Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 5 2022 10 26 524 536 Chang Xu Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, Jilin, China AND Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji, Jilin, China Yilan Song Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, Jilin, China AND Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji, Jilin, China Chongyang Wang Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, Jilin, China AND Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji, Jilin, China Jingzhi Jiang Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, Jilin, China AND Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji, Jilin, China Zhiguang Wang Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, Jilin, China AND Department of Respiratory Medicine, Affiliated Hospital of Yanbian University, Yanji, Jilin, China Liangchang Li Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, Jilin, China AND Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji, Jilin, China Guanghai Yan Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, Jilin, China AND Department of Anatomy, Histology and Embryology, Yanbian University Medical College, Yanji, Jilin, China 2021 08 30 2022 05 23 MicroRNAs (miRNAs) can participate in airway remodeling by regulating immune molecule expression. Here, we aimed to identify the differential miRNAs involved in airway remodeling. Airway remodeling was induced by ovalbumin in female BALB/C mice. The differentially expressed miRNAs were screened with microarray. GO (Gene Ontology) and KEGG enrichment analysis was performed. The miRNA target gene network and miRNA target pathway network were constructed. Verification with real-time PCR and Western blot was performed. We identified 63 differentially expressed miRNAs (50 up-regulated and 13 down-regulated) in the lungs of ovalbumin-induced airway remodeling mice. Real-time PCR confirmed that 3 miRNAs (mmu-miR-1931, mmu-miR-712-5p, and mmu-miR-770-5p) were significantly up-regulated, and 4 miRNAs (mmu-miR-128-3p, mmu-miR-182-5p, mmu-miR-130b-3p, and mmu-miR-20b-5p) were significantly down-regulated. The miRNA target gene network analysis identified key mRNAs in the airway remodeling, such as Tnrc6b (trinucleotide repeat containing adaptor 6B), Sesn3 (sestrin 3), Baz2a (bromodomain adjacent to zinc finger domain 2a), and Cux1 (cut like homeobox 1). The miRNA target pathway network showed that the signal pathways such as MAPK (mitogen-activated protein kinase), PI3K/Akt (phosphoinositide 3-Kinase/protein kinase B), p53 (protein 53), and mTOR (mammalian target of rapamycin) were closely related to airway remodeling in asthma. Collectively, differential miRNAs involved in airway remodeling (such as mmu-miR-1931, mmu-miR-712-5p, mmu-miR-770-5p, mmu-miR-128-3p mmu-miR-182-5p, and mmu-miR-130b-3p) as well as their target genes (such as Tnrc6b, Sesn3, Baz2a, and Cux1) and pathways (such as MAPK, PI3K/Akt, p53, mTOR pathways) have been identified. Our findings may help to further understand the pathogenesis of airway remodeling. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3341 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3341/1879

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 5 2022 10 26 594 599 Mohammad Nabavi Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran Faezeh Mohammadi School of Medicine, Iran University of Medical Sciences, Tehran, Iran Saba Arshi Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran Mohammad Hasan Bemanian Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran Morteza Fallahpour Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran Fatemeh Atashrazm Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran Sima Shokri Department of Allergy and Clinical Immunology, Rasool e Akram Hospital, Iran University of Medical Sciences, Tehran, Iran 2021 12 14 2022 04 24 Coronavirus disease 2019 (COVID-19) affects millions of people worldwide. Clinical manifestations range from asymptomatic to severe viral pneumonia. CVID patients with COVID-19 infection are not adequately studied. In some studies, CVID patients had higher mortality rates, although other studies showed that CVID patients might have an uncomplicated COVID-19 infection. We describe 14 cases of COVID-19 infection in Iranian CVID patients in this study, including clinical manifestations, laboratory findings, and treatment strategies. There were 29% of patients with mild disease, 43% with moderate disease, and 29% with severe disease in this study. A critical case and a death occurred in none of our patients. There were six cases of infection more than two weeks after receiving the second dose of Sinopharm BIBP COVID-19 vaccine; all had mild to moderate disease. Among these patients, Remdesivir was the most frequently prescribed medication. According to this study, most of our patients presented with an uncomplicated disease course. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3417 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3417/1888

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 5 2022 10 26 494 511 Soheila Asoudeh Moghanloo Department of Genetics, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran AND Immunology, Asthma and Allergy Research Institute (IAARI), Tehran University of Medical Sciences, Tehran, Iran Mohsen Forouzanfar Department of Genetics, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran Mojtaba Jafarinia Department of Genetics, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran Mohammad Reza Fazlollahi Immunology, Asthma and Allergy Research Institute (IAARI), Tehran University of Medical Sciences, Tehran, Iran Gholam Ali Kardar Immunology, Asthma and Allergy Research Institute (IAARI), 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 2022 03 13 2022 07 05 Allergen-specific immunotherapy (AIT) involves administering allergen extracts. It is used to desensitize allergic patients. Herbal allergen extracts that are optimum in efficacy and fewest in side effects are still challenging to produce. To overcome these limitations, oral immunotherapy, epicutaneous immunotherapy, intralymphatic immunotherapy, and artificial recombinant allergen preparations have been evaluated. Recombinant allergens have become more popular with the development of molecular diagnostics and therapeutics. Besides food and drug allergens, pollen, fungal spores, and other allergens have been studied. Based on related clinical studies, this comprehensive overview will present the latest perspectives on AIT methods and available allergenic products, as well as discuss the challenges and opportunities for treating allergic disorders. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3481 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3481/1886

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 5 2022 10 26 512 523 Hossein Esmaeilzadeh Department of Allergy and Clinical Immunology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran AND Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Maryam Zare Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Soheila Alyasin Department of Allergy and Clinical Immunology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran AND Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Hesamedin Nabavizadeh Department of Allergy and Clinical Immunology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran AND Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Negar Mortazavi Department of Clinical Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran Zahra Kanannejad Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 2022 04 11 2022 07 06 Aspirin-exacerbated respiratory disease (AERD) is a chronic inflammatory disease. It is defined by asthma, chronic rhinosinusitis with nasal polyposis, and a hypersensitivity reaction to aspirin or nonsteroidal anti-inflammatory drugs. Aspirin desensitization (AD) has been confirmed as an effective treatment to control AERD inflammation through the modulation of immune responses. We aimed to review AERD with an overview of the epidemiology, pathophysiology, and treatment. We also discussed the effect of AD on immunological markers involved in AERD pathogenesis. A search of electronic databases on AERD was performed. We included five randomized clinical trials (RCTs) on AD. We also searched databases for recent studies that investigated the effect of AD on the immunological mechanisms of AERD. RCTs have demonstrated the therapeutic effectiveness of AD on the patients’ quality of life, asthma symptom score, inhaled and oral steroid use, forced expiratory volume in 1 sec (FEV1), and inflammatory mediators. The clinical benefits of AD can occur though the regulation of innate and adaptive immune responses that are involved in the pathogenesis of AERD. In addition to the valuable effects of AD in RCTs, some side effects such as gastrointestinal bleeding, asthma exacerbation, or rash have been reported that should be considered for reaching an optimal protocol for AD. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3510 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3510/1878

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 5 2022 10 26 537 548 EN Zhenzhen Su Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China Lin Chen Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China Qian Niu Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China Bin Yang Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China Zhuochun Huang Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China 2021 10 27 2022 07 06 Rheumatoid arthritis (RA) is caused by complicated interactions between genes and the environment. CXC chemokine receptor 5 (CXCR5) is required for B and T follicular helper cell migration and humoral immunity generation. Therefore, this study aimed to assess whether polymorphisms of the CXCR5 gene are implicated in RA development and progression. This case-control study enrolled 285 RA patients and 291 healthy controls. The polymerase chain reaction-ligase detection reaction method was used to genotype rs630923, rs497916, rs3922, and rs676925 in the CXCR5 gene. Epidemiological, clinical, and laboratory data were collected retrospectively. The rs630923 A allele was associated with a higher risk of RA (AOR [adjusted odds ratio]=2.00, 95% confidence interval [CI] =1.14–3.53). However, in the RA group, the frequency of the rs497916 T allele was lower (AOR=0.69, 95% CI=0.51–0.93). Regarding rs3922, AG+GG genotype carriers were at a significantly lower risk for RA than AA genotype carriers (AOR=0.70, 95% CI=0.49–0.99). In the RA group, we found that the different genotypes were significantly associated with specific laboratory values, including rheumatoid factor, total bilirubin, total cholesterol, low-density lipoprotein cholesterol, and alkaline phosphatase. This is the first report indicating that CXCR5 polymorphisms were associated with RA susceptibility. These findings lead to a rising possibility of identifying RA-susceptible individuals based on genetic markers. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3390 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3390/1881

