Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 2 2024 04 07 127 138 EN Fakhry Shafiee Afzalipour Research Development Unit, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran Afshin Sarafinejad Clinical Informatics Research and Development Lab, Clinical Research Development Unit, Shafa Hospital, Kerman University of Medical Sciences, Kerman, Iran Nasrin Bazargan Harandi Department of Pediatrics, School of Medicine Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran Ali Hossininasab Department of Pediatrics, School of Medicine Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran Sareh Saadat Ebrahimi Department of Pediatrics, School of Medicine Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran 2023 08 03 2023 12 03 The tragic COVID-19 pandemic affected many children worldwide. Among the factors that may influence the course of viral infections including COVID-19, it is still uncertain whether atopy has a protective or predisposing role. The study aims to address the knowledge gap by investigating the prevalence and severity of COVID-19 among atopic children in Kerman, in 2022. A descriptive-analytical cross-sectional study on children with a history of atopy was performed in Kerman Medical University. Demographic information, type of atopy (including allergic rhinitis, Hyper-Reactive Airway Disease (HRAD) or asthma, eczema, urticaria, anaphylaxis, and food allergy), history of COVID-19 infection, and disease severity were recorded. A total of 1007 children and adolescents, (boys: 56.4%, girls: 43.6%, age:5.61±2.64 years) were included in the study. History of COVID-19 infection was positive in 53.5%, with 75.9% of the cases exhibiting mild disease severity. The frequency of atopies was HRAD or asthma (67.2%), allergic rhinitis (42.6%), and food allergy (27.4%). The frequency of COVID-19 cases was significantly higher among patients with HRAD or asthma, whereas it was significantly lower among those with food allergies, anaphylaxis, and eczema. Among atopic individuals, COVID-19 severity was significantly lower in those with allergic rhinitis, while the opposite trend was observed among food-allergic individuals. This study sheds light on the relationship between atopy and COVID-19 among pediatric patients. It seems specific types of atopies may influence the risk and severity of COVID-19 infection differently. A better understanding of these associations can inform clinical management and preventive measures for vulnerable pediatric populations. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3861 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3861/2024

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 2 2024 04 07 139 148 Bahareh Abtahi-Naeini Division of Pediatric Dermatology, Department of Pediatrics, Imam Hossein Children’s Hospital, Isfahan University of Medical Sciences, Isfahan, Iran AND Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Reza Makhmali Department of Pediatrics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Niloufar Amini Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran AND Department of Pediatrics, Isfahan University of Medical Sciences, Isfahan, Iran Mohammad Reza Maracy Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran Nikta Nouri Department of Pediatrics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Tooba Momen Department of Allergy and Clinical Immunology, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran 2022 07 04 2024 02 03 Background: There are limited data on severe cutaneous adverse reactions (SCARs) associated with antiepileptic medications. The current study aims to investigate the clinical and epidemiological characteristics of antiepileptic medication-induced SCARs in hospitalized children. Materials and Methods: The current five-year retrospective study was conducted at Isfahan University of Medical Sciences, Iran. This study included all children with a definite diagnosis of SCARs secondary to the use of antiepileptic medications based on the world health organization (WHO) definition. In our study SCARs were categorized into three fields: Hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Results: Among 259 children with SCARs induced by antiepileptic medications, 199 (76.83%), 42 (16.22%), and 18 (6.95%) had hypersensitivity syndrome, DRESS, and SJS/TEN, respectively. Phenobarbital was the most common offending drug in all types of SCARs. The multinomial logistic regression model revealed that lymphadenopathy increased the occurrence of DRESS by 35 times compared to hypersensitivity syndrome (P < 0.001). Girls were at risk of SJS/TEN approximately 6 times more than boys (P = 0.027). Age (P = 0.021), weight (P = 0.036), and mucosal involvement (P < 0.001) affected the hospitalization duration in children with SCARs related to antiepileptic medication. Conclusion: There are some similarities and differences in the clinical and epidemiological features of Iranian children suffering from antiepileptic medication-induced SCARs. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3594 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3594/2058

