Biology Direct最新文献

{"title":"Mapping the knowledge landscape of planarian regeneration: a century of bibliometric insights.","authors":"Xinyang Wu, Fang Zhan, Xiaoran Zhang, Haoyang Zhang, Ya Wang, Ting Wang","doi":"10.1186/s13062-026-00906-0","DOIUrl":"10.1186/s13062-026-00906-0","url":null,"abstract":"<p><strong>Background: </strong>Despite over two centuries of research, the knowledge landscape of planarian regeneration-a pivotal model for stem cell biology and regenerative medicine-remains fragmented, hindering interdisciplinary integration and translational progress. To address this gap, we conducted the first large-scale bibliometric analysis integrating machine learning-enhanced burst detection, hierarchical clustering analysis, and cross-disciplinary network mapping.</p><p><strong>Results: </strong>We systematically analyzed 1,685 publications (1900-2025) from the Web of Science Core Collection, constructing a high-resolution knowledge map that reveals the field's dynamic evolution. Our analysis identifies three distinct phases: initial morphological exploration (1900-2010), molecular mechanism elucidation (2011-2020), and the current era of interdisciplinary convergence (2021-2025). The United States leads in output and global collaboration, while China ranks third but exhibits limited international engagement. Burst detection highlights emerging frontiers in stem cell regulation, environmental toxicology, and computational modeling. Hierarchical clustering and discipline overlay mapping further uncover convergence between developmental biology and environmental science, neuroscience, education, and engineering. By constructing a high-resolution knowledge map, we identify underexplored thematic intersections suggested by publication trends, thereby providing a data-driven roadmap to navigate future research priorities.</p><p><strong>Conclusion: </strong>This work provides a structured synthesis of planarian regeneration research, offering a data-driven roadmap to inform future studies, while illustrating how bibliometric approaches can complement traditional literature reviews.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOSL1 upregulation contributes to ischemia/reperfusion-induced acute kidney injury by regulating GPX4-dependent ferroptosis.","authors":"Xuesong Yu, Jiaqing Peng, Yundong Zou, Liguo Du","doi":"10.1186/s13062-026-00899-w","DOIUrl":"10.1186/s13062-026-00899-w","url":null,"abstract":"<p><p>Fos-like antigen 1 (FOSL1) has been implicated in the pathology of acute kidney injury (AKI), but its specific mechanism remains unclear. In this study, we investigated the role of FOSL1 in the regulation of ferroptosis and inflammation in the context of ischemia-reperfusion (I/R)-induced AKI. Our results showed that renal I/R resulted in renal injury as evidenced by renal tissue damage and decreased renal function accompanied by increased FOSL1 expression, all of which was effectively restored by FOSL1 knockout (KO) in mice. FOSL1 KO downregulated the levels of pro-inflammatory cytokines and the number of CD4⁺ T cells in I/R mice model. Furthermore, FOSL1 KO decreased ROS, MDA, and Fe²⁺ levels, elevated GSH levels, and normalized the expression of the acyl-CoA synthetase long-chain family member 4 (ACSL4)/glutathione peroxidase 4 (GPX4) axis. Consistent with the in vivo results, FOSL1 inhibition suppressed HK-2 cell ferroptosis induced by oxygen-glucose deprivation and reoxygenation (OGD/R), erastin, or co-culture with CD4⁺ T cells. Notably, GPX4 knockdown (KD) in HK-2 cells reversed the ferroptosis-resistant effect mediated by FOSL1 KD, suggesting that GPX4 is a key downstream molecule of FOSL1. Besides, dual-luciferase reporter (DLR) and chromatin immunoprecipitation (ChIP) assays further confirmed that FOSL1 directly binds to the GPX4 promoter to repress its transcription. Collectively, these results suggest that FOSL1 inhibition alleviates I/R-induced AKI by enhancing ferroptosis resistance through GPX4 transcriptional regulation.