Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 25 1 2026 01 01 16 23 EN Maedeh Khoshkam Division of Allergy and Clinical Immunology, Department of Pediatrics, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Mahshid Movahedi Division of Allergy and Clinical Immunology, Department of Pediatrics, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Mohammad Gharagozlou Division of Allergy and Clinical Immunology, Department of Pediatrics, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Monir Farokhzadeh Soltani Division of Allergy and Clinical Immunology, Department of Pediatrics, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran Masoud Movahedi Division of Allergy and Clinical Immunology, Department of Pediatrics, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran 2025 04 12 2025 06 23 Component- Resolved Diagnosis (CRD) is an effective tool in allergy diagnosis, that detects specific IgE to allergenic molecules. The ALEX (Allergy Explorer) test, commercially available since 2019, measures specific IgE to allergenic extracts and components associated with inhalant, food, animal, latex, and insect allergens. CRD results should be interpreted based on the patient's clinical history. Since Children's Medical Center Hospital is one of the largest referral centers for allergic patients, we evaluated the results of the ALEX2 test in patients referred to this center and compared them with the patients’ clinical symptoms. Clinical symptoms were concordant with positive CRD (ALEX2) test in 76.7% of cases. The overall agreement between positive allergen components and clinical symptoms was 58%. These findings indicate that the ALEX2 test can improve diagnostic accuracy in allergic patients; however, positive test results should be interpreted in the context of the patient’s clinical history. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4327 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4327/2230

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 25 1 2026 01 01 1 15 Mehrangiz Ghafari Department of Pathology, School of Medicine, Zabol University of Medical Sciences, Zabol, Iran Javad Poursamimi Department of Immunology, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran. Foroogh Asli Department of Internal Medicine, School of Medicine, Zabol University of Medical Sciences, Zabol, Iran 2025 05 06 2025 07 25 Metformin is a primary treatment for type 2 diabetes (T2D), well-known for its ability to lower blood glucose levels through both AMP-activated protein kinase (AMPK)-dependent and -independent pathways. Recent evidence suggests that metformin also possesses immunomodulatory properties, indicating its potential as a therapeutic agent that extends beyond metabolic regulation. This review summarizes the current understanding of metformin's dual roles in managing diabetes and modulating the immune system. It also explores the underlying mechanisms, clinical implications, and potential directions for future research. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4434 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4434/2253

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 25 1 2026 01 01 24 31 Zahra Valizadeh Department of Infectious Diseases, Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Sara Ghaderkhani Department of Infectious Diseases, Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Sahereh Eshraghi Department of Infectious Disease and Tropical Medicine, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Ladan Abbasian Department of Infectious Diseases, Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Department of Infectious Disease and Tropical Medicine, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Alireza Abdollahi Department of Pathology, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Tahereh Soori Department of Infectious Disease and Tropical Medicine, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Mohammad Mahdi Roozbahani Department of Infectious Diseases, Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 2025 05 10 2025 07 16 Since late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) pandemic has dramatically affected public health worldwide. Although systemic antibodies like Immunoglobulin G (IgG) and Immunoglobulin M (IgM)have been widely studied in Coronavirus disease 2019 (COVID-19), the role of Immunoglobulin A (IgA) in mucosal immunity remains less understood. This study evaluated whether salivary IgA levels could serve as prognostic markers for disease severity, progression, and outcomes in hospitalized patients with COVID-19. In this cross-sectional study, 61 hospitalized patients with COVID-19 were enrolled. After obtaining informed consent, saliva samples were collected at admission to measure IgA levels using an ELISA-based assay. Comprehensive clinical and laboratory data, including chest CT results, oxygen saturation, inflammatory markers, and clinical outcomes, were also recorded. Statistical tests were used to examine the association between salivary IgA levels and disease severity, progression, and outcomes. We enrolled 61 hospitalized patients with COVID-19 (30 females, 31 males; mean age: 56.20 ± 17.45 years; mean admission oxygen saturation: 89.98 ± 5.77%). At admission, 39.3% of patients reported dyspnea, and 40% demonstrated severe lung involvement on chest CT scans. The mean salivary IgA level was 1729.69 ± 391.35 mg/dL. No significant associations were found between salivary IgA levels and COVID-19 severity, disease progression, or clinical outcomes, including mortality. Our findings show that salivary IgA levels did not significantly correlate with COVID-19 severity, disease progression, or clinical outcomes in hospitalized patients. Therefore, salivary IgA alone cannot be recommended as a prognostic biomarker for COVID-19. Further research is needed to identify more reliable immunological indicators for predicting COVID-19 severity and outcomes. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4438 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4438/2237