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 2 2024 04 07 149 157 Maryam Khoshkhui Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Farahzad Jabbari Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Fateme Shafiee Zargar Department of Radiology, Qaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Nasrin Motavalli Haghi Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Nazila Ariaee Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 2023 06 07 2024 01 17 Allergen-specific immunotherapy is the only disease-modifying treatment for IgE-mediated allergic disorders. Intra lymphatic immunotherapy (ILIT) is an efficacious and time-saving alternative to subcutaneous immunotherapy (SCIT). This study aimed to evaluate the effects and safety of ILIT in patients with moderate to severe allergic rhinitis.  In this clinical trial, patients between 18 and 65 years old with moderate to severe allergic rhinitis were enrolled. They received monthly intra-lymphatic inguinal injections of an active allergen (1000 SQ-U Salsola kali pollen). Their clinical symptoms were assessed before and four weeks after treatments. The clinical signs were also evaluated during two consecutive pollination seasons and the following non-pollination season in April. No moderate or severe reactions were recorded following ILIT treatment. Lymph node enlargement, angioedema/urticaria, and local itching were seen instantly after injection. Patients who received ILIT experienced a significant clinical improvement in self-recorded seasonal allergic symptoms after the treatments, compared to themselves before ILIT. Furthermore, their quality of life significantly improved. This study suggests ILIT with Salsola-pollen extract may decrease symptoms of allergic rhinitis. It was safe and did not cause any crucial complications. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3852 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3852/2055

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 2 2024 04 07 158 167 Mahshid Movahedi Division of Allergy and Clinical Immunology, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Masoud Movahedi Division of Allergy and Clinical Immunology, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Nima Parvaneh Division of Allergy and Clinical Immunology, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Hassan Abolhassani Research Center for Primary Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran. AND Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden Mohadese Mahdavi Division of Allergy and Clinical Immunology, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Mohadese Mosavikhorshidi Division of Allergy and Clinical Immunology, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Fatemeh Alizadeh Division of Allergy and Clinical Immunology, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Mehdi Shokri Department of Pediatrics, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran Arash Kalantari Department of Immunology and Allergy, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran 2023 11 26 2024 01 30 Patients with inborn errors of immunity (IEI) are among the high-risk groups regarding COVID-19. Receiving booster doses (third and fourth) in addition to the standard doses is recommended in these patients. This study investigated the antibody response before and after a booster dose of Sinopharm vaccine in IEI patients.  Thirty patients (>12 years) with antibody deficiencies, referred to Imam Khomeini Hospital and Children's Medical Center in Tehran, were enrolled in this prospective cross-sectional study. All patients were fully vaccinated with the BBIBP-CorV vaccine (2 doses of Sinopharm). Initial measurements of anti-receptor-binding domain (anti-RBD) and anti-nucleocapsid (anti-N) IgG antibody responses were conducted by enzyme-linked immunosorbent assay (ELISA). Subsequently, all patients received a booster dose of the vaccine. Four to six weeks after booster injection, the levels of antibodies were re-evaluated.  Twenty patients with common variable immunodeficiency (CVID), 7 cases with agammaglobulinemia and 3 patients with hyper IgM syndrome were studied. Anti-RBD IgG and anti-N IgG antibodies increased in all patients after the booster. Our results indicated the need of receiving booster doses of the COVID-19 vaccine in patients with antibody deficiencies, even for enhancing humoral immune response specially in patients with CVID. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3959 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3959/2053

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 2 2024 04 07 168 181 EN Katarzyna Napiórkowska-Baran Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Grzegorz Grześk Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Jan Błażejewski Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Marcin Ziętkiewicz Department of Rheumatology, Clinical Immunology, Geriatrics and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland Ewa Więsik-Szewczyk Department of Internal Medicine, Pulmonology, Allergy and Clinical Immunology, Central Clinical Hospital of the Ministry of National Defense, Military Institute of Medicine, Warsaw, Poland Aleksandra Matyja-Bednarczyk 2nd Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland Marta Tykwińska Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Elżbieta Grześk Department of Pediatrics, Hematology and Oncology, LudwikRydygier Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Jakub Lubański Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland Oskar Schmidt Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland Bartłomiej Szymczak Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland Robert Zacniewski Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Ewa Szynkiewicz Department of Nursing in Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Michał Owsiany Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Zbigniew Bartuzi Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland 2023 09 18 2023 11 28 The 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 &amp; Health Sciences &amp; Biotechnology of the Police, Directorate of Health, Rescue &amp; Treatment, Police Headquarter, Tehran, Iran Seyed Amin Mousavi Nezhad Research Center for Life &amp; Health Sciences &amp; Biotechnology of the Police, Directorate of Health, Rescue &amp; 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

