Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 6 2023 12 28 510 511 Maryam Nourizadeh IAARI, TUMS Mostafa Moin Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran 2023 11 20 2023 11 20 No Abstract No Abstract No Abstract https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3951 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3951/2003

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 6 2023 12 28 512 526 EN Reza Dabbaghipour Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz, Iran AND Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Elham Ahmadi Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Mona Entezam Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz, Iran Omid Rahbar Farzam Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Amir Baghbanzadeh Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Ali Saber Sichani 3 Department of Biology, Texas A&M University, College Station, TX, USA Nazila Jalilzadeh Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Mahdi Jafarlou Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Behzad Baradaran Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 2023 04 05 2023 09 18 Scientific research over the past decades has proven the pivotal role of long non-coding RNAs (LncRNAs) in regulating gene expression. The immune responses are controlled through the interaction of pro-inflammatory (predominance of T helper 17 cells (Th17)) and anti-inflammatory cytokines excretion (predominance of Regulatory T cells (Treg)). Recent studies have marked the impact of many diverse LncRNAs on Treg/Th17 imbalances. Moreover, some of the roots and causes of human diseases can be associated with the alterations in the Th17/Treg ratio. In this review study, we overviewed the association between LncRNAs and Th17/Treg, with the potential of providing novel prognostic and diagnostic biomarkers and promising therapeutic targets in various diseases, particularly cancer.  https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3806 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3806/2005

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 6 2023 12 28 527 535 Mansour Sadeghzadeh Department of Pediatrics, Zanjan University of Medical Sciences, Zanjan, Iran Parisa Khoshnevisasl Social Determinants of Health Research Center, Zanjan University of Medical Sciences, Zanjan, Iran Akefeh Ahmadiafshar Department of Pediatrics, Zanjan University of Medical Sciences, Zanjan, Iran AND Social Determinants of Health Research Center, Zanjan University of Medical Sciences, Zanjan, Iran Nima Motamed Department of Community Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Azadeh Pourmarjani Department of Pediatrics, Ayatollah Moussavi Hospital, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran 2022 09 25 2023 10 15 The aim of asthma treatment is to reduce airway inflammation by avoiding environmental triggers and using daily anti-inflammatory medications. This study aimed to compare the effects of fluticasone propionate (FP) and budesonide (Bud) on the clinical symptoms and control of asthma in children with moderate to severe asthma. In this open-label study, children with moderate to severe asthma were randomly selected to receive either FP 250 mcg or Bud 400 mcg for 3 months. Asthma control test scores were measured in both groups monthly. The clinical symptoms, drug adherence, and rescue medication were also evaluated. A total of 50 patients with ages between 4 and 7 years old were included in the study (25 cases received Bud and 25 cases received FP). Asthma control test scores, daily and nocturnal symptoms, and cough rates were significantly improved in both groups. The average asthma control scores for the fluticasone group were 21.68±3.32 in the second month and 24.84±2.67 in the third month, whereas the budesonide group had scores of 18.52±3.32 and 22.48±4.12 during the same periods. These variances were statistically significant. Additionally, the requirement for salbutamol use was notably reduced in the fluticasone group compared to the budesonide group throughout all three months. The efficacy of fluticasone propionate in decreasing the need for rescue medication and enhancing asthma control test scores was markedly superior to that of budesonide. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3661 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3661/2004

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 6 2023 12 28 536 550 Sepideh Ghodoosifar Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Gholamreza Dehghan Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Reza Safaralizadeh Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Behzad Baradaran Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Mehrzad Hajialiloo Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 2023 06 27 2023 12 03 MicroRNAs (miRs) play a role in several diseases, such as rheumatoid arthritis (RA). The purpose of this study was to discover new microRNAs and investigate their involvement in RA, examining their connections with inflammation and metabolic markers. New microRNAs related to RA were predicted using Mirbase and TargetScan databases based on RA target genes. The relationships between miRNAs and targets were visualized with Cytoscape software. Real-time polymerase chain reaction confirmed detectable miRNAs and metabolic factors were assessed using immunoassay and spectrometry methods in RA patients and healthy subjects. Four microRNAs (hsa-miR-153-5p, hsa-miR-4270, hsa-miR-4441, and hsa-miR-6754-5p) showed the highest correlation with RA target genes among millions of microRNAs. The expression of miR-146b (fold change=1.8) and miR-4441 (fold change=1.7) was notably reduced, while miR-4270 showed upregulation (fold change=1.8) in plasma from RA patients compared to healthy individuals. MiR-6754 exhibited a decrease (fold change=1.3) but was statistically insignificant. MiR-153-5p expression was undetectable in plasma. Receiver operating characteristic (ROC) curve analysis indicated that miR-4441, with an area under the ROC curve (AUC) of 0.7728, and miR-4270 (AUC=0.7353) were promising biomarkers for RA. The expression of these studied miRNAs significantly correlated with essential clinical characteristics, including liver enzymes, cholesterol, phosphorus, and vitamin D3. Our findings suggest that miR-4270 and miR-4441, present in the circulation, exhibit distinct expression patterns in RA. These microRNAs may serve as links between inflammation and metabolism and represent promising new biomarkers for this disease. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3866 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3866/2006

