Theranostics最新文献

{"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^Prx1</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^Prx1</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^Prx1</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^Prx1</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}

{"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}

{"title":"Targeting complement C3 with Tanshinone I decreases microglia-mediated synaptic engulfment to exert antidepressant effects.","authors":"Huaqing Lai, Pinglong Fan, Pengxiang Zhang, Meng Zhang, Xinmu Li, Boyu Kuang, Run Zhou, Wenfei Wang, Hong Jiang, Zhenzhen Wang, Naihong Chen","doi":"10.7150/thno.115587","DOIUrl":"https://doi.org/10.7150/thno.115587","url":null,"abstract":"<p><p><b>Background:</b> The limitations of current depression treatments highlight the importance of developing new therapeutic strategies. Tanshinone I (Tan I), a naturally occurring lipophilic diterpene compound, has promising activities including inflammation inhibition, cellular autophagy or apoptosis modulation, and anti-oxidative stress. However, the potential antidepressant effects of Tan I and the mechanism behind its action have yet to be established. <b>Methods:</b> The antidepressant effect of Tan I was evaluated using animal behavior tests. The chronic unpredictable stress (CUS) mice and C3 overexpressing mice were used to investigate the mechanism of Tan I in microglia-mediated synaptic engulfment, and to explore the effect of Tan I on the improvement of functional magnetic resonance imaging (fMRI)-based network changes in depression-like mice. <b>Results:</b> Here, it is found that Tan I efficiently improved the CUS-induced depressive-like behaviors, attenuated synaptic loss, and inhibited microglial activation. The drug affinity responsive target stability assay and microscale thermophoresis revealed that the specific target of Tan I is complement C3. Furthermore, Tan I decreased the CUS-induced synaptic loss by inhibiting the deposition of C3 deposition onto synapses and subsequent microglia-mediated synaptic engulfment. Importantly, Tan I also improved fMRI-based network changes in CUS mice. Overexpression of C3 in the medial prefrontal cortex (mPFC) of normal mice leads to depressive-like behavior, accompanied by synaptic loss and reduced fMRI-based network changes. In contrast, administration of Tan I inhibits microglia-mediated synaptic phagocytosis and improves fMRI-based network changes, which in turn ameliorate the depressive-like behaviors in C3-overexpressing mice. <b>Conclusions:</b> Collectively, the study demonstrated that Tan I acts as a potent natural C3 modulator that binds directly to C3, blocks the C3-CR3 axis and downstream signal transducer and activator of transcription 3 (STAT3) signaling pathway, inhibits microglia-mediated synaptic engulfment, and improves fMRI-based network changes, which in turn exert antidepressant effects.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8150-8175"},"PeriodicalIF":13.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970063","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":"An unrecognized mechanism of self-protection in degenerating neurons mediated by astrocytic YAP through Wnts/β-catenin/EAAT2 signaling in C9orf72-poly-GA mice.","authors":"Dongmei Li, Yan Wei, Rui Yang, Xuan Luo, Yanzhu Liu, Weiqiao Zhao, Hui Yang, Yumin Wu, Ying Wang, Zhihui Huang","doi":"10.7150/thno.113599","DOIUrl":"https://doi.org/10.7150/thno.113599","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Rationale:&lt;/b&gt; Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons in the central nervous system (CNS). Non-neuronal cells, particularly astrocytes, have been recognized as pivotal contributors to ALS onset and progression. However, the underlying mechanisms of interactions between astrocytes and motor neurons during ALS remain unclear. Recent studies have identified the neuronal Hippo kinase mammalian sterile 20-like kinase 1 (MST1) as a key regulator of neurodegeneration in ALS. Yes-associated protein (YAP), a major downstream effector of the Hippo pathway, is predominantly expressed in astrocytes. However, the role of astrocytic YAP in ALS and its underlying mechanisms remain unexplored. &lt;b&gt;Methods:&lt;/b&gt; To evaluate the function of YAP in ALS, we established a C9orf72-poly-GA mouse model (ALS mice) via intracerebroventricular injection of AAV viruses. Furthermore, mice with conditional knockout (CKO) of YAP in astrocytes (YAP&lt;sup&gt;GFAP&lt;/sup&gt;-CKO mice) were generated and then YAP&lt;sup&gt;GFAP&lt;/sup&gt;-CKO ALS mice and their littermate controls (YAP&lt;sup&gt;f/f&lt;/sup&gt; ALS mice) were used as experimental subjects. Behavioral tests, immunostaining, Nissl staining, quantitative real-time PCR (qPCR), and Western blotting were used to assess the effects of astrocytic YAP deletion in ALS progression. In addition, we investigated the role and mechanism of astrocytic YAP in the pathogenesis of ALS by integrating RNA sequencing (RNA-seq) from primary