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

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

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

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

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 23 2 2024 04 07 168 181 EN Katarzyna Napiórkowska-Baran Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Grzegorz Grześk Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Jan Błażejewski Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Marcin Ziętkiewicz Department of Rheumatology, Clinical Immunology, Geriatrics and Internal Medicine, Medical University of Gdańsk, Gdańsk, Poland Ewa Więsik-Szewczyk Department of Internal Medicine, Pulmonology, Allergy and Clinical Immunology, Central Clinical Hospital of the Ministry of National Defense, Military Institute of Medicine, Warsaw, Poland Aleksandra Matyja-Bednarczyk 2nd Department of Internal Medicine, Jagiellonian University Medical College, Kraków, Poland Marta Tykwińska Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Elżbieta Grześk Department of Pediatrics, Hematology and Oncology, LudwikRydygier Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Jakub Lubański Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland Oskar Schmidt Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland Bartłomiej Szymczak Student Research Club of Clinical Immunology, Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland Robert Zacniewski Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Ewa Szynkiewicz Department of Nursing in Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Michał Owsiany Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland Zbigniew Bartuzi Department of Allergology, Clinical Immunology and Internal Diseases, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland 2023 09 18 2023 11 28 TUS">Evaluation of T-cell Function after Blood Transfusion in Patients Undergoing Coronary Artery Bypass Grafting 304 312 Nasim Golafshani Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Narges Golafshani Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Ali Reza Mohseni Department of Laboratory Sciences, School of Allied Sciences, Mazandaran University of Medical Sciences, Sari, Iran Mahboubah Mohseni Fatemeh Zahra Hospital, Mazandaran University of Medical Sciences, Sari, Iran AND Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Ahmad Najafi Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Shervin Ziabakhsh-Tabari Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Hossein Asgarian-Omran Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Mohsen Tehrani Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Aliakbar Pourfathollah Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran 2024 01 24 2024 05 12 Blood transfusion is associated with increased mortality and morbidity. This study aimed to determine the effect of blood transfusion on T-helper 1 (TH1), TH2, and TH17 function in patients undergoing coronary artery bypass grafting (CABG). Two blood samples were obtained from patients undergoing CABG, before and 14 days after surgery. Production of interleukin (IL)-2, IL-4, interferon (IFN)-γ, IL-17A, and IL-10 by CD4+ T cells was measured using enzyme-linked immunosorbent assay (ELISA). mRNA expression of T-box expressed in T cells (T-bet), GATA binding protein 3 (GATA3), RAR-related orphan receptor-γ (ROR-γt), signal transducer and activator of transcription 3 (STAT3), STAT4, and STAT6 were measured using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). mRNA expression of T-bet and STAT4 showed a significant decrease after blood transfusion. However, the concentration of IFN-γ in the culture supernatant showed no significant difference after blood transfusion. mRNA expression of GATA3 and STAT6 showed a significant decrease after blood transfusion. However, the concentration of IL-4 in the culture supernatant showed no significant difference after blood transfusion. mRNA expression of ROR-γt showed no significant decrease after blood transfusion; however, the expression of STAT3 and the concentration of IL-4 in the culture supernatant did significantly decrease following blood transfusion. IL-10 production increased significantly postoperatively. Decreased TH1, TH2, and TH17 signaling pathway activity and increased IL-10 concentration indicate an immunomodulatory effect on the immune system after blood transfusion. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4010 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4010/2151

