TheranosticsPub Date : 2025-07-25eCollection Date: 2025-01-01DOI: 10.7150/thno.112009
Lu Li, Liting You, Zhenfei Bi, Ziqi Zhang, Binwu Ying, Min Luo, Xiawei Wei
{"title":"Chitosan activates NLRP3 inflammasome and cGAS-STING to suppress cancer progression through hexokinase 2 dissociation and mitochondrial dysfunction.","authors":"Lu Li, Liting You, Zhenfei Bi, Ziqi Zhang, Binwu Ying, Min Luo, Xiawei Wei","doi":"10.7150/thno.112009","DOIUrl":"https://doi.org/10.7150/thno.112009","url":null,"abstract":"<p><p><b>Background:</b> Chitosan, a natural polysaccharide with known immunostimulatory potential, has shown promise in cancer therapy. However, its direct role in modulating antitumor immunity and the underlying mechanisms remain unclear. This study aimed to explore how unmodified chitosan influences tumor progression and immune responses through innate immune signaling pathways. <b>Methods:</b> Murine tumor models (CT26, B16-F10) were used to evaluate the antitumor effects of chitosan in vivo. Flow cytometry and histological analyses assessed changes in immune cell infiltration. Primary macrophages and gene knockout models were used to investigate the molecular mechanisms, including inflammasome activation, mitochondrial function, and hexokinase 2 (HK2) location, via ELISA, western blotting, mitochondrial assays. <b>Results:</b> Chitosan treatment suppressed tumor growth and metastasis, while promoting infiltration of neutrophils, monocytes, and activated T cells in the tumor microenvironment. Mechanistically, chitosan and its bioactive degradation product, N-acetylglucosamine (NAG), induced the dissociation of HK2 from mitochondria, triggering mitochondrial dysfunction, ROS overproduction, and mtDNA release. These signals jointly activated both the NLRP3 inflammasome and the cGAS-STING pathway. The antitumor effect of chitosan was attenuated in <i>Nlrp3</i> <sup>-/-</sup> and <i>Sting</i> <sup>-/-</sup> mice, confirming the essential roles of both pathways. <b>Conclusions:</b> Chitosan orchestrates dual activation of NLRP3 and cGAS-STING signaling via HK2 dissociation and mitochondrial dysfunction, reprogramming the tumor immune microenvironment and enhancing antitumor immunity. These findings support chitosan's potential as a multifunctional immunoadjuvant for improving immunotherapy in resistant cancers.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8473-8487"},"PeriodicalIF":13.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibitory leukocyte immunoglobulin-like receptors, subfamily B (LILRBs) in human diseases: structure, roles, mechanisms, and clinical applications.","authors":"Yuxiu Zhang, Yuanyuan Xu, Qihui Wu, Xiaodan Fu, Yimin Li, Anqi Li","doi":"10.7150/thno.116951","DOIUrl":"https://doi.org/10.7150/thno.116951","url":null,"abstract":"<p><p>Leukocyte immunoglobulin-like receptors, subfamily B (LILRBs), are a class of critical immunosuppressive receptors that contribute to immune homeostasis by transmitting suppressive signals upon binding to ligands such as major histocompatibility complex class I molecules. They play key roles in modulating both innate and adaptive immune responses. This review summarizes the structural features, ligand interactions, signaling pathways, and expression regulation of LILRBs, and discusses their roles in immune cell function and disease progression, particularly in the tumor microenvironment. We also review current progress in the development of LILRB-targeted therapies for hematological malignancies and solid tumors and outline the challenges and future directions in translating these findings into clinical applications. By integrating recent advances, this review provides a framework for understanding the potential of LILRBs as therapeutic targets in cancer and immune-related disorders.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8222-8258"},"PeriodicalIF":13.