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Objective: The collagen-induced arthritis (CIA) model is the most commonly studied autoimmune model of rheumatoidarthritis (RA). In this study, we investigated the usefulness of collagen type II emulsified in Freund's incompleteadjuvant (CII/IFA) as a suitable method for establishing RA in Lewis rats. The aim of the present study was to presenta straightforward and effective method for inducing CIA in rats.Materials and Methods: In this experimental study, animals were divided into two equal groups (n=5); control andCIA. Five rats were injected intradermally at the base of the tail with a 0.2 ml CII/IFA emulsion. On the seventh day,a 0.1 ml CII/IFA emulsion booster was injected. Arthritis symptoms that arose were evaluated at clinical, histological,radiological, and at protein expression levels to find out if the disease had been induced successfully.Results: Our finding showed a decreasing trend in the body weight during the RA induction period, while the arthritisscore and paw thickness were increased during this period. The results of the enzyme-linked immunosorbent assay(ELISA) for serum samples revealed that the levels of proinflammatory cytokines, interleukin (IL)-1β, IL-6, IL-17, andtumor necrosis factor (TNF)-α and anti-CII IgG were significantly increased in CIA rats compared to the control group.After CIA induction, the level of anti-inflammatory protein IL-10 was decreased significantly. Radiographic examinationof the hind paws showed soft tissue swelling, bone erosion, and osteophyte formation in CIA rats. Additionally, basedon histological evaluations, the hind paws of the CIA group showed pannus formation, synovial hyperplasia, and boneand cartilage destruction.Conclusion: It seems that CII/IFA treatment can be an appropriate and effective method to induce RA disease in Lewisrats. This well-established and well-characterized CIA model in female Lewis rats could be considered to study aspectsof RA and develop novel anti-arthritic agents.

Abstract Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease of unknown etiology. The most common form of this disease is chronic inflammatory arthritis, which begins with inflammation of the synovial membrane of the affected joints and eventually leads to disability of the affected limb. Despite significant advances in RA pharmaceutical therapies and the availability of a variety of medicines on the market, none of the available medicinal therapies has been able to completely cure the disease. In addition, a significant percentage (30–40%) of patients do not respond appropriately to any of the available medicines. Recently, mesenchymal stromal cells (MSCs) have shown promising results in controlling inflammatory and autoimmune diseases, including RA. Experimental studies and clinical trials have demonstrated the high power of MSCs in modulating the immune system. In this article, we first examine the mechanism of RA disease, the role of cytokines and existing medicinal therapies. We then discuss the immunomodulatory function of MSCs from different perspectives. Our understanding of how MSCs work in suppressing the immune system will lead to better utilization of these cells as a promising tool in the treatment of autoimmune diseases.

Objective: Animal models provide a deeper understanding about various complications and better demonstratethe effect of therapeutic approaches. One of the issues in the low back pain (LBP) model is the invasiveness ofthe procedure and it does not mimic actual disease conditions in humans. The purpose of the present study wasto compare the ultrasound-guided (US-guided) percutaneous approach with the open-surgery method in the tumornecrosis factor-alpha (TNF-α)-induced disc degeneration model for the first time to showcase the advantages of thisrecently developed, minimally invasive method.Materials and Methods: In this experimental study, eight male rabbits were divided into two groups (open-surgery andUS-guided). Relevant discs were punctured by two approaches and TNF-α was injected into them. Magnetic resonanceimaging (MRI) was performed to assess the disc height index (DHI) at all stages. Also morphological changes (annulusfibrosus, nucleus pulposus) were evaluated by assessing Pfirrmann grade and histological evaluation (Hematoxylin &Eosin).Results: The findings indicated targeted discs became degenerated after six weeks. DHI in both groups was significantlyreduced (P

Abstract Introduction Mesenchymal stromal cells (MSCs) have opened a new window to treat inflammatory and non-inflammatory diseases. Nonetheless, their clinical applications require rigorous control and monitoring procedures to ensure full compliance with the principles of good manufacturing practice (GMP). Various evaluations should be passed in conjunction with the development of these newly emerging therapeutic products from bench-to-bedside. These evaluations include in vitro characterization, preclinical studies, and clinical trials to ensure product safety and efficacy. Therefore, a robust and well-designed preclinical study is critical to confirm product safety. This study aims to determine the probable toxicity effects of local and systemic injections of cryopreserved human bone marrow-derived clonal MSCs (BM-cMSCs) during subacute and subchronic periods of time. Methods BM-cMSCs were characterized according to the International Society for Cell and Gene Therapy (ISCT) criteria for MSCs. Both safety and toxicity of the BM-cMSCs population produced under GMP-compatible conditions were assessed in both sexes of Sprague Dawley (SD) rats via systemic intravenous (IV) administration and local injection in intervertebral disc (IVD). Behavioral changes, clinical signs of toxicity, and changes in body weight, water and food consumption were the important variables for product toxicity testing over 14 consecutive days during the subacute period and 90 consecutive days during the subchronic period. At the end of the assessment periods, the rats were killed for histopathology analysis of the target tissues. The BM-cMSCs potential for tumorigenicity was checked in nude mice. Results Single IV and IVD injections of BM-cMSCs did not cause significant signs of clinical toxicity, or changes in laboratory and histopathology data during the subacute (14 day) and subchronic (90 day) periods. Ex vivo-expanded and cryopreserved BM-cMSCs did not induce tumor formation in nude mice. Conclusion The results suggest that local and systemic administrations of xenogeneic BM-cMSCs in both sexes of SD rats do not cause toxicity during the subacute and subchronic periods of time. Also, BM-cMSCs were non-tumorigenic in nude mice.