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 3 2025 05 05 313 333 Sajjad Shekarchian Department of Immunology, Faculty of Medicine, Shahed University, Tehran, Iran Marzieh Eghtedardoost Arena Best Diagnostics Lab Ltd., Tehran, Iran Hannaneh Golshahi Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran Helia Behrouzfar Faculty of Veterinary Medicine, Science and Research Branch of Islamic Azad University, Tehran, Iran Zahra Fakhroueian 5 School of Chemical Engineering-Nanomedicine, College of Engineering and IPE, University of Tehran, Tehran, Iran Roya Yaraee Department of Immunology, Faculty of Medicine, Shahed University, Tehran, Iran 2024 10 06 2024 11 23 Lung cancer is a leading cause of cancer deaths worldwide and new therapeutic approaches are needed. This study investigates the efficacy of a new zinc oxide-based nanomedicine in a mouse model of heterotopic lung cancer. C57BL/6 mouse model with Lewis lung carcinoma (LL2) cells was used. The mice were treated with different doses of nanodrug, cisplatin, or phosphate-buffered saline. Tumor growth, metastasis, markers for oxidative stress, and immune responses, in particular the infiltration of CD8+ T cells, were examined. The nanodrug significantly reduced tumor size, inhibited metastasis, and improved survival compared to the control group. Moreover, no significant toxic effect was observed in hematological, biochemical and histopathological analyses. Furthermore, the nanodrug altered the tumor microenvironment in favor of immune system activation by modulating the level of oxidative stress and increasing CD8+ cell infiltration. The results show that this new nanomedicine may be a candidate for an effective treatment for lung cancer. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4215 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4215/2176

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 3 2025 05 05 334 346 Wu Chen Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China Lijun Xu Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China Haibo Deng Department of Urology, Suzhou Integrative Traditional Chinese and Western Medicine Hospital, Suzhou, China Zhenyan Zhu Department of Urology, Suzhou Integrative Traditional Chinese and Western Medicine Hospital, Suzhou, China Dongrong Yang Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China 2024 06 14 2024 08 18 The aim of this study was to investigate the role of the ubiquitin specific peptidase 10 (USP10/methyltransferase like 3 (METTL3)/C-X-C chemokine receptor type 4 (CXCR4) axis in immunotherapy of castration-resistant prostate cancer (CRPC). Knockdown experiments were conducted in CRPC cell lines to assess the effect of targeting CXCR4 on cell proliferation invasion and migration. Coculture experiments of CXCR4 knockdown CRPC cells with THP1-M0 were performed to evaluate their impact on macrophage polarization and migration ability. With CD8+ T cells was conducted to assess their effects on CD8+ T cell proliferation and apoptosis. CXCR4-overexpressing CRPC cells were treated with the JAK-2 specific inhibitor AG490 to assess the effect of CXCR4 through the JAK2/STAT3 pathway on CRPC. The mechanisms by which USP10 regulates CXCR4 expression through targeting METTL3 were explored through dataset analysis, bioinformatics prediction, and Western blot. In CRPC tissues and cells, there was an observed increase in CXCR4 expression. Suppressing CXCR4 through knockdown methods resulted in the inhibition of CRPC cell growth, movement, and infiltration. Additionally, it led to a reduction in M2 polarization and the recruitment of Tohoku Hospital Pediatrics-1 (THP1) M0 macrophages, along with a mitigation of CD8+ T cell exhaustion. Dataset analysis, bioinformatics prediction, and Western blot validation indicated that CXCR4 activates the JAK2/STAT3 pathway to promote the expression of CCL2 and PD-L1, while USP10 promotes CXCR4 expression through METTL3. Our study underscores the significance of the USP10/METTL3/CXCR4 axis in immunotherapy for CRPC and CXCR4 as a potential target for therapeutic intervention in CRPC treatment. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4123 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4123/2110

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 3 2025 05 05 347 360 Xiangdong Guo Department of Otolaryngology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, China Yamin Liu Department of Clinical TCM and Pharmacology, School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan Province, China Xiaoning Chen Department of Otolaryngology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, China 2024 10 09 2024 12 07 Luteolin (LO) possesses pharmacological benefits like anti-inflammatory, antioxidant, and immune-boosting properties. This study aims to clarify the effect of LO on allergic rhinitis (AR) and its mechanisms and provide new insights for the clinical application of LO. A mouse model for AR was developed through ovalbumin (OVA) stimulation. AR mice were gavaged with saline, low, medium, and high concentrations of LO, and montelukast. Nasal symptoms and scores were evaluated. The levels of OVA-specific immunoglobulins (OVA-sIgs), T helper cells (Th1, Th2, Th17), regulatory T cells (Tregs) cytokines, along with proinflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA). Histopathological alterations were observed utilizing hematoxylin-eosin staining. Interleukin (IL)-1β and IL-18 levels were assessed through immunohistochemistry. Flow cytometry measured the percentage of T lymphocytes. The levels of endoplasmic reticulum stress (ERS)-related and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-related mRNAs and proteins were analyzed through reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. LO reduced nasal symptom scores in AR mice, upregulated OVE-sIgG2a levels, and downregulated OVE-sIgE, OVE-sIgG1, and histamine levels. After the administration of LO, AR mice showed an increase in Th1 and Treg cytokines levels, while Th2 and Th17 cytokines levels were reduced. LO ameliorated the splenic T cell subset imbalance and attenuated inflammatory cell infiltration. LO reduced the levels of ERS-related and NLRP3 inflammasome activation-related mRNAs and proteins in the nasal mucosa. LO ameliorated AR symptoms by regulating T cell subset imbalance, hindering ERS and NLRP3 inflammasome activation. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4216 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4216/2177