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineered nanovesicle platform simultaneously triggers YAP-dependent ferroptosis and reprograms T-cell immunity through miR-150-3p codelivery in melanoma microenvironment.","authors":"Jiemin Wang, Zhenguo Zhao, Haopeng Yang, Ruixuan Wang, Shu Wang, Jiale Yu, Yujia Wang, Ruihua Liu, Yani Chen, Yueshi Liu, Kesong Shi, Pengyong Han, Miao Liu, Jing Miao, Xiaoyang Li, Xiangnan Li, Haiquan Yu","doi":"10.7150/thno.115860","DOIUrl":"https://doi.org/10.7150/thno.115860","url":null,"abstract":"<p><p><b>Rationale:</b> Melanoma remains a highly aggressive malignancy with limited effective therapies and frequent resistance to immune checkpoint blockade (ICB). Extracellular vesicles (EVs) represent a promising platform for RNA-based therapeutics, but their clinical translation is impeded by inefficient cargo loading and insufficient tumor-specific targeting. To address these limitations, we developed an engineered EV strategy integrating efficient miRNA packaging with tumor-targeting surface modifications to enhance therapeutic outcomes in melanoma. <b>Methods:</b> Engineered EVs (iEV-150) were generated by co-expressing miR-150-3p and Annexin A2 (ANXA2) in HEK293T cells, followed by surface modification with tumor-targeting iRGD peptides. Mechanistic insights were obtained using RNA sequencing, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and luciferase reporter assays. Ferroptosis induction was evaluated through lipid peroxidation analysis, mitochondrial membrane potential assays, and transmission electron microscopy (TEM). Therapeutic efficacy and biodistribution were assessed <i>in vivo</i> using subcutaneous and metastatic melanoma mouse models. Immune modulation was examined by analyzing CD8⁺ T cell activation via flow cytometry in co-cultures of patient-derived CD8⁺ T cells and melanoma cells treated with iEV-150. <b>Results:</b> miR-150-3p was elevated in melanoma-derived EVs, and ANXA2 was identified as a key RNA-binding protein that selectively facilitated its loading into EVs. iEV-150 exhibited enhanced uptake by melanoma cells and improved tumor-specific accumulation <i>in vivo</i>. Mechanistically, iEV-150 suppressed NF2 expression, disrupted the NF2-LATS1 interaction, activated YAP signaling, and subsequently upregulated ferroptosis-related genes ACSL4 and CHAC1, thereby inducing ferroptosis through the NF2-Hippo-YAP axis. In addition to its direct anti-tumor effects, iEV-150 promoted CD8⁺ T cell infiltration and activation within the tumor microenvironment, and significantly enhanced the therapeutic efficacy of ICB in melanoma models. <b>Conclusions:</b> iEV-150 integrates ANXA2-mediated miRNA loading, tumor-specific targeting, ferroptosis induction, and immune microenvironment reprogramming. This engineered EV strategy provides an effective RNA-based therapeutic platform to overcome ICB resistance and enhance precision treatment in melanoma.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8377-8403"},"PeriodicalIF":13.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TheranosticsPub Date : 2025-07-25eCollection Date: 2025-01-01DOI: 10.7150/thno.112209
Zhuang Chen, Zuo Yang, Zhiping Rao, Yi Luo, Weijing Liu, Chaoqiang Qiao, Qian Jia, Peng Yang, Ruili Zhang, Zhongliang Wang
{"title":"A pyroptosis proportion tunable nano-modulator for cancer immunotherapy.","authors":"Zhuang Chen, Zuo Yang, Zhiping Rao, Yi Luo, Weijing Liu, Chaoqiang Qiao, Qian Jia, Peng Yang, Ruili Zhang, Zhongliang Wang","doi":"10.7150/thno.112209","DOIUrl":"https://doi.org/10.7150/thno.112209","url":null,"abstract":"<p><p><b>Rationale:</b> Pyroptosis, a form of programmed cell death mediated by gasdermin proteins, holds significant potential in cancer immunotherapy. However, precise control of pyroptosis in cancer cells is essential to avoid biosafety concerns. This study aimed to develop a tumor-targeted and tunable pyroptosis-inducing strategy to enhance antitumor efficacy while minimizing systemic side effects. <b>Methods:</b> An innovative H<sub>2</sub>S-activated nanomodulator equipped with an optical switch was designed for tumor-specific and adjustable pyroptosis induction. The nanomodulator was activated by H<sub>2</sub>S in the tumor microenvironment of colorectal cancer and further regulated by laser irradiation. Gasdermin-E-mediated pyroptosis was triggered through the synergistic effects of photothermal temperature modulation and demethylation. The proportion of cells undergoing pyroptosis was precisely controlled within a tunable range. <b>Results:</b> The nanomodulator successfully induced pyroptosis in microsatellite-stable colorectal cancer cells within a tunable range of 0-31%. This precise regulation significantly enhanced antitumor efficacy while minimizing systemic side effects. The combination of photothermal modulation and demethylation ensured effective and safe pyroptosis induction. <b>Conclusions:</b> This study presents a novel and precise method for controlling pyroptosis using photothermal temperature modulation. The findings provide essential guidance for in vivo applications and offer valuable insights into the development of nanomedicines capable of safely and effectively inducing adjustable proportion of pyroptosis in cancer therapy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8320-8336"},"PeriodicalIF":13.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TheranosticsPub Date : 2025-07-25eCollection Date: 2025-01-01DOI: 10.7150/thno.115572
Mengdi Li, Yuting Lin, Jiayu Wang, He Yang, Danhui Ma, Ye Tian, Yi Wang, Liu Yang, Umar Farooq, Yinyin Wang, Fangli Ren, Jian Sheng, Guoqing Zhang, Liang Chen, Jun Li, Xiangnan Li, Zhijie Chang
{"title":"CREPT promotes LUAD progression by enhancing the CDK9 and RNAPII assembly to promote ERK-driven gene transcription.","authors":"Mengdi Li, Yuting Lin, Jiayu Wang, He Yang, Danhui Ma, Ye Tian, Yi Wang, Liu Yang, Umar Farooq, Yinyin Wang, Fangli Ren, Jian Sheng, Guoqing Zhang, Liang Chen, Jun Li, Xiangnan Li, Zhijie Chang","doi":"10.7150/thno.115572","DOIUrl":"https://doi.org/10.7150/thno.115572","url":null,"abstract":"<p><p><b>Background:</b> Despite advancements in EGFR- and KRAS-targeted therapies for lung adenocarcinoma (LUAD), novel targets are needed for patients unresponsive or resistant to current treatments. This study demonstrates the critical role of CREPT in modulating ERK-downstream gene transcription in LUAD progression. <b>Methods:</b> CREPT expression and function were investigated using human LUAD tissues, EGFR/KRAS mutant LUAD cell lines, and mouse models. Micro-CT was used to monitor tumor progression. Adeno-associated virus (AAV)-mediated CREPT depletion was employed as a therapeutic strategy. RNA sequencing and luciferase reporter assays identified differentially expressed genes (DEGs) and affected signaling pathways. Protein interactions and CDK9 occupancy were assessed using multiplex immunofluorescence, immunoprecipitation, and chromatin immunoprecipitation (ChIP). <b>Results:</b> CREPT overexpression correlated with poor LUAD patient survival and enhanced tumorigenesis in EGFR or KRAS mutant LUAD cells. <i>CREPT</i> deletion impaired LUAD initiation and progression in the CC10-rtTA;TetO-<i>KRAS<sup>G12D</sup></i> mouse model. Mechanistically, CREPT promoted CDK9 assembly with RNA polymerase II (RNAPII) following ERK activation, enhancing transcription of malignancy-related genes downstream of KRAS-ERK-Elk-1 signaling. CREPT depletion and the mutants R106A and S134A disrupting CREPT-RNAPII interaction reduced CDK9 occupancy at Elk-1 downstream gene promoters and their expression. Targeting CREPT in both CC10-rtTA;TetO-<i>KRAS<sup>G12D</sup></i> and xenograft mouse models resulted in tumor growth arrest. Furthermore, in a humanized mouse model, AAV-mediated CREPT silencing inhibited tumor progression and showed synergistic potential with pembrolizumab. <b>Conclusion:</b> Our findings highlight CREPT as a pivotal regulator of LUAD progression and suggest it could be a potential therapeutic target for patients with EGFR or KRAS mutations insensitive or resistant to targeted therapies.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8337-8359"},"PeriodicalIF":13.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TheranosticsPub Date : 2025-07-25eCollection Date: 2025-01-01DOI: 10.7150/thno.117523
Mengyu Li, Yu Wang, Zhiqiang Hu, Shiqian Huang, Pu Chen, Lin Chen, Jing Wu, Zhouyang Wu, Shanglong Yao, Yiyi Yang
