Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 2 2023 04 30 138 149 Mohammad Amin Rajizadeh Student Research Committee, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran AND Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran AND Department of Physiology and Pharmacology, Afzalpour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran Mohammad Abbas Bejeshk Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran AND Department of Physiology and Pharmacology, Afzalpour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran Amir Hossein Doustimotlagh Department of Clinical Biochemistry, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran AND Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran Hamid Najafipour Department of Physiology and Pharmacology, Afzalpour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran AND Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran Maryam Eftekhari Department of Genetics, Hormozgan University of Medical Science, Hormozegan, Iran Merat Mahmoodi Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran Mahdokht Azizi Department of Pathology, Shahid Beheshti Hospital, Yasuj University of Medical Science, Yasuj, Iran Fahimeh Rostamabadi Department of Medical Immunology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran AND Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran Hossein Pourghadamyari Student Research Committee, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran ANDDepartment of Clinical Biochemistry, Afzalipour Medical Faculty, Kerman University of Medical Sciences, Kerman, Iran AND Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran AND Research Center for Hydatid Disease, Kerman University of Medical Sciences, Kerman, Iran 2022 10 01 2023 01 29 Asthma is an inflammatory disease of the airways. We assessed the anti-inflammatory and antioxidative impacts of quercetin, a plant derivative, on inflammatory and oxidative indices in lung tissue and serum of rats with asthma.Asth ma was induced by ovalbumin. Rats were divided into 4 groups: control, asthma+vehicle (Receieved normal saline), asthma+dexamethasone, and asthma+quercetin. After asthma induction, quercetin (50 mg/kg) and dexamethasone (2.5 mg/kg) were injected intraperitoneally once daily for 1 week. On day 50, lung histopathology indices; inflammatory factors; tissue gene expression, including GATA Binding Protein 3 (Gata-3), Tbx21 (T-bet), Transforming growth factor-β (TGF-β), Il10 (IL-10), Il1b (IL-1β), Il6 (IL-6), Acta2 (α-SMA), and Tnf (TNF-α); and oxidative stress indices (malondialdehyde [MDA], catalase [CAT], glutathione peroxidase [GPX], superoxide dismutase [SOD], and total antioxidant capacity [TAC]) in tissue and serum, were evaluated. The results showed that quercetin reduced Gata3, Tnf, Tgfb1, Il1b, and Acta2 gene expression and increased Tbx21 gene expression following asthma. Quercetin also improved oxidative stress by decreasing MDA levels and increasing TAC, CAT, SOD, and GPX levels in serum and lung tissue. Furthermore, quercetin decreased IL6 and TNFα levels and increased IL10 levels in lung tissue after asthma was treated with quercetin. Quercetin ameliorates oxidative stress and inflammation caused by asthma, especially at the tissue level. Therefore, quercetin can be considered a potent antiasthmatic agent. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3668 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3668/1935

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 2 2023 04 30 124 137 Hua Feng School of Public Health, Nanchang University, Nanchang, Jiangxi, China AND State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China Yongning Wu State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China AND Corresponding Author, NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment, Beijing, China 2021 11 02 2022 11 22 The global prevalence of allergies is on the rise. Food allergies are of special concern among children under 5 years of age, leading to morbidity and mortality. Though the standard management is avoidance, probiotics are being used widely to prevent and treat food allergies. We aimed to determine the effect of probiotics as a therapeutic option for controlling food and cow’s milk allergy among children under 5 years of age. A systematic search of electronic medical literature databases was conducted. We included all eligible randomized controlled trials available from inception until May 2021. The primary outcome of interest was the relief of allergic symptoms, while the secondary outcome was the induction of tolerance. Two investigators undertook the literature search, screening, data extraction, and quality appraisal independently. Data analysis and synthesis were performed using STATA 14 software. Subgroup analysis was performed for the duration of use and follow-up, and the age category of children included in the outcome were done. Twenty trials involving 4043 pediatric patients with food allergies were included in the review. Subgroup analysis also revealed that probiotics were effective in treating food allergies across the various subgroups included in the model. Around 15 trials reported our primary outcome, relief of symptoms, as a binary variable, which was pooled to obtain a risk ratio of 0.86 (95% confidence interval [CI], 0.77–0.95), with very low heterogeneity (I2 7.7%). Six trials were included for the secondary outcome of interest, which gave an imprecise pooled estimate of 1.29 (95% CI, 0.98–1.70) with significant heterogeneity (I2 7). Thus, we conclude that probiotics can serve as a vital therapeutic option in tackling food allergies among children less than 5 years of age. Further larger studies exploring the effectiveness of individual strains and their safety pattern are essential.  https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3393 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3393/1937