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 5 2022 10 26 549 560 Erfan Basirat Student Research Committee, Medical School, Alborz University of Medical Sciences, Karaj, Iran Danial Dehghan Student Research Committee, Medical School, Alborz University of Medical Sciences, Karaj, Iran Ardeshir Abbasi Department of Immunology, Medical School, Tarbiat Modarres University, Tehran, Iran Nafiseh Pakravan Division of Immunology, Medical School, Alborz University of Medical Sciences, Karaj, Iran 2022 02 07 2022 07 16 It is believed that preformed antibodies are responsible for blood transfusion reactions and transplant rejections. In order to remove a tumor, the tissue must be rejected. On the basis of transfusion reaction and transplantation immunology, we hypothesized that allogeneic serum can inhibit tumor growth when injected intra-tumor. Initially, an in vitro cytotoxicity test was conducted using the C57BL/6 serum (intact or decomplemented) in combination with the BALB/c-originating CT26 cell line.  The CT26 cell line was used to establish a mouse model of colon cancer. When the tumor was palpable, C57BL/6 serum was injected intra-tumor. In addition to tumor size, hypoxia, metastatic capacity, angiogenesis, and metabolic and inflammatory stat> 2023 01 11 2023 03 19 Compared to common asthma, obese asthma is difficult to control. Previous studies have shown that vitamin D (Vit D) has a therapeutic effect on asthma. Nevertheless, the action mechanism of Vit D for obese asthma are not well known. In this study, we, therefore, induced obesity and established an obese asthma mouse model using ovalbumin (OVA) stimulation and applied treatment with Vit D (100 ng/kg). Accordingly, thirty mice were randomly divided into 5 equal groups of normal control, asthma, obese asthma, asthma+Vit D, and obese asthma+ Vit D. The levels of inflammatory factors and adipokines were measured by the ELISA assay; then the quantitative reverse transcription PCR (qRT-PCR) method was used to evaluate the expression of high mobility group box 1(HMGB1) and receptor for advanced glycation end products [RAGE] genes.T he results showed that OVA sensitization significantly increased airway resistance, the levels of inflammatory cytokines, and HMGB and RAGE expression in asthmatic and obese asthmatic mice, as compared to the control group. Also, these changes in the obese asthmatic group were notably higher than those in the asthmatic one. In addition, the treatment of asthmatic and obese asthmatic mice with Vit D significantly reduced the raw, serum and BALF levels of inflammatory cytokines, as well as the expression of HMGB1 and RAGE mRNA. To conclude, the present study showed that vitamin D might attenuate lung injury by up-regulating HMGB1 and RAGE expression. Our findings, thus, may offer new concepts and approaches for the treatment and prevention of obese asthma. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3749 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3749/1955

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 3 2023 06 16 281 289 Parastoo Shaban Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran. Niloofar Honari Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran Nafiseh Erfanian Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran Mehran Hosseini Department of Anatomical Sciences, Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran Hossein Safarpour Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran Saeed Nasseri Department of Molecular Medicine, Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran 2022 05 28 2023 03 11 Ziziphus Jujuba Mill (Z.J) is a well-known ethnomedical source of biologically active compounds with anti-inflammatory effects. However, its significance in acute lung injury (ALI) has never been studied. The present study aimed to explore whether Z.J could attenuate lipopolysaccharide (LPS)-induced inflammatory responses in an experimental model of ALI. Male BALB/c mice received an intratracheal administration of LPS (n=32) or phosphate buffer saline (PBS) (control, n=8). Within 1, 11, and 23 h post-LPS injection, mice were randomly assigned to receive intraperitoneal treatments of saline, dexamethasone (2 mg/kg), and 100 and 200 mg/kg of Z.J extracts, respectively. 24 h after intratracheal administration of LPS, bronchoalveolar lavage fluid and lung tissues were harvested and assessed for inflammatory cell influx, tumor necrosis factor-α (TNF-α) levels, and histological assessments. Treatment with Z.J extracts (100 and 200 mg/kg) and dexamethasone effectively reduced LPS-induced neutrophil and other inflammatory cell influx into the lung tissue compared to the untreated group. additionally, both doses of Z.J extracts (100 and 200 mg/kg) significantly ameliorated the lung wet-to-dry ratio and histopathological damage. Furthermore, compared to the untreated ALI mice, Z.J extract at the highest dose could significantly reduce the TNF-α level.   The present findings indicated that Z.J could effectively ameliorate LPS-induced ALI inflammatory responses and might be considered a promising alternative therapy for the ALI phenotype. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3558 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3558/1948

