Frontiers in Immunology最新文献

{"title":"Corrigendum: <i>Brucella suis</i> Δ<i>mapB</i> outer membrane vesicles as an acellular vaccine against systemic and mucosal <i>B. suis</i> infection.","authors":"Florencia Muñoz González, Magali G Bialer, Maria L Cerutti, Silvia M Estein, Lila Y Ramis, Pablo C Baldi, Ángeles Zorreguieta, Mariana C Ferrero","doi":"10.3389/fimmu.2025.1565688","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1565688","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fimmu.2024.1501791.].</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1565688"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamics of blood microsatellite instability (bMSI) burden predicts outcome of a patient treated with immune checkpoint inhibitors: a case report of hyperprogressive disease.","authors":"Daria Kravchuk, Alexandra Lebedeva, Olesya Kuznetsova, Alexandra Kavun, Anastasiia Taraskina, Ekaterina Belova, Tatiana Grigoreva, Egor Veselovsky, Vladislav Mileyko, Vladislav Nikulin, Lidia Nekrasova, Alexey Tryakin, Mikhail Fedyanin, Maxim Ivanov","doi":"10.3389/fimmu.2025.1492296","DOIUrl":"10.3389/fimmu.2025.1492296","url":null,"abstract":"<p><p>Microsatellite instability (MSI) is a widely studied molecular signature, which is associated with long-term benefit in patients treated with immune checkpoint inhibitor therapy. This approach has been proven to be effective in the treatment of patients with MSI-positive colorectal cancer (CRC). Analysis of serial liquid biopsy samples allows to detect changes in the tumor in response to therapy. Typically, somatic mutations are used for tracing the dynamics of the tumor, and the assessment of DNA signatures such as MSI is not currently used for these purposes. Here, we describe a case of a MSI-positive CRC, who received nivolumab monotherapy. Sequential sampling of the patient's plasma demonstrated an increase in MSI burden (bMSI), which was found to correlate with the increase of driver mutation burden one month after starting nivolumab, and hyperprogressive disease. Thus, analysis of bMSI in liquid biopsy via NGS may be a promising method for timely assessment of the treatment effectiveness received by patients with MSI-positive CRC.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1492296"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequence-structure based prediction of pathogenicity for amino acid substitutions in proteins associated with primary immunodeficiencies.","authors":"Ekaterina S Porfireva, Anton D Zadorozhny, Anastasia V Rudik, Dmitry A Filimonov, Alexey A Lagunin","doi":"10.3389/fimmu.2025.1492751","DOIUrl":"10.3389/fimmu.2025.1492751","url":null,"abstract":"<p><strong>Introduction: </strong>Primary immunodeficiencies (PIDs) are a group of rare genetic disorders characterized by dysfunction of the immune system components. Early diagnosis and treatment are essential to prevent severe or life-threatening complications. PIDs are manifested by diverse clinical symptoms, posing challenges for accurate diagnosis. A key aspect of PID diagnosis is identifying specific amino acid substitutions in the proteins related with heritable diseases. In this study, we have developed classification sequence-structure-property relationships (SSPR) models for predicting the pathogenicity of amino acid substitutions (AAS) in 25 proteins associated with the most important and genetically studied PIDs and encoded genes: <i>IL2RG, JAK3, RAG1, RAG2, ADA, DCLRE1C, CD40LG, WAS, ATM, STAT3, KMT2D, BTK, FOXP3, AIRE, FAS, ELANE, ITGB2, CYBB, G6PD, GATA2, STAT1, IFIH1, NLRP3, MEFV, and SERPING1</i>.</p><p><strong>Methods: </strong>The data on 4825 pathogenic and benign AASs in the selected proteins were extracted from ClinVar and gnomAD. SSPR models were created for each protein using the MultiPASS software based on the Bayesian algorithm and different levels of MNA (Multilevel Neighborhoods of Atoms) descriptors for the representation of structural formulas of protein fragments including AAS.</p><p><strong>Results: </strong>The accuracy of prediction was assessed through a 5-fold cross-validation and compared to other bioinformatics tools, such as SIFT4G, Polyphen2 HDIV, FATHMM, MetaSVM, PROVEAN, ClinPred, and Alpha Missense. The best SSPR models demonstrated high accuracy, with an average ROC AUC of 0.831 ± 0.037, a Balanced accuracy of (0.763 ± 0.034), MCC (0.457 ± 0.06), and F-measure (0.623 ± 0.07) across all genes, outperforming the most popular bioinformatics tools.