should be made due to its high false-positive results which can lead to increased financial burden on the health system.
Arak Medical University Journal, Dec 1, 2020
Background and Aim The new Coronavirus Disease 2019 (COVID-19) outbreak initiated from China in l... more Background and Aim The new Coronavirus Disease 2019 (COVID-19) outbreak initiated from China in late December 2019, has posed a great global health threat. Since patients with high blood pressure, diabetes, and cardiovascular diseases are at high risk of COVID-19, this study aims to investigate the prevalence, severity, clinical manifestations, and mortality rate in COVID-19 patients with underlying diseases compared to those without underlying diseases. Methods & Materials This study was performed on 1408 patients with COVID-19 admitted to Golestan, Hajar, Khanevadeh and Besat hospitals in Tehran, Iran. Required data including disease prevalence, severity, clinical manifestations and mortality rate in patients with and without underlying diseases were collected and then analyzed using statistical tests in SPSS software, considering a significance level of P<0.05. Ethical Considerations This study was approved by the AJA University of Medical Sciences (Code: IR.AJAUMS.REC.1399.091). Ethical principles have been observed in accordance with the guidelines of the National Ethics Committee and the COPE regulations. Results Patients were 912 men (64.8%) and 496 women (35.2%) aged 18-98 years (Mean age= 57.8 years). Results reported that 27% of patients were intubated and 21.9% were died. Blood oxygen level in 53.7% of patients was less than 93 mg/dL; 36.1% had a history of hypertension, 24.1% had a history of diabetes, and 21.7% had a history of cardiovascular disease. Conclusion The severity, clinical manifestations, and mortality rate of COVID-19 patients with cardiovascular disease, diabetes and hypertension are significantly different compared to those without underlying diseases.
Drug Development Research, Apr 29, 2019
Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system. Although ... more Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system. Although the exact etiology of the disease is largely unknown, it is identified that cytokines may play an important role in the pathogenesis of MS. In this study, the effects of curcumin has been investigated on the expression levels of selected cytokine coding genes as well as the extent of demyelination in the corpus callosum of C57BL/6 experimental autoimmune encephalomyelitis (EAE) model of MS. Gene expression analyses revealed that treatment with curcumin could lead to a significant reduction in the expression levels of pro-inflammatory cytokine coding genes including IL-6 (p = 0.001), IL-17 (p = 0.001), tumor necrosis factor (TNF)-α (p = 0.008), and interferon (IFN)-γ (p = 0.033) as well as a significant increase in the expression level of transforming growth factor (TGF)-β (p = 0.006) as an anti-inflammatory cytokine. Moreover, the expression of glutathione peroxidase (GPX)-1 gene and the activity of anti-oxidant enzymes were significantly higher (p < 0.001) in curcumin-treated mice. Luxol fast blue staining also confirmed a significant reduction in the extent of demyelination in the curcumin-treated group (p < 0.001). Our results have confirmed that curcumin is an effective therapeutic agent that could ameliorate the severity of EAE.
Iranian journal of public health, Aug 1, 2021
Iranian Journal of Public Health
Mulibrey Nanism is a rare multisystem disorder inherited in an autosomal recessive manner caused ... more Mulibrey Nanism is a rare multisystem disorder inherited in an autosomal recessive manner caused by mutations in the TRIM37 gene. Most of the reported cases are from Finland, but this condition has rarely occurred in other countries. Although the clinical diagnosis of Mulibrey nanism is a challenge during the first months of life, the disease can be suspected clinically due to the distinctive features of the patients. A 4-year-old female with pneumonia, cardiomyopathy, growth retardation, peripheral edema, and characteristic craniofacial features was referred to Tehran Hope Generation Foundation Genetic diagnosis Center, in October 2021. Genomic DNA was isolated from peripheral blood samples of the patient and her parents and Whole exome sequencing was performed for the patient. Whole exome sequencing revealed a homozygous G>A splice site variant (TRIM37; c.370-1G>A). Sanger sequencing confirmed the segregation of the variant with phenotype in this family. Whole exome sequenc...
