Asthma is a complex, heterogeneous and chronic airway inflammatory disease with different clinical phenotypes caused by diverse triggers and pathophysiological mechanisms. Asthma heritability has been established in many genetic studies but it is evident that only genetic elements are not responsible for the development of asthma. Increasing rate of asthma incidence during past decades has implicated the role of epigenetics in development of asthma. Environmental factors perform as initiator signals through epigenetic mechanisms. Three epigenetic mechanisms have been identified, including DNA methylation, histone modifications, and small noncoding RNAs. These mechanisms regulate the immune responses and inflammatory genes expression in asthma and allergy. This review explains the role of epigenetic modifications in controlling Th2 response and IgE production in asthma and also briefly overviews the role of environmental factors such as pollutions, allergens, prenatal exposures and diet in developing asthma. Recognizing environmental risk factors and their effects on epigenetic mechanisms would be of great interest for prognostic and preventive aspect in treatment of asthma. 

The aim of current study was to determine women´s maternal asthma in pregnancy, delivery and birth outcomes. Using a retrospective cohort design, data of 580 pregnant women were gathered form a large teaching hospital in Tehran, Iran. The medical records of pregnant women who had attended this hospital between 2009 and 2011 were assessed. Data of delivery and birth outcomes were gathered by observation and medical records of women. Multiple logistic regression and adjusted odds ratio (OR) were used to assess the independent association of asthma and outcomes. 274 patients (47.2%) were in “asthmatic group” and 306 patients (52.8%) were in the “non-asthmatic group”. Basic and demographic variables showed the same distribution across two groups. Maternal asthma showed an adjusted relationship with gestational diabetes (OR=2.64), gestational hypertension (OR=3.79), cesarean delivery (OR=2.68), small for gestational age (OR=2.86), premature rupture of membrane (OR=2.18), preterm delivery (OR=1.74), abnormal vaginal bleeding (OR=3.75), and low birth weight (OR=1.78) significantly (p<0.05 for all associations). The majority of pregnancy, delivery and birth outcomes except fetal death, abortion, placenta previa and placenta abruption) were significantly associated with maternal asthma. The largest association of maternal asthma was with gestational hypertension and abnormal vaginal bleeding respectively. 

Rheumatoid arthritis (RA) is a chronic autoimmune disease, which can lead to joint destruction and disability. Pannus formation due to chronic synovitis is the hallmark of RA. Oxidative stress as a consequence of immune cell activation and disease-modifying anti-rheumatic drugs can prevent inflammation and tissue destruction. Silymarin, an antioxidant extract from Silybum marianum, has been traditionally used for the treatment of liver diseases for decades. In the present non-randomized single-arm clinical trial (NRSACT) study we evaluated the effects of silymarin tablet (Livergol^®) on inflammatory markers in stable RA patients. Disease activity score (DAS-28) was measured before and after adding silymarin to standard drug regimen used for controlling inflammation in RA patients. Silymarin significantly reduced the DAS28 related symptoms in 44 RA patients after 90 days (3.02±0.98 versus 2.3±0.74, p<0.001). The exact mechanism of therapeutic effects of silymarin in RA patients is not clear but it could be as the results of its anti-inflammatory and anti-oxidative properties. Conducting the study on larger number of patients and also measuring cytokines levels including TNF-α and IL-1β may clarify the underlying mechanisms of the anti-inflammatory effects of silymarin in RA patients. 