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SERPINH1 expression represents a reliable biomarker of human breast cancer aggressiveness.","authors":"Manuel Scimeca, Valeria Palumbo, Francesca Servadei, Erica Giacobbi, Lukas Funke, Jonathan Woodsmith, Oreste Claudio Buonomo, Eleonora Candi, Gerry Melino, Alessandro Mauriello, Rita Bonfiglio","doi":"10.1186/s13062-026-00869-2","DOIUrl":"10.1186/s13062-026-00869-2","url":null,"abstract":"<p><strong>Background: </strong>Extracellular matrix (ECM) remodeling is a central driver of breast cancer progression, invasion, and metastatic dissemination. Heat shock protein 47 (HSP47), encoded by SERPINH1, is a collagen-specific molecular chaperone essential for proper collagen folding and secretion, but its clinical and biological relevance in human breast cancer remains incompletely defined.</p><p><strong>Methods: </strong>We applied an integrated multi-omics approach combining RNA sequencing, quantitative proteomics, immunohistochemistry, and spatial single-cell transcriptomics to analyze SERPINH1 expression in 21 human breast carcinomas. Internal cohort and public datasets were investigated to assess expression patterns, pathway associations, and clinical relevance across breast cancer patients.</p><p><strong>Results: </strong>SERPINH1 expression strongly correlated with key ECM-remodeling genes, including COL1A1, CTGF, and DDR2, and showed robust concordance with HSP47 protein abundance. High SERPINH1 levels were tightly linked to epithelial-mesenchymal transition (EMT) programs, including ZEB1-, MMP2-, and TGF-β-driven signaling, while displaying minimal association with immune-checkpoint pathways or immune-cell infiltration. Spatial and single-cell analyses revealed enrichment of SERPINH1 in cancer-associated fibroblasts and malignant epithelial cells. Clinically, SERPINH1 expression increased from normal breast tissue to primary tumours and metastatic lesions, was highest in advanced-stage disease, and predicted reduced overall survival, particularly in luminal B breast cancer. Notably, high SERPINH1 expression was associated with improved pathological response to chemotherapy.</p><p><strong>Conclusions: </strong>These findings identify SERPINH1 as a marker of ECM-driven tumour aggressiveness and stromal reprogramming in breast cancer. By linking collagen homeostasis, EMT, and TGF-β signaling to adverse clinical outcomes, the SERPINH1-HSP47 axis emerges as a promising prognostic biomarker and a tractable therapeutic target in breast cancer.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contributions of dorsal medial prefrontal cortex GABAergic mu opioid receptors on acute restraint stress-induced anxiety-like behavior.","authors":"Yinan Du, Fenghua Xu, Junmin Zhang, Yukui Zhao, Shuyi Liu, Yuan Chang, Yiwei Liu, Yingchun Yang, Yingying Li, Hongyu Qin, Chunling Wei, Qiaohua Zheng, Yanning Qiao, Yihui Liu, Wei Ren, Jing Han, Aozhuo Zhang, Zhiqiang Liu, Fei Gao","doi":"10.1186/s13062-026-00893-2","DOIUrl":"10.1186/s13062-026-00893-2","url":null,"abstract":"<p><p>The body's defensive emotional reaction to stress presents as anxiety. Nevertheless, long-term anxious stimuli can cause pathological anxiety disorders together with endocrine system, neural system, and immune system dysfunctions. Thus, researchers should understand the neural processes that govern anxiety during stress to create preventive and care plans. By combining behavioral tests, chemogenetic strategies, c-fos stainings, and whole-cell patch clamp recordings, this study looked into the function of dorsal medial prefrontal cortex (dmPFC) mu opioid receptors (MORs), specifically GABAergic MORs (MOR_GABA), in anxiety-like behavior brought on by acute restraint stress (ARS). The dmPFC MOR_GABA is triggered during ARS. This activation reduced the inhibitory synaptic input onto projection neurons that target the basolateral amygdala (BLA) by suppressing the activity of neighboring dmPFC GABAergic interneurons. In turn, mice that showed anxiety-like behavior also had higher neural activity of dmPFC-BLA projection neurons. When combined, these results describe a local, MOR_GABA-mediated dmPFC pathway that governs acute stress-induced anxiety reactions. These findings could offer a possible logical foundation for dmPFC-focused medication screening and anxiety treatment.