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

The objective of this study was to compare the concentrations of relative and absolute regulatory T cells (Tregs) in preterm neonates diagnosed with necrotizing enterocolitis (NEC) with those in the control group. The study consisted of 60 preterm neonates, 30 with NEC and 30 without NEC. Blood samples were obtained and processed for the enumeration of Treg cells by multiparameter flow cytometry with markers such as CD4, CD25, and FOXP3, and the activation markers CD45RA, CD45RO, HLA-DR, and CTLA-4. There were no significant differences in gestational age, body weight, Apgar score, delivery mode, or incidence of maternal infection between the NEC group and the control group. The relative Treg percentage (% of CD4+ T cells) in the NEC group was 7.5 ± 1.2%, which was significantly lower than that in the control group (9.8 ± 1.5%). Compared with that in the control group, the absolute Treg count in the NEC group showed the same trend, and the total CD4+ T-cell count decreased significantly. The percentage of naive Tregs (% of Tregs) was significantly higher, whereas those of memory Tregs (% of Tregs), Ki-67+ (% of Tregs), and CD39+ (% of Tregs) cells were significantly lower. Tregs may be activated more as the severity of NEC increases, and the elevated levels of interleukin (IL)-10 in NEC may reflect attempts at an effective anti-inflammatory response to the proinflammatory effects of IL-6 and TNF-ɑ. Treg pathways may hold promise for NEC prognosis, although additional samples should be evaluated to validate these results.   Keywords: ; ; ; ;

MicroRNA (miR)-425-5p is used as a molecular biomarker to identify cervical cancer (CxCa). However, few studies have examined the miR-425-5p-based modulation of the vital activities of CxCa cells. The levels of neural cell adhesion molecule 1 (NCAM1) and miR-425-5p in CxCa tissues and cells were tested using western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) tests. CxCa cells' malignant phenotype was examined through clone formation tests, and transwell tests. CD8+T cells were co-cultured with CxCa cells and then analyzed for apoptosis rates and the expression of activation proteins (granzyme B (GZMB) and perforin) as well as immune factors (tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)) using flow cytometry, western blot, and enzyme-linked immunosorbent assay (ELISA) methods. Finally, in nude mouse experiments, the tumor size was measured for subcutaneous tumors, and the expression of CD8+T cell-related factors was detected. The NCAM1 and miR-425-5p were down-regulated and up-regulated in CxCa tissue and cells, respectively. After silencing miR-425-5p, CxCa cells showed attenuation in vitality, clone formation rate, and their capacities to migrate, penetrate, and evade immune responses. NCAM1 was targeted and silenced by miR-425-5p. When NCAM1 was silenced, it partially counteracted miR-425-5p's inhibitory effects on the immune escape and proliferation. In nude mice, the tumor size and weight decreased after silencing miR-425-5p, and levels of CD8, IFN-γ, TNF-α, perforin, and GZMB were elevated. However, these changes were reversed when NCAM1 was silenced. In conclusion, miR-425-5p mediates the biological behavior and immune evasion of CxCa cells by regulating NCAM1.

Cow's milk allergy (CMA) is one of the most prevalent Immunoglobulin E (IgE)-dependent food allergies in children. Currently, the only accepted treatment for food allergy is avoiding the relevant allergen. The purpose of this study is to investigate the immunological changes following the consumption of heated cow's milk products compared to the usual method of oral desensitization in children aged over two years old with cow's milk allergy. In a prospective double-blind clinical trial study, 25 children aged two years and older with a definite diagnosis of IgE-dependent cow's milk allergy referred to the allergy clinic of the Children's Medical Center from 2016 to 2017 were enrolled. The eligible patients were randomly divided into two groups: the first group was desensitized with raw milk (normal desensitization: n=13), and the second group was desensitized with heated cow's milk products (intervention group, n=12). The mean ages in the raw milk group and heated milk group were 3.92±1.44 and 4.50±1.73 years, respectively. The rate of anaphylaxis in the heated milk group was higher than in the raw milk group (50% vs. 15.4%), although the incidence of urticaria and angioedema was not significantly different between the two groups. The mean concentration of serum IgE in the two groups decreased after desensitization compared to before, although there was no significant difference between the two groups. The increase in the number of CD4+Foxp3+ and CD4+ CD25+ cells was less in the heated milk group than the raw milk group, but this difference was not statistically significant. Additionally, the number of eosinophil cells was higher in the heated milk group than in the raw milk group, but this difference was not statistically significant difference. We concluded that the changes in the level of eosinophil, IgE, and regulatory T cells in the conventional desensitization group were not significantly different compared to desensitization with heated milk. Further multicenter studies with a higher sample size are recommended to confirm these results.