</p><p><strong>Conclusions: </strong>The best created SSPR models for the prediction of pathogenicity of amino acid substitutions related with PIDs have been implemented in a freely available web application SAV-Pred (Single Amino acid Variants Predictor, http://www.way2drug.com/SAV-Pred/), which may be a useful tool for medical geneticists and clinicians. The use of SAV-Pred for some clinical cases of PIDs are provided.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1492751"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding HLA-DQ in renal transplantation: a mini-review.","authors":"Rajdeep Das, Neil S Greenspan","doi":"10.3389/fimmu.2025.1525306","DOIUrl":"10.3389/fimmu.2025.1525306","url":null,"abstract":"<p><p>Human leukocyte antigen (HLA) mismatching, particularly with HLA-DQ, significantly impacts the development of donor-specific antibodies (DSA) and transplant outcomes. HLA-DQ antibodies are highly immunogenic and detrimental, necessitating advanced high-resolution HLA typing to improve mismatch assessment and clinical risk evaluation. Traditional serological or low-resolution typing often misclassifies mismatches, leading to inaccuracies in assessing immunogenicity and predicting outcomes. Emerging molecular mismatch algorithms refine immunogenicity assessments by analyzing amino acid differences and structural interactions. These tools show promise for personalizing transplant protocols but have limitations, such as variability in predicting individual patient outcomes. Immunogenicity of mismatches also depends on evolutionary divergence and specific amino acid differences, with studies revealing that certain evolutionary lineages and polymorphisms influence T-cell alloreactivity and DSA development. Complexities in HLA-DQ protein expression, including combinatorial diversity of heterodimers and inter-isotypic heterodimers, further complicate risk evaluation. Expression levels, influenced by tissue specificity and inflammatory stimuli, and alternative splicing of HLA-DQ transcripts add additional layers of variability. Future clinical applications, enabled by high-resolution HLA typing, may include refined graft selection, improved DSA monitoring, and individualized therapy. However, understanding the precise mechanisms of HLA-DQ immunogenicity remains a priority for advancing transplantation science and enhancing patient outcomes.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1525306"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome analysis reveals hypoxic response key genes and modules as well as adaptive mechanism of crucian carp (<i>Carassius auratus</i>) gill under hypoxic stress.","authors":"Mengchao Xing, Zhen Rong, Xin Zhao, Xiaowei Gao, Zhiguang Hou, Lihan Zhang, Waiho Khor, Yihuan Xu, Li Chen, Chengbin Wu","doi":"10.3389/fimmu.2025.1543605","DOIUrl":"10.3389/fimmu.2025.1543605","url":null,"abstract":"<p><p>Fish gill tissue is a primary organ responsive to acute oxygen deprivation or dissolved oxygen (DO) fluctuations in aquatic environments. However, the adaptive mechanism of crucian carp to hypoxic stress remains largely unknown. Here, we investigated gill physiological and transcriptomic changes of crucian carp exposed to hypoxic conditions (dissolved oxygen concentration of 0.6 ± 0.3 mg/L) for different durations (0 d, 1 d, 2d, 3d, 4 d, and 5d). Transcriptomic analysis revealed that the hypoxia group (0.6 ± 0.3 mg/L DO) exhibited a reduction in interlamellar cell mass (ILCM) on the gill filaments, compared with the control group (6.6 ± 0.3 mg/L DO). With prolonged hypoxia stress, the epithelial cells in the gill lamellae became sparse at 3 d to 5 d, and gill vacuoles were increased. A total of 3,502 differentially expressed genes (DEGs) were identified, and 3 hypoxia-specific modules were screened through differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Bayesian network analysis. The apoptosis, necroptosis, efferocytosis and FoxO signaling pathways were significantly enriched based on the KEGG enrichment pathway analysis. The VEGF pathway genes are significantly expressed, enhancing the generation of microvessels in the gill filaments, and improving the capacity to carry oxygen, thus enabling the crucian carp to adapt to hypoxia stress. Hypoxia activated glycolysis, enhanced anaerobic metabolism, promoted β-oxidation of fatty acids, providing energy and maintaining normal physiological metabolism, eventually improving antioxidant and immune capabilities in crucian carp. In summary, this study reveals the molecular mechanism by which crucian carp adapt to hypoxic stress. Our findings provide valuable references for promoting the healthy aquaculture of hypoxic-sensitive fish and breeding hypoxia-tolerant fish varieties.