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANKRD49 promotes immune evasion in lung adenocarcinoma by activating the MEF2A/PD‑L1 axis.","authors":"Tian-Qi Sun, Shuo Wu, Jing Qiao, Gang Liang, Chao-Feng Liu, Hui-Yu Jiang, Kai-Yuan Liu, Hai-Long Wang, Min Pang","doi":"10.1186/s13062-026-00904-2","DOIUrl":"10.1186/s13062-026-00904-2","url":null,"abstract":"<p><p>Non‑small cell lung cancer (NSCLC), particularly lung adenocarcinoma (LUAD), exhibits a high rate of primary resistance to immune checkpoint inhibitors, underscoring the need to decipher the molecular mechanisms of immune evasion. Here, we identify ANKRD49 as a critical regulator of PD‑L1 expression and immunosuppression in LUAD. Immunohistochemical analysis of clinical LUAD specimens revealed that high ANKRD49 expression correlates with reduced CD4⁺ and CD8⁺ T cell infiltration, increased FOXP3⁺ regulatory T cells, and elevated PD‑L1 levels. Functional experiments demonstrated that ANKRD49 overexpression in LUAD cells suppresses T cell cytotoxicity, promotes T cell apoptosis, and impairs granzyme B and IFN‑γ production in vitro. Mechanistically, ANKRD49 directly binds the transcription factor MEF2A via its second ankyrin repeat domain, upregulates MEF2A expression, and promotes its transcriptional activity at two specific sites within the PD‑L1 promoter. Chromatin immunoprecipitation and luciferase reporter assays confirmed that MEF2A directly activates PD‑L1 transcription in an ANKRD49‑dependent manner. In subcutaneous and metastatic mouse models, ANKRD49 overexpression accelerates tumor growth and metastasis, while PD‑L1 blockade reverses these effects and restores antitumor immunity. Collectively, our findings establish the ANKRD49-MEF2A-PD‑L1 axis as a novel driver of immune evasion in LUAD, and identify ANKRD49 ankyrin repeat domain 2 as a potential therapeutic target for overcoming immunotherapy resistance.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL1 facilitates colorectal cancer progression through internal m7G methylation of MACC1 and SDCCAG8 mRNA.","authors":"Yang Yu, Wenfang Bao, Yandong Li, Yong Gao, Jingde Chen","doi":"10.1186/s13062-026-00895-0","DOIUrl":"10.1186/s13062-026-00895-0","url":null,"abstract":"<p><p>N7-Methylguanosine (m7G) modification, as one of main types of RNA modification, has been implicated in several cancers. However, its function and regulatory mechanism in colorectal cancer (CRC) progression remain poorly understood. In this study, we found methyltransferase-like protein-1 (METTL1), the key m7G methyltransferase, is highly expressed in CRC tissues via whole-transcriptome sequencing, qRT-PCR and immunohistochemical analysis. Functional investigations revealed that METTL1 promotes CRC growth and proliferation both in vitro and in vivo, which depends on its m7G methyltransferase activity. Through m7G-MeRIP-sequencing and high-throughput mRNA sequencing, metastasis-associated in colon cancer 1 (MACC1) and serologically defined colon cancer antigen 8 (SDCCAG8) were identified as new targets of METTL1-mediated internal m7G modification. Further explorations confirmed that METTL1 regulates expression of the two genes by enhancing their mRNA stabilities. Overexpression of MACC1 or SDCCAG8 could rescue those phenotypic defects induced by METTL1 knockdown. Additionally, METTL1 expression is closely related to MACC1 or SDCCAG8 expression in CRC clinical samples. Collectively, these findings unveil that METTL1 facilitates CRC progression by regulating MACC1 and SDCCAG8 in an m7G-dependent manner, highlighting that METTL1 could be a potential therapeutic target in CRC.