Multiple sclerosis (MS) is a neuroinflammatory disorder that is characterized by demyelination, neurodegeneration, and immune dysregulation. The experimental autoimmune encephalomyelitis (EAE) model has helped to elucidate MS pathophysiology and test therapies. This review synthesizes current literature on the development, applications, and translational significance of EAE models in MS research. It discusses various EAE induction protocols, including active and passive immunization, and highlights advancements such as humanized mice and induced pluripotent stem cell (iPSC)-derived neuronal models. The review evaluates the role of EAE in identifying immune pathways, validating therapeutic agents like glatiramer acetate and natalizumab, and exploring precision medicine approaches through biomarker discovery. The EAE model replicated the key features of MS, including inflammation, demyelination, and axonal loss, facilitating therapy development. However, its predictive validity faces limitations, such as heterogeneity in disease induction, underrepresentation of chronic progression, and species differences. Innovations, such as humanized mouse models and iPSC-derived neurons, show promise in addressing these challenges. EAE research has advanced biomarker-based personalized treatments, although further validation is required. Despite its widespread use, EAE has limitations in terms of variability in disease induction, incomplete MS feature replication, species-specific responses, and clinical translation. Addressing these limitations remains crucial for therapeutic development, focusing on analyzing model limitations and strategies to overcome translational barriers. This review offers immunologists a comprehensive overview of EAE's contributions of EAE to MS research and its potential to inform the development of novel therapeutic approaches for this debilitating disease.

This study aimed to explore the relationship between the preoperative pan-immune-inflammation value (PIV) and the clinicopathological characteristics and surgical prognosis of thyroid cancer. This retrospective cohort study included 165 patients with thyroid cancer who underwent surgery. The value and clinical applicability of PIV and other immune-inflammatory biomarkers in assessing disease-free survival (DFS) were compared based on the area under the receiver operating characteristic (ROC) curve (AUC) and decision curve analysis (DCA). Patients were divided into high and low PIV groups according to the optimal cutoff value to assess the correlation between PIV and pathological characteristics. The Kaplan-Meier method was used for DFS analysis, and a Cox proportional hazards model was used to analyze the factors affecting DFS. The AUC of PIV for predicting DFS was higher than that of other immune-inflammatory biomarkers, and PIV demonstrated the highest clinical utility. Compared with the low PIV group, the high PIV group had a lower proportion of papillary thyroid carcinoma, a higher proportion of anaplastic thyroid carcinoma, and higher rates of stage III-IV disease, lymph node metastasis, maximum tumor diameter ≥2 cm, and multiple lesions. The DFS was significantly shorter in the high PIV group than in the low PIV group. After adjusting for confounding factors, a high PIV level was an independent risk factor for poor surgical outcomes. In conclusion, preoperative PIV is associated with the pathological type of thyroid cancer, TNM stage, lymph node metastasis status, and maximum tumor diameter. Furthermore, a high PIV level can increase the risk of poor surgical outcomes.

Cisplatin resistance presents a significant challenge in cancer therapy, emphasizing the necessity for identifying new regulatory elements that influence drug response. Recent research has revealed the importance of long noncoding RNAs (lncRNAs) in chemotherapy resistance, with LINC02381 identified as a potential regulatory factor. Through an in-depth bioinformatics analysis, we investigated the impact of LINC02381 on cisplatin resistance in ovarian cancer across various datasets. By conducting differential expression analysis, survival analysis, gene set enrichment analysis (GSEA), and constructing protein-protein interaction (PPI) networks, we identified key pathways associated with LINC02381 expression. The results indicated that the altered expression of LINC02381 in patients treated with cisplatin was associated with reduced survival. Functional studies and correlation analyses further demonstrated that this LncRNA influences critical pathways and genes related to apoptosis, efflux, DNA repair, and EMT. Lastly, through an examination of its interactions with microRNA and protein networks, we identified LINC02381 as a ceRNA implicated in cisplatin resistance. Our findings suggest that LINC02381 may influence cisplatin sensitivity in ovarian cancer and establish a basis for further experimental validation, including molecular assays or in vivo analyses, and suggest the potential therapeutic targeting of LINC02381 to combat chemoresistance.

Cervical cancer is a significant public health concern, particularly in women infected with the human papillomavirus (HPV). Recent evidence suggests that host genetic factors, specifically those related to the human leukocyte antigen (HLA) system, may also play a crucial role in determining susceptibility to cervical cancer in HPV-infected individuals. In this study, 86 patients with HPV and 27 healthy donors were selected from May 2023 to February 2024. HLA-DRB1 genotypes were determined using polymerase chain reaction followed by high-resolution melting curve analysis (HRM). Genotype frequencies in patients were compared with those in the control group from donors. Based on the HRM analysis, 10 genotypes were found in both patients and controls (profiles A-J). In the analysis of HLA-DRB1 genotypes, C, F, and I showed significant associations with HPV infection, indicating a possible protective effect against infection. Notably, genotype B was strongly linked to high-risk HPV, while genotype A was associated with low-risk HPV and is relevant to infection history. However, the remaining genotypes examined in the study did not exhibit significant associations with the analyzed parameters. This study contributes valuable evidence regarding the role of HLA-DRB1 genotypes in cervical cancer susceptibility and highlights the potential clinical implications for risk assessment and targeted immunotherapies. The use of HRM for HLA typing offers advantages that are efficient, accurate, and scalable, making it suitable for large-scale studies and clinical applications.

