Publications by authors named "Arezou Rezaei"

34 Publications

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

Pediatr Allergy Immunol 2021 Mar 27. Epub 2021 Mar 27.

Department of Pediatrics, Hamedan University of Medical Sciences, Hamedan, Iran.

Background: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations.

Methods: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data.

Results: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity.

Conclusions: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pai.13510DOI Listing
March 2021

Contamination of obsterics and gynecology hospital air by bacterial and fungal aerosols associated with nosocomial infections.

J Environ Health Sci Eng 2021 Feb 27:1-8. Epub 2021 Feb 27.

Department of Environmental Health Engineering, Social Determinants of Health (SDH) Research Center, Kashan University of Medical Sciences, Kashan, Iran.

Bacterial and fungal bioaerosols are a global concern due to nosocomial infections, especially in developing countries. Our study aimed to detect fungal and bacterial bioaerosols in different wards of an obstetrics and gynecology hospital air samples. 240 bioaerosol samples were collected by performing impaction method from different wards of a hospital in the central part of Iran, during two seasons. Fungi genera and bacteria species are recognized by cultivation. Concentrations of bacteria and fungi were ranged from 44 to 75 CFU/m and 8 to 22 CFU/m, respectively. Labor Delivery and Recovery (LDR) and Emergency room had first and second most contaminated air among all the hospital wards. No significant difference between microbial load of wards which used natural ventilation and heating, ventilating, and air conditioning (HVAC) system was observed. The microbial load was not affected significantly by temperature, working shift, and Inpatient Bed Occupancy Rate (IBOR). Fungal load related significantly with relative humidity. (detected in 48.3% of samples) and (27%) were the most predominant isolated bacteria and fungi, respectively. The results revealed that the level of bacteria and fungi responsible for nosocomial infections in the air of this hospital is very low. Although levels of microbial contamination are relatively low, it is important to investigate the effect of bioaerosols on nosocomial infections, especially in neonates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40201-021-00637-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914036PMC
February 2021

Design and characterization of new antimicrobial peptides derived from aurein 1.2 with enhanced antibacterial activity.

Biochimie 2021 Feb 30;181:42-51. Epub 2020 Nov 30.

School of Biology, Damghan University, Damghan, Iran; Institute of Biological Sciences, Damghan University, Damghan, Iran.

Antimicrobial peptides (AMPs) are promising alternative agents for treating multidrug-resistant bacterial infections. Aurein 1.2 is a natural 13-amino acid AMP with antibacterial activity against Gram-positive bacteria. In this study, we designed three novel AMPs: aurein M1 (A10W), aurein M2 (D4K, E11K), and aurein M3 (A10W, D4K, E11K) to analyze the effect of Trp substitution and enhancement of positive charge on the activity of aurein 1.2. The AMP probability, physicochemical properties, secondary and tertiary structures, and amphipathic structure were predicted by various bioinformatics tools. After the synthesis of the peptides, their antibacterial activity, hemolysis, cytotoxicity, and structural analysis were assayed. Compared to the selectivity of aurein 1.2, the selectivity of aurein M2 and M3 with a net positive charge of +5 was improved 11.30- and 8.00-fold against Gram-positive and -negative bacteria, respectively. The hemolytic activity of aurein M2 was lower than that of aurein 1.2 and M3, while the higher percentage of human fibroblast cells were alive in the presence of aurein M3. Also, the MICs of aurein M3 toward Staphylococcus aureus and Escherichia coli at the physiologic salt were ≤16, which is recommended as a promising candidate for clinical investigation. Circular dichroism analysis indicated an alpha-helical structure in the peptide analogs that is similar to aurein 1.2 in the presence of 10 mM SDS. Therefore, increasing positive charge can be used successfully as an approach for improving the potency and selectivity of AMPs. Moreover, the beneficial effect of Trp substitution depends on its position and the sequence of peptides.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biochi.2020.11.020DOI Listing
February 2021

Impact of SARS-CoV-2 Pandemic on Patients with Primary Immunodeficiency.

J Clin Immunol 2021 02 1;41(2):345-355. Epub 2020 Dec 1.

Research Center for Primary Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Although it is estimated that COVID-19 life-threatening conditions may be diagnosed in less than 1:1000 infected individuals below the age of 50, but the real impact of this pandemic on pediatric patients with different types of primary immunodeficiency (PID) is not elucidated. The current prospective study on a national registry of PID patients showed that with only 1.23 folds higher incidence of infections, these patients present a 10-folds higher mortality rate compared to population mainly in patients with combined immunodeficiency and immune dysregulation. Therefore, further management modalities against COVID-19 should be considered to improve the survival rate in these two PID entities using hematopoietic stem cell transplantation and immunomodulatory agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10875-020-00928-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707812PMC
February 2021

The effects of Elaeagnus angustifolia L. on lipid and glycaemic profiles and cardiovascular function in menopausal women: A double-blind, randomized, placebo-controlled study.

Int J Clin Pract 2021 Apr 2;75(4):e13812. Epub 2020 Dec 2.

School of Biology, Damghan University, Damghan, Iran.

Aims: The reduced production of ovarian hormones is considered to be the cause of an increase in the incidence of heart disease in women after menopause. Phytoestrogens are found in various herbal sources and are considered as an alternative to hormone therapy because of structural similarity with oestrogen. Elaeagnus angustifolia L., known as Senjed in Persian, is used in Iranian traditional medicine with various medicinal properties, contains valuable compounds, including two types of phytoestrogens. The aim of the present study was to investigate the efficacy of E. angustifolia fruit on the cardiovascular function, lipid and glycaemic profiles in postmenopausal women.

