Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 1 11 EN Saloomeh Fouladi Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Mohsen Masjedi Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Mazdak Ganjalikhani Hakemi Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Nahid Eskandari Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 2017 11 22 2018 05 16 Allergic asthma is the most common type of allergy which have become increasingly prevalent in all around the world. Airway eosinophilic inflammation is a major feature of allergic asthma. Glycyrrhiza uralensis (licorice) is one of the regular herbs in traditional Chinese medicine (TCM) as it has many effects on the immune system such as anti-inflammatory and immune regulatory activity; antiviral and antitumor effects. This review focuses on the "licorice” components, mainly glycyrrhizic acid (GA) and derivatives structure that evaluate its effects on the allergic asthma. We performed searching articles in Pubmed, Web of Science, and Scopus data bank from 1990 to 2017. The search syntax were: "glycyrrhizin" OR " glycyrrhizic acid" OR " glycyrrhizinic acid" OR" glycyrrhiza glabra" OR " liquorice root" OR "G. glabra" OR "glycyrrhizic Acid" AND "allergic asthma" OR "bronchial asthma" OR "asthma, bronchial" OR "airway hyper-responsiveness" OR "airway inflammation". Several molecular mechanisms and inflammatory mediators may possibly be responsible for efficacy of glycyrrhizin. Some in vitro studies indicated to the fact that possible mechanisms of anti-inflammatory effects could be through reduction of pro-inflammatory mediator's synthesis that motivates eosinophil, basophils and mast cells to release cytokines for the differentiation of T helper cells into Th2 cells to secrete interleukins. Furthermore, some transcription factors such as NF-κB, STAT6 and HDAC2 go between modulations of anti-asthmatic effects. The last but not the least it can be said that glycyrrhizin is potentially a good herbal drug with the lower most adverse effects for asthma treatment. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1740 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1740/1398

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 12 26 EN Farzaneh Shakeri Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran Vahideh Ghorani Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran AND Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Saeideh Saadat Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran AND Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Zahra Gholamnezhad Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran AND Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Mohammad Hossein Boskabady Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran AND Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 2017 12 28 2018 05 09 Medicinal plants have been identified and used as primary sources in prevention and treatment of pulmonary diseases (mainly obstructive pulmonary diseases) from ancient times due to various pharmacological activities. In this review, the stimulatory effects of extracts, some fractions and constituents of medicinal plants on β2-adrenoceptors which could be used as possible therapeutic agents in the future were reviewed. Various databases including; Medline, PubMed, ScienceDirect, Scopus, and Google Scholar were searched using stimulatory effect, β2-adrenoceptors, possible mechanism, tracheal smooth muscle (TSM), medicinal plants and their constituents as keywords from 1985 to 2017. All studied plants including; Nigella sativa, Rosa damascena, Thymus vulgaris, Carum copticom, Carum carvi, Zataria multiflora, Crocus sativus, Cuminum cyminum, Liomnia acidissima, Portulaca oleraceae, Satureja hortensis, Ephedra sinica and Achillea millefolium showed relaxant effect on tracheal smooth muscle with a stimulatory effect on β2-adrenoceptors mechanism. The studied plants and their constituents could be of therapeutic value in clinical practice as a bronchodilatory drug by β2-adrenoceptors stimulatory mechanism for treatment of obstructive pulmonary diseases. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1803 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1803/1378