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 6 2023 12 28 551 560 Liangfeng Lin Department of Pediatrics, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China Xiaohao Hu Department of Pediatrics, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China Qiaoyu Li Department of Pediatrics, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China Linlin Huang Department of Respiratory Medicine, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China 2023 07 18 2023 08 19 Asthma, a prevalent chronic airway inflammatory condition, poses a significant health challenge. In this study, we delved into the regulatory mechanisms governing asthma, focusing on Methyltransferase-like 3 (METTL3). Through an ovalbumin (OVA)-induced mouse model and interleukin-13 (IL-13)-induced cell model, we mimicked the in vivo and in vitro functions of METTL3 in asthma. Our research revealed that METTL3 expression significantly decreased in asthma-induced mice and IL-13-stimulated cells compared to the control group. Moreover, METTL3 overexpression enhanced bronchial epithelial cell viability and proliferation. Mechanistically, we observed elevated levels of total iron, Fe2+, malondialdehyde (MDA), lipid reactive oxygen species (ROS), alongside reduced glutathione (GSH) levels in IL-13-stimulated cells. Remarkably, METTL3 overexpression counteracted these effects, suggesting a pivotal role in mitigating asthma-related oxidative stress. Furthermore, our study highlighted the involvement of N6-methyladenosine methylation (m6A) modification, where METTL3 regulated the m6A modification of glutathione peroxidase 4 (GPX4) RNA, impacting RNA stability. Knockdown of METTL3 suppressed m6A modification on GPX4 RNA, impairing its stability and contributing to IL-13-induced ferroptosis. Interestingly, METTL3 overexpression not only inhibited cell ferroptosis but also alleviated asthma symptoms. Our findings shed light on the epigenetic regulation of asthma through METTL3-mediated m6A modification, offering potential therapeutic avenues for this prevalent inflammatory disease. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3876 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3876/2007

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 6 2023 12 28 561 574 Sajad Dehnavi Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran AND Department of Immunology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran AND Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran Maryam Dadmanesh Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran AND Department of Infectious Diseases, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran Negin Hosseini Rouzbahani Department of Immunology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran AND Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran Mahmood Karimi Department of Pulmonology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran Ali Asadirad Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran AND Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Mohammad Gholami Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran AND Department of Medical Microbiology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran Khodayar Ghorban Department of Immunology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran 2023 02 07 2023 11 05 Increasing the efficacy of allergen-specific intranasal immunotherapy (INIT) has recently been the main goal of several studies to establish this route as a safe delivery method through mucosal pathways. In this case, the present study evaluated the potential of INIT using ovalbumin (OVA)-loaded mesenchymal stromal/stem cell (MSC)-derived exosomes (Exo-OVA) in an allergic asthma mouse model. Together with control groups, sensitized Balb/c mice underwent intranasal immunotherapy with Exo-OVA (10 μg OVA per dose) for three consecutive weeks. Serum-specific immunoglobulin E (IgE) levels, transforming growth factor-beta (TGF-β), interleukin (IL)-4, and interferon-gamma (IFN-γ) production by cultured spleen cells, lung histopathologic analysis, and nasopharyngeal lavage fluid cellular examinations were then conducted. The results showed that INIT using Exo-OVA significantly increased IFN-γ and TGF-β secretion, while allergen-specific IgE and IL-4 production were dramatically decreased compared to the control group receiving phosphate-buffered saline. In addition, the eosinophil and total cell counts in the nasopharyngeal lavage fluid were reduced, and inflammatory conditions and cell accumulation in lung tissue were ameliorated. In conclusion, the Exo-OVA improved the INIT efficacy compared to free OVA. Therefore, this formulation could be introduced as an effective approach for immunomodulatory purposes with a shorter treatment duration and reduced side effects. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3767 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3767/2001