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1543605"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ruxolitinib synergizes with regulatory T cells to improve inflammation but has no added benefits in decreasing albuminuria in SLE.","authors":"Mi-Ae Lyu, Ximing Tang, Maria Gabriela Raso, Meixian Huang, Ke Zeng, Tara Sadeghi, Christopher R Flowers, Simrit Parmar","doi":"10.3389/fimmu.2025.1449693","DOIUrl":"10.3389/fimmu.2025.1449693","url":null,"abstract":"<p><strong>Background: </strong>Umbilical cord blood (UCB)-derived CD4⁺CD25⁺CD127^low regulatory T cells (Tregs) can decrease albuminuria and anti-dsDNA IgG in systemic lupus erythematosus (SLE). Ruxolitinib, a JAK/STAT inhibitor, has been shown to improve cutaneous manifestations of SLE. We hypothesize that the addition of ruxolitinib to UCB-Tregs may improve SLE outcomes.</p><p><strong>Methods: </strong><i>In vitro</i> cell suppression, phenotype change, IL-10 secretion, and cytokine levels in coculture supernatants were determined to quantify the impact of adding ruxolitinib to UCB-Tregs. A xenogeneic SLE model was utilized to study their <i>in vivo</i> combination.</p><p><strong>Results: </strong>In a dose-dependent manner, ruxolitinib addition synergizes with UCB-Tregs to suppress SLE-PBMC proliferation, inhibit CD8⁺ T cells, and reduce phosphorylation of STAT3/STAT5/AKT in CD8⁺ T cells. UCB-Treg and ruxolitinib combination also downregulates the soluble form of inflammatory cytokines including IFN-γ, IP-10, TNF-α, IL-6, sCD40L, IL-17A, IL-17F, IL-1α, and LIF in cocultures. The addition of ruxolitinib increases UCB-Treg cell persistence in peripheral blood <i>in vivo</i> and decreases the soluble form of human inflammatory cytokines including IFN-γ, TNF-α, and sCD40L in plasma along with improvement of skin lesions in SLE xenografts. Compared to control, significantly lesser CD3⁺, CD4⁺, CD8⁺, and Ki-67⁺ infiltrates are observed in the lung and kidney of UCB-Tregs and/or ruxolitinib recipients. No added benefit of addition of ruxolitinib is observed on the significant improvement in the urine albumin/creatinine ratio and the anti-dsDNA IgG levels induced by UCB-Tregs.</p><p><strong>Conclusions: </strong>Our results demonstrate that the addition of ruxolitinib to UCB-Tregs increases UCB-Tregs suppressor function and their persistence <i>in vivo</i>, downregulates systemic inflammation, and controls cutaneous SLE but does not add to UCB-Treg-mediated improvement in renal manifestations.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1449693"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of lacrimal gland ultrasonography in the evaluation of chronic ocular graft-versus-host-disease.","authors":"Mingxia Zhong, Siyuan Liu, Jinghan Luo, Qin Zhang, Zhou Yang, Shanshan Zhang","doi":"10.3389/fimmu.2025.1490390","DOIUrl":"10.3389/fimmu.2025.1490390","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate the effectiveness of lacrimal gland ultrasonography in the assessment of chronic ocular graft-versus-host-disease (oGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to establish the correlation between the ocular surface and ultrasonographic results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;The cross-sectional study included 57 participants aged 18 and older, who were at least 100 days after allo-HSCT. The study was conducted at the oGVHD clinic of Peking University People's Hospital between March to June 2023. Patients were categorized into groups according to the International Chronic oGVHD (ICCGVHD) consensus group diagnostic criteria or the 2005 National Institutes of Health (NIH) classification criteria for Chronic GVHD. Demographics and transplantation-related information were collected for all participants, including age, gender, donor-recipient HLA matching, donor-recipient ABO matching, donor-recipient gender combination and duration after allo-HSCT. The disease activity of oGVHD and the severity of ocular surface involvement were assessed using various parameters such as Ocular Surface Disease Index (OSDI), Schirmer test, tear film break-up time (BUT), tear meniscus height, corneal/conjunctival staining and meibomian gland dropout. Lacrimal gland structures were assessed by B-mode and Doppler ultrasonography to measure parameters such as