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 02 27 37 EN Emel Ceylan Department of Pulmonary Medicine, Adnan Menderes University Medical School, Aydın, Turkey Sertan Bulut Department of Pulmonary Medicine, Atatürk Chest Diseases and Chest Surgery Education and Research Hospital, Ankara, Turkey Mustafa Yilmaz Department of Biochemistry, Adnan Menderes University Medical School, Aydın, Turkey Hüseyin Örün Department of Pulmonary Medicine, Adnan Menderes University Medical School, Aydın, Turkey Fisun Karadağ Department of Pulmonary Medicine, Adnan Menderes University Medical School, Aydın, Turkey İmran Ömürlü Department of Biostatistics, Adnan Menderes University Medical School, Aydın, Turkey Sevin Kirdar Department of Clinical Microbiology, Adnan Menderes University Medical School, Aydın, Turkey Aslıhan Karul Department of Biochemistry, Adnan Menderes University Medical School, Aydın, Turkey 2017 11 25 2018 05 09 The effects of comorbidities on systemic inflammation markers in stable asthmatics and the consequences of such effects have not been well evaluated. We aimed to evaluate the effect of comorbidities on clinical manifestations and systemic inflammation in asthmatic patients under control. The study group consisted of asthmatic patients who applied to our pulmonology outpatient clinic and volunteered to participate. 120 clinically stable asthma patients (71 females and 49 males) and 35 healthy controls (19 females and 16 males) with similar age, gender, and body mass index distributions were admitted to the study. The levels of osteopontin, interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 13 (IL-13), eosinophilic cationic protein, adiponectin, and high-sensitivity C-reactive protein of the individuals were evaluated using commercial ELISA kits by taking venous blood samples. Of 120 asthmatic subjects, 47 (39, 2%) had comorbidities and allergic rhinitis (15%) coexisted most frequently. Other comorbidities associated with asthma were gastroesophageal reflux, sinusitis, hypertension, diabetes, gastritis, and peptic ulcus respectively. There was no physician-diagnosed comorbidity in the control group. The levels of IL-6 and IL-8 were found higher in asthma group with comorbidities when compared to those with no comorbidities (p were 0.032 and 0.046, respectively). Comorbidities interfere with the diagnosis and treatment of asthma, besides affecting the disease control. Our findings suggest the possibility of the impact of comorbidities on systemic inflammation markers, especially IL-6 and IL-8. To evaluate the impact of comorbidities on asthma control and systemic markers, further studies are needed. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1750 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1750/1390

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 38 47 EN Shole Faridi Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran Norouz Delirezh Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran Seyyed Meysam Abtahi Froushani Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran 2018 03 02 2018 07 30 Streptozocin (STZ) is a strong alkalizing agent which is capable of destroying the beta cells of the pancreatic islets. Multiple low doses (40 mg/kg, intraperitoneally for 5 consecutive days) prescription of STZ to mice can lead to the T cell-dependent immune response and induction of autoimmune diabetes (AD) with complete similarity to the human type 1 diabetes (T1D). This study has evaluated the effects of hydroalcoholic extract of saffron on the clinical and immunological profile of experimental autoimmune diabetes in C57BL/6 mice. After the establishment of the AD, mice were treated orally with hydroalcoholic extract of saffron (500 mg/kg) for 3 weeks. The results with p<0.05 were considered significant. Obtained data showed that treatment with the hydroalcoholic extract of saffron significantly reduced the incidence of hypoglycemia and restored insulin secretion and histopathological changes in pancreas sections. In addition, treatment with saffron reduced lymphocyte proliferation index in the cells isolated from the pancreas of diabetic mice. Also, the extract of saffron markedly decreased the production of pro-inflammatory interleukin-17 (IL-17) increased anti-inflammatory IL-10 and transforming growth factor-β in the pancreatic cell population. Moreover, the production of proinflammatory nitric oxide and reactive oxygen substances were down-regulated by the saffron extract. It seems that the hydroalcoholic extract of saffron can be considered as a useful strategy in the treatment of type 1 diabetes. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1886 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1886/1389

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 48 61 EN Hassan Ghobadi Department of Internal Medicine, Pulmonary Division, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran Mohammad Reza Alipour Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Rana Keyhanmanesh Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Mohammad Hossein Boskabady Neurogenetic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Mohammad Reza Aslani Ardabil Imam Khomeini Educational and Clinical Hospital, Ardabil University of Medical Sciences, Ardabil, Iran 2018 02 15 2018 07 18 Epidemiological and clinical studies have demonstrated a close association between obesity and asthma. The current study investigated the effect of high-fat diet on tracheal responsiveness to methacholine and insulin resistance in ovalbumin (OVA) sensitized male and female rats. The rats were divided into eight groups (n=6 per group): female with the normal diet (F+ND), male with the normal diet (M+ND), female OVA-sensitized with the normal diet (F+SND), male OVA-sensitized with the normal diet (M+SND), female with high-fat diet (F+HFD), male with high-fat diet (M+HFD), female OVA-sensitized with high-fat diet (F+SHFD), and male OVA-sensitized with high-fat diet (M+SHFD). All rats were fed for 8 weeks with high-fat diet or standard pelts, and for another 4 weeks, they were sensitized with OVA or saline. At the end of the study, the tracheal responsiveness to methacholine, serum insulin, and blood glucose levels was measured. Also, insulin resistance indexes were determined. OVA-sensitization and diet-induced obesity caused the curve of methacholine concentration response to shifting to the left. In addition, results indicated that the EC50 (the effective concentration of methacholine generating 50% of peak response) in F+SHFD rats was statistically lower than M+SHFD group (p<0.05). Moreover, insulin resistance was higher in the F+SHFD than the M+SHFD group (p<0.001). These results suggest that insulin resistance and metabolic syndrome may be involved in the pathogenesis of obesity associated with OVA-sensitized rats condition, especially in female animals.   https://ijaai.tums.ac.ir/index.php/ijaai/article/view/1874 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/1874/1394