Methods: In this double-blind placebo-controlled clinical trial, 58 postmenopausal women were randomly assigned into two experimental groups of medicinal herb (15 g/day of the whole E. angustifolia fruit powder) and placebo (15 g/day of isomalt + corn starch). Before the trial and after 10 weeks of the treatment, cardiovascular function (heart rate, blood pressure), serum glycaemic profile (fasting blood glucose; glycated haemoglobin, HbA1C), insulin and lipid profile (total cholesterol, TC; triglyceride, TG; LDL-C and HDL-C) were measured.

Results: Heart rate, and serum level of LDL-C and HDL-C significantly decreased after treatment with E. angustifolia. Changes in glycaemic profile were not clinically significant. In addition, some studied biochemical parameters significantly changed in the placebo group.

Conclusions: E. angustifolia was somewhat effective in improving cardiovascular function and lipid profile, as well as the overall health of postmenopausal women. However, the use of isomalt and corn starch in menopausal women needs further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijcp.13812DOI Listing
April 2021

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

Int Arch Allergy Immunol 2020 2;181(9):706-714. Epub 2020 Jul 2.

Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis.

Methods: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data.

Results: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity.

Conclusion: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000508817DOI Listing
February 2021

Effect of Class Switch Recombination Defect on the Phenotype of Ataxia-Telangiectasia Patients.

Immunol Invest 2021 Feb 2;50(2-3):201-215. Epub 2020 Mar 2.

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, University of Medical Science , Tehran, Iran.

: Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder with multisystem involvement caused by homozygous or compound heterozygous mutations in the gene which encodes a serine/threonine protein kinase. The aims of this study were to investigate class switch recombination (CSR) and to review the clinical and immunologic phenotypes of 3 groups of A-T patients, including A-T patients with CSR defects (CSR-D), A-T patients with selective immunoglobulin A deficiency (IgA-D) and A-T patients with normal Ig level. : In this study, 41 patients with confirmed diagnosis of A-T (16 A-T patients with HIgM, 15 A-T patients with IgA-D, and 10 A-T patients with normal Ig levels) from Iranian immunodeficiency registry center were enrolled. B-cell proliferation, CSR toward IgE and IgA were compared between three groups as well as G2 radiosensitivity assay. : Earliest presentation of telangiectasia was a significant hallmark in A-T patients with CSR-D ( = .036). In this investigation, we found that the frequency of respiratory infection ( = .002), pneumonia ( = .02), otitis media ( = .008), chronic fever ( < .001), autoimmunity ( = .02) and hepatosplenomegaly ( = .03) in A-T patients with HIgM phenotype were significantly higher than the other groups. As expected IgE production stimulation and IgA CSR were perturbed in HIgM patients that were aligned with the higher readiosenstivity scores in this group. : A-T patients with HIgM compared to other A-T patients presenting more infections and noninfectious complications, therefore, early detection and careful management of these patients is necessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08820139.2020.1723104DOI Listing
February 2021

Interleukin 10 and Transforming Growth Factor Beta Polymorphisms as Risk Factors for Kawasaki Disease: A Case-Control Study and Meta-Analysis.

Avicenna J Med Biotechnol 2019 Oct-Dec;11(4):325-333

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Alteration in serum expression of Transforming Growth Factor-beta (TGF-β) and IL-10 have been suggested to play a role in the pathogenesis of Kawasaki Disease (KD). Inconsistent reports exist on the association of IL-10 polymorphisms with KD susceptibility and Coronary Artery Aneurysms (CAA).

Methods: A number of 110 paediatric patients with KD and 140 healthy individuals were recruited to investigate the frequency of Single Nucleotide Polymorphisms (SNPs) of TGF-β C/T at codon 10 (rs1982073), C/G at codon 25 (rs1800471) and IL-10 A/G at -1082 (rs1800896), C/T at -819 (rs1800871) and A/C at -592 (rs1800872) and their respective genotype and haplotypes. A comprehensive search was performed in MEDLINE and SCOPUS using the keywords of interleukin 10, transforming growth factor beta, and Kawasaki disease. Moreover, previous studies investigating the TGF-β and IL-10 polymorphisms in KD were evaluated. Review Manager Version 5.1 Software was used to perform meta-analysis.

Results: There was no significant association between allelic or genotypic variants in the mentioned polymorphisms in TGF-β or IL-10 with KD or CAA. The only significant haplotypic variant was TC variant at codon 10, and 25 of TGF-β polymorphisms were associated with higher risk of KD. Meta-analysis of a total number of 770 patients 1471 healthy controls showed no difference in the frequency of any of the IL-10 genetic variants in KD patients, regardless of the presence of CAA.

Conclusion: Polymorphisms of TGF-β or IL-10 are not associated with additional risk for KD in Iranian population. IL-10 polymorphisms at -1082, -819 and -592 positions are not associated with KD, nor do they predict coronary artery aneurysm formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925396PMC
January 2020

The effects of Elaeagnus angustifolia L. whole fruit on the sex hormone profile in menopausal women: A double-blind, randomized, placebo-controlled study.

J Ethnopharmacol 2020 Jan 9;246:112229. Epub 2019 Sep 9.

School of Biology, Damghan University, Damghan, Iran. Electronic address:

Ethnopharmacological Relevance: Menopause is a product of interrupted ovarian activity and decrease in its estradiol production. Herbal medicines as an alternative to hormone therapy are increasingly used by menopausal women. Elaeagnus angustifolia L. (Senjed in Persian) is a well-known herbal remedy with various therapeutic effects according to Iranian traditional medicine which is recommended to relieve the menopausal side effects. The aim of present study was to evaluate the effects of oral intake of whole fruit powder of E. angustifolia on the sex hormones profile in menopausal women.