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 25 1 2026 01 01 32 44 Yanlin Qiao Digestive Surgery, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China Xiang Gao Digestive Surgery, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China 2024 12 23 2025 08 01 This study examines the interaction between the microbiota and the immune system in diseases of the gastrointestinal tract, with a special emphasis on the synergistic use of pharmacological agents. This was a retrospective, observational study of 100 patients with moderate to severe gastrointestinal disorders, including irritable bowel syndrome and inflammatory bowel disease, receiving control, monotherapy, or combination therapy. Over 12 weeks, combination therapy demonstrated superior efficacy in enhancing gut microbial diversity. Improvements were achieved in alpha diversity, and a decrease in inflammatory indices and a shift in the immune phenotype were observed. Patients experienced significant improvements in symptom severity, pain, and general health. In addition, the general health of patients also improved. Importantly, the combination therapy group had better responses compared with the other groups. With respect to the identified factors, regression analysis revealed that microbial diversity, immune system regulation, and inflammation had positive effects on disease symptom alleviation. These findings therefore help support the perspective of combination therapy as a more comprehensive mode of approaching and treating gastroenteric diseases. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4290 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4290/2271

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 25 1 2026 01 01 45 57 Somayeh Mami Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Sajjad Shekarchian Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran Alireza Naderi Sohi Department of Stem Cells and Regenerative Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran Jafar Kiani Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran Masoud Soleimani Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Mohammad Hossein Nicknam Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AND Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran 2025 04 06 2025 06 06 Predominantly a widespread beta herpesvirus, human cytomegalovirus (HCMV) triggers lifelong latent infection in most of the people, and HCMV vaccine development has been designated a high public health priority. In the current study, the in vitro safety profile and potential immunotoxic effects of a novel messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccine designed against human cytomegalovirus (HCMV) were assessed. The aim was to measure inflammation, allergic reactions, complement activation, cytotoxicity, and hemolytic effects of the mRNA-LNP vaccine. Proinflammatory cytokine secretion, evident in human peripheral blood mononuclear cells (hPBMCs) treated with unmodified mRNA-LNP, was markedly attenuated by incorporating modified nucleotides. The vaccine appeared incapable of sparking allergic cytokine production or complement activation. Cell viability assays indicated no pronounced cytotoxicity, and hemolysis assays showed no notable hemolytic activity. The findings suggest that the modified mRNA-LNP vaccine exhibits a promising in vitro safety profile, supporting further development of this vaccine candidate. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4409 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4409/2223