Avicenna Journal of Medical Biotechnology
Background: Non-syndromic cleft lip occurs by the interaction of environmental and genetic factor... more Background: Non-syndromic cleft lip occurs by the interaction of environmental and genetic factors. The purpose of the current study was to analyze the association of Single Nucleotide Polymorphisms (SNPs) in IRF6 and NSCL/P in an Iranian population. Methods: A group of 105 children with NSCL/P and 185 normal controls were included in the current study. Genotyping of IRF6 rs2013162 and rs2235375 was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results: A substantial association of AA and CA genotypes in rs2013162 with the risk of NSCL/P (AA vs. CC; OR=2.36; 95%CI [1.05-5.29], p=0.004; and CA vs. CC; OR=0.47; 95%CI [0.28-0.79], p=0.018) was found. However, there were no important associations between A allele and risk of NSCL/P (p=0.980). According to logistic regression analysis results, subjects with GG genotype and G allele in rs2235375 polymorphism had increased risk of NSCL/P. Conclusion: The IRF6 polymorphisms are associated...
Multiple sclerosis and related disorders, Nov 1, 2022
Background Multiple sclerosis is a common auto-immuno-in ammatory diseases of the central nervous... more Background Multiple sclerosis is a common auto-immuno-in ammatory diseases of the central nervous system in adults. There are several underlying mechanisms for pathogenesis of the disease, including in ammation, oligodendrocyte apoptosis, and oxidative stress. Methods We have investigated the mechanism of Shikonin action in C57BL/6 experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Results Our results revealed that EAE induction signi cantly increased the extent of demyelination in the corpus callosum tissues of the animals, while treatment of the mice with Shikonin, signi cantly decreased the extent of demyelination. Real-time PCR based analyzing the brain samples from the EAE mice, revealed a signi cant enhancement in the expression level of TNF-α , IFN-γ and Bax genes as well as a reduction in the expression level of TGF-β and Bcl2. Shikonin treatment signi cantly reduced the expression level of TNF-α , IFN-γ and Bax. On the other hand, the expression levels of TGF-β and Bcl2 as well as the Glutathione peroxidase-1 (GPX-1) enzyme were signi cantly increased following Shikonin treatment. Conclusion This study emphasizes the immune-modulatory, anti-apoptotic, and anti-oxitive effects of Shikonin, which may have an important healing in uence on the severity of EAE.
Clinical Rheumatology, Jun 26, 2021
Systemic lupus erythematosus (SLE) is a multifactorial systemic autoimmune disease, in which gene... more Systemic lupus erythematosus (SLE) is a multifactorial systemic autoimmune disease, in which genetic susceptibility plays a pivotal role. The nucleotide oligomerization domain 2 (NOD2) gene is one of the main regulators of chronic inflammatory conditions and could be involved in SLE pathogenesis. Single nucleotide polymorphisms (SNPs) in miRNA binding sites which are located in 3′UTR of the NOD2 gene could be associated with SLE risk by dysregulation of NOD2 expression. In the present study, we assessed the possible association between SNPs rs3135500 and rs3135499 in the NOD2 gene with SLE risk in the Iranian population. A case–control study using 110 SLE patients and 120 control subjects was undertaken to estimate rs3135500 (G > A) and rs3135499 (A > C) genotypes via real-time PCR high-resolution melting method (HRM). No significant association was observed between allele and genotype frequencies of rs3135500 and rs3135499 polymorphisms and SLE risk in this population (P > 0.05). However, there was an obvious association between rs3135500 (A allele) with laboratory factors that are associated with disease activity (P < 0.05) and some clinical manifestations that are associated with disease severity such as neurological symptoms, skin manifestations, renal involvements, and higher serum concentration of creatinine (P < 0.05). Besides, rs3135499 (C allele) was correlated with renal involvement and also the concentration of creatinine (P < 0.05). Moreover, in the patients group, the risk alleles in these polymorphisms were associated with lower age of onset (P < 0.05). Our results suggest a substantial association between NOD2 polymorphisms with clinicopathological characteristics and SLE disease activity. Key Points • Single nucleotide polymorphisms (SNPs) in miRNA binding sites which are located in 3′UTR of the NOD2 gene could be associated with SLE risk by dysregulation of NOD2 expression. • Our results suggested that two miRSNPs (rs3135500 and rs3135499) in the NOD2 gene were meaningfully correlated with clinicopathological characteristics and disease activity of SLE. Key Points • Single nucleotide polymorphisms (SNPs) in miRNA binding sites which are located in 3′UTR of the NOD2 gene could be associated with SLE risk by dysregulation of NOD2 expression. • Our results suggested that two miRSNPs (rs3135500 and rs3135499) in the NOD2 gene were meaningfully correlated with clinicopathological characteristics and disease activity of SLE.