Materials And Methods: In present double-blind randomized placebo-controlled trial, 58 eligible women who were referred to Kamali Women Hospital (Karaj, Iran, 2017) were randomly assigned into herbal medicine (15 g E. angustifolia) and placebo (7.5 g cornstarch +7.5 g isomalt) groups. Initially and after 10 weeks of the treatment, serum levels of estradiol, progesterone, testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) hormones were measured.

Results: According to between-group analyses, the changes in the studied parameters were not significant between herbal medicine and placebo groups, except for joint pain that improved significantly in herbal medicine group. However, by within-group analysis the levels of FSH and FSH to testosterone showed a significant increase, whereas the level of progesterone decreased significantly after 10 weeks of E. angustifolia consumption.

Conclusions: The improvement of the sex hormone profile was not in a full accordance with Iranian folklore after E. angustifolia consumption in the present menopausal participants. However, considering a strong belief on the beneficial effects of E. angustifolia in Iranian folklore, a long-term studies of larger group participants are needed to evaluate the efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2019.112229DOI Listing
January 2020

Clinical Manifestations, Immunological Characteristics and Genetic Analysis of Patients with Hyper-Immunoglobulin M Syndrome in Iran.

Int Arch Allergy Immunol 2019 22;180(1):52-63. Epub 2019 May 22.

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran,

Background: Hyper-immunoglobulin M (HIGM) syndrome is a rare heterogeneous group of primary immunodeficiency disorders characterized by low or absent serum levels of IgG and IgA along with normal or elevated serum levels of IgM.

Methods: Clinical and immunological data were collected from the 75 patients' medical records diagnosed in Children's Medical Center affiliated to Tehran University Medical Sciences and other Universities of Medical Sciences in Iran. Among 75 selected patients, 48 patients (64%) were analyzed genetically using targeted and whole-exome sequencing.

Results: The ratio of male to female was 2.9:1. The median age at the onset of the disease, time of diagnosis, and diagnostic delay were 10.5, 50, and 24 months, respectively. Pneumonia and lower respiratory tract infections (61.3%) were the most common complications. Responsible genes were identified in 35 patients (72.9%) out 48 genetically analyzed patients. Cluster of differentiation 40 ligand gene was the most mutated gene observed in 24 patients (68.5%) followed by activation-induced cytidine deaminase gene in 7 patients, lipopolysaccharide-responsive and beige-like anchor (1 patient), nuclear factor-kappa-B essential modulator (1 patient), phosphoinositide-3-kinase regulatory subunit 1 (1 patient), and nuclear factor kappa B subunit 1 (1 patient) genes. Nineteen (25.3%) patients died during the study period, and pneumonia was the major cause of death occurred in 6 (31.6%) patients.

Conclusion: Physicians in our country should carefully pay attention to respiratory tract infections and pneumonia, particularly in patients with a positive family history. Further investigations are required for detection of new genes and pathways resulting in HIGM phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000500197DOI Listing
September 2019

Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis.

J Clin Immunol 2018 10 9;38(7):816-832. Epub 2018 Oct 9.

Pediatric Infections Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders.

Method: The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013-2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing.

Results: Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort.

Conclusions: During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10875-018-0556-1DOI Listing
October 2018

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort.

J Allergy Clin Immunol Pract 2019 03 19;7(3):864-878.e9. Epub 2018 Sep 19.

Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.

Background: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses.

Objective: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings.

Methods: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID.

Results: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 μ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with μ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with μ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008).

Conclusions: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2018.09.004DOI Listing
March 2019

Conditioned Medium Protects Dopaminergic Neurons in Parkinsonian Rats.

Cell J 2018 Oct 15;20(3):348-354. Epub 2018 May 15.

Institute of Biological Sciences, Damghan University, Damghan, Iran.

Objective: Adipose derived stem cells (ASCs) secrete numerous neurotrophic factors and cytokines in conditioned medium (CM), which protect neurons by its antioxidative and trophic effects. This research assesses the neuroprotective effect of ASCCM on neurotrophins genes expressions and tyrosine hydroxylase positive (TH) cell density in male Wistar rats lesioned by 6-hydroxydopamine (6-OHDA).

Materials And Methods: In this experimental study, the groups consisted of lesioned and sham rats with unilateral injections of 20 μg of 6-OHDA neurotoxin and phosphate buffered saline (PBS) into the striatum, respectively. Another groups received intravenous injections of 3×106 cells (ASCs group), 500 μl of CM (ASC-CM group) or medium [α-minimal essential medium (α-MEM) group)]. All rats underwent evaluations with the rotarod and apomorphine-induced rotation tests at 2, 4, 6, and 8 weeks post-injection. At 8 weeks we sacrificed some of the animals for real-time polymerase chain reaction (PCR) analysis, and evaluation of TH cell counts.

Results: We observed a significant decrease in contralateral turns to the lesions in the ASCs and ASC-CM groups compared to the neurotoxin lesioned or α-MEM groups at 8 weeks post transplantation. Cell and CM- injected rats showed a significant increase of staying on the rotarod compared to the lesion or α-MEM groups. Cell and CM-treated rats showed significant increases in the NGF and NT3 genes, respectively, compared with the lesion group. Both treated groups showed significant increases in BDNF gene expression and TH cell density.

Conclusion: The results suggested that ASCs and ASC-CM protected dopaminergic neurons through the expressions of neurotrophin genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22074/cellj.2018.5343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004993PMC
October 2018

Association of interferon regulatory factor 5 (IRF5) gene polymorphisms with juvenile idiopathic arthritis.

Clin Rheumatol 2018 Oct 8;37(10):2661-2665. Epub 2018 Feb 8.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, 14194, Iran.