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 2 2023 04 30 212 216 Norio Kodaka Division of Respiratory Medicine, Department of Internal Medicine, Toho University Ohashi Medical Center, Ohashi, Meguro-ku, Tokyo, Japan Chihiro Nakano Division of Respiratory Medicine, Department of Internal Medicine, Toho University Ohashi Medical Center, Ohashi, Meguro-ku, Tokyo, Japan Takeshi Oshio Division of Respiratory Medicine, Department of Internal Medicine, Toho University Ohashi Medical Center, Ohashi, Meguro-ku, Tokyo, Japan Takatomo Hirouchi Division of Respiratory Medicine, Department of Internal Medicine, Toho University Ohashi Medical Center, Ohashi, Meguro-ku, Tokyo, Japan Yuka Yamada Division of Respiratory Medicine, Department of Internal Medicine, Toho University Ohashi Medical Center, Ohashi, Meguro-ku, Tokyo, Japan Hiroto Matsuse Division of Respiratory Medicine, Department of Internal Medicine, Toho University Ohashi Medical Center, Ohashi, Meguro-ku, Tokyo, Japan 2022 03 23 2023 03 13 No Abstract No Abstract No Abstract https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3489 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3489/1939

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 2 2023 04 30 208 211 Simona Barni Allergy Unit, Meyer Children’s Hospital IRCCS, Florence, Italy Marta Vazquez-Ortiz National Heart & Lung Institute, Imperial College London, London, United Kingdom Mattia Giovannini 1 Allergy Unit, Meyer Children’s Hospital IRCCS, Florence, Italy AND Department of healt Science, University of Florence, Florence, Italy Giulia Liccioli Allergy Unit, Meyer Children’s Hospital IRCCS, Florence, Italy Lucrezia Sarti Allergy Unit, Meyer Children’s Hospital IRCCS, Florence, Italy Giulia Lascialfari Allergy Unit, Meyer Children’s Hospital IRCCS, Florence, Italy Laura Pisano Immunology and Molecular Microbiology Unit, Meyer Children's Hospital IRCCS, Florence, Italy Silvia Boscia Immunology and Molecular Microbiology Unit, Meyer Children's Hospital IRCCS, Florence, Italy Francesca Mori Allergy Unit, Meyer Children’s Hospital IRCCS, Florence, Italy 2022 06 07 2023 03 13 Shellfish is defined as any edible marine invertebrate and refers to crustaceans and mollusks. Crustaceans belong to the phylum Arthropods. Mollusks belong to the phylum Mollusca. This report illustrates a rare case of a 6-year-old girl with challenge-proven acute food protein–induced enterocolitis syndrome (FPIES) to cuttlefish (phylum Mollusca, class Cephalopoda), anaphylaxis to crustaceans (phylum Arthropoda), and tolerance to other mollusks, including clams and mussels (phylum Mollusca, class Bivalvia). The association of IgE-mediated food allergy and acute FPIES seen in this case is rare. To our knowledge, this is the first case of FPIES to cuttlefish reported in a child. This challenge highlights the need for further research into the allergens and mechanisms underpinning FPIES at a molecular level, enabling a better understanding of cross-reactivity patterns and the development of diagnostic and predictive tests to assist in clinical practice. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3566 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3566/1940

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 2 2023 04 30 150 162 EN Shadi Paydarfar Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mohammad Amin Abbasi Firoozabadi Hospital Clinical Research Development Unit (FHCRDU), School of Medicine, Iran University Medical Science (IUMS), Tehran, Iran Ali Hashemi Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Sodabe Taheri Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mojgan Bandehpour Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran AND Department of Medical Biotechnology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Nariman Mosaffa Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2022 03 01 2022 10 25 Extensively drug-resistant Acinetobacter baumannii is considered one of the most dangerous threats to global health, requiring novel therapeutic interventions. The outer membrane protein A (OmpA) is an immunogenic agent that triggers immune responses. The current study evaluated serum antibody levels against previously determined immunogenic OmpA peptides from A baumannii in ICU staff. Serum samples were collected from 62 ICU staff members (representing the exposed group), healthy controls (representing the nonexposed group), and patients with systemic lupus erythematosus (SLE) (as controls for nonspecific antibody reactions). After excluding the cross-reactive antibodies via Escherichia coli lysate pretreatment, all the samples were assessed in the vicinity of A baumannii lysate by enzyme-linked immunosorbent assay (ELISA). All the positive samples were assessed for interaction with previously designed and selected peptides using ELISA. The protective potential of positive serum antibodies was surveyed in vitro using an opsonophagocytic study. The most antibody positive samples against one of the dominant peptides were determined in the ICU personnel (75%).  SLE serum samples did not react with candidate peptides. The strongest positive reaction was observed in serum treatment with one of the OmpA peptides (No. 5) with significant differences compared to other designed peptides. Our findings showed that ICU samples have substantially higher antibody levels than the nonexposed group; Positive samples show strong results in the opsonophagocytosiis assay. This study demonstrates A baumannii colonization at human mucosal surfaces, especially in exposed healthy workers. Novel OmpA-derived peptides could be used to identify immunogenic vaccine candidates. Therefore, more studies are needed  before this peptide and antibody levels are used in diagnosis, prevention, or treatment.   https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3473 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3473/1932

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 2 2023 04 30 172 182 EN Elham Shokati Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran Morteza Motallebnezhad Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran Elaheh Safari Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran 2022 08 22 2023 01 09 Astragalus polysaccharide (APS) is a functional component of Astragalus membranaceus with antitumor and immunomodulatory properties. This study evaluated the effect of APS on thai.tums.ac.ir/index.php/ijaai/article/view/3628 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3628/1901

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 6 2022 12 24 657 669 EN Morteza Motallebnezhad Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Tehran, Iran Shirin Taghizadeh Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND School of Medicine, Shahroud University of Medical Sciences. Shahroud, Iran Tayebe Aghaie Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Tehran, Iran Maryam Azimi Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Tehran, Iran Ali-Akbar Salari Salari Institute of Cognitive and Behavioral Disorders (SICBD), Karaj, Alborz, Iran Mahmoud Bozorgmehr Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran Elahe Safari Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Tehran, Iran Reza Falak Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Tehran, Iran Mir-Hadi Jazayeri Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Tehran, Iran 2022 07 01 2022 09 12 Placental extract (PE) and exosomes from pregnant mice appear to have immunomodulatory and neuroprotective effects. In this study, we assessed the potential therapeutic effects of PE and exosomes obtained from pregnant mice in experimental autoimmune encephalomyelitis (EAE) mouse models. C57BL/6 mice, 8 to 12 weeks of age, were prepared and administered PE, exosomes, and glatiramer acetate (GA), as an FDA-approved treatment for multiple sclerosis (MS), after EAE induction. Thereafter, the therapeutic effects of treatment were evaluated by measuring the clinical courses of the mice as well as determining the number of regulatory T (Treg) cells using flow cytometry, cytokine levels, and microRNA-326 expression via real-time PCR. GA, PE, and exosomes reduced clinical severity, the extent of spinal cord demyelination, and the infiltration of inflammatory cells into the spinal cord. The frequency of CD4+CD25+FoxP3+ Treg cells increased after treatment of EAE mice with GA, PE, and exosomes. The mRNA expression of the inflammatory cytokines (interleukin-17  and interferon-gamma), as well as miR-326 expression, decreased significantly in the EAE mice after treatment with GA and exosomes. PE and exosomes from pregnant mice are involved in the modulation of Treg/Th17 balance and provide a therapeutic approach for MS. Further clinical studies will hopefully confirm the safety and efficacy of such treatments in MS patients. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3592 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3592/1898

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 6 2022 12 24 670 676 Shaghayegh Pezeshki Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mir Hadi Jazayeri Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran Bahram Chahardouli Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran Nader Tajik Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran AND Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran Seyyed Massood Nabavi Department of Regenerative Medicine, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran Mahdi Akbarzadeh School of Nursing, Baqiyatallah University of Medical Science, Tehran, Iran 2022 08 06 2022 09 04 Chronic lymphocytic leukemia (CLL) is the clonal expansion of mature CD5+ B cells and the most common lymphoproliferative disease in adults (B1-CLL). B1 cells' anti-inflammatory effects include the production of natural IgM (nIgM) by the spleen and bone marrow, decreased inflammatory cytokines as a primary response to maintaining tissue homeostasis, and enhanced release of transforming growth factor β (TGFβ). We used the flow cytometry technique in peripheral blood from patients with CLL and multiple sclerosis (MS) to immunophenotype B cells and their subpopulations. Whole blood from CLL and MS patients, as well as healthy controls, was used to detect nIgM using the VH4-34 gene copy number and real-time RT-PCR. We found that the proportion of CD5+ B cells was significantly lower in MS patients than in the control group and that CD5+ B lymphocytes were significantly higher in CLL patients than in the control group. Compared to the control group, CLL patients had significantly higher levels of the VH4-34 gene copy number. On the contrary, MS patients had significantly lower VH4-34 gene copy number levels compared to the control group. As the number of antibodies in CLL patients increases due to the high number of B1 cells, we propose a new way to treat MS by extracting this natural antibody from the sera of CLL patients and injecting it into MS patients. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3620 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3620/1889