{"title":"PTEN-mediated senescence of lung epithelial cells drives ventilator-induced pulmonary fibrosis.","authors":"Mengyu Li, Yu Wang, Zhiqiang Hu, Shiqian Huang, Pu Chen, Lin Chen, Jing Wu, Zhouyang Wu, Shanglong Yao, Yiyi Yang","doi":"10.7150/thno.117523","DOIUrl":"https://doi.org/10.7150/thno.117523","url":null,"abstract":"<p><strong>Rationale: </strong>Mechanical ventilation (MV), a life-saving intervention for acute respiratory distress syndrome (ARDS), may exacerbate pulmonary fibrosis (PF) through unclear mechanisms. Although Phosphatase and Tensin homolog (PTEN) suppresses chronic PF, its role in MV-induced PF remains unknown. This study will determine whether PTEN mediates MV-PF via lung epithelial cell senescence. <b>Methods:</b> Human lung epithelial cells exposed to hydrochloric acid (HCl) and mechanical stretch (48 hours) and a murine \"two-hit\" (HCl+MV) model (14-day observation) were used. PTEN's role was assessed via siRNA (<i>in vitro</i>) and knockout (<i>in vivo</i>). Single-cell transcriptomics analyzed senescence-associated secretory phenotype (SASP) and pathway enrichment. RG7388 (MDM2-P53 inhibitor) was administered to PTEN knockout mice to evaluate P53-mediated senescence. <b>Results:</b> HCl+MV induced epithelial-mesenchymal transition (EMT) and fibrosis <i>in vitro</i> and <i>in vivo</i>. PTEN knockout or knockdown attenuated these effects. Single-cell profiling indicated PTEN's role in EMT and fibrosis via cell senescence pathways, particularly in epithelial cells exhibiting imbalances in the SASP scores. Furthermore, our experiments confirmed that senescence activation during fibrosis was reversed by PTEN inhibition. RG7388 treatment in PTEN knockout mice implicated P53-mediated senescence in PTEN's regulatory role. <b>Conclusions:</b> Our study demonstrates that PTEN plays a pivotal role in MV-PF, by mediating pulmonary epithelial cell senescence. Future studies may focus on developing strategies to modulate PTEN activity and cell senescence to prevent or treat this devastating disease.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8360-8376"},"PeriodicalIF":13.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TheranosticsPub Date : 2025-07-25eCollection Date: 2025-01-01DOI: 10.7150/thno.116153
Shijing Wang, Lei Zhang, Minghao Wang, Xiumei Yin, Xinyao Dong, Xingyu Wu, Weijie Li, Wen Xu, Xiaoyun Mao
{"title":"Engineered upconversion nanoparticles for breast cancer theranostics.","authors":"Shijing Wang, Lei Zhang, Minghao Wang, Xiumei Yin, Xinyao Dong, Xingyu Wu, Weijie Li, Wen Xu, Xiaoyun Mao","doi":"10.7150/thno.116153","DOIUrl":"https://doi.org/10.7150/thno.116153","url":null,"abstract":"<p><p>Breast cancer (BC) remains the most prevalent cancer among women and a leading cause of cancer-related mortality worldwide, posing a significant threat to public health. Rare earth (RE)-doped upconversion nanoparticles (UCNPs) have emerged as a promising nanoplatform for BC management, owing to their exceptional photophysical properties and design flexibility. Unlike conventional fluorescent probes, engineered UCNPs absorb near-infrared (NIR) light, enabling deep tissue penetration while mitigating tissue damage and spontaneous fluorescence interference. Furthermore, through core-shell structure engineering and functionalization, multiple diagnostic and therapeutic modules can be integrated within a single NP, enabling theranostic applications for BC. This review comprehensively summarizes recent advances in engineered UCNPs for BC theranostics. It begins by introducing the luminescence mechanisms, controllable synthesis methods, and surface modification strategies of UCNPs. Next, it explores the fundamental biological effects of UCNPs, including biodistribution, metabolic pathways, and biotoxicity. Subsequently, we systematically review applications of engineered UCNPs in BC molecular imaging, biomarker detection, phototherapy, smart drug/gene delivery, and immunotherapy. Finally, current challenges and clinical translation prospects of UCNPs are discussed.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8259-8319"},"PeriodicalIF":13.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TheranosticsPub Date : 2025-07-25eCollection Date: 2025-01-01DOI: 10.7150/thno.112332
Zhonghao Mao, Yan Tian, Lisha Wu, Yu Zhang
{"title":"Epitranscriptomic mechanisms and implications of RNA m<sup>5</sup>C modification in cancer.","authors":"Zhonghao Mao, Yan Tian, Lisha Wu, Yu Zhang","doi":"10.7150/thno.112332","DOIUrl":"https://doi.org/10.7150/thno.112332","url":null,"abstract":"<p><p>Cancer is an extremely complex disease characterized by abnormal cell growth due to genetic and environmental factors. With the rise of the field of epigenetic transcriptomics, 5-methylcytidine (m<sup>5</sup>C) modification has been identified as one of the most common chemical modifications occurring in various RNA types. The writers, erasers, and readers of m<sup>5</sup>C modification regulate cancer initiation, progression, and therapeutic responses, such as the proliferation, metastasis, angiogenesis, metabolic reprogramming, immune escape, and therapeutic resistance of tumour cells, by regulating RNA stability, translation, nuclear export, and splicing processes. In this review, we elucidate the biological process of m<sup>5</sup>C modification, summarize the abnormal expression of RNA-modifying proteins (RMPs) in common malignant tumours, explore their functional effects on malignant hallmarks of cancer and molecular mechanisms, and prospect the potential clinical application value of m<sup>5</sup>C.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8404-8428"},"PeriodicalIF":13.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Overactivation of EGFR signaling in skeletal stem/progenitor cells promotes bone formation and repair.","authors":"Yuxiang Hu, Yangyang Chen, Xiaoyao Peng, Haitao Li, Guosilang Zuo, Hao Xu, Fashuai Wu, Yi Wang, Zengwu Shao, Yulong Wei","doi":"10.7150/thno.115406","DOIUrl":"https://doi.org/10.7150/thno.115406","url":null,"abstract":"<p><p><b>Background:</b> Epidermal growth factor receptor (EGFR) signaling plays an important role in bone development. However, knowledge of its specific function in skeletal stem cells during bone healing remains scant. <b>Methods:</b> We used a lineage tracing approach and a stem/progenitor cell-specific EGFR overactivation mouse model which is generated by overexpressing heparin-binding EGF-like growth factor (HBEGF), an EGFR ligand, in Prx1-cre mice (<i>HBEGF Over<sup>Prx1</sup></i> ), to analyze the crucial roles of EGFR signaling in periosteal progenitor cells during fracture healing. <b>Results:</b> Compared with wild type, <i>HBEGF Over<sup>Prx1</sup></i> mice are found to have thicker trabecular and cortical bone structure and exhibit accelerated fracture healing. Single-cell RNA sequencing reveals that <i>HBEGF</i> is highly expressed in a periosteal progenitor cluster that constitutes a large portion of the callus cells and lays at the center of a developmental path that gives rise to chondrocytes and osteoblasts within the callus. <i>In vitro</i> experiments further demonstrate that periosteal progenitors isolated from <i>HBEGF Over<sup>Prx1</sup></i> mice display strong chondrogenic, osteogenic and angiogenic abilities, thus promoting fracture healing. Treating mice with gefitinib, an EGFR inhibitor, completely abolishes the promotional effects in <i>HBEGF Over<sup>Prx1</sup></i> mice. <b>Conclusion:</b> Our data reveal a cellular mechanism of EGFR signaling underlying fracture healing, and suggest that targeting EGFR may provide a potential therapeutic tool for delayed fracture healing or fracture non-union.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8117-8136"},"PeriodicalIF":13.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TheranosticsPub Date : 2025-07-24eCollection Date: 2025-01-01DOI: 10.7150/thno.115131
Meruyert Imanbekova, Mohul Sharma, Sebastian Wachsmann-Hogiu
{"title":"On the dilemma of using single EV analysis for liquid biopsy: the challenge of low abundance of tumor EVs in blood.","authors":"Meruyert Imanbekova, Mohul Sharma, Sebastian Wachsmann-Hogiu","doi":"10.7150/thno.115131","DOIUrl":"https://doi.org/10.7150/thno.115131","url":null,"abstract":"<p><p>Single extracellular vesicle (EV) analysis holds great promise for non-invasive cancer diagnostics, offering insights into tumor-specific biomarkers and enabling personalized treatment strategies. However, a significant challenge in the path towards clinical applications is the low abundance of tumor-derived EVs (<i>tEV</i>s) in biofluids, which reduces the sensitivity, specificity, and accuracy of detection. This review emphasizes the importance of analyzing a large number of single EVs to overcome this limitation. We estimate that less than 0.1% of total EVs could be from cancer cells in a mixed sample. Additionally, the development of more efficient <i>tEV</i>s isolation methods and targeted enrichment strategies, as well as high-throughput analysis techniques are crucial for improving diagnostic accuracy and advancing liquid biopsy applications in cancer care.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8031-8048"},"PeriodicalIF":13.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}