Lupus, May 6, 2021
Objective Nod-like receptor pyrin domain containing 3 ( NLRP3) gene encodes an intracellular rece... more Objective Nod-like receptor pyrin domain containing 3 ( NLRP3) gene encodes an intracellular receptor whose dysregulation in systemic lupus erythematosus (SLE) has been reported in multiple studies. Activation of NLRP3 inflammasome leads to the induction of inflammatory response via cleaving and producing of specific cytokines. In the present study, we assessed the possible association between three functional polymorphisms in this gene and SLE risk in the Iranian population. These variants include two gain of function (rs4612666 and rs10754558) and one loss of function (rs6672995) which are correlated with modulation of expression of NLRP3. Methods A case-control study involving 110 SLE patients and 116 control subjects was undertaken to estimate the frequency of rs4612666, rs10754558, and rs6672995 genotypes using real-time PCR high resolution melting method (HRM). Results Our findings revealed significant associations between GG genotype and G allele of rs10754558 with increased risk of SLE (OR for GG genotype= 2.82; 95%CI [1.45–5.46]/OR for G allele= 1.97; 95%CI [1.36–2.87]). Although, no significant associations were recognized between allele and genotype frequencies of rs4612666 and rs6672995 polymorphisms with SLE risk ( P > 0.05). Also, our analysis revealed that the C allele in rs4612666 and G allele in rs10754558 was correlated with the severity of disease activity (P < 0.001). Moreover, these common variants were associated with lower age of onset and some clinical symptoms in the patient group, such as skin manifestation, neurological symptom and, renal involvement (P < 0.05). Conclusion This study demonstrates a substantial association between NLRP3 polymorphisms with increased risk, clinical symptoms, and the severity of disease activity of SLE.
Lupus, Jan 24, 2022
Background Signal transducer and activator of transcription 3 (STAT3) is a major regulator of imm... more Background Signal transducer and activator of transcription 3 (STAT3) is a major regulator of immune response and chronic inflammatory conditions acting through regulation of B cells, T-helper 17 (Th17) cells, and IL-17 production. Previous studies have demonstrated that dysregulation of STAT3 is crucial for SLE pathogenesis and disease severity. It is believed that single nucleotide polymorphisms (SNPs) located at the 3′-UTR sequence of the target genes could dysregulate their expression by disrupting the binding site of miRNAs. In the present study, we assessed the possible association between rs1053005 and rs1053023 SNPs at miRNA binding sites in the STAT3 gene and the risk of SLE in the Iranian population for the first time. Methods 112 SLE cases and 120 healthy controls were genotyped for rs1053005 (A>G) and rs1053023 (A>G) polymorphisms in STAT3 using real-time PCR high resolution melting method (HRM). Results Our results revealed substantial associations between GG genotype and G allele of rs1053023 with enhanced risk of SLE (OR for GG genotype= 3.13; 95%CI [1.61–6.1], OR for G allele = 2.22; 95%CI [1.51–3.25]). However, no important correlations have been found between rs1053005 polymorphism and SLE susceptibility in this population ( p>0.05). Moreover, stratification analysis showed that these polymorphisms are correlated with parameters indicating disease activity and more severe course of the disease. These factors include some laboratory test results and clinical manifestations such as renal involvements. Conclusion The current study suggests a significant association between STAT3 polymorphisms and augmented risk of SLE, clinical symptoms, disease activity, and severity.