This study explored the mechanisms of action of inflammation related central genes in severe depression (MDD) and analyzes their potential as therapeutic targets. By identifying key genes and establishing the link between immune regulatory mechanisms and depression, we provide a theoretical basis for developing more accurate diagnostic and treatment methods. Gene expression datasets related to MDD were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) associated with inflammatory processes were identified and analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Protein-protein interaction (PPI) networks were constructed to identify hub genes. Additionally, we explored regulatory networks of miRNAs, transcription factors, and potential drug interactions were explored. Immune infiltration analysis was performed to examine immune cell profiles. Seven key genes-HMGB1, HSP90AB1, MAPK1, MMP9, MYD88, S100A12, and TLR2-were identified as central players in the inflammatory pathways underlying MDD. These genes demonstrated moderate diagnostic accuracy with AUC values ranging from 0.5 to 0.7. Enrichment analyses revealed significant associations with immune signaling pathways, including IL-17 and Toll-like receptor signaling. Immune infiltration analysis highlighted altered abundances of regulatory T cells, neutrophils, and dendritic cells in MDD samples. Inflammatory-related hub genes play crucial roles in linking immune dysregulation to the pathophysiology MDD pathophysiology. These findings offer insights into the immunological underpinnings of MDD and present potential therapeutic targets for intervention through immune-modulatory approaches.

The impacts of the CXC motif chemokine 12 (CXCL12)/ C-X-C chemokine receptor type 4 (CXCR4) axis on the infiltration of anti-tumor and pro-tumor immune cells in the tumor microenvironment (TME) of breast cancer (BCa) have been noted in previous studies. Accordingly, regulating the downstream signals of this axis can effectively increase CD8+ cytotoxic T cells and decrease the frequency of immunosuppressive cells in the TME. This study investigated the anti-tumor effects of N, N''-thiocarbonylbis (N'-(3,4-dimethylphenyl)-2,2,2 trifluoroacetimidamide) (A1), a novel fluorinated CXCR4 inhibitor on a BCa cell line. In this study, the impacts of A1 on cell viability, proliferation, apoptosis, and cell cycle were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays. Moreover, the effect of A1 on the number of CXCR4+ 4T1 cells was measured by flow cytometry. A1 treatment exhibited cytotoxic effects on 4T1 cells, promoting cell apoptosis and G2/M cell cycle arrest. In addition, A1-treated cells showed a reduced cell proliferation than CXCL12 treated cells. Furthermore, treatment with A1 alongside CXCL12 significantly decreased the number of CXCR4+ cells compared to the control group treated with only CXCL12 as a proliferator factor. These results indicate that A1 exerts potential anti-tumor effects and may serve as a possible therapeutic agent for BCa treatment; however, further studies are required.

Colorectal cancer (CRC) remains a significant global health challenge, characterized by high morbidity and mortality. Despite advances in surgical techniques, chemotherapy, targeted therapies, and immunotherapy, many CRC cases exhibit treatment resistance and immune evasion, necessitating the identification of novel therapeutic targets. Follistatin-like protein 3 (FSTL3) has recently emerged as a key regulator in CRC progression, influencing immune suppression and therapy resistance. FSTL3 modulates the tumor microenvironment by promoting epithelial-mesenchymal transition (EMT), sustaining β-catenin signaling, and stabilizing c-Myc, which collectively enhance tumor invasiveness and metastatic potential. Additionally, FSTL3 contributes to immune evasion by upregulating immune checkpoint molecules such as programmed death-ligand 1  (PD-L1) and indoleamine-2,3-dioxygenase 1 (IDO1), thereby suppressing cytotoxic T-cell activity. High FSTL3 expression correlates with poor prognosis and resistance to conventional chemotherapy, targeted agents, and immune checkpoint inhibitors. Given its pivotal role in CRC pathophysiology, FSTL3 represents a promising biomarker for disease prognosis and a potential therapeutic target. Future research should focus on developing FSTL3-targeted interventions, including monoclonal antibodies, small-molecule inhibitors, and combination strategies with immunotherapy. Understanding the precise molecular mechanisms underlying FSTL3-mediated tumor progression and immune escape will be essential for translating these insights into clinical applications.