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 6 2023 12 28 575 587 Saeid Khosropour Department of Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Elahe Shahvarooghi Departement of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran Hossein Rezaeizadeh Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran Maryhe life expectancy and the risk of developing cardiovascular diseases in patients with inborn errors of immunity are systematically increasing. The aim of the study was to assess cardiovascular risk factors and to evaluate the heart in echocardiography in patients with primary antibody deficiency (PAD). Cardiac echography and selected cardiovascular risk factors, including body mass index, sedentary lifestyle, nicotine, glucose, C-reactive protein, lipid profile, uric acid level, certain chronic diseases, and glucocorticoid use, were analyzed in 94 patients >18 years of age with PAD. Of the patients,25.5% had a cardiovascular disease (mostly hypertension, 18%), 10.5% smoked, 17% were overweight, 14% were obese, and 15% were underweight. Abnormal blood pressure was found in 6.5% of the patients. Lipid metabolism disorders were found in 72.5% of in the studied cohort, increased total cholesterol (45.5%), non-high-density lipoprotein (HDL) (51%), low-density lipoprotein (LDL) (47%), and triglycerides (32%) were observed. Furthermore, 28.5% had a decrease in HDL and 9.5% had a history of hyperuricemia. The average number of risk factors was 5 ± 3 for the entire population and 4 ± 2 for those under 40 years of age. Elevated uric acid levels were found de novo in 4% of participants. In particular, 74.5% of the patients had never undergone an echocardiogram with a successful completion rate of 87% among those tested. Among them, 30% showed parameters within normal limits, primarily regurgitation (92.5%). New pathologies were identified in 28% of patients. Prevention in patients with PAD, aimed at reducing cardiovascular risk, should be a priority. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3913 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3913/2019

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 2 2024 04 07 182 196 Shirin Jalili Institute of Police Equipment and Technologies, Policing Sciences and Social Studies Research Institute, Tehran, Iran Hadi Shirzad Research Center for Life & Health Sciences & Biotechnology of the Police, Directorate of Health, Rescue & Treatment, Police Headquarter, Tehran, Iran Seyed Amin Mousavi Nezhad Research Center for Life & Health Sciences & Biotechnology of the Police, Directorate of Health, Rescue & Treatment, Police Headquarter, Tehran, Iran 2023 10 16 2024 02 09 Multiple sclerosis (MS) is an autoimmune neurodegenerative disease and has adverse implications. The exact mechanism of its pathogenesis is not fully understood and remains to be elucidated. In the current study we aimed to identify key genes that can serve as potential biomarkers and therapeutic targets for MS and shed light on pathogenesis mechanisms involved in MS. We analyzed a gene expression dataset (GES21942) and found 266 differentially expressed genes (DEGs) including 183 upregulated and 83 downregulated genes in MS patients compared to controls. Then we conducted pathway enrichment on DEGs and selected the top enriched pathway i.e., B cell receptor signaling pathway, and 5 genes of this pathway (CR2, BLK, BLNK, RASGRP3, and KRAS) for further investigation in our clinical samples. We recruited 50 MS patients and 50 controls and assessed the expression of selected genes in the circulation of patients versus controls. Expression of CR2, BLK, BLNK, and RASGRP3 were significantly higher in MS cases compared with controls. There was no significant difference in expression of KRAS between patients and controls. All of the selected genes with differential expression had noticeable diagnostic power and CR2 was the most robust gene in differentiating MS cases from controls. Additionally, a combination of genes resulted in enhanced diagnostic power. Collectively our results suggest that the B cell receptor signaling pathway and the selected genes from this pathway may be implicated in the pathogenesis of MS and each of these genes can be considered as potential diagnostic biomarkers and therapeutic targets. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3933 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3933/2038

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 2 2024 04 07 197 220 EN Mohsen Rokni Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Department of Immunology, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran Elham Farhadi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Research Center for Chronic Inflammatory Diseases, Tehran University of Medical Sciences, Tehran, Iran Hoda Kavosi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Research Center for Chronic Inflammatory Diseases, Tehran University of Medical Sciences, Tehran, Iran Maryam Akhtari Tobacco Prevention and Control Research Center (TPCRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran Elham Madreseh Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Research Center for Chronic Inflammatory Diseases, Tehran University of Medical Sciences, Tehran, Iran Samaneh Enayati Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Mina Sadeghi Shaker Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Shayan Mostafaei Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Farhad Gharibdoost Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Mahdi Mahmoudi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Research Center for Chronic Inflammatory Diseases, Tehran University of Medical Sciences, Tehran, Iran Mohammad Vodjgani Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 2023 10 30 2024 01 02 Systemic sclerosis (SSc) is an autoimmune systemic disease that is characterized by immune dysregulation, inflammation, vasculopathy, and fibrosis. Tissue fibrosis plays an important role in SSc and can affect several organs such as the dermis, lungs, and heart. Dysregulation of interferon (IFN) signaling contributes to the SSc pathogenesis and interferon regulatory factor 1 (IRF1) has been indicated as the main regulator of type I IFN. This study aimed to clarify the effect of IFN-gamma (-γ) and dexamethasone (DEX) on the IRF1, extracellular signal-regulated kinase 1/2 (ERK1/2), and the expression of alpha-smooth muscle actin (α-SMA) in myofibroblasts and genes involved in the inflammation and fibrosis processes in early diffuse cutaneous systemic sclerosis (dcSSc). A total of 10 early dcSSc patients (diffuse cutaneous form) and 10 unaffected control dermis biopsies were obtained to determine IFNγ and DEX effects on inflammation and fibrosis. Fibroblasts were treated with IFNγ and DEX at optimum time and dose. The expression level of genes and proteins involved in the fibrosis and inflammation processes have been quantified by quantitative real-time PCR (RT-qPCR) and western blot, respectively. IFNγ could up-regulate some of the inflammation-related genes (Interleukin-6; IL6) and down-regulate some of the fibrosis-related genes (COL1A1) in cultured fibroblasts of patients with early dcSSc compared to the untreated group. Besides, it has been revealed that IFNγ can induce fibroblast differentiation to the myofibroblast that expresses α-SMA. Concerning the inhibitory effect of IFNγ on some fibrotic genes and its positive effect on the inflammatory genes and myofibroblast differentiation, it seems that IFNγ may play a dual role in SSc. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3941 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3941/2021

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 2 2024 04 07 211 219 Xiang Fan Henan University of Chinese Medicine, Zhengzhou, China Chen Wei Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China Yongguang Han Henan University of Chinese Medicine, Zhengzhou, China 2023 11 28 2024 01 02 Asthma is a chronic respiratory disease that is characterized by airway inflammation, excessive mucus production, and airway remodeling. Prevention and treatment for asthma is an urgent issue in clinical studies. In recent years, N6-methyladenosine methylation (m6A) has emerged as a promising regulatory approach involved in multiple diseases. ALKBH5 (alkB homolog 5) is a demethylase widely studied in disease pathologies. This work aimed to explore the regulatory mechanisms underlying the ALKBH5-regulated asthma. We established an interleukin-13 (IL-13)-stimulated cell model to mimic the in vitro inflammatory environment of asthma. ALKBH5 knockdown in bronchial epithelial cells was performed using siRNAs, and the knockdown efficacy was analyzed by quantitative PCR (qPCR). Cell viability and proliferation were measured by cell counting kit 8 (CCK-8) and colony formation assay. The ferroptosis was assessed by measuring the total iron, Fe2+, lipid reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. The enrichment of N6-methyladenosine methylation (m6A) modification was detected by the MeRIP assay. Knockdown of ALKBH5 significantly elevated the survival and colony formation ability of bronchial epithelial cells in the IL-13 induction model. The levels of total iron, Fe2+, lipid ROS, and MDA were remarkedly elevated, and the SOD level was reduced in IL-13-induced bronchial epithelial cells, and depletion of ALKBH5 reversed these effects. Knockdown of ALKBH5 elevated the enrichment of m6A modification and expression of glutathione peroxidase 4 (GPX4). Knockdown of GPX4 abolished the pro-proliferation and anti-ferroptosis effects of siALKBH5. Knockdown of ALKBH5 improved the proliferation of bronchial epithelial cells and alleviated cell ferroptosis.    https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3962 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3962/2034