cultured astrocytes with single-nucleus transcriptomic (snRNA-seq) from C9orf72-ALS/FTD patients. Then, &lt;i&gt;in vitro&lt;/i&gt; experiments including primary cultured astrocytes and neurons were used to further elucidate the potential molecular mechanism of astrocytic YAP in ALS. Finally, we evaluated the therapeutic effects of the excitatory amino acid transporter-2 (EAAT2) activator LDN-212320 and the Hippo kinase MST1/2 inhibitor XMU-MP-1 as candidate treatments for ALS. &lt;b&gt;Results:&lt;/b&gt; We found that YAP was upregulated and activated specifically in astrocytes, but not in neurons or microglia, within the motor cortex of ALS mice. Conditional knockout of YAP in astrocytes exacerbated motor deficits, neuronal loss, pathological translocation of TDP-43, inflammatory infiltration, and reduced astrocytic proliferation in ALS mice. Mechanistically, Wnts secreted by degenerating neurons and astrocytes activated YAP/β-catenin signaling and further promoted the expression of EAAT2 in astrocytes, which prevented neuronal glutamate excitotoxicity, neuronal loss, and motor dysfunction in ALS mice. Interestingly, treatment with LDN-212320 promoted EAAT2 expression and partially restored motor deficits and neuronal loss in YAP&lt;sup&gt;GFAP&lt;/sup&gt;-CKO ALS mice. Finally, activation of YAP by XMU-MP-1 upregulated β-catenin and EAAT2 expression, and partially alleviated motor deficits and neurodegeneration in ALS mice. &lt;b&gt;Conclusions:&lt;/b&gt; These results identify an ","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8176-8201"},"PeriodicalIF":13.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970067","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":"Co-delivery of targeted hypoallergens and resiquimod powders using silk fibroin microneedles for effective allergen-specific immunotherapy.","authors":"Zhen Wang, Xiaolei Lu, Lingzhi Wu, Xin Jiang, Wei Wang, Yahua Wang","doi":"10.7150/thno.114152","DOIUrl":"https://doi.org/10.7150/thno.114152","url":null,"abstract":"<p><p><b>Rationale:</b> The cutaneous route exploits the immunocompetence of the skin, making it a favourable route for allergen-specific immunotherapy (AIT), but there must be a balance between minimal skin disruption and precise allergen delivery. Thus, we propose the use of powder-laden microneedles (pMNs) for the sustained epidermal delivery of powdery hypoallergens and immunomodulators. <b>Methods:</b> In this study, targeted hypoallergenic derivatives, namely, mannan-ovalbumin (mOVA) conjugates, were synthesized in a single-step process. For minimally invasive self-administration into the skin, pMNs were constructed using highly biocompatible silk fibroin (SF) with a cavity in the basal portion of each needle, which was filled with lyophilized mOVA and resiquimod powders (mOVA/R848 pMN). The resulting mOVA/R848 pMN arrays were thoroughly examined for their physical morphology, mechanical property, accumulation ability, and immune profile. <b>Results:</b> The deposition of powdery mOVA and R848 improved uptake by skin dendritic cells (DCs) and stimulated the immune system more than 10 d after application. On the basis of these features, mOVA/R848 pMN arrays increased the induction of protective immune mechanisms to suppress Th2 immunity, including the Treg/Th1 bias, as well as the production of anti-inflammatory cytokines and neutralizing antibodies in an asthmatic mouse model. Compared with traditional subcutaneous immunotherapy (SCIT), a total dose of only 75 μg of OVA over three treatments was sufficient to restore immune balance and alleviate allergic symptoms during allergen exposure, highlighting the dose-sparing and frequency-sparing potential of mOVA/R848 pMN. <b>Conclusion:</b> Optimal mOVA/R848 pMN arrays represent a new therapeutic strategy for allergy treatment with convenient administration and satisfactory outcomes.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8096-8116"},"PeriodicalIF":13.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970097","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":"Mucus-derived biomaterial dressings: a novel approach to accelerate wound healing.","authors":"Xuanqi Peng, Ziyi Wang, Leo Wang, Weiliang Hou","doi":"10.7150/thno.115988","DOIUrl":"https://doi.org/10.7150/thno.115988","url":null,"abstract":"<p><p>Wound management remains a clinical challenge due to the complexity of healing processes. Traditional dressings with passive protection mechanisms and modern synthetic alternatives often fail to recapitulate the dynamic biological interactions in the wound microenvironment. Mucus is a naturally widely available biomaterial, exhibiting superior bioactive properties as a viscoelastic gel-like substance. Notably, natural mucus derived from diverse biological sources has garnered significant attention as advanced wound dressings. This review explores the potential of natural mucus from animals, plants, microorganisms, and other complex sources as multifunctional wound healing platforms. By analyzing the therapeutic effects of natural mucus, we evaluate its key molecular mechanisms and performance metrics against clinical wound dressings. This establishes a scientific framework for mucus-inspired biomaterials design. The comprehensive assessment not only reveals the untapped potential of renewable biological resources in developing eco-friendly, high-performance wound care alternatives but also provides theoretical guidance for developing next-generation dressings with bioactive, self-adaptive, and environmentally responsive characteristics.