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 25 1 2026 01 01 58 68 Liangliang Xie School of Medicine, Xinxiang University, Xinxiang, China Fei Gao School of Medicine, Xinxiang University, Xinxiang, China Jianmin Xu School of Medicine, Xinxiang University, Xinxiang, China Wenhui Xiong School of Medicine, Xinxiang University, Xinxiang, China Junlei Yin School of Medicine, Xinxiang University, Xinxiang, China Weiwei Sun School of Medicine, Xinxiang University, Xinxiang, China 2025 05 12 2025 06 23 Lipopolysaccharide (LPS)–induced inflammation in macrophages involves complex signaling pathways. This investigation explored the regulatory roles of triggering receptor expressed on myeloid cells-1 (TREM1) and interleukin (IL)-26 in the Janus kinase/signal transducer and activator of transcription (JAK/STAT) and nuclear factor-kappa B (NF-κB) p65 pathways in LPS-stimulated RAW 264.7 macrophages. RAW 264.7 cells were treated with LPS to assess TREM1 expression. TREM1 or IL-26 was silenced using short hairpin RNA (shRNA), while IL-26 was overexpressed via plasmid transfection. The JAK2 inhibitor AG490 was used to block JAK/STAT signaling. Western blot, reverse transcription–quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were employed to analyze the protein and mRNA levels of inflammatory markers and signaling molecules. Results showed that LPS upregulated TREM1 expression. In addition, TREM1 knockdown suppressed p65 activation and reduced inflammatory cytokine levels. Moreover, silencing TREM1 inhibited IL-26 and JAK/STAT phosphorylation (p-JAK1, p-JAK2, p-STAT1, and p-STAT3). Similarly, IL-26 knockdown or AG490 treatment attenuated p65 activation and inflammation. Furthermore, IL-26 overexpression reversed the anti-inflammatory effects of TREM1 silencing. Overall, TREM1 promoted LPS-induced macrophage inflammation via IL-26–mediated JAK/STAT and NF-κB pathway activation, suggesting that TREM1 and IL-26 are potential therapeutic targets. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4443 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4443/2272

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 25 1 2026 01 01 69 79 Mohammad Ali Akbar Esfahani Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Ruhollah Dorostkar Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah Univeand number of underlying diseases with PASI and DAPSA scores. Mean PASI and DAPSA scores were 5.19 and 15.13, respectively. The severity of psoriasis was mild in 58.1%, moderate in 36.5%, and severe in 4.5% of the cases. The activity of psoriatic arthritis was improved in 2.1%, low in 55.4%, moderate in 24.3%, and high in 1.8% of the patients. A significant association was found between erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), platelet (PLT) count, mean platelet volume (MPV), and PASI scores, while no statistically significant association was reported for PLR. A significant correlation was observed between ESR, CRP, RDW, NLR, PLR, PLT, and DAPSA scores, while no statistically significant association was found for MPV. The findings indicated that inflammatory and hematological markers can be helpful factors in evaluating the severity of psoriasis and psoriatic arthritis. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4072 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4072/2109

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 6 2024 12 29 662 675 EN Yashgin Hassanzadeh Department of Microbiology, North Tehran Branch, Islamic Azad University, Tehran, Iran Ramin Yaghobi Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Parviz Pakzad Department of Microbiology, North Tehran Branch, Islamic Azad University, Tehran, Iran Bita Geramizadeh Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 2024 04 16 2024 08 12 Cytotoxic CD4+ T cells eliminate human cytomegalovirus (HCMV)-infected cells through direct cytotoxic granules exocytosis. We aimed to evaluate the functional cytotoxic gene profile of CD4+ T cells alongside the frequency of the cytotoxic phenotype in renal transplant recipients with cytomegalovirus reactivation. Blood samples were collected from twenty renal recipients with and without HCMV reactivation (HCMV+ and HCMV- groups) and ten healthy adults (control group). CD4+ T cells were isolated to assess the frequency of cytotoxic CD4+ T cells via CD107a surface staining using flow cytometry and to evaluate gene expression of perforin, granzyme B, Runt-related transcription factor 3 (RUNX3), and Eomesodermin (Eomes) by quantitative PCR. The frequency of CD4+ CD107a+ T cells was higher in the HCMV+ group compared to the HCMV- group and significantly higher than in the control group (22.69 ± 3.47 vs 16.41 ± 2.24 and 11.60 ± 1.17, respectively). Perforin gene levels were reduced in the HCMV+ group compared to the other two groups, while granzyme B gene levels were similar between HCMV+ and HCMV- groups but lower than in the control group (0.63 ± 1.24 vs 0.67 ± 2.27 and 1.00 ± 0.00, respectively). This study demonstrated an increased frequency of cytotoxic CD4+ T cells with potentially reduced functionality in kidney transplant patients with HCMV infection. It also suggests that these cells might employ other mechanisms, such as death receptor-mediated killing, or the production of other granules. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4079 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4079/2131