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 1 2019 02 24 62 71 EN Lei Chong Institute of Pediatrics, National Key Clinical Specialty of Pediatric Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Liu Liu Department of Pediatrics, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Lili Zhu Discipline of Pediatric Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Haiyan Li Discipline of Pediatric Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Youyou Shao Discipline of Pediatric Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Hailin Zhang Discipline of Pediatric Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Gang Yu Discipline of Pediatric Respiratory Medicine, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China 2017 11 21 2018 05 06 Obese asthma is a new asthma phenotype. The underlying mechanisms are not clearly understood. Leptin and adiponectin are two predominant adipokines produced by adipose tissue. Studies have demonstrated a role of leptin on regulating the Janus kinase/signal transducer and ativator of transcription protein (JAK/STAT) signaling pathway and STAT3, STAT6 were known to have essential role on inflammatory cytokines production. However, whether STAT3 and STAT6 are activated and related to leptin merit further investigation. The aim of this study was to investigate the expression levels of leptin/adiponectin ratio and the activations of STAT3 and STAT6 in the lungs of obese asthma mice. Experiments were carried out on male C57/B6J mice. The proteins in bronchoalveolar lavage fluid (BALF) were measure Hamid Gholami Pourbadie Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran Ali Sharifi-Zarchi Department of Computer Engineering, Sharif University of Technology, Tehran, Iran Saeed Aslani Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Leila Nejatbakhsh Samimi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Ahmadreza Jamshidi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran Mahdi Mahmoudi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran 2020 08 12 2021 04 06 Ankylosing spondylitis (AS) is a systemic inflammatory disorder of joints and entheses. Recent studies have reported an increased prevalence of dementia in AS patients. However, data for exploring the association between dementia and AS remain uncertain. In this study, enriched pathways and differentially expressed genes (DEGs) were identified in whole blood transcription data of AS patients obtained from the gene expression omnibus (GEO) database; using gene set enrichment analysis (GSEA) and differential expression analysis. Four pathways, including oxidative phosphorylation, Alzheimer’s, Parkinson’s, and Huntington’s diseases were significantly enriched in AS patients compared to the controls. We identified 22 common genes among the pathways that showed an increasing trend in AS compared to the controls. Five of them including COX7B, NDUFB3, ATP5PF, UQCRB, and NDUFS4 were the most significant genes which were selected for gene expression analysis; using real-time PCR on RNA contents of peripheral blood mononuclear cells (PBMCs) of AS patients and controls (20 samples from each group). The gene expression analysis indicated considerable overexpression of COX7B (p<0.0001) and ATP5J (p=0.0001) genes in AS patients group in comparison to the control samples. The role of oxidative phosphorylation has previously been established in dementia pathogenesis. Given that AS patients have also a remarkably higher prevalence of dementia than the their healthy counterparts, hence our results may propose that the common pathway of oxidative phosphorylation can be regarded as a possible shared contributing factor in the etiopathogenesis of AS and dementia. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2934 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2934/1729

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 5 2021 09 28 574 583 Faezeh Jamali Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran Arman Ahmadzadeh Department of Rheumatology, Loghman-e Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Zahra Sahraei Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran AND Department of Infectious Disease, Loghman-e Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Jamshid Salamzadeh Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran AND Food Safety Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2021 03 15 2021 07 06 Rheumatoid arthritis (RA) is considered as an autoimmune-related condition in which the overproduction of pro-inflammatory cytokines leads to an inflammatory cascade. N-acetylcysteine (NAC) is a potent anti-inflammatory and anti-oxidant agent. We aimed to explore the impact of oral NAC on cytokines activities and clinical indicators in RA patients. In this placebo-controlled randomized double-blind clinical trial, 41 active RA patients were allocated in either NAC (600 mg, twice a day) or placebo group, as add-on therapy to the routine regimen, for 8 weeks. Disease activity score with an erythrocyte sedimentation rate (DAS28-ESR), and serum concentrations of interleukin (IL)-1β and IL-17 were assessed at baseline and end of the trial for all participants in the test and control groups. The reduction of the DAS28-ESR was higher considerably in the NAC group compared to that of the control group. No statistically significant differences were seen in the reduction of IL-1β and IL-17 cytokines between the NAC and control groups. In addition, improvements in the patient global assessment, number of tender joints, number of swollen joints, and the ESR rates were in favor of the NAC group. Our findings reveal that NAC may have a beneficial effect on all of the clinical features of RA. However, non-significant variations in the IL-1β and IL-17 levels suggest an alternative way of NAC effectiveness without influencing the measured cytokines. Nevertheless, these results need to be confirmed by further investigations. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3153 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3153/1743