the long diameter, thick diameter, homogeneity and parenchymal vascularization. Statistical analyses were performed to determine differences in ocular surface conditions and lacrimal gland ultrasonographic parameters between groups as well as to determine the correlation between ocular surface condition and lacrimal gland ultrasonographic findings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;(1) Patients with definite and probable oGVHD exhibited a significantly longer duration after allo-HSCT compared to non-oGVHD patients (H=11.264, p&lt;0.01), The median durations were 247(164,894) days and 525(310,928) days, respectively, compared to 204(169,323.25) days for non-oGVHD patients. (2) Compared to non-oGVHD patients, both definite oGVHD patients and probable oGVHD patients showed lower average of Schirmer test (H=31.188, p&lt;0.01), TBUT (H=11.853, p&lt;0.01), tear meniscus height (H=13.630, p&lt;0.01) and higher average of OSDI (F=27.992, p&lt;0.01), corneal staining scores (χ²=23.66, p&lt;0.05) and temporal conjunctival staining scores (χ²=14.84, p&lt;0.05). (3) The B-mode and Doppler ultrasonography parameters in lacrimal glands including long diameter, thick diameter, homogeneity and parenchymal vascularization did not exhibit significant differences between the three groups. (4) The long diameter in lacrimal ultrasonography had significantly positive correlations with tear meniscus height (r=0.297, p&lt;0.05) and significantly negative correlations with temporal conjunctival staining scores (r=-0.313, p&lt;0.05) and staining total scores (r=-0.285, p&lt;0.05). The thick diame","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1490390"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and assessment of an intestinal tri-cellular model to investigate the pro/anti-inflammatory potential of digested foods.","authors":"Marina Ramal-Sanchez, Chiara Bravo-Trippetta, Veronica D'Antonio, Elena Corvaglia, Angela A M Kämpfer, Roel P F Schins, Mauro Serafini, Donato Angelino","doi":"10.3389/fimmu.2025.1545261","DOIUrl":"10.3389/fimmu.2025.1545261","url":null,"abstract":"<p><strong>Introduction: </strong>Immunonutrition, defined as the potential of foods, nutrients and dietary patterns to modulate the immune system activity, has been proposed as a strategy to enhance the immune response in both metabolic and immune-mediated diseases. However, the anti-/pro-inflammatory role of foods and diets is far to be fully ascertained, and thus there is a continued needed for appropriate in vitro cell-culture models to investigate the role of foods in modulating cell-mediated inflammatory processes. This study aims to develop and test an in vitro tri-culture model, simulating the complexity of the intestinal tract and its multiple cell interactions.</p><p><strong>Methods: </strong>To achieve this, the intestinal epithelial barrier was established by co-culturing human Caco-2 enterocyte-like and HT29-MTX-E12 mucus producing goblet-like colon cells, then adding human monocyte THP-1 cells to the basolateral compartment. The integrity and stability of the epithelial barrier were monitored and the inflammatory response of the model was assessed using various stressors at different concentrations, both individually and in combination (phorbol-12- myristate-13-acetate or PMA, and lipopolysaccharide or LPS), in terms of cytokines production. To test the model, different concentrations of <i>in vitro</i> digested broccoli (BD) were added to the apical section of the model.</p><p><strong>Results: </strong>Supernatants from the basolateral compartment were collected and analyzed for cytokines production (IL-6, TNF-α, IL-12p70, IL-18 and IL-8) using automated ELISA (ELLA). Additionally, ZO-1 protein from the tight junctions of epithelial cells was analyzed by flow cytometry. The results indicated that 100 nM PMA added to the whole model for 20 h was the best stressor to simulate a mild-inflammatory status of the gut. Following treatment with BD, IL-6, TNF-α, IL-8 and IL-18 were significantly reduced compared to the control group, while ZO-1 expression increased at the lowest BD concentration.</p><p><strong>Conclusions: </strong>These findings confirm the feasibility of the model for assessing the effects of food digesta on specific cytokines and permeability markers, representing a valuable strategy for investigating the role of foods in modulating the inflammatory response. The results obtained may support dietary strategies aimed at promoting wellbeing and preventing inflammatory-related metabolic diseases.