Iranian journal of allergy, asthma, and immunology最新文献

To explore the immunological underpinnings and prognostic potential of gene expression profiles in bladder cancer through comprehensive analyses of The Cancer Genome Atlas (TCGA) data. We used the TCGA data to identify differentially expressed genes (DEGs) and performed enrichment analysis to reveal the related biological pathways. Meanwhile, the least absolute shrinkage and selection operator (LASSO) algorithm was adopted to develop a prognostic model. Then we evaluated the performance of the model in both TCGA and GSE13507 datasets. Furthermore, we conducted a comprehensive investigation on the feature genes utilized in model construction, encompassing both gene expression profiling and survival analysis. Finally, immune infiltration analysis and drug sensitivity analysis were applied to elucidate the immunological basis of the disease and provide potential therapeutic strategies. We identified a total of 837 DEGs, with a focus on immune-related genes. Using the LASSO algorithm, we developed a prognostic model incorporating seven key genes-NXPH4, FAM110B, GPC2, STXBP6, CYP27B1, GARNL3, and PTGER3-which demonstrated strong predictive accuracy in both TCGA and GSE13507 datasets. Moreover, immune infiltration analysis revealed a higher abundance of M0 and M2 macrophages in high-risk patients, suggesting that macrophage polarization could be a potential therapeutic target to modulate the immune microenvironment. Drug sensitivity analysis further suggested that high-risk patients exhibit differential responses to several chemotherapy agents, with potential therapeutic implications. This study constructed an effective prognostic model, providing new insights and potential therapeutic targets for the personalized treatment of bladder cancer, which needs further validation.

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.

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.

This study explores recent advances in harnessing the immunotherapeutic potential of hydatid cyst antigens for the treatment of allergies and autoimmunity. The aim is to elucidate the immunotherapeutic mechanisms employed by these parasite antigens. The hydatid cyst is considered the larval stage of Echinococcus granulosus, a parasitic helminth with life cycles involving a carnivorous definitive host (usually dogs) and an intermediate herbivore host (human, ungulate, or rodent). The two major species of this parasite with human public health importance are E granulosus and E multilocularis. E granulosus is a highly immunogenic organism that stimulates proinflammatory responses, significant antibody production, and T cell-mediated responses. Host adaptive immune responses to the parasite are TH2 dominant, but responses are absent in one-fifth of patients. Diagnostic antigens from cyst fluid are well-known, and the high abundance of hydatid cysts in the lungs and livers of slaughtered farm animals has made it easy to access the source of cyst antigens. Emerging from current preclinical studies, antigens derived from hydatid cyst cells and fluid show potential for suppressing and regulating immune responses associated with allergic and autoimmune conditions, disorders which increase with Western-type human development.

Autoimmune activities in chronic spontaneous urticaria (CSU) are claimed to be one of the most common causes of disease pathogenesis. This study aims to evaluate the prevalence and patterns of antinuclear antibodies (ANA) in patients with CSU, investigate the relationship between ANA positivity and autologous serum skin test (ASST) results, and explore the implications of these findings for understanding the potential autoimmune nature of CSU, particularly in relation to immunoglobulin E (IgE) levels. We analyzed data from 60 patients with CSU at Jahad Daneshgahi Clinic, Tehran, Iran. Patients were categorized based on ASST results (30 positive and 30 negative). Laboratory evaluations included ANAs via indirect immunofluorescence using the HEp-20-10 biochip kit. Data analysis was performed using chi-square and Mann-Whitney U tests. Among the 60 CSU patients, 37 were ANA-positive, with common patterns being nuclear fine-speckled and nucleolar. A decrease in IgE levels among ANA-positive patients compared to ANA-negative ones was also observed. Our study uncovered a notable 61.6% prevalence of ANA positivity among CSU patients, exceeding previously reported rates. The identification of nuclear fine-speckled and punctate nucleolar patterns may indicate associations with specific autoimmune conditions that warrant further investigation. Additionally, the observed lower IgE levels in ANA-positive patients suggest a distinct immunological profile, potentially reflecting type IIb autoimmunity.

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with relapsing and remitting periods. Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with relapsing and remitting periods. It has been reported that alterations of gut microbiota can affect disease activity in SLE. Probiotics which can modify the gut microbiota may be useful to control disease activity. Therefore, the effect of probiotic yogurt was evaluated on SLE disease activity. In this triple-blind, randomized, controlled trial, the patients were randomized and divided into 2 groups. The patients had Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) ≤6 and were on a stable dose of immunosuppressant in the last 3 months. The intervention group was given 200 g of probiotic yogurt containing Lactobacillus rhamnosus and Bifidobacterium bifidum for 13 weeks. The control group was given 200 g of yogurt without bacteria for 13 weeks. Demographic measurements, SLEDAI, and Health Assessment Questionnaire (HAQ) were analyzed before and after the intervention. The probiotic group (19 patients) and the control group (14 individuals) were compared. At the beginning and baseline of the trial, the probiotic and control groups' average energy intake, micronutrients, and macronutrients did not differ significantly. In the probiotic group, the amount of protein, cholesterol, magnesium, zinc, selenium, and iron intake increased significantly after intervention. There are no significant changes in SLEDAI score and disability (HAQ) between case and control groups at the end of the study. Consumption of probiotic yogurt containing L rhamnosus and B bifidum did not have a significant short-term effect on SLEDAI and disability in SLE patients.

Studies have investigated montelukast and budesonide aerosol inhalation for treating allergic rhinitis (AR) and bronchial asthma (BA) in children. However, there are significant variations in dosage and duration of administration. This research evaluated the efficacy in children with AR and BA and analyzed montelukast's impact on the inflammatory response. This retrospective cohort study involved 100 children with AR and BA who were admitted to "Baoding Hospital, Beijing Children's Hospital Affiliated with the Capital Medical University" from October 2022 to September 2023. They were divided into a budesonide group (budesonide n=50) and a combination group (montelukast and budesonide, n=50). Comparisons were made between the two groups in terms of clinical efficacy, severity scores of AR and BA before and after treatment, inflammatory indicators (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)), pulmonary function indicators (forced expiratory volume in the first second (FEV1), peak expiratory flow rate (PEF)), and adverse reactions. After treatment, the severity scores of AR and BA in the combination group were 4.00±0.93 points and 2.64±0.56 points, which were lower than those in the budesonide group (5.14±0.66 points and 3.31±0.65 points, respectively). The total response rate of the combination group (96.00%) was higher than that of the budesonide group (80.00%). The levels of IL-6 and TNF-α in the combination group were lower than those in the budesonide group, and the levels of FEV1 and PEF in the combination group were higher than those in the budesonide group. Mometasone combined with budesonide shows good treatment effects in children with AR and BA.

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 of PDCD4 gene in human tissues and the prognostic expression heat map of cancer. Human Protein Atlas (HPA) database was used to explore the expression differences of PDCD4 RNA in different cell lines, and PDCD4 expression and clinical data were obtained from Gene Expression Omnibus (GEO) database. We found significant differences in the expression of PDCD4 in different cancers and associated with patient prognosis. PDCD4 is closely related to the tumor microenvironment, sensitive to immunomodulators, and involved in immune regulation. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that PDCD4 plays a crucial role in tumor metastasis, affecting the survival and prognosis of tumor patients. The differential expression of PDCD4 in various tumor tissues and its involvement in immunomodulatory mechanisms suggest its potential as a biomarker for prognosis and immunotherapy. PDCD4 was closely related to tumor immune microenvironment and immune efficacy indexes. It is suggested that it may be used as a biomarker to predict immune efficacy.

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.

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.