Interferon regulatory factor 5 (IRF5) is a member of IRF family which induce signaling pathways and are involved in modulation of cell growth, differentiation, apoptosis, and immune system activity. Juvenile idiopathic arthritis (JIA) is an auto-inflammatory syndrome where the inflammatory markers are believed to play a fundamental role in its pathogenesis. In this study, we aimed to assess the association of IRF5 gene polymorphisms with susceptibility of JIA in Iranian population. Three IRF5 single-nucleotide polymorphisms (rs10954213 A/G, rs2004640 G/T, and rs3807306 G/T) were genotyped using TaqMan assays in 55 patients with JIA and 63 matched healthy individuals. The frequency of the IRF5 rs2004640 T allele was significantly higher (69 vs 45%, P value = 0.0013) in JIA group as compared to control. The frequency of the IRF5 rs 2004640 G allele was significantly higher in the control group in comparison to JIA group (54 vs 32%, P value = 0.001). Allele and genotype frequencies of the rs10954213 and rs3807306 did not show any significant difference between JIA and control group. IRF5 rs 2004640 T allele can be considered as a risk factor for the development of JIA and presence of rs 2004640 G may be act as protective factor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-018-4010-9DOI Listing
October 2018

Multiple spectroscopic studies of the interaction between a quaternary ammonium-based cationic Gemini surfactant (as a carrier) and human erythropoietin.

J Biomol Struct Dyn 2018 Oct 26;36(13):3479-3486. Epub 2017 Oct 26.

a School of Biology , Damghan University , Damghan , Iran.

Erythropoietin (EPO) is a hematopoietic growth factor. This substance, as a strong cell protector, can increase cell maintenance during different damages of central nervous system. Since the brain-blood barrier prevents the entrance of large proteins similar to EPO into the brain, its systemic delivery gets limited. The aim of this study was to find an alternative approach for EPO delivery into the brain to skip the blood-brain barrier prevention. So, a new quaternary ammonium-based cationic Gemini surfactant has been used to study the interaction of the cationic Gemini surfactant (as a carrier) with EPO using various spectroscopic techniques of (fluorescence and circular dichroism (CD)) and thermal denaturation. Fluorescence spectroscopy studies show the formation of Gemini-EPO complex and also static quenching of protein upon this interaction. The binding parameters of number of binding sites, binding affinity, Gibbs free energy, enthalpy, and entropy were calculated according to fluorescence quenching studies. Also, CD results have further represented that the content of regular secondary structure of EPO did not show any significant alterations by increasing the Gemini concentration. Finally, thermal denaturation behavior of EPO results indicates decreasing the thermal stability of protein in the presence of Gemini. In conclusion, the obtained results proposed that Gemini as a cationic surfactant can bind to EPO without any significant diverse effects on the structure of this drug (EPO) which can be considered as a candidate for EPO delivery in future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2017.1391123DOI Listing
October 2018

Association of PTPN22 Single Nucleotide Polymorphisms with Celiac Disease.

Fetal Pediatr Pathol 2017 Jun 8;36(3):195-202. Epub 2017 May 8.

a Children's Medical Center, Tehran University of Medical Sciences , Tehran , Iran.

Objectives: Celiac disease is a chronic autoimmune disease in which gene-environment interactions cause the immune system to unfavorably react to naturally gluten-containing foods. PTPN22 plays a crucial role in regulating the function of various cells of the immune system, particularly T cells. Polymorphisms of the PTPN22 gene have been associated with many autoimmune diseases. The present genetic association study was conducted to investigate the possible associations between PTPNTT single nucleotide polymorphisms (SNPs) and celiac disease in an Iranian population.

Materials And Methods: The study population consisted of 45 patients with celiac disease and 93 healthy controls. The study genotyped five SNPs of the PTPN22 gene: rs12760457, rs1310182, rs1217414, rs33996649, and rs2476601.

Results And Conclusions: Control and patient groups did not differ on the genotype distribution of four of five investigated SNPs in the PTPN22 gene, for example, rs12760457, rs2476601, rs1217414, and rs33996649. The only investigated PTPN22 variant, which could be associated with CD, was rs1310182. A significant increase in the carriage of the T allele of rs1310182 in CD patients was observed (OR (95% CI) = 11.42 (5.41, 24.1), p value < 0.0001). The TT genotype of this SNP was significantly associated with celiac disease. Our study suggests that the rs1310182 SNP of PTPN22 gene may be a predisposing factor of celiac disease in the Iranian population. Further studies are required to investigate the issue in other racial and ethnic subgroups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15513815.2017.1290725DOI Listing
June 2017

PTPN22 Single-Nucleotide Polymorphisms in Iranian Patients with Type 1 Diabetes Mellitus.

Immunol Invest 2017 May 4;46(4):409-418. Epub 2017 Apr 4.

d Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences , Tehran , Iran.

Background: PTPN22 plays a crucial role in regulating the function of various cells of the immune system, particularly T cells. Polymorphisms of the PTPN22 gene have been associated with many autoimmune diseases, including type 1 diabetes (T1D) which is a T-cell-mediated disease.

Objective: The present study was aimed at genotyping of an Iranian population for five polymorphisms of the PTPN22 gene.

Methods: The study population consisted of 99 T1D patients and 100 healthy controls. We genotyped five single-nucleotide polymorphisms (SNPs) (rs12760457, rs1310182, rs1217414, rs33996649, and rs2476601) of the PTPN22 gene.

Results: Regarding the variant rs2476601, genotypes AG and GG were increased and decreased in T1D patients compared with controls, respectively. Further, alleles G and A of this SNP were found to be decreased and increased in T1D patients, respectively (p value = 0.001). However, T1D and control groups did not differ on genotype distribution or allele frequency for other investigated SNPs.

Conclusions: The PTPN22 rs2476601 minor allele (A) was associated with T1D in Iran, accounting for its pathophysiology in autoimmune diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08820139.2017.1288239DOI Listing
May 2017

Interleukin-4 cytokine single nucleotide polymorphisms in kawasaki disease: a case-control study and a review of knowledge.

Int J Rheum Dis 2018 Jan 30;21(1):266-270. Epub 2016 Dec 30.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Aim: Kawasaki disease (KD) is a systemic vasculitis of medium-sized arteries. High levels of interleukin 4 (IL-4) and the dominance of Th2 cytokines seem to be a key feature in the acute phase of KD. In this study, the role of IL-4 and IL-4R gene polymorphisms were investigated in Iranian children with KD.

Methods: Fifty-five patients with KD and 140 healthy subjects as a control group were enrolled in this study. Single nucleotide polymorphisms (SNPs) of IL-4 gene at positions -1098 (rs2243248), -590 (rs2243250) and -33 (rs2070874), as well as IL-4RA gene at position +1902 (rs180275) were assessed in patients and the control group.

Results: The C allele and CC genotype of IL-4 gene at position -590 and at position -33 had positive associations and the CT genotype at -590 was negatively associated with KD (odds ratio (95% CI) = 0.04 [0.01-0.09]). The haplotype TCC was more frequent among the patients, while the haplotypes TTT and TTC had a negative association with KD.

Conclusion: IL-4 polymorphisms might be associated with KD in an Iranian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1756-185X.12968DOI Listing
January 2018

APRIL gene polymorphism and serum sAPRIL levels in children with systemic lupus erythematosus.

Clin Rheumatol 2017 Apr 23;36(4):831-836. Epub 2016 Nov 23.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Systemic lupus erythematosus (SLE) is a multi-factor autoimmune disorder with diverse clinical manifestations and unclear pathogenesis. Genetic components play important roles in the incidence and development of SLE. Among these, APRIL as a cytokine has roles in the stimulation and antibody production in B cells. APRIL was hypothesized to be associated with SLE. The aim of this study was to assess the involvement of the APRIL gene in SLE susceptibility in Iranian patients. A single-nucleotide polymorphism (SNP) for rs11552708 of APRIL gene was analyzed by real-time PCR in 60 SLE Iranian children and 64 healthy controls. DNA samples of patients and healthy controls were extracted from peripheral blood leukocytes by phenol-chloroform. Serum samples obtained from 45 children with SLE and 45 healthy controls were assayed by enzyme-linked immunosorbent assay (ELISA). The G/G genotype (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.22-2.07; P = 0.68) and G allele (OR 0.81, 95% CI 0.25-2.56; P = 0.89) frequencies of polymorphism at codon 67 (67G) do not differ significantly in the SLE patients compared with those in the healthy controls. The serum APRIL levels in the SLE patients (mean ± SD = 29.27 ng/ml ± 20.77, range from 0 to 55.33 ng/ml) were significantly higher than those in the healthy controls (P = 0.02). Our results demonstrated that rs11552708 of the APRIL gene is not associated with SLE susceptibility in Iranian children. Likewise, these findings suggest that APRIL antagonist could be a potential therapeutic target to control SLE in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-016-3466-8DOI Listing
April 2017

Association of interleukin-6 single nucleotide polymorphisms with juvenile idiopathic arthritis.

Clin Rheumatol 2017 Jan 20;36(1):77-81. Epub 2016 Sep 20.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, 14194, Iran.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Genetics and inflammatory elements seem to act as major underlying factors in its pathogenesis. The aim of this study is to identify the associations between interleukin-6 (IL-6) gene polymorphisms and individuals' vulnerability to JIA in a group of Iranian pediatric patients. Fifty-four patients with JIA were enrolled in this investigation and compared with 139 healthy individuals. Using polymerase chain reaction with sequence-specific primers, cytokine genotyping was performed. The allele and genotype frequencies of two single nucleotide polymorphisms (SNPs) within the IL-6 gene at -174 and +565 positions were assessed. A significant positive association was observed for IL -6 -174 G allele in the patient group (p = 0.02). Furthermore, a positive association was observed in patients with JIA for the GG genotype at the same position (p < 0.01), thus revealing a predisposing effect in JIA patients. On the other hand, a significant negative association was found for IL-6 -174 CG genotype (p < 0.01) in the case group. No significant difference was discovered in both the allelic and genotypic frequencies of IL-6 +565 position between patients and controls. Additionally, haplotype analysis divulged over representation of IL-6 GG haplotype in patient group (p < 0.01) as well as IL-6 CG haplotype in healthy controls (p < 0.01). Certain allele, genotype, and haplotype in IL-6 gene were over expressed in patients with JIA, which probably could render individuals more susceptible to this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-016-3407-6DOI Listing
January 2017

Pro-inflammatory cytokine single nucleotide polymorphisms in Kawasaki disease.

Int J Rheum Dis 2018 May 25;21(5):1120-1126. Epub 2016 Jul 25.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Aim: Kawasaki disease (KD) is a systemic vasculitis of children associated with cardiovascular sequelae. Proinflammatory cytokines play a major role in KD pathogenesis. However, their role is both influenced and modified by regulatory T-cells. IL-1 gene cluster, IL-6 and TNF-α polymorphisms have shown significant associations with some vasculitides. Herein we investigated their role in KD.

Methods: Fifty-five patients with KD who were randomly selected from referrals to the main pediatric hospital were enrolled in this case-control study. Single nucleotide polymorphisms (SNPs) of the following genes were assessed in patients and 140 healthy subjects as control group: IL-1α at -889 (rs1800587), IL-1β at -511 (rs16944), IL-1β at +3962 (rs1143634), IL-1R at Pst-I 1970 (rs2234650), IL-1RN/A at Mspa-I 11100 (rs315952), TNF-α at -308 (rs1800629), TNF-α at -238, IL-6 at -174 (rs1800795) and IL-6 at +565.