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 6 2024 12 29 676 687 Atena Alifarsangi Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran Mohammad Khaksari Endocrinology and Metabolism Research Center, Kerman University of Medical Sciences, Kerman, Iran Rostam Seifaddini Neurology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran 2024 09 04 2024 09 30 Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system. Current treatments aim to manage symptoms and slow disease progression, but there is a need for effective interventions that target underlying disease mechanisms. In this study, we investigated the effects of exercise, MitoQ (a mitochondria-targeted antioxidant), and their combination on the gene expression of various biomarkers associated with MS in postmenopausal and premenopausal women. We measured interleukin-6 (IL-6) and key molecular pathways involved in MS pathogenesis, including suppressor of mother against decapentaplegic 2 (SMAD2), signal transducer and activator of transcription 1 (STAT1), and transforming growth factor beta (TGF-β) using real-time polymerase chain reaction. All interventions significantly lowered IL-6 levels and STAT1, especially in premenopausal women. Also, both exercise and MitoQ led to a significant increase in the SMAD2 and TGF-β expression, with a more pronounced effect on premenopausal women. Noteworthy, the effectiveness of the combination of exercise and MitoQ was considerably higher than each one alone. These findings suggest that exercise and MitoQ, either alone or combined, can modulate various biological pathways implicated in MS pathogenesis. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4191 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4191/2128

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 6 2024 12 29 688 698 Hadi Esmaeili Gouvarchinghaleh Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Ali Farhadi Biregani Biotechnology Research Center, Islamic Azad University, Shahrekord Branch, Shahrekord, Iran Abbas Doosti Biotechnology Research Center, Islamic Azad University, Shahrekord Branch, Shahrekord, Iran Ramezan Ali Taheri Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran Morteza Mirzaei Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran Ali Zahiri Students Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran Gholamreza Farnoosh Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran 2024 03 03 2024 07 22 Melittin is a natural toxin used in traditional medicine as an anti-inflammatory drug. It seems that the anti-inflammatory properties of melittin are caused by suppressing the expression of inflammatory genes and inhibiting signaling pathways. However, the use of melittin is limited due to instability, rapid degradation, and impurity. The aim of this study was to investigate the intranasal administration of a melittin-encoded plasmid as a new melittin delivery method for allergic diseases. After the induction of a mouse model of allergic rhinitis, mice received intranasal melittin plasmid. After the final challenge with allergen and allergic symptom assessment, the required samples were collected and transforming growth factor-beta (TGF-β), interferon-gamma (IFN-γ), and interleukin-4 (IL-4) cytokine levels, serum levels of ovalbumin-specific immunoglobulin (Ig) E, and histopathological changes were assessed. In addition to investigating the immune response, the effect of melittin on the expression level of genes involved in apoptosis was also investigated. The melittin plasmid significantly improved nasal symptoms and decreased eosinophil infiltration into the nasal mucosa. Moreover, melittin decreased the expression levels of IL-4 and TGF-β in nasal lavage fluid, while IFN-γ expression was increased. Regarding the expression level of genes involved in apoptosis, melittin led to an increase in BAX mRNA expression. These results suggest intranasal administration of a plasmid encoding melittin can suppress nasal symptoms, eosinophil infiltration, and immunomodulation of the immune response, which can be considered a promising approach in the treatment of inflammatory diseases. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4043 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4043/2130

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 6 2024 12 29 699 726 Atieh Pourbagheri-Sigaroodi Pediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Majid Momeny Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran Nima Rezaei Research Center for Immunodeficiencies, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran AND Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran AND Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Fatemeh Fallah Pediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran Davood Bashash Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2024 04 22 2024 06 24 Despite therapeutic advancements, treatment failure in hepatocellular carcinoma (HCC) continues to pose a significant obstacle. Given the vital role of the tumor immune microenvironment (TIM) in HCC and the promising effectiveness of immune therapies, we aimed to elucidate potential predictive biomarkers by developing a prognostic model based on immune-related genes (IRGs). After obtaining data, differentially expressed IRGs were identified, and prognostic models were developed using Cox regression analyses. Key contributors of the model were identified and the results were validated by experimental assays in HCC cell lines. Our eight-IRG signature can serve as an independent prognostic factor in HCC. The low-risk group exhibited superior overall survival and lower tumor mutation burden (TMB). The high-risk group showed elevated proportions of immune cells, including regulatory T cells and resting CD4+ memory T cells. We found that the NEAT1-C1/miR-542-5p/BIRC5 regulatory network may serve as a potential target in HCC. The experimental investigations showed that BIRC5 inhibition reduced the metabolic activity in four HCC cell lines. The results of this study facilitate patient stratification and the development of more effective treatment strategies, particularly for high-risk HCC patients. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4088 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4088/2126