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1545261"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell sequencing elucidates the mechanism of NUSAP1 in glioma and its diagnostic and prognostic significance.","authors":"Meng-Yu Zhao, Zhao-Lei Shen, Hongzhen Dai, Wan-Yan Xu, Li-Na Wang, Yu- Gu, Jie-Hui Zhao, Tian-Hang Yu, Cun-Zhi Wang, Jia-Feng Xu, Guan-Jun Chen, Dong-Hui Chen, Wen-Ming Hong, Fang Zhang","doi":"10.3389/fimmu.2025.1512867","DOIUrl":"10.3389/fimmu.2025.1512867","url":null,"abstract":"<p><strong>Background: </strong>Personalized precision medicine (PPPM) in cancer immunology and oncology is a rapidly advancing field with significant potential. Gliomas, known for their poor prognosis, rank among the most lethal brain tumors. Despite advancements, there remains a critical need for precise, individualized treatment strategies.</p><p><strong>Methods: </strong>We conducted a comprehensive analysis of RNA-seq and microarray data from the TCGA and GEO databases, supplemented by single-cell RNA sequencing (scRNA-seq) data from glioma patients. By integrating single-cell sequencing analysis with foundational experiments, we investigated the molecular variations and cellular interactions within neural glioma cell subpopulations during tumor progression.</p><p><strong>Results: </strong>Our single-cell sequencing analysis revealed distinct gene expression patterns across glioma cell subpopulations. Notably, differentiation trajectory analysis identified NUSAP1 as a key marker for the terminal subpopulation. We found that elevated NUSAP1 expression correlated with poor prognosis, prompting further investigation of its functional role through both cellular and animal studies.</p><p><strong>Conclusions: </strong>NUSAP1-based risk models hold potential as predictive and therapeutic tools for personalized glioma treatment. In-depth exploration of NUSAP1's mechanisms in glioblastoma could enhance our understanding of its response to immunotherapy, suggesting that targeting NUSAP1 may offer therapeutic benefits for glioma patients.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1512867"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic modifications in bladder cancer: crosstalk between DNA methylation and miRNAs.","authors":"Wei Li, Peiyue Luo, Qi Chen, Le Cheng, Lifeng Gan, Fangtao Zhang, Haidong Zhong, Liying Zheng, Biao Qian","doi":"10.3389/fimmu.2025.1518144","DOIUrl":"10.3389/fimmu.2025.1518144","url":null,"abstract":"<p><p>Bladder cancer (BC) is a malignant tumor characterized by a high incidence of urinary system diseases. The complex pathogenesis of BC has long been a focal point in medical research. With the robust development of epigenetics, the crucial role of epigenetic modifications in the occurrence and progression of BC has been elucidated. These modifications not only affect gene expression but also impact critical biological behaviors of tumor cells, including proliferation, differentiation, apoptosis, invasion, and metastasis. Notably, DNA methylation, an important epigenetic regulatory mechanism, often manifests as global hypomethylation or hypermethylation of specific gene promoter regions in BC. Alterations in this methylation pattern can lead to increased genomic instability, which profoundly influences the expression of proto-oncogenes and tumor suppressor genes. MiRNAs, as noncoding small RNAs, participate in various biological processes of BC by regulating target genes. Consequently, this work aims to explore the interaction mechanisms between DNA methylation and miRNAs in the occurrence and development of BC. Research has demonstrated that DNA methylation not only directly influences the expression of miRNA genes but also indirectly affects the maturation and functionality of miRNAs by modulating the methylation status of miRNA promoter regions. Simultaneously, miRNAs can regulate DNA methylation levels by targeting key enzymes such as DNA methyltransferases (DNMTs), thereby establishing a complex feedback regulatory network. A deeper understanding of the crosstalk mechanisms between DNA methylation and miRNAs in BC will contribute to elucidating the complexity and dynamics of epigenetic modifications in this disease, and may provide new molecular targets and strategies for the early diagnosis, treatment, and prognostic evaluation of BC.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1518144"},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}