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 6 2022 12 24 677 686 Behrouz Robat-Jazi Department of Medical Immunology, School of Medicine, Aja University of Medical Sciences, Tehran, Iran Khodayar Ghorban Department of Medical Immunology, School of Medicine, Aja University of Medical Sciences, Tehran, Iran AND Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran Mohammad Gholami Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran AND Department of Microbiology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran Esmaeil Samizadeh Department of Pathology, Imam Reza Hospital, Aja University of Medical Sciences, Tehran, Iran Zahra Aghazadeh Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Mohammad Amin Shahrbaf Department of Medicine, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Maryam Dadmanesh Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran AND Department of Infectious Diseases, School of Medicine, Aja University of Medical Sciences, Tehran, Iran Negin Hosseini Rouzbahani Department of Medical Immunology, School of Medicine, Aja University of Medical Sciences, Tehran, Iran AND Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran Abbas Mirshafiey Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 2022 08 15 2022 11 27 coronavirus disease of 2019 (COVID-19) can be complicated by acute respiratory distress syndrome (ARDS) and may be associated with cytokine storm and multiorgan failure. Anti-inflammatory agents, such as systemic corticosteroids, monoclonal antibodies, and nonsteroidal anti-inflammatory drugs (NSAIDs) can be used for this purpose. In this study, we evaluated the immunomodulatory effect of mannuronic acid (M2000), which is a novel NSAID, on COVID-19-related cytokine storms. This study was conducted in vitro on blood samples of 30 COVID-19 patients who presented with ARDS to a referral center. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples and incubated with phorbol myristate acetate for 24 hours. M2000 was administered with the dosages of 25 µg/well and 50 µg/well after 4 hours of incubation at 37°C. The quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess mRNA gene expression. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the supernatant PBMC levels of interleukin (IL)-6, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Both mRNA expression and the supernatant PBMC levels of IL-17, TNF-α, IL‑6, and IFN‑γ were decreased in PBMCs of COVID-19 patients treated with M2000 compared with the control  group. For the first time, it was observed that M2000 could be effective in alleviating the inflammatory cascade of COVID-19 patients based on an in vitro model. After further studies in vitro and in animal models, M2000 could be considered a novel NSAID drug in COVID-19 patients. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3627 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3627/1895

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 6 2022 12 24 687 703 Najmeh Kaffash Farkhad Department of Immunology, Immunology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran AND Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Alireza Sedaghat Lung Disease Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Hamidreza Reihani Department of Emergency Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Amir Adhami Moghadam Department of Internal Medicine and Critical Care, Islamic Azad University, Mashhad, Iran Ahmad Bagheri Moghadam Department of Anesthesiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Nayereh Khadem Ghaebi Neonatal Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Mohammad Ali Khodadoust Department of Immunology, Immunology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Amin Reza Nikpoor Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran Jalil Tavakol Afshari Department of Immunology, Immunology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 2022 08 27 2022 09 22 Acute respiratory distress syndrome (ARDS) is a systemic inflammation resulting from immune system overactivity. ARDS is also a fatal complication of COVID-19. Mesenchymal stem cells (MSCs) have immune modulatory properties. This study evaluated the safety and efficacy of three times transplantation of umbilical cord-derived MSCs (UC-MSCs) in terms of specific immunological and clinical changes in mild-to-moderate COVID-19-induced ARDS patients. In this single-center, open-label, phase 1 clinical trial, 20 patients diagnosed with COVID-19 and mild-to-moderate ARDS were included and were divided into two groups: a control group receiving standard care and an intervention group receiving UC-MSC in addition to standard care. Three consecutive intravenous transplants of UC-MSC (1×  cells/kg body weight per each transplant) were performed in the intervention group on days 1, 3, and 5. The biological assay was investigated four times (days 0, 5, 10, and 17). UC-MSCs improved the patients' clinical and paraclinical parameters, including leukocytosis, lymphopenia, thrombocytopenia, and liver enzyme abnormalities compared to the control group. They also decreased pro-inflammatory lymphocytes (TH1 and TH17) and increased anti-inflammatory T lymphocytes. Cell therapy also reduced the mean fluorescence intensity (MFI) in overactivated CD8+ T cells.  These findings show that three UC-MSC injections could regulate a hyperactivated immune system in COVID-19-induced ARDS patients by decreasing the inflammatory T lymphocyte subset and can improve the patient's hematological condition and liver function. However, more studies are needed in this area.    https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3641 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3641/1902

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