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8068-8095"},"PeriodicalIF":13.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969884","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":"Point-of-care mass spectrometry metabolomic analysis enabling intraoperative brain tumor diagnosis.","authors":"Junhan Wu, Xinqi Fang, Haoyue Zhang, Hao Xu, Peter Jih Cheng Wong, Ying Mao, Wenpeng Zhang, Zheng Ouyang, Wei Hua","doi":"10.7150/thno.113336","DOIUrl":"https://doi.org/10.7150/thno.113336","url":null,"abstract":"<p><p><b>Rationale:</b> While mass spectrometry (MS) is known for being capable of analyzing a wide range of biomarkers, its usages in clinical settings have been hindered by the stringent requirements for operating the MS analysis system as well as performing the analytical procedure at the point of care (POC). We have developed a miniature MS system and extremely simplified analytical protocols for POC analysis of tumors. It enabled comprehensive metabolite profiling with brain tissue biopsy, which allowed accurate and real-time diagnosis of brain tumors and guiding of surgical resection strategy. <b>Methods:</b> A miniature linear ion trap MS system with direct sampling ionization for tissue biopsy analysis was developed, which is suitable for performing real-time analysis in a surgical room. A segment scan method was developed to allow coverage of a wide range of metabolites while providing adequate sensitivity. An extremely simplified protocol was developed to allow a real-time analysis of the tissue samples taken from patients. The development and validation of this method involved 137 brain tissue samples from 109 patients. The miniature MS system could operate on battery without requiring compressed gas or large amounts of solvents like traditional MS analysis systems in lab. <b>Results:</b> With optimized sampling and scanning method, 183 metabolites in the range of m/z 50 - 500 could be identified from human brain tissues after a 2 min analysis time. Metabolomic features were extracted that allowed distinctions between glioma and normal tissues (at an area under the curve (AUC) of 0.932), isocitrate dehydrogenase (IDH) mutant and wildtype gliomas (at an AUC of 1.000), and IDH mutant gliomas and glioblastoma (at an AUC of 1.000). A comparison study was also carried out between fresh and stored tissue samples and decrease in abundance was observed for metabolites such as glutamate and N-acetylaspartic acid, which indicates the importance of real-time analysis of the biological samples for clinical applications. <b>Conclusions:</b> This study shows the potential of performing intraoperative or bedside MS analysis of a panel of metabolomic biomarkers in real time to facilitate the diagnosis of the disease as well as the decision making for surgery or therapy. Miniature mass spectrometry system with direct sampling ionization method serves as a valid platform for transferring MS analysis from traditional laboratories to clinical settings.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8137-8149"},"PeriodicalIF":13.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970095","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":"Comprehensive exome profiling identifies <i>ARHGEF12</i> mutation as a driver in gastric cancer with ovarian metastasis.","authors":"Mingda Zhang, Guoyu Chen, Xiaolin Lin, Yingwen Zhang, Longyu Shi, Shanshan Li, Yanxin Li, Xiuying Xiao, Haizhong Feng","doi":"10.7150/thno.113382","DOIUrl":"https://doi.org/10.7150/thno.113382","url":null,"abstract":"<p><p><b>Rationale:</b> Gastric cancer (GC) with ovarian metastasis (OM) represents a distinct subtype of peritoneal metastasis in female patients, characterized by limited therapeutic options and poor prognosis, with molecular features and mechanisms that remain unknown. <b>Methods:</b> We performed whole-exome sequencing (WES) analysis of matched GC samples, with OM or peritoneal metastasis (PM), to identify mutational profiles that contribute to OM. We further validate these findings through in vitro and in vivo experiments. <b>Results:</b> We characterized specific mutated genes in GC with OM, including <i>FLCN</i>, <i>DNAJC13</i>, <i>DSC3</i>, <i>SLC9A3</i>, <i>ADGRV1</i>, <i>SCAPER</i>, and <i>ARHGEF12</i>. Moreover, these genomic mutations are recurrent in both GC and ovarian cancer. We further identified the E620K mutation of <i>ARHGEF12</i>, a Rho guanine nucleotide exchange factor, as a novel risk locus in GC with OM. Ectopic expression of the E620K mutant increased cell migration, invasion and colony formation in vitro, as well as OM in animals bearing GC xenograft tumors. Mechanistically, <i>ARHGEF12</i> E620K mutation upregulated <i>ITGA6</i> expression through Rap1 signaling pathway activation and promoted tumor-derived ITGA6-high exosome formation, which were preferentially uptaken by ovarian fibroblasts. Reciprocally, ovarian fibroblasts educated by ITGA6<i>-</i>high exosomes exhibited cancer-associated fibroblasts (CAFs) phenotypes and enhanced tumor cell proliferation, thereby initiating the early stage of pre-metastatic niche formation. <b>Conclusions:</b> Our study provides comprehensive clinical exome profiling, identifies <i>ARHGEF12</i> mutation as a new driver, and reveals that ITGA6 acts as an early predictive marker in GC with OM.