Iranian Journal of Pharmaceutical Research, 2020
The present study was designed to primarily examine the therapeutic potential of the herbal extra... more The present study was designed to primarily examine the therapeutic potential of the herbal extract of Melilotus Officinalis for the treatment of multiple sclerosis in the experimental autoimmune encephalomyelitis (EAE) model of the disease. The animal model was induced in C57BL/6 female mice, and then the herbal extract was intraperitoneally administered for a total of 21 days after the first day of post-immunization. The phenotypic signs, a gene expression profile of inflammatory cytokines, antioxidant state, and pathological hallmarks of the disease in the corpus callosum were evaluated. The prophylactic administration of Melilotus Officinalis attenuates the clinical signs of the disease. It significantly declined the gene expression of proinflammatory cytokines like IL-6, TNF-α, and IFN-γ. This herbal extract also surged the gene expression, as an anti-inflammatory cytokine. The gene expression of Glutathione peroxidase and Catalase (antioxidant enzymes) was meaningfully higher in the treatment group. Pathological evaluation of corpus callosum cross-sections by Luxol Fast Blue staining revealed preserved myelin sheath in the treated group compared to the EAE mice. The results of our assay confirmed that immunomodulatory and antioxidant features of the herbal extract of Melilotus Officinalis ameliorated the EAE severity. This study finding disclosed the therapeutic efficiency of this compound in MS treatment.
Cancer genetics, Nov 1, 2019
Single nucleotide polymorphisms (SNPs) in the recognition sites of microRNAs (miRNAs), located at... more Single nucleotide polymorphisms (SNPs) in the recognition sites of microRNAs (miRNAs), located at 3 untranslated region (UTR) of mRNAs, interfere with posttranslational gene regulation. Deregulation of genes may contribute to some disease susceptibility including colorectal cancer (CRC). In the present study, in a case-control setup, 167 CRC patients and 161 control subjects were studied for allele and genotype frequency of rs10889677 polymorphism in miRNAs Let-7e and Let-7f binding sites at 3 UTR of IL23R gene using PCR-RFLP assay. Also, related articles were retrieved from MEDLINE, Cochrane review, Google Scholar and Scopus databases for meta-analysis study. According to our results, AA genotype of SNP rs10889677 was significantly correlated with increased risk of CRC (OR = 3.10; 95% CI [1.86-5.18]; P: < 0.001). In a meta-analysis on 10 risk estimates for the CC versus AA genotype, we found an inverse association between CC SNPs and risk of all cancer (OR = 0.59; 95% CI [0.49-0.71]; P < 0.001). In conclusion, our results demonstrate that rs10889677 polymorphism is significantly associated with CRC risk.
CEN Case Reports, Mar 1, 2023
Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microang... more Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia caused by small vessel thrombosis, thrombocytopenia, and renal failure. The common cause of aHUS is a dysregulation in the alternative complement pathway. Mutations in none complement genes such as diacylglycerol kinase epsilon (DGKE) can also result in this syndrome. Case presentation: Here, we report on a 19-year-old female with the clinical diagnosis of aHUS, who has unaffected consanguineous parents and an older sibling who was deceased from aHUS when she was seven months old. We performed whole exome sequencing (WES) followed by evaluation of detected variants for functional significance, using several online prediction tools. Next, in order to confirm the detected pathogenic variant in proband and segregation analysis in her family, Sanger sequencing was done. The novel variant was analyzed in terms of its impact on the protein 3-dimensional structure by computational structural modeling. The results revealed that the proband carried a novel homozygous missense variant in DGKE located in exon 6 of the gene (NM_003647.3, c.942C > G [p.Asn314Lys]), and in silico analysis anticipated it as damaging. Protein computational study confirmed the influence of potential pathogenic variant on structural stability and protein function. Conclusion: We suggest that some variations in the catalytic domain of DGKE like p.Asn314Lys which can cause alterations in secondary and 3-D structure of protein, might lead to aHUS.
Journal of Pharmacy and Pharmacology, Sep 6, 2020
Background Multiple sclerosis is a common auto-immuno-in ammatory diseases of the central nervous... more Background Multiple sclerosis is a common auto-immuno-in ammatory diseases of the central nervous system in adults. There are several underlying mechanisms for pathogenesis of the disease, including in ammation, oligodendrocyte apoptosis, and oxidative stress. Methods We have investigated the mechanism of Shikonin action in C57BL/6 experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Results Our results revealed that EAE induction signi cantly increased the extent of demyelination in the corpus callosum tissues of the animals, while treatment of the mice with Shikonin, signi cantly decreased the extent of demyelination. Real-time PCR based analyzing the brain samples from the EAE mice, revealed a signi cant enhancement in the expression level of TNF-α , IFN-γ and Bax genes as well as a reduction in the expression level of TGF-β and Bcl2. Shikonin treatment signi cantly reduced the expression level of TNF-α , IFN-γ and Bax. On the other hand, the expression levels of TGF-β and Bcl2 as well as the Glutathione peroxidase-1 (GPX-1) enzyme were signi cantly increased following Shikonin treatment. Conclusion This study emphasizes the immune-modulatory, anti-apoptotic, and anti-oxitive effects of Shikonin, which may have an important healing in uence on the severity of EAE.
Molecular Biology Reports, Nov 1, 2020
Deregulation of microRNAs, as key elements in colorectal cancer (CRC) pathogenesis, is correlated... more Deregulation of microRNAs, as key elements in colorectal cancer (CRC) pathogenesis, is correlated with various stages of this cancer. miR-196 is involved in the initiation and progression of a verity of malignances, especially CRC. miR-196 in CRC cells could target different types of genes with oncogenic and/or tumor suppressor function such as HOX genes, GATA6, SOCS1, SOCS3, ANXA1, DFFA, PDCD4, ZG16 and ING5. Therefore, these genes could be up or down-regulated in cells and subsequently change the capacity of CRC cells in terms of tumor development, progression and, response to therapy. Comprehension of miR-196-associated aberrations underlying the CRC pathogenesis might introduce promising targets for therapy. Additionally, it seems that miR-196 expression profiling, especially circulatory exosomal miR-196, might be useful for diagnosis and prognosis determination of the CRC patients. In this review, at first, we summarize the roles of miR-196 in different types of cancers. After that, a detailed discussion about this miRNA and also their targets in CRC pathogenesis, progression, and response to treatment are represented. Moreover, we highlight the potential utilization of miR-196 and its targets as therapeutic targets and novel biomarkers in early detection and prediction of prognosis in CRC patients.
Clinical Rheumatology, Jul 20, 2022
Journal of Human Hypertension, Aug 20, 2018
The multifactorial basis of preeclampsia (PE) implies that there are several genes and risk facto... more The multifactorial basis of preeclampsia (PE) implies that there are several genes and risk factors that are important in the development of the disease. Therefore, the exact etiology and pathogenesis of preeclampsia remains unclear. It is suggested that inappropriate regulation of the renin-angiotensin system (RAS) is a risk factor for hypertension during pregnancy. The angiotensin I-converting enzyme (ACE) serum level, a key component of the RAS, affects the blood pressure. It is hypothesized that the ACE gene polymorphisms contribute to preeclampsia development. In a case-control study containing 296 subjects (165 PE patients and 131 normotensive controls), we aimed to examine the association of the ACE gene I/D and rs4343 polymorphisms with preeclampsia in Iranian women. Genotyping for rs4343 and ACE I/D polymorphisms was performed by using TP-ARMS-PCR and conventional PCR, respectively. The rs4343 G allele frequency was higher in the case group (OR = 1.90, 95% CI, 1.37-2.65; P = 0.0001). Besides, a significant difference was detected for the genotype frequencies between the studied groups under dominant (OR = 3.94, 95% CI, 2.05-7.56; P < 0.0001) and recessive (OR = 2.21, 95% CI, 1.22-4.01; P = 0.009) inheritance models. For the I/D polymorphism, no significant differences were detected in the genotype and allele frequencies or any of the inheritance models between PE patients and controls. To verify the current results and validate the significance of the studied genetic variations, additional studies in diverse ethnic populations are required.