Results: Twenty-one percent of the control group had A allele at TNF-α -238 while only 8% of KD patients had A allele at this position (P = 0.003, OR [95%CI] = 0.32 [0.14-0.71]). Consistently, TNF-α genotype GG at -238 had significant association with KD (OR [95% CI] = 4.31 [1.79-10.73]). Most controls carried the CG genotype at IL-6 -174 (n = 93 [66.9%]) while GG genotype was the most common genotype (n = 27 [49%]) among patients. Carriers of the GG haplotype at TNF-α (-308, -238) were significantly more prevalent among the KD group. No association was found between IL-1 gene cluster, allelic or haplotypic variants and KD.

Conclusion: TNF-α GG genotype at -238 and GG haplotype at positions -308 and -238 were associated with KD in an Iranian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1756-185X.12911DOI Listing
May 2018

Polymorphisms of genes encoding interleukin-4 and its receptor in Iranian patients with juvenile idiopathic arthritis.

Clin Rheumatol 2016 Aug 7;35(8):1943-1948. Epub 2016 Mar 7.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr Qarib St, Keshavarz Blvd, Tehran, 14194, Iran.

As cytokines, including interleukin-4 (IL-4), seem to have a pivotal role in the pathogenesis of juvenile idiopathic arthritis (JIA), this study is aimed at investigating of association of polymorphisms in IL-4 and IL-4 receptor α (IL-4RA) genes with susceptibility to JIA. A case-control study was conducted on 53 patients with JIA and 139 healthy unrelated controls. Single nucleotide polymorphisms of IL-4 gene at positions -1098, -590, and -33, as well as IL-4RA gene at position +1902 were genotyped using polymerase chain reaction with sequence-specific primers method and compared between patients and healthy individuals. At the allelic level, C allele at IL-4 -33 was found to be more frequent in patients compared to control (P value <0.01). At the genotypic level, CC genotype at IL-4 -590 (P value <0.01), together with CC and TT genotypes at IL-4 -33 (P value <0.01), were significantly higher in patients with JIA, while TC genotypes at IL-4 -590 and -33 positions were found to be lower in case group (P value <0.01). At the haplotypic level, IL-4 (positions -1098, -509, -33) TTC, GCC, and TTT haplotypes were significantly lower than controls (P value <0.01, P value = 0.03, and P value = 0.04, respectively). Although, TCC haplotype at the same positions was found to be higher in patients (P value <0.01). Polymorphic site of +1902 IL-4RA gene did not differ between cases and controls. Polymorphisms in promoter region of IL-4 but not IL-4RA genes confer susceptibility to JIA and may predispose individuals to adaptive immune responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-016-3224-yDOI Listing
August 2016

Serum IL-33 Is Elevated in Children with Asthma and Is Associated with Disease Severity.

Int Arch Allergy Immunol 2015 21;168(3):193-6. Epub 2016 Jan 21.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: The role of IL-33, a member of the IL-1 family, in airway hyperresponsiveness and asthma has still to be fully understood.

Objectives: This study is aimed at investigating serum IL-33 in children with asthma and its association with asthma severity.

Methods: This age- and sex-matched case-control study comprised 61 children with asthma and 63 healthy controls. The mean age of the participants was 9.21 years (range: 6-14). Serum IL-33 was measured using ELISA and was compared between children with asthma and controls. In addition, the association of serum IL-33 with asthma severity was investigated.

Results: The level of serum IL-33 was significantly higher in children with asthma than in controls (15.17 ± 32.3 vs. 0.61 ± 2.16 pg/ml; p = 0.028). It was significantly increased proportionately to asthma severity, namely 9.92 ± 30.26 pg/ml in children with mild asthma, 13.68 ± 29.27 pg/ml in children with moderate asthma and 31.92 ± 41.45 pg/ml in children with severe asthma (p = 0.026).

Conclusion: Serum IL-33 is increased in children with asthma and is associated with disease severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000442413DOI Listing
June 2016

Association of Interleukin-1 Gene Cluster and Interleukin-1 Receptor Polymorphisms With Febrile Seizures.

J Child Neurol 2016 May 23;31(6):673-7. Epub 2015 Oct 23.

Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Interleukin-1 (IL-1) plays a key role in inflammation, has an effect on a wide variety of cells, and often leads to tissue destruction. While the ratio between IL-1 and IL-1Ra could influence the development of different diseases of the central nervous system, its gene polymorphisms were investigated in a group of patients with febrile seizures. Ninety patients with febrile seizures were enrolled and compared with 140 controls. The allele and genotype frequency of single nucleotide polymorphisms within the IL-1α, β, IL-1 R and IL-1Ra gene were determined. The frequency of the IL-1Ra/C allele at position Mspa-I 11100 was decreased significantly (P= .002) and the IL-1Ra/T frequency was significantly increased in patients (P= .002). In addition, the CT genotype frequency at the same position was significantly overrepresented in controls compared to patients (P= .001). Certain alleles and genotypes in the IL-1 gene were overrepresented in patients with febrile seizures, which possibly could predispose individuals to this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0883073815610429DOI Listing
May 2016

Diabetes mellitus and its management with medicinal plants: A perspective based on Iranian research.

J Ethnopharmacol 2015 Dec 14;175:567-616. Epub 2015 Aug 14.

Institute for Advanced Studies in Basic Sciences, Zanjan, Iran.

Ethnopharmacological Relevance: Complementary and alternative medicine has been increasingly used to treat chronic illnesses, such as diabetes mellitus. However, various limitations in terms of their application and efficacies exist. Furthermore, there is still much to be done to discover the right herbal medicine for diabetes.