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDZK1 is downregulated in ovariectomized mice with angiotensin II-induced hypertension and interacts with β2-AR to regulate endothelial ERK1/2/c-Fos signaling.","authors":"Haoran Zhang, Yan Meng, Wenjing Zheng, Wenjie Bu, Wenxiu Liu, Xiaohui Zhang, Zhiyu Shi, Chunnan Liu, Meng Zhao, Huiying Wang, Yufeng Bai, Dechao Zhao, Jinyu Chi","doi":"10.1186/s13062-026-00897-y","DOIUrl":"10.1186/s13062-026-00897-y","url":null,"abstract":"<p><strong>Background: </strong>Estrogen deficiency is a major risk factor for postmenopausal hypertension. PDZK1, an estrogen-responsive scaffold protein, may interact with the β2-adrenergic receptor (β2-AR) to regulate vascular function, but this axis has not been characterized in the context of estrogen-deficient hypertension.</p><p><strong>Methods: </strong>We used ovariectomized and PDZK1 knockout mice infused with angiotensin II to model hypertension in vivo, and HUVECs for mechanistic studies in vitro. Techniques included hemodynamic measurements, histology, molecular interaction assay, chromatin immunoprecipitation, and functional cellular assays.</p><p><strong>Results: </strong>Ovariectomy exacerbated Ang II-induced hypertension and vascular remodeling, which correlated with reduced PDZK1 expression. PDZK1 KO mice showed enhanced hypertensive responses and impaired endothelium-dependent relaxation. Mechanistically, PDZK1 interacted with β2-AR via its PDZ1 and PDZ4 domains, stabilizing β2-AR and activating the downstream ERK1/2/c-Fos pathway to promote endothelial proliferation. PDZK1 knockdown or β2-AR inhibition attenuated this signaling and suppressed endothelial repair.</p><p><strong>Conclusion: </strong>Our study identifies a novel PDZK1/β2-AR/ERK1/2/c-Fos axis that is essential for maintaining endothelial function under estrogen-sufficient conditions. Disruption of this pathway in the context of estrogen deficiency contributes to hypertension, highlighting PDZK1 as a potential therapeutic target for postmenopausal hypertension.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"V-ATPase-targeted siRNA library screening reveals ATP6V1A negatively regulates UVB-induced keratinocyte senescence.","authors":"Peiqi Lian, Xuyi Deng, Qingqiu Wen, Yinyun Deng, Fenghao Liu, Hui Liu, Zhenhua Ding, Meijuan Zhou, Yinghui Wang","doi":"10.1186/s13062-026-00891-4","DOIUrl":"10.1186/s13062-026-00891-4","url":null,"abstract":"<p><p>Photoaging is a form of premature skin aging mainly induced by long-term exposure to ultraviolet exposure. Lysosomes are key organelles responsible for the degradation and recycling of intracellular components and are essential for maintaining metabolic and nutrient homeostasis. Although lysosomal dysfunction is closely associated with cellular aging, the role of V-ATPase in regulating lysosomal function during photoaging remains incompletely understood. By screening a V-ATPase-targeted siRNA library and validating the results using publicly available single-cell transcriptomic datasets, we identified ATP6V1A as a key regulator of UVB-induced cellular senescence. Furthermore, ATP6V1A knockdown exacerbated the UVB-induced cellular senescence and impaired lysosomal acidification and membrane integrity, whereas ATP6V1A overexpression effectively alleviated keratinocyte senescence, lysosomal dysfunction and autophagy inhibition. Moreover, treatment with the V-ATPase inhibitor BafA1 aggregated cellular senescence phenotype and autophagy inhibition and this phenomenon partially reversed by ATP6V1A overexpression. Collectively, ATP6V1A promotes autophagy by regulating lysosomal function, thereby relieving UVB-induced cellular senescence.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights into TXNDC17-mediated ferroptosis suppression in glioblastoma progression.","authors":"Zixuan Jing, Qingbo Wang, Chenglong Li, Xinyu Zhao, Dianhan Zhang, Zhibing Liu, Zefu Li","doi":"10.1186/s13062-026-00898-x","DOIUrl":"10.1186/s13062-026-00898-x","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is a lethal brain tumor with limited treatment options. Molecular targeted therapy is considered safe and promising for GBM. Ferroptosis is regulated by lipid, iron and cysteine metabolism. Induction of ferroptosis is a promising strategy.