Autism is a neurodevelopmental disorder that is recognized by stereotypic and repetitive behaviors after 2 years of old. Dysregulation of the immune system, especially inflammation which is mostly regulated by IL-6, imposes a deficit in CNS development. Along with this crucial biomarker, researchers have proposed BCL-2, micro RNA-23a-3p (miR-23a-3p), miR-181b-5p as other probable biomarkers involved in inflammation and apoptosis. The aim of the study was to evaluate the alteration in the expression of these biomarkers in a group of autism spectrum disorder (ASD) children. Peripheral blood mononuclear cells (PBMCs) were obtained from 37 autistic patients. After RNA extraction with precipitation method, the Syber green qReal-time Polymerase Chain Reaction (PCR) was performed in order to evaluate the possible alteration in the expression of IL-6, BCL-2, miR-181b-5p, and miR-23a-3p. The results were compared with healthy controls. IL-6 was significantly upregulated in ASD patients (p=0.003). On the other hand, miR-23a was upregulated and BCL-2 downregulated in ASD patients but the changes were not significant. In initial evaluations, expression changes of miR-181b-5p were not statistically significant. However, when Patients were divided into two groups of upregulated and downregulated, re-evaluation showed that both up- (p=0.005) and down-regulation (p=0.004) (i.e. changes regardless of the direction) of miR-181b were significant in autistic children. IL-6 and miR-181b-5p can have proper diagnostic values and are reliable biomarkers with high sensitivity and specificity. On the other hand, PBMC can be utilized for such studies and also evaluation of patients' condition instead of brain tissue as it is less accessible.

Background and aim: Standardized techniques help us to better diagnosis and follow up of allergic diseases. In this study, we determined the sensitivity, accuracy, and specificity of an Immunoblotting test compared to ImmunoCAP as the reference in vitro test for detection of specific IgE in allergic patients. Methods: In this cross-sectional study, specific IgE level was determined in patients with allergic symptoms who referred to the Immunology, Asthma and Allergy Research Institute, Tehran, Iran from 2010-2016, by two techniques. Eleven different allergens (six aeroallergens and five food allergens) were determined, and 303 specific IgE tests were performed for the patients by each method. The Immunoblotting test is a multiplex assay on a nitrocellulose membrane coated with 20 selected allergens. ImmunoCAP is considered as the reference method for determination of in vitro specific IgE. Its principle is an automated sandwich immunoassay, and allergens were bound to the solid phase, covalently. Finally, the fluorescence of elute was determined. Specific IgE more than 0.35 KU/L was considered as a positive test. Sensitivity, specificity, accuracy, kappa coefficient, positive and negative likelihood ratio (+/- LR), and correlation coefficient (calculated with Spearman test) between two tests were determined using statistical analysis (SPSS software, version 18). Results: One hundred and thirty five patients entered this study. The median age of the patients was 3.75 years with the males constituting 54.8% of the population. The most common cheif complaints were respiratory (51.6%), skin (41.8%) and gastrointestinal (27.9%) symptoms, respectively. The sensitivity, specificity, accuracy, +LR and -LR were 83%, 97%, 92%, 27.66 and 0.17, respectively. The kappa coefficient of the immunoblotting test was 0.81 compared to the reference technique. The correlation coefficient for positive tests between the two methods was 0.71 (p

Background: Alteration of environmental factors and air pollution affects the trend of allergic diseases especially in cities such as Tehran. This study aimed to determine the prevalence of allergic rhinitis, conjunctivitis, atopic dermatitis and asthma among adults in the capital city of Iran. Methods: This cross-sectional study was performed between 2013 and 2016 in Tehran, Iran. The participants were adults between 18 and 45 yr of age. A specific questionnaire including demographic data and clinical symptoms was filled out by a trained interviewer. The diagnosis of allergic diseases was performed based on standard questionnaires and criteria. Results: The prevalence of allergic rhinitis, conjunctivitis, asthma and atopic dermatitis were 28.3%, 15.9%, 7.6% and 3.9%, respectively. Allergic rhinitis and conjunctivitis together were reported in 12.3% of the participants. Among patients with asthma, 47.4% had AR. Additionally, 25.7% of atopic dermatitis subjects were reported to have asthma. The subjects with at least one of these allergic diseases were 36.3%. Women showed a higher prevalence of allergic symptoms than men. There was a significant relationship between allergic symptoms and family history of atopic diseases. Conclusion: The most common allergic disease was allergic rhinitis. Regarding the comorbidity of asthma and allergic rhinitis, paying more attention to controlling these allergic diseases is deemed necessary.