Aim Of The Study: This paper aims to evaluate previous herbal studies on the management of diabetes mellitus, to address their strengths and weaknesses and propose a general framework for future studies.

Approach And Methods: Data sources such as PubMed, ScienceDirect, Scopus, SpringerLink, and Wiley were searched, limited to Iran, using 36 search terms such as herbal, traditional, medicine, and phytopharmacy in combination with diabetes and related complications. Reviewed articles were evaluated regarding the use of botanical nomenclature and included information on (1) identity of plants and plant parts used, (2) the processing procedure, and (3) the extraction process. The main outcomes were extracted and then surveyed in terms of the efficacies of herbs in the management of diabetes mellitus. Then a comparative study was performed between Iranian and non-Iranian studies with respect to herbs best studied in Iran.

Results: Of the 82 herbs studied in Iran, only six herbs were endemic and 19 were studied in detail. Although most of the reviewed herbs were found to decrease the level of blood glucose (BG) and/or glycated hemoglobin (HbA1C) in both Iranian and non-Iranian studies, information on their pharmacological mechanisms is scarce. However, the level of HbA1C was measured in a limited number of clinical trials or animal studies. Available information on both short- and long-term use of studied herbs on diabetes related complications and functions of involved organs as well as comorbid depression and/or simultaneous changes in lifestyle is also insufficient. Furthermore, little or no information on their phytochemical, toxicological, and herb-drug interaction properties is available. It is worth noting that the efficacy of the reviewed herbs has been studied scarcely in both humans and animals regarding both Iranian and non-Iranian studies. A significant number of reviewed articles failed to cite the scientific name of herbs and include information on the processing procedure and the extraction process.

Conclusions: Treatment of diabetes mellitus as a multifactorial disease using herbal medicines requires a comprehensive approach. In order to discover the right herbal medicine for the management of diabetes many other important factors than the levels of BG, HbA1C and insulin should be considered. According to our criteria, all the reviewed herbs suffered from inadequate investigation in human, animal and in vitro models in this respect, whereas they are worth investigating further. However, more research on endemic plants and the traditional history of herbal medicine is warranted. In our opinion, the pharmacological, toxicological, and phytochemical information should be obtained before clinical trials. Furthermore, information such as botanical scientific nomenclature, side effects, and toxicity will improve the quality and validity of publications in herbal research. In particular, designing a database covering all valid information about herbs and/or diseases will decrease unnecessary costs and increase the efficiency of research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2015.08.010DOI Listing
December 2015

Tumor necrosis factor-alpha single nucleotide polymorphisms in juvenile systemic lupus erythematosus.

Hum Immunol 2015 Aug 24;76(8):533-6. Epub 2015 Jun 24.

Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Molecular Immunology Research Center, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Juvenile systemic lupus erythematosus (JSLE) is a multi-system autoimmune disorder of unknown origin. Given the importance of the contribution of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), towards the pathogenesis of JSLE, this study was performed to assess TNFA gene polymorphisms in a case-control study.

Methods: Fifty nine patients with JSLE were enrolled in this study as case group and compared with healthy control subjects. The frequency of alleles, genotypes, and haplotypes of TNFA single-nucleotide polymorphisms (SNPs) at positions -308 and -238 were evaluated, using polymerase chain reaction with sequence-specific primers method.

Results: The G allele at position -238 in TNFA promoter region was significantly more frequent in patients with JSLE than in the healthy controls (P value<0.001), while the frequency of A allele at the same position was significantly lower than controls. Furthermore, a significant positive association for G/G genotype at the same position was detected in patients' group compared with control subjects (P value<0.001). The GA haplotype of TNFA (positions -308, -238) was significantly less frequent in case group than in controls (P value<0.001), while GG was the most frequent haplotype for TNFA in the patient group, compared to controls (P value<0.01).

Conclusions: Pro-inflammatory cytokine gene polymorphisms may influence susceptibility to JSLE. Particular TNFA gene variants are associated with JSLE and could be used as a genetic marker for susceptibility to JSLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humimm.2015.06.011DOI Listing
August 2015

IL23R gene polymorphism with juvenile idiopathic arthritis and its association with serum IL-17A.

Int J Rheum Dis 2016 Nov 27;19(11):1189-1196. Epub 2015 May 27.

Department of Immunology, School of Medicine, Tehran, Iran.

Aim: Interleukin 23 (IL-23) and its receptor (IL-23R) seem to play a major role in differentiation of CD4 T cells into Th17 cells, induction of IL-17 production, and activation of inflammatory pathways. Recent studies have suggested the association of IL-23R polymorphisms with bone and articular inflammation in diseases such as ankylosing spondylitis and rheumatoid arthritis. The aim of this study was to determine the association between IL-23R polymorphisms and juvenile idiopathic arthritis (JIA).

Method: A case-control study on 55 patients with JIA and 78 healthy controls was performed. All samples were genotyped for eight single nucleotide polymorphisms (SNPs) of IL23R (rs1004819, rs2201841, rs10889677, rs1495965, rs7517847, rs10489629, rs11209026 and rs1343151), using real-time polymerase chain reaction Taqman genotyping technique. Forty-two patients and 42 healthy controls were chosen randomly to measure the level of serum IL-17A using enzyme-linked immunosorbent assay.

Results: Although the heterozygous genotype of rs1004819 (GA) showed a weak, but statistically significant protective effect on polyarticular subtype (P = 0.03), none of the selected SNPs were associated with JIA overall. Indeed the analysis of haplotypes did not show any significant association with JIA. Serum IL-17A level was not significantly different among patients and healthy controls and between JIA subtypes, as well. Moreover, there was no significant correlation between SNPs and serum IL-17A concentration.