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 5 2021 09 28 584 592 Parisa Rahimzadeh Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran AND Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran Sahar Mortezagholi Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mojgan Ghayedi Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Haideh Namdari Iranian Tissue Bank and Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran Mitra Rahimzadeh Social Determinants of Health Research Center, Alborz University of Medical Sciences, Karaj, Iran Roobina Boghozian Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Maryam Azimi Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran Eisa Salehi Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 2020 07 14 2021 03 17 Mechanisms underlying the systemic lupus erythematosus (SLE) have not yet been elucidated. In this study, we evaluated the balance of T cell subsets in BALB/c mice model of SLE induced; using Con A and polyamines as DNA immunogenicity modifiers. BALB/c mice were immunized subcutaneously with 50 µg extracted DNA from cells cultured in different conditions: splenocytes+ polyamines (group P), splenocytes+ Con A (group A), splenocytes+ polyamines+ Con A (group PA) and splenocytes only (control). Anti-double-stranded DNA –(ds-DNA) antibodies, proteinuria, and antinuclear autoantibodies were assessed by enzyme-linked immunosorbent assay, Bradford method, and immunofluorescence respectively. Transcription factors of different T helper subsets were examined by real-time polymerase chain reaction. The serum level of the anti-dsDNA antibody in group PA was higher than that in the other groups (p>0.05). Antinuclear antibody (ANA) titer increased in groups A and PA. Proteinuria level in group PA was significantly higher than that in the control group (p<0.001). Expression of Foxp3 was decreased in group A (p=0.001). Additionally, the ratios of T-bet/GATA3 and T-bet/Foxp3 were also increased in group A. (p>0.05). Our results revealed an increased ratio of Th1 to Th2 and decreased expression of Foxp3 in group A, but group PA manifested more obvious signs of the disease. These results suggest that other mechanisms rather than disturbance in T cells' balance may involve the development of disease symptoms. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2900 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/2900/1723

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 5 2021 09 28 593 599 Hossein Akbari Department of Biostatistics and Public Health, Faculty of Health, Kashan University of Medical Sciences, Kashan, Iran Rezvan Talaee Autoimmune Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran Seyedeh Fatemeh Zaker Students Research Committee, Kashan University of Medical Sciences, Kashan, Iran Hassan Nikoueinejad Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran 2020 12 21 2021 03 15 Psoriasis is a chronic inflammatory dermatitis characterized by an inflammatory epidermal hyperproliferation. Growth differentiation factor‐15 (GDF-15), a member of the transforming growth factor‐β family, has immune modulatory roles in autoimmune condition of Psoriasis. This study aimed to evaluate the relationship between GDF-15 serum levels as well as gene expression with psoriasis and its severity. This case-control study was performed on 45 patients with psoriasis Vulgaris and 45 healthy individuals. The severity of the disease was determined based on the psoriasis area and severity index (PASI score). Serum levels of GDF-15 were measured by enzyme-linked immunosorbent assay (ELISA) and its gene expression in peripheral blood mononuclear cells was quantified by real-time polymerase chain reaction (RT-PCR). The mean serum levels of GDF-15 in patients and controls were 1.98±1.57 ng/mL and 0.93±0.48 ng/mL, respectively. GDF-15 gene expression was measured as 9.7±6.6% in the patient group and 7.6±2.5% in the healthy group. The mean of GDF-15 serum levels in mild, moderate, and severe cases of psoriasis were 0.45±0.35, 2.27±0.7, and 3.5±1.6 ng/mL, respectively, indicating that elevated serum levels of GDF-15 correlate significantly with disease severity. The mean of GDF-15 gene expression in the mild, moderate, and severe forms of psoriasis were 5.25±3.2, 7.6±2.8, and 17.8±5.7, respectively which indicate a significant relationship between GDF-15 gene expression and psoriasis severity. Based on this study, in psoriatic patients, GDF-15 serum levels and gene expression are significantly higher than those in healthy controls. Such values were correlated with disease activity, especially in severe cases. Therefore, GDF-15 may be used as a prognostic marker of psoriasis.   https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3072 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3072/1715