Iranian journal of public health, Sep 5, 2021
Background: Human Leukocyte Antigen (HLA) system composed of a group of related proteins with imp... more Background: Human Leukocyte Antigen (HLA) system composed of a group of related proteins with important functions in the immune system. Several studies have reported that there is a significant association between specific HLA alleles and the susceptibility to different infectious diseases. This study aimed to detect the specific HLA alleles that cause higher susceptibility to COVID-19, we analyzed the HLA allele frequency distribution in Iranian patients with a severe form of COVID-19. Methods: Overall, 48 severe cases of COVID-19 that were hospitalized and required intensive care unit (ICU) admission between Oct and Dec 2020 were included in this study. Genomic DNA was extracted from the peripheral blood samples and HLA typing (Locus A, B, and DR) was performed for the patients. Results: After analyzing and comparing the results with a reference group of 500 Iranian individuals, a significant association was found for HLA-B*38, HLA-A*68, HLA-A*24, and HLA-DRB1*01. Conclusion: These results may be valuable for studying the potential association of specific HLA alleles with susceptibility to COVID-19 and mortality due to the disease.
Arak Medical University Journal, Dec 1, 2020
Background and Aim Since late 2019, with the emergence of a new type of coronavirus that causes a... more Background and Aim Since late 2019, with the emergence of a new type of coronavirus that causes a new respiratory disease called COVID-19, there have been many concerns about the spread of this disease and how to deal with it. Due to the ability of the virus to be transmitted rapidly, diagnosing the infected individuals in the early stages for isolating them is critical. This study aims to evaluate the reliability of Computed Tomography (CT) scan in diagnosing COVID-19. Methods & Materials Participants were 212 patients admitted to hospital with confirmed diagnosis of CO-VID-19. Demographic information, medical history, symptoms, and the chest CT scan results were collected and analyzed. Finally, the power of CT scans in the diagnosis of this disease was compared with the Real-Time Polymerase Chain Reaction (RT-PCR) molecular test. Ethical Considerations This study received ethical approval from the ethics committee of AJA University of Medical Sciences (Code: IR.AJAUMS.REC.1399.091). Results The sensitivity of CT scan in the diagnosis of COVID-19 was relatively high, but its false-positive results were also high. Conclusion CT scan is a relatively sensitive method for diagnosing COVID-19, but caution should be made due to its high false-positive results which can lead to increased financial burden on the health system.
Arak Medical University Journal, Dec 1, 2020
Background and Aim The new Coronavirus Disease 2019 (COVID-19) outbreak initiated from China in l... more Background and Aim The new Coronavirus Disease 2019 (COVID-19) outbreak initiated from China in late December 2019, has posed a great global health threat. Since patients with high blood pressure, diabetes, and cardiovascular diseases are at high risk of COVID-19, this study aims to investigate the prevalence, severity, clinical manifestations, and mortality rate in COVID-19 patients with underlying diseases compared to those without underlying diseases. Methods & Materials This study was performed on 1408 patients with COVID-19 admitted to Golestan, Hajar, Khanevadeh and Besat hospitals in Tehran, Iran. Required data including disease prevalence, severity, clinical manifestations and mortality rate in patients with and without underlying diseases were collected and then analyzed using statistical tests in SPSS software, considering a significance level of P<0.05. Ethical Considerations This study was approved by the AJA University of Medical Sciences (Code: IR.AJAUMS.REC.1399.091). Ethical principles have been observed in accordance with the guidelines of the National Ethics Committee and the COPE regulations. Results Patients were 912 men (64.8%) and 496 women (35.2%) aged 18-98 years (Mean age= 57.8 years). Results reported that 27% of patients were intubated and 21.9% were died. Blood oxygen level in 53.7% of patients was less than 93 mg/dL; 36.1% had a history of hypertension, 24.1% had a history of diabetes, and 21.7% had a history of cardiovascular disease. Conclusion The severity, clinical manifestations, and mortality rate of COVID-19 patients with cardiovascular disease, diabetes and hypertension are significantly different compared to those without underlying diseases.