Silybum marianum, is known to have anti-inflammatory, hepatoprotective and anticarciogenic effects. The aim of this study was to compare effects of Silymarin, Rapamycin and FK506 on proliferation and apoptosis of human T cells stimulated with Con A. Peripheral blood mononuclear cells (PBMC) were stimulated with concavalin A (Con A) (5µg/mL) and then treated with different inhibitors (silymarin, rapamycin and FK506) in various concentrations (5 days). Cells were examined using carboxyfluorescein succinimidyl ester (CFSE) assay for proliferation. Then cell apoptosis was analyzed by FITC annexin V/PI staining and flow cytometry. The effects of drugs on the activation of poly ADP ribose polymerase (PARP) pathway in PBMCs stimulated with Con A and treated with IC50 dose of drugs for 5 days were evaluated using the PathScan cleaved PARP sandwich ELISA kit. The results indicated that silymarin inhibited T cell proliferation. In addition, our results pointed out that 100 μM and 200 μM of silymarin significantly have more inhibitory effect on T cells proliferation than FK506 and rapamycin. None of these drugs at IC50 concentration had affected the level of cleaved PARP. Overall, with superior efficacy and lesser toxicity in comparison with other immunosuppressive drugs, silymarin could be a suitable choice of therapy for certain diseases.

Oryzatensin (ORZ) can reduce potentially IFN-γ secretion by natural killer (NK) cells. Therefore, current study was designed to evaluate the effects of ORZ treatment on peripheral blood mono-nuclear cells (PBMCs) cytokine secretion, proliferation and also to evaluate vascular endothelial growth factor (VEGF) and Matrix Metalloproteinase 9 (MMP-9) expression in HEP-G2 cell line after culture with ORZ-stimulated PBMCs. In this ex-vivo study, PBMCs from apparently healthy male volunteers (n=25) aged 20-30 were isolated by ficoll density gradient. Tetrazolium colorimetric test (MTT assay), ELISA test and real time PCR were performed to evaluate PBMCs proliferation, PBMCs cytokine secretion and the genes expression accordingly. The results of MTT assay showed that ORZ significantly stimulated proliferation of the isolated PBMCs. The results also indicated that ORZ treatment significantly decrease and increase IFN-γ and IL-4 secretion by isolated PBMCs, respectively. Also, VEGF and MMP-9 expression significantly increased in HEP-G2 cells after culture with ORZstimulated PBMCs. The previous studies have introduced ORZ-like peptide for pharmacological purpose and in this study we get to the conclusion that the administration of this peptide may change the immune system response and sensitize target populations to cancer.

IgE- mediated food allergy affects 6-8% of children. Our study aimed to define the correlations between the results obtained with skin prick tests (SPTs) using commercial extracts and fresh foods, and the correlations between these result and those obtained with specific IgE (sIgE) and/ or challenge. Children aged from 2 months to 6 years were recruited prospectively. Overall 571 children were positive to one food. In all children we performed  SPT using commercial extracts of suspected food and fresh foods and sIgE. If SPT and sIgE test results did not correspond to the history, we performed open oral food challenge. Sensitivity of SPT with commercial extracts for all tested food was poor (3-35%), while  sensitivity of fresh food skin prick tests (FFSPT) was excellent (50-100%), and showed correlation with open oral food challenge (p<0.001). Our results suggest that fresh food extracts are more effective in detecting sensitization and with levels of sIgE greater than class 3 could predict clinical reactivity, without the need for potentially hazardous food challenges.

The aim of this study was to identify the species and prevalence of house dust mites (HDMs) in kindergartens in Bandar Abbas, south of Iran. In this study 10 kindergartens were selected randomly in five areas of Bandar Abbas. Two dust samples were collected from each sampling place with a vacuum cleaner. Mites were isolated and mounted in Hoyer's medium and identified using a morphology-based key. In total, 1758 mites were collected and identified, whichconsisted of five species: Dermatophagoides pteronyssinus (31.06%), D. evansi (23.49%), D. farinae (17.75%), Ornithonyssus bacoti (19.45%), and Cheyletus malaccensis (8.25%). Two main allergenic dust mite species D. pteronyssinus and D. farinae, coinhabited and were collected from all of kindergartens. Results of this study have revealed that D. pteronyssinus is the most prevalent HDMs in Bandar Abbas Kindergartens and all studied areas are contaminated by more than one dust mite Regarding the high prevalence of HDMs in Bandar Abbas kindergartens, implementation of strict control measures is necessary for reduction of mite population and prevention of children respiratory diseases and other allergic disorders in this city.