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 6 2024 12 29 727 737 Yong Tao Department of General Surgery, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China Chengniu Chu Department of General Surgery, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China Dongjun Sun Department of Information, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China Junfeng Xiang Department of General Surgery, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China Bo Wu Department of General Surgery, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China Cong Li Department of General Surgery, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China Wei Cui Department of General Surgery, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China 2024 02 05 2024 07 17 Pancreatic ductal adenocarcinoma (PDAC) is a common digestive system tumor with high mortality rates and a poor prognosis. Reports suggest that microRNA (miR)-486-3p in PDAC can be used as a diagnostic biomarker. This research aimed to elucidate the mechanisms by which miR-486-3p regulates PDAC progression. miR-486-3p and chymotrypsin C (CTRC) expression in PDAC were measured using quantitative real-time polymerase chain reaction. Changes in the biological properties of PDAC cells were assessed by Transwell assay, scratch-wound assay, cell counting kit (CCK)-8 assay, and plate cloning assay. The protein expression of immunosuppressive factors (vascular endothelial growth factor, interleukin-6, and transforming growth factor-β) in PDAC cells was detected by western blot. Additionally, a subcutaneous graft tumor model was constructed to explore the influence of silencing miR-486-3p on PDAC in vivo. PDAC showed a pronounced increase in miR-486-3p expression. Upregulation of miR-486-3p stimulated PDAC cell proliferation, migration, invasion, and immunosuppressive factor protein expression, whereas silencing miR-486-3p hindered PDAC malignant development. miR-486-3p targets and negatively regulates CTRC expression. Silencing CTRC partially rescued the restraining impact of silencing miR-486-3p on PDAC malignant progression. In vivo experiments also indicated that silencing miR-486-3p inhibited PDAC malignant progression and immunosuppressive factor expression in vivo. In summary, miR-486-3p promotes immunosuppressive factor protein expression by targeting and negatively regulating CTRC expression, which in turn promotes PDAC malignant progression. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4027 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4027/2137

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 6 2024 12 29 738 745 EN Zeinab Karbalaei Pazoki Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Mostafa Hosseini Chemical Injuries Research Center, System Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Shiva Irani Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran Bahram Mohammad Soltani Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran 2024 10 15 2024 10 28 Cisplatin resistance presents a considerable hurdle in the treatment of ovarian cancer, significantly impacting patient outcomes and limiting the effectiveness of chemotherapy. This study employs advanced bioinformatics techniques-including RNA sequencing (RNA-seq), DNA sequencing (DNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq)-to elucidate the molecular mechanisms underlying this resistance, with a particular focus on the long non-coding RNA (lncRNA) LINC02381. Our findings reveal that LINC02381 is significantly upregulated in ovarian cancer cells exhibiting resistance to cisplatin, suggesting its pivotal role in mediating this phenomenon. We further demonstrate that cytokines, particularly interleukin-12 (IL-12), secreted by immune cells within the tumor microenvironment, activate the Wnt signaling pathway. This activation leads to the binding of the transcription factor TCF7 to the promoter region of LINC02381, resulting in enhanced expression of this lncRNA. Notably, this interaction establishes a positive feedback loop in which LINC02381 not only promotes its own expression but also amplifies Wnt signaling activity. This cascade ultimately drives the upregulation of ATP-binding cassette (ABC) transporters, which are crucial for the efflux of cisplatin from