</p><p><strong>Methods: </strong>Integrated bioinformatics analysis of GBM datasets (TCGA) and RNA-seq data from human gliomas was used to identify candidate genes. TXNDC17 expression was validated in glioma tissues and cell lines by qPCR, western blotting and immunofluorescence. In vitro functional assays (CCK-8, wound healing, Transwell) were performed to assess proliferation, migration and invasion following TXNDC17 knockdown (siRNA). Ferroptosis sensitivity was evaluated by measuring GSH and LPO levels after TXNDC17 manipulation. GPX4 rescue experiments were conducted. In vivo therapeutic efficacy was examined in orthotopic GBM mouse models using TXNDC17-silenced cells treated with RSL3 (an inhibitor of GPX4) with tumor growth monitored by bioluminescence.</p><p><strong>Results: </strong>Bioinformatics analysis identified TXNDC17 as a key prognostic risk factor. Molecular validation confirmed grade-dependent TXNDC17 overexpression in gliomas. TXNDC17 knockdown markedly suppressed GBM cell proliferation, migration and invasion. Mechanistically, TXNDC17 promoted glioma progression by regulating ferroptosis, specifically through cooperation with GPX4 to inhibit ferroptosis. Knockdown reduced GPX4 expression, thereby increasing ferroptosis sensitivity. GPX4 overexpression rescued proliferation and invasion defects caused by TXNDC17 knockdown, confirming its functional dependence. TXNDC17 silencing combined with RSL3 synergistically suppressed GBM growth in vitro.</p><p><strong>Conclusion: </strong>TXNDC17 functions as a novel oncoprotein and ferroptosis suppressor in GBM by regulating GPX4 and promoting tumor progression. Targeting the TXNDC17-GPX4 axis through TXNDC17 silencing and RSL3 treatment represents a potent synergistic therapeutic strategy.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD13 identifies S100A4⁺ immunosuppressive monocytes and predicts temozolomide benefit in glioblastoma.","authors":"Dong Yu, Ruiyao Hu, Qing Zhu, Xiao Wang","doi":"10.1186/s13062-026-00889-y","DOIUrl":"10.1186/s13062-026-00889-y","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is an immunologically \"cold\" tumor in which S100A4-driven immunosuppressive myeloid cells promote progression and resistance. However, the specific immune subpopulation that intrinsically expresses S100A4 and the corresponding cell surface targets remain poorly defined.</p><p><strong>Materials and methods: </strong>S100A4 expression was profiled across immune subsets in healthy human bone marrow and peripheral blood by flow cytometry. TCGA GBM datasets were used to identify S100A4-correlated surface markers, and CD13 (encoded by ANPEP) was validated across the Human Protein Atlas, Immgen, GEO and single-cell RNA-seq datasets. The functional link between CD13, S100A4, and TGFβ was assessed by network analysis and correlation. Drug response analysis was conducted using GEPIA 3 platform.</p><p><strong>Results: </strong>Monocytes were the predominant S100A4-expressing population in both bone marrow and peripheral blood. CD13 emerged as the surface marker most significantly correlated with S100A4 in GBM. CD13⁺ monocytes co-expressed high levels of S100A4 and were transcriptionally positioned between monocytic and granulocytic lineages. These cells displayed a strong association with TGFβ signaling, suggesting a CD13-TGFβ-S100A4 immunosuppressive axis. Notably, temozolomide conferred a significant survival benefit specifically in CD13-high GBM patients.</p><p><strong>Conclusions: </strong>CD13 marks S100A4-high immunosuppressive monocytes in GBM and represents an accessible surface target for monitoring and potentially depleting this pathogenic population. The CD13-S100A4-TGFβ axis and the predictive value of CD13 for temozolomide response offer a translational framework for advancing GBM immunotherapy.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}