Drug Development Research, Apr 29, 2019
Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system. Although ... more Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system. Although the exact etiology of the disease is largely unknown, it is identified that cytokines may play an important role in the pathogenesis of MS. In this study, the effects of curcumin has been investigated on the expression levels of selected cytokine coding genes as well as the extent of demyelination in the corpus callosum of C57BL/6 experimental autoimmune encephalomyelitis (EAE) model of MS. Gene expression analyses revealed that treatment with curcumin could lead to a significant reduction in the expression levels of pro-inflammatory cytokine coding genes including IL-6 (p = 0.001), IL-17 (p = 0.001), tumor necrosis factor (TNF)-α (p = 0.008), and interferon (IFN)-γ (p = 0.033) as well as a significant increase in the expression level of transforming growth factor (TGF)-β (p = 0.006) as an anti-inflammatory cytokine. Moreover, the expression of glutathione peroxidase (GPX)-1 gene and the activity of anti-oxidant enzymes were significantly higher (p < 0.001) in curcumin-treated mice. Luxol fast blue staining also confirmed a significant reduction in the extent of demyelination in the curcumin-treated group (p < 0.001). Our results have confirmed that curcumin is an effective therapeutic agent that could ameliorate the severity of EAE.
Iranian journal of public health, Aug 1, 2021
Iranian Journal of Public Health
Mulibrey Nanism is a rare multisystem disorder inherited in an autosomal recessive manner caused ... more Mulibrey Nanism is a rare multisystem disorder inherited in an autosomal recessive manner caused by mutations in the TRIM37 gene. Most of the reported cases are from Finland, but this condition has rarely occurred in other countries. Although the clinical diagnosis of Mulibrey nanism is a challenge during the first months of life, the disease can be suspected clinically due to the distinctive features of the patients. A 4-year-old female with pneumonia, cardiomyopathy, growth retardation, peripheral edema, and characteristic craniofacial features was referred to Tehran Hope Generation Foundation Genetic diagnosis Center, in October 2021. Genomic DNA was isolated from peripheral blood samples of the patient and her parents and Whole exome sequencing was performed for the patient. Whole exome sequencing revealed a homozygous G>A splice site variant (TRIM37; c.370-1G>A). Sanger sequencing confirmed the segregation of the variant with phenotype in this family. Whole exome sequenc...
Avicenna Journal of Medical Biotechnology
Background: Non-syndromic cleft lip occurs by the interaction of environmental and genetic factor... more Background: Non-syndromic cleft lip occurs by the interaction of environmental and genetic factors. The purpose of the current study was to analyze the association of Single Nucleotide Polymorphisms (SNPs) in IRF6 and NSCL/P in an Iranian population. Methods: A group of 105 children with NSCL/P and 185 normal controls were included in the current study. Genotyping of IRF6 rs2013162 and rs2235375 was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results: A substantial association of AA and CA genotypes in rs2013162 with the risk of NSCL/P (AA vs. CC; OR=2.36; 95%CI [1.05-5.29], p=0.004; and CA vs. CC; OR=0.47; 95%CI [0.28-0.79], p=0.018) was found. However, there were no important associations between A allele and risk of NSCL/P (p=0.980). According to logistic regression analysis results, subjects with GG genotype and G allele in rs2235375 polymorphism had increased risk of NSCL/P. Conclusion: The IRF6 polymorphisms are associated...