Conclusion: This is the first study of the IL-23R gene in Iranian patients with JIA. Our results did not show any strong association between IL-23R polymorphisms and JIA disease or serum IL-17A levels. The only association was seen between rs1004819 and polyarticular JIA. Further larger studies may help clarify the role, if any, of the IL-23/IL-17 pathway in the pathogenesis of JIA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1756-185X.12674DOI Listing
November 2016

Encapsulation of curcumin in diblock copolymer micelles for cancer therapy.

Biomed Res Int 2015 22;2015:824746. Epub 2015 Feb 22.

Cancer Research Center, Tehran University of Medical Sciences, Tehran 14197-33141, Iran.

Application of nanoparticles has recently promising results for water insoluble agents like curcumin. In this study, we synthesized polymeric nanoparticle-curcumin (PNPC) and then showed its efficiency, drug loading, stability, and safety. Therapeutic effects of PNPC were also assessed on two cell lines and in an animal model of breast cancer. PNPC remarkably suppressed mammary and hepatocellular carcinoma cells proliferation (P < 0.05). Under the dosing procedure, PNPC was safe at 31.25 mg/kg and lower doses. Higher doses demonstrated minimal hepatocellular and renal toxicity in paraclinical and histopathological examinations. Tumor take rate in PNPC-treated group was 37.5% compared with 87.5% in control (P < 0.05). Average tumor size and weight were significantly lower in PNPC group than control (P < 0.05). PNPC increased proapoptotic Bax protein expression (P < 0.05). Antiapoptotic Bcl-2 protein expression, however, was lower in PNPC-treated animals than the control ones (P < 0.05). In addition, proliferative and angiogenic parameters were statistically decreased in PNPC-treated animals (P < 0.05). These results highlight the suppressing role for PNPC in in vitro and in vivo tumor growth models. Our findings provide credible evidence for superior biocompatibility of the polymeric nanocarrier in pharmacological arena together with an excellent tumor-suppressing response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/824746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352453PMC
January 2016

Lack of association between interleukin-10, transforming growth factor-beta gene polymorphisms and juvenile-onset systemic lupus erythematosus.

Clin Rheumatol 2015 Jun 30;34(6):1059-64. Epub 2015 Jan 30.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr Qarib St, Keshavarz Blvd, Tehran, 14194, Iran.

As abundant types of genetic predisposition and environmental factors seem to be associated with the development of juvenile-onset systemic lupus erythematosus (JSLE), we investigated the gene polymorphisms of two anti-inflammatory cytokines, including interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), which were previously found to be associated with SLE in adults, in a group of patients with JSLE. We studied a group of 59 Iranian patients with JSLE in comparison with 140 healthy controls and assessed the frequency of alleles, genotypes, and haplotypes of IL-10 and TGF-β single-nucleotide polymorphisms (SNPs) using polymerase chain reaction with sequence-specific primers method. The CA genotype was significantly more frequent at position -592 in IL-10 in patients with juvenile-onset systemic lupus erythematosus than in the controls (P = 0.01). Genotype CC was detected at the same position in 32.7 % of the patients; this frequency was significantly lower than the frequency of 50.7 % recorded in the healthy controls (P = 0.03). The TC haplotype of TGF-β (codon 10, codon 25) was significantly more frequent in the patients with juvenile-onset systemic lupus erythematosus than in the healthy controls (P = 0.02). Nevertheless, these significant associations disappear after Bonferroni correction. Our findings suggest that IL-10 (-1082, -819, -592) and TGF-β (codon 10, codon 25) gene variants may not be associated with the development of JSLE in Iranian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-015-2877-2DOI Listing
June 2015

Reference values of lymphocyte sub-populations in healthy human immunodeficiency virus-negative Iranian adults.

Iran J Immunol 2014 Dec;11(4):221-32

Molecular Immunology Research Center and Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran.

Background: Lymphocyte subsets enumeration is considered prominent in the management of primary and acquired immunodeficiency disorders. Because of local variations due to race, age, gender, and environmental conditions on lymphocyte subsets, and to improve the accuracy of interpretation of laboratory findings, reference intervals must be determined in every population.

Objective: To establish a normal reference range for CD3+, CD4+, CD8+, CD19+ and CD56+ lymphocytes in a healthy Iranian adult population using flowcytometry.

Method: Blood samples were collected from 221 HIV seronegative individuals, including 112 females and 109 males, with ages ranging from 20 to 40 years old. The percentage of lymphocytes expressing either of CD3, CD4, CD8, CD19 and CD56 surface markers were determined by flowcytometry assay.

Result: Total mean percentage and absolute count of lymphocyte subsets were as follows: CD3+: 70.90 ± 7.54%, 1800.87 ± 471.09 cells/µl; CD4+: 41.04 ± 7.86%, 1039.99 ± 338.02 cells/µl; CD8+: 31.11 ± 6.60%, 783.95 ± 234.87 cells/µl; CD19+: 12.77 ± 4.56%, 328.37 ± 153.17 cells/µl; CD56+: 15.53 ± 6.34%, 388.62 ± 176.17 cells/µl, respectively. The ratio of CD4+/CD8+ lymphocytes for the studied population was 1.39 ± 0.48. Significant differences were observed between male and female subjects indicating that the average percentage of CD3+ cells (p=0.017) and CD4+ T cells (p=0.003) were higher in the female population, whereas the average percentage of CD19+ cells (p=0.02) tended to be higher among males. However, investigations on the CD56+ NK cell and CD8+ T cell sub-populations did not show any statistical differences between the two genders. In comparison with reports of other populations, we were confronted with different results.

Conclusion: Establishing reference values of lymphocyte subsets for each population is helpful in achieving standard criteria for the prognosis of HIV infection. Therefore, normal ranges established by this survey can be used as a reference for decisions made in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/IJIv11i4A1DOI Listing
December 2014