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 5 2021 09 28 600 613 EN Fereshteh Taghipour Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran AND Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran Omolbanin Oladpour Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran AND Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran Mohammad Taghi Rezayati Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran Hossain Khorramdelazad Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran Maryam Nemati Department of Hematology and Laboratory Sciences, School of Para-Medicine, Kerman University of Medical Sciences, Kerman, Iran Zahra Taghipour Department of Histology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran Javad Masoumi Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran Zuhair Mohammad Hassan Department of Immunology, School of Medicine, Tarbiat Modarres University, Tehran, Iran Abdollah Jafarzadeh Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran AND Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran AND Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran 2021 01 10 2021 06 13 Metformin, cimetidine, and ibuprofen separately exhibit immunomodulatory and anti-tumorigenic effects. Herein, the impacts of metformin alone and in combination with cimetidine/ibuprofen on some Th1- and regulatory T (Treg) cell-related parameters were evaluated using a breast cancer (BC) model. For establishing the BC model, four groups of Balb/c mice were challenged with the carcinoma cell line. After 11-30 days post-induction, they were treated intraperitoneally (with metformin (200 mg/kg), "metformin plus cimetidine (20 mg/kg)"; "metformin plus ibuprofen (20 mg/kg)", or with all three drugs in mentioned doses. Untreated BC and without tumor mice were enrolled as control groups. On day 31, splenic Th1 and Treg cell frequencies, serum interferon-gamma (IFN-γ), and transforming growth factor-beta (TGF-β) concentration, and intra-tumoral T-bet, TGF-β, and forkhead box protein P3 (FOXP3) expression were measured; using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and real-time-PCR, respectively. Treatment of the BC mice with metformin alone and in combination with cimetidine and/or ibuprofen enhanced the frequency of Th1 cells, and IFN-γ concentration, while it resulted in a decrease in the frequency of Treg cells, serum TGF-β concentration, and the expression of FOXP3 and TGF-β compared with un-treated BC mice. FOXP3 expression in the metformin-treated group was lower in mice who received combination therapy. Survival rate and body weight were increased, while tumor size and spleen index were reduced in mice treated with metformin alone and its combination with cimetidine and/or ibuprofen. No remarkable differences were found between metformin-treated mice and those who received combination therapies regarding Th1 and Treg cell percentages, TGF-β expression, body weight, tumor size, and spleen index. The benefits of combinational therapy may be largely attributed to metformin. Immunotherapeutic potentials of metformin in cancers need further considerations. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3091 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3091/1741

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 5 2021 09 28 614 622 Azam Kia Basic Science School, East branch, Payame Noor University, Tehran, Iran Mona Nadi Department of Cell and Molecular Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran Vahideh Hajhasan Department of Cell and Molecular Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran Jafar Salimian Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 2021 03 03 2021 06 12 The mitochondrion has a substantial role in innate immunity and inflammasome signaling pathways. Sulfur mustard (SM) induces toxicity in cytoplasmic organelles. We aimed to evaluate the potential therapeutic effect of curcumin on the toxicity of SM analog through measuring gene expression levels of mitochondrial dynamics followed by induction of the inflammasome signaling pathway. After the treatment of pulmonary epithelial cell line (A549) by 2-chloroethyl ethyl sulfide (CEES) (2500 mM) for 48h, the transcriptional activity of mitochondrial fission and fusion genes such as dynamin-related protein 1 (Drp1), mitochondrial fission 1 protein (Fis1), mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and Dominant optic atrophy (Opa1) and inflammasome pathway genes including absent in melanoma 2 (AIM2), NLR family containing protein 3 (NLRP3), and Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) was measured. Furthermore, the inhibitory effect of curcumin (160 mM) concurrent with SM analog on the expression level of mitochondria and inflammasome genes was investigated. CEES was able to over-express the fission, fusion (Drp1 ~ 8, Fis1 4.5, Mfn2 15, and Opa1 16-fold) and inflammasome genes (AIM2, NLRP3,  8 and 6-fold, respectively), whereas Mfn1 was significantly decreased (0.5-fold) and a not statistically significant decrease was observed in the ASC gene. Curcumin could modulate the effect of CEES, mitigate the expression of fission, fusion, and inflammasome genes exceedingly. However, a major increase in the repairer fusion gene (Mfn1, 6-fold) and complete suppression of the ASC gene were the outcomes of using the curcumin. In conclusion, we suggest curcumin alleviates the disturbance of mitochondrial dynamics and downregulates the inflammasome genes exposed to the CEES. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3139 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3139/1746

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 20 5 2021 09 28 623 634 EN Dongzhi Chen Department of Immunology, School of Basic Medicine, Hebei University, Baoding, China AND Key Laboratory of Pathogenesis Mechanism and Control of Inflammatory-autoimmun