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 2 2024 04 07 220 230 Zohreh Mehmandoostli Department of Biology, Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran Mahmood Dehghani Ashkezari Department of Biology, Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran Seyed Morteza Seifati Department of Biology, Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran Vida Sadeghi Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Reza Falak Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Gholam Ali Kardar Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran 2023 05 14 2024 01 02 During epithelial to mesenchymal transition, the ability of cancer cells to transform and metastasize is primarily determined by N-cadherin-mediated migration and invasion. This study aimed to evaluate whether the N-cadherin promoter can induce diphtheria toxin expression as a suicide gene in epithelial to mesenchymal transition (EMT)-induced cancer cells and whether this can be used as potential gene therapy. To investigate the expression of diphtheria toxin under the N-cadherin promoter, the promoter was synthesized, and was cloned upstream of diphtheria toxin in a pGL3-Basic vector. The A-549 cells was transfected by electroporation. After induction of EMT by TGF-β and hypoxia treatment, the relative expression of diphtheria toxin, mesenchymal genes such as N-cadherin and Vimentin, and epithelial genes such as E-cadherin and β-catenin were measured by real-time PCR. MTT assay was also performed to measure cytotoxicity. Finally, cell motility was assessed by the Scratch test. After induction of EMT in transfected cells, the expression of mesenchymal markers such as Vimentin and N-cadherin significantly decreased, and the expression of β-catenin increased. In addition, the MTT assay showed promising toxicity results after induction of EMT with TGF-β in transfected cells, but toxicity was less effective in hypoxia. The scratch test results also showed that cell movement was successfully prevented in EMT-transfected cells and thus confirmed EMT occlusion. Our findings indicate that by using structures containing diphtheria toxin downstream of a specific EMT promoter such as the N-cadherin promoter, the introduced toxin can kill specifically and block EMT in cancer cells. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3834 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3834/2036

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 2 2024 04 07 231 234 EN Homa Sadri Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran Mohammad Reza Fazlollahi Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran 2022 05 23 2024 01 22 The static charge on the plastic body of spacers attracts drug aerosols, reducing the drug available for inhalation from plastic spacers. Some instructions exist to decrease the electric charge on plastic spacers, such as priming them with salbutamol (20 puffs) before use. This study investigates whether priming plastic spacer devices with this method can improve the bronchodilator test result. This study included children with stable mild to moderate asthma. All subjects underwent two pulmonary function tests to evaluate their bronchodilator response on separate days at 24-48 hours intervals. On each day, spirometry was performed at the baseline and 15 min after inhalation of four puffs of salbutamol (100 μg/puff) through either a primed or a new spacer. The change in forced expiratory volume in the first second (FEV1) after inhaling salbutamol was the primary outcome measure. When the patients used a new spacer, the mean baseline FEV1 (% predicted) and FEV1/FVC (forced vital capacity) were 89.56±11.95 and 86.17±6.87, respectively. However, the mean increase in FEV1 from the baseline was 10.87±8.99 in this group. On the other hand, with the primed spacer, the respective mean baseline FEV1 and FEV1/FVC values were 89.41±12.14 and 85.49±6.76, while it increased by 12.1±11.01 after salbutamol inhalation. There were no significant differences between the techniques regarding the variation in FEV1 before and after bronchodilator use via a new spacer or primed spacer. Priming new plastic spacers with 20 puffs of salbutamol did not cause additional bronchodilation in asthmatic children, suggesting this practice is inefficient in clinics https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3552 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3552/2061