Allergic sensitization to inhalant allergens could be considered as a predictor in allergic diseases. The objective of this study was to assess IgE-mediated sensitization to inhalant allergens in allergic and non-allergic adults as well as the evaluation of its association with allergic diseases. This cross-sectional study was conducted from 2013 to 2016 in 604 allergic and 102 non-allergic adults selected from blood donor volunteers in Tehran, Iran. After taking informed consent, a standard questionnaire was filled to determine asthma, allergic rhinitis and/or conjunctivitis and atopic dermatitis in participants. Specific IgE assay to common inhalant allergens was performed for all subjects. Logistic regression analysis was used to evaluate the impact of IgE sensitization on allergic diseases. A total of 371(61.4%) allergic subjects and 41(40.2%) non-allergic patients were males. The weeds (especially saltwort) and grasses (particularly meadow fescue and ryegrass) were identified as the most common inhalant allergens. The prevalence of IgE sensitization to trees, weeds, and grasses was higher in subjects with allergic rhino-conjunctivitis and trees sensitization was a significant factor in them [OR=2.32, 95% CI (1.58-3.41)]. IgE sensitization to any inhalant allergens could be a predictor for allergic rhinitis, conjunctivitis and rhino-conjunctivitis in adults [OR=2.20, 95% CI (1.54-3.15], [OR=1.81, 95% CI (1.28-2.54)] and [OR=2.55, 95% CI (1.72-3.78)], respectively. With an increase in the sum of specific IgE concentrations, the prevalence of allergic conjunctivitis and rhino-conjunctivitis also increased. Our results showed the association between positive specific IgE and its concentration with some allergic diseases which could help physicians to prevent such diseases by recognizing and treating them, particularly in individuals with a positive family history of allergic diseases.

Aeroallergens play an important role in developing allergic diseases. The aim of this study was to determine the outdoor and indoor sensitization using a specific regional panel of aeroallergens in allergic patients. All patients with allergic symptoms referred to Immunology, Asthma and Allergy Research Institute (IAARI) in Tehran, Iran from December 2010 to July 2013 entered this cross sectional study. We evaluated serum samples for specific IgE against 20 selected aeroallergens provided by a specific panel (RIDA Allergy Screen test, IAARI panel). A p value less than 0.05 was considered as significant. The patients (n=602) were 49.8 % male and 50.2% female. The median age was 9 years. Positive specific IgE at least to one allergen was 53.2%. The percentages of patients with only outdoor or indoor sensitization were 37.5 and 19.7%, respectively. Moreover, 42.8% showed sensitization to both indoor and outdoor aeroallergens. The most common outdoor aeroallergens in decreasing order were plane tree (32.8%), Bermuda grass (32.2%), timothy grass (30.6%), saltwort (28.4%). The percentage of specific IgE to indoor allergens including mold and mite were 23.8 % and 22.2%, respectively. There was a statistically significant relationship between specific IgE to timothy grass and mold allergens between two genders (p=0.04 and p=0.02, respectively).The results of this study shows that outdoor aeroallergens can be considered as the most common causes of allergic symptoms in our allergic patients.

Background: Bone marrow derived mesenchymal stem cells (MSCs) are a population of multipotent progenitors which have the capacity of proliferation and differentiation into mesenchymal lineage cells. Hypoxia could promote the proliferation of MSCs. Micro-RNAs are endogenous RNAs that can play an important role in some processes such as proliferation and differentiation. MiR-210 could help for better proliferation of MSCs since this miRNA could activate HIF pathway. In current study we investigated if MSCs can preserve their differentiation and proliferation ability under normoxic conditions by upregulation of miR-210. Materials and Methods: MSCs isolated from C57 BL/6 mice by flushing it's femurs into the cell culture media. After 72 hours, MSCs which are plastic adherent cells were attached to the flask and non-adherent cells were removed. Subsequently, MSCs induced to differentiate into osteocytes and adipocytes with specific differentiation media in order to confirm their identity and multipotency. Then miR-210 was inserted in Lentiviruse vectors and affected MSCs. In each passage, the number and viability of cells were evaluated. Results: Comparison between miR-210 infected MSCs with control cells showed that miR-210 has ability to increase proliferation of MSCs significantly. Conclusion: We showed that miR-210 has ability to induce proliferation of MSCs without any negative effect on their differentiation abilities. Further studies are needed for evaluation of probable effects of miR-210 mechanisms on MSCs proliferation.