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 3 2023 06 16 299 311 Mehrnoosh Pashei Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Farahnaz Ghahremanfard Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran Ehsan Manouchehri Doulabi Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden Maral Hemmati Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran Fatemeh Pak Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran Parviz Kokhaei Department of Immunology, Arak University of Medical Sciences, Arak, Iran AND Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden 2022 10 15 2023 03 02 T cell dysregulation and shift to T helper 2 responses, boosting tumor microenvironment support, contributes to the survival of leukemic B cells in Chronic Lymphocytic Leukemia. Interleukin (IL)-25 is involved in the initiation of T helper 2 cell responses. Signal transduction of IL-25 begins with the heterodimer receptor (IL-17RA/IL-17RB). The presence of IL-25 in the tumor microenvironment may affect the supportive effects of T cells in the surrounding tumor cell environment. The purpose of this study was to evaluate the role of IL-25 in the biology of CLL. IL-17RB expression in CD3+ and CD19+ cells was assessed in isolated peripheral blood mononuclear cells (PBMCs) of nine CLL patients and nine healthy subjects by real-time polymerase chain reaction and flow cytometry. B cells were positively enriched from PBMCs using magnetic-activated cell sorting (MACS). PBMCs and purified leukemic B cells were cultured with recombinant human IL-25 (20ng/ml) for 72 hours, then the viability and apoptosis of cultured cells were measured by MTT assay and AnnexinV/7AAD. Furthermore, the levels of CD69 expression on T lymphocytes and IL-17RB in T and B cells were determined by flow cytometry. The basal level of IL-17RB expression in CLL patients was significantly higher than that in control individuals. In addition, the percentage of IL-17RB+/CD3+, IL-17RB+/CD19+ cells and CD69+/CD3+ cells increased after 72 hours of culture with IL-25 in CLL patients compared to healthy subjects. IL-25 also reduces the apoptosis rate of tumor cells. We found that IL-25 could stimulate T cells in CLL patients and lower B cell death. This suggests that IL-25 might have a role in enhancing the survival of tumor cell by expressing receptors for inflammation, such as IL-17RB, and might be involved in the development of CLL. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3676 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3676/1946

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 3 2023 06 16 265 280 Mohammad Amin Rajizadeh Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran AND Department of Physiology and Pharmacology, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran Mohammad Hadi Nematollahi Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran Elham Jafari Department of Pathology, Pathology and Stem Cells Research Center, School of Medicine, Kerman University of Medical Science, Kerman, Iran Mohammad Abbas Bejeshk Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran AND Department of Physiology and Pharmacology, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran Mehrnaz Mehrabani Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran Farzaneh Rostamzadeh Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran Mitra Samareh fekri Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran Hamid Najafipour Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran 2023 01 08 2023 03 24 Asthma is a common chronic allergic disease that affects a significant percentage of the world’s population. Niosomes are nanoparticles consisting of non-ionic surfactants that can be used for drug delivery. This research was designed to investigate the impacts of inhalation of simple and niosomal forms of myrtenol against adverse consequences of asthma in rats. Asthma induction was performed via injection of ovalbumin, followed by its inhalation. Niosomes were created by a heating protocol, and their physicochemical features were evaluated. Forty-nine male Wistar rats were allotted into 7 groups (n=7 each): Control (CTL), vacant niosome (VN), Asthma, Asthma+VN, Asthma+SM (simple myrtenol), Asthma+NM (niosomal myrtenol), and Asthma+B (budesonide). Lung remodeling, serum immunoglobulin E (IgE), inflammatory  and cytokines, and antioxidant factors in the lung tissue and bronchoalveolar fluid (BALF), as well as), were evaluated. The results showed that myrtenol-loaded niosomes had appropriate encapsulation efficiency, kinetic release, size, and zeta potential. The thickness of the epithelial cell layer in the lungs, as well as cell infiltration, fibrosis, IgE, reactive oxygen species, interleukin (IL)-6, and tumor nuclear factor alpha (TNF-α) levels, decreased significantly. In contrast, superoxide dismutase and glutathione peroxide activity increased significantly in the serum and BALF of the treated groups. The niosomal form of myrtenol revealed a higher efficacy than simple myrtenol and was similar to budesonide in ameliorating asthma indices.  Inhalation of simple and niosomal forms of myrtenol improved the