Stroke is one of the most leading causes of death and disability in the world. Complement system activation contributes to pathogenesis and neuronal damage following stroke. There are no defined biological serum markers to determine the severity of stroke in acute phases. The purpose of current study was to determine the association of three complement activators, namely Pentraxin-3 (PTX3),M-ficolin, and Surfactant protein A (SPA) with the severity of ischemic stroke. This cross-sectional study was done on 82 patients diagnosed with ischemic stroke at 24-96 hours of initiation of the clinical symptoms during 2014-2015. The serum levels of PTX3, M-ficolin, and SPA were measured by enzyme-linked immunosorbent assay ( ELISA). The patients were divided in three stroke severity groups according to modified National Institute of Health Stroke Scale mNIHSS. The results showed that the more severity of the stroke was, the higher serum levels of three evaluated molecules (p<0.001) were. The correlation of serum level of PTX3, M-ficolin, and SPA with stroke severity was 0.732, 0.736, and 0.731, respectively. There is a strong association between serum levels of PTX3, M-ficolin, and SPA with the severity of ischemic stroke. Clinically, such association may be considered to evaluate the severity of the ischemic stroke.

Our previous study reported that Lactobacillus acidophilus(L.acidophilus)  key laboratory of dairy science  (KLDS) 1.0738 had an effective impact on inhibiting β-lactoglobulin (β-lg) allergy. This study further investigated the anti-allergic activity of peptidoglycan (PGN) isolated from KLDS 1.0738. This study aimed to assess whether toll-like receptor 2 (TLR2)/NF-kappaB (NF-κB) signaling activated by PGN was responsible for reducing allergic inflammation.  Our data showed that administration of  L. acidophilus PGN inhibited IgE production and improved the Treg/Th17 balance toward a Treg response in a mouse model of β-lg allergy. In addition, treating different doses L. acidophilus PGN to sensitized mice significantly increased TLR2 levels, along with enhancing NF-κB expression, especially in medium and high concentration (p<0.05). Further analysis revealed that the mRNA expression of TLR2 and NF-κB were positively correlated with the Foxp3 mRNA expression (p<0.05), but were negatively correlated with the RORγt mRNA expression in L. acidophilus PGN-treated group compared to allergy group (p<0.05). This study suggests PGN was similar to probiotics in preventing β-lg allergy through regulating Treg/Th17 imbalance, and activation of TLR2/NF-κB signaling may be involved in this process.

Allergen-specific immunotherapy (AIT) has been recently considered as an alternative approach to ameliorate the symptoms of allergen exposure and improvement the patients’ quality of life. Dendritic cells (DC) in the forms of tolerogenic or Th1-induced cells have been investigated in several studies as one of the promising approaches of AIT in allergic diseases. The aim of this study was to evaluate the potency of casein-loaded DCs in eliciting the Th1 immune responses in Balb/c mice as a potential therapeutic approach in allergic condition. Immature bone marrow-derived DCs were loaded with casein (protein or mRNA) or green fluorescent protein (GFP) mRNA. DCs were evaluated based on the expression of specific markers and production of proinflammatory cytokines.  Expression of DC markers in all groups was significantly higher than immature DCs, but lower than LPS-activated DCs. Despite an increase in TNF-α and IL-12, IL-6 was decreased in casein-DC treatments. Caseinloaded DCs could induce proliferation in lymphocytes and stimulate them to produce higher amounts of IFN-γ and in some extent IL-10 and TGF-β, while they could not stimulate IL-4 secretion. Casein-loaded DCs could partially elicit the Th1 responses; this would be a promising approach to use them as an allergic protective way for applying immune cell therapy in cow’s milk allergy.

No Abstract###