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 3 2025 05 05 361 374 You Wang Department of Nephrology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei, China Pei Pi Department of Nephrology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei, China Manli Hu Department of Nephrology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei, China Dan Luo Department of Nephrology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei, China 2024 11 19 2024 12 07 Latent transforming growth factor-β binding protein-2 (LTBP2) plays a significant role in tissue fibrosis. This research aimed to elucidate whether LTBP2 influences the progression of diabetic nephropathy (DN) through the phosphatidylinositol 3-kinases/protein kinase B (PI3K/Akt)/nuclear factor kappa-B (NF-κB) pathway. The HBZY-1 cells were exposed to high glucose to create diabetic nephropathy cell model. LTBP2 levels were examined by Western blot and immunofluorescence. After verifying the transfection efficiency of si-LTBP2, cell counting kit-8, 5-ethynyl-2-deoxyuridine staining, Western blot, flow cytometry and immunofluorescence were utilized to assess the proliferation, apoptosis and fibrosis of HBZY-1 cells, respectively. Collagen deposition was also detected by Sirius red staining, and inflammatory factors levels were determined by Elisa. PI3K/Akt/NF-κB pathway activators were applied to explore whether LTBP2 silencing could play a role in DN by modulating this pathway. After treatment with high glucose, the expression of LTBP2 was elevated in HBZY-1 cells. LTBP2 silencing hindered the aberrant proliferation of HBZY-1 cells, with no significant effect on apoptosis; meanwhile, it reduced fibrosis, decreased collagen content, and decreased inflammatory factors levels in HBZY-1 cells. Following treatment with high glucose, the PI3K, Akt, and p65 phosphorylation levels were increased, whereas silencing LTBP2 reduced them. Activators of the PI3K/Akt/NF-κB pathway weakened the inhibition of LTBP2 silencing on cell proliferation, fibrosis, and inflammation. In conclusion, silencing of LTBP2 weakened the proliferation, fibrosis, and inflammation of HBZY-1 cells treated with high glucose by hindering the PI3K/Akt/NF-κB pathway. This research offers a new reference for the targeted therapy of DN. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4247 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4247/2181

Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 3 2025 05 05 375 395 Haili Jiang Nanjing University of Chinese Medicine, Nanjing, China AND Department of Oncology Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China Anni Xie Anhui University of Chinese Medicine, Hefei, Anhui, China Ting Wang Department of Oncology Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China Wenjing Shi Anhui Medical University, Hefei, Anhui, China Die Hu Anhui University of Chinese Medicine, Hefei, Anhui, China Rui Sheng Anhui University of Chinese Medicine, Hefei, Anhui, China Chaozheng Gao Anhui University of Chinese Medicine, Hefei, Anhui, China Tian Xie Nanjing University of Chinese Medicine, Nanjing, China AND School of Pharmacy, Hangzhou Normal University, Hangzhou, China 2024 10 06 2024 11 22 Programmed cell death protein 4 (PDCD4) is an oncogene involved in the cell cycle and apoptosis, enhancing drug sensitivity in tumor cells and inhibiting tumor development. However, the relationship between PDCD4 and tumor immune microenvironment remains unclear. The Cancer Genome Atlas (TCGA) database was used to collect PDCD4 data and somatic mutation data for 33 cancer types. Gene Expression Profiling Interactive Analysis (GEPIA) database was used to obtain the distribution map