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8202-8221"},"PeriodicalIF":13.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970075","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":"Disturbance of cytoskeleton induced by ligustilide promotes hepatic stellate cell senescence and ameliorates liver fibrosis.","authors":"Jiaorong Qu, Jianan Li, Le Wang, Yufei Li, Yinqiang Zhang, Jingtao Li, Zixuan Huo, Junsong Han, Runping Liu, Guifang Fan, Yinhao Zhang, Xiaoyong Xue, Xiaojiaoyang Li","doi":"10.7150/thno.108869","DOIUrl":"https://doi.org/10.7150/thno.108869","url":null,"abstract":"<p><p><b>Background and aims:</b> Inducing the senescence of activated hepatic stellate cells (HSCs) has emerged as a promising therapeutic strategy for liver fibrosis, with potential connections to the Yes-associated protein (YAP)-controlled cGAS-STING pathway. However, the regulatory role of cytoskeletal dynamics on HSC senescence and its potential as a target for natural products have remained poorly understood. <b>Methods:</b> We employed preclinical <i>in vivo</i> and <i>in vitro</i> transcriptome analyses, experimental systems, Tmem173^-/- mice and liver-specific STING knockdown mice to demonstrate the anti-fibrotic effects and mechanism of ligustilide (LIG). <b>Results:</b> LIG selectively bound to monomeric globular actin (G-actin), thereby preventing its polymerization into polymeric filamentous actin (F-actin), which disturbed its interaction with intermediate filament component lamin A/C and initially destroyed the nuclear membrane. Moreover, the disruption of nuclear membrane caused YAP leakage from nuclear, which in turn suppressed lamin A/C and created a deleterious feedback loop that exacerbated nuclear membrane destabilization. Consequently, nuclear double stranded DNA (dsDNA) leakage caused by the above damage cascade ultimately triggered the activation of the cGAS-STING signaling pathway, promoting senescence-associated secretory phenotypes (SASPs) release and inducing HSC senescence. Moreover, the induction of HSC senescence and anti-fibrotic effects of LIG were completely abrogated in both whole-body STING knockout and liver-specific STING knockdown mice. <b>Conclusions:</b> By interacting with G-actin, LIG disrupted the cytoskeleton to compromise nuclear integrity with the involvement of YAP and further stimulated the cGAS-STING pathway, leading to the release of SASPs and HSC senescence, which ultimately mitigated liver fibrosis.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8049-8067"},"PeriodicalIF":13.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970052","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":"Imaging hypoxia for head and neck cancer: current status, challenges, and prospects.","authors":"Wenhui Huang, Nemin Li, Sheng Zhu, Yuze Zhang, Xinyang Song, Bin Zhang, Hao Yan, Jie Tian, Kun Wang, Shuixing Zhang","doi":"10.7150/thno.112781","DOIUrl":"https://doi.org/10.7150/thno.112781","url":null,"abstract":"<p><p>Hypoxia can substantially impact clinical outcomes in patients with head and neck cancer (HNC) by promoting tumor invasion, metastasis, immune escape, and therapy resistance. Given the growing interest in targeting hypoxia for cancer therapy, noninvasive methods are needed to accurately detect hypoxia and evaluate the tumor response to treatment. This review summarizes recent advances in hypoxia-targeted probes and imaging techniques, emphasizing their imaging mechanisms, strengths, and limitations. We focused on the promising clinical applications of hypoxia imaging, especially those currently used in clinics, such as positron emission tomography and magnetic resonance imaging, and highlighted their roles in guiding personalized therapy. Future directions include optimizing imaging probes to improve safety profiles, integrating multimodal imaging, applying machine learning models to analyze multiparametric data, and establishing standardized 3-dimensional <i>in vitro</i> models to better mimic hypoxia heterogeneity. These advancements are expected to considerably improve the management of patients with HNC.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8012-8030"},"PeriodicalIF":13.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969942","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}