TheranosticsPub Date : 2025-08-16eCollection Date: 2025-01-01DOI: 10.7150/thno.119545
Sun-Hee Cho, Byeongkwon Choi, Jisun Lee, Yu-Sun Lee, Mi-Ock Baek, You-Jeung Lee, Chae-Ok Gil, Min-Kyung Choi, Sana Abdul Khaliq, Syeda Maham, Jae-Kyung Hyun, Gahyun Roh, Huijeong Choi, Sowon Lee, Seo-Hyeon Bae, Seonghyun Lee, Hyo-Jung Park, Jae-Hun Ahn, Na-Young Lee, Byeong-Cheol Kang, Young Kyo Seo, Byung-Kwan Lim, Jae-Hwan Nam, Mina Rho, Mee-Sup Yoon
{"title":"ApoE deficiency protects from mRNA vaccine-induced mitochondrial dysfunction at the injection site under metabolic stress.","authors":"Sun-Hee Cho, Byeongkwon Choi, Jisun Lee, Yu-Sun Lee, Mi-Ock Baek, You-Jeung Lee, Chae-Ok Gil, Min-Kyung Choi, Sana Abdul Khaliq, Syeda Maham, Jae-Kyung Hyun, Gahyun Roh, Huijeong Choi, Sowon Lee, Seo-Hyeon Bae, Seonghyun Lee, Hyo-Jung Park, Jae-Hun Ahn, Na-Young Lee, Byeong-Cheol Kang, Young Kyo Seo, Byung-Kwan Lim, Jae-Hwan Nam, Mina Rho, Mee-Sup Yoon","doi":"10.7150/thno.119545","DOIUrl":"10.7150/thno.119545","url":null,"abstract":"<p><p><b>Rationale:</b> The local tissue effects of mRNA vaccination remain incompletely understood. We investigated how SARS-CoV-2 mRNA vaccination impacts injection site tissues in the context of different metabolic states and apolipoprotein E (ApoE) status. <b>Methods:</b> We administered intramuscular SARS-CoV-2 mRNA vaccination to wild-type and ApoE-deficient mice under regular and high-fat diets, as well as macaques. We performed transcriptomic analysis, ultrastructural examination, functional assessments including grip strength testing, and immunological evaluations to characterize local and systemic responses. <b>Results:</b> Intramuscular vaccination induced localized injury characterized by inflammation, mitochondrial disruption, and reduced grip strength in wild-type animals. Transcriptomic and ultrastructural analyses revealed denervation-associated changes, downregulation of mitochondrial genes, cristae disruption, and activation of immune and apoptotic pathways. ApoE-deficient mice, particularly under Western diet conditions, demonstrated protection from mitochondrial and inflammatory responses despite comparable vaccine expression levels. This protection involved attenuated mitochondrial gene downregulation, preserved mitochondrial DNA integrity, and reduced inflammatory responses. While ApoE deficiency resulted in diminished antibody production, T cell responses remained intact, indicating selective immunomodulation. Cardiac tissue showed minimal transcriptional changes, confirming injection site-specific effects. <b>Conclusions:</b> ApoE deficiency provides protection against vaccine-induced mitochondrial and inflammatory damage at the injection site, with enhanced protective effects under metabolic stress conditions. These findings reveal important interactions between metabolic status, lipid metabolism, and local vaccine responses that may inform vaccination strategies in different patient populations.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8964-8984"},"PeriodicalIF":13.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081571","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 : 2025-08-16eCollection Date: 2025-01-01DOI: 10.7150/thno.114797
Jiaxuan Yang, Jiahui Sun, Zili Liu, Xia Tang, Yunyun Hu, Weida Shen, Yicheng Xie, Yue Jin, Haifeng Li, Xuekun Li, Yanjun Jiang, Matthew Tak Vai Chan, William Ka Kei Wu, Zhigang Liu, Xiaodong Liu, Yaoqin Hu, Jinpiao Zhu, Daqing Ma
{"title":"Dopamine D2 receptor modulating mPFC-BLA circuit contributes to chronic sleep deprivation-induced memory impairment in mice.","authors":"Jiaxuan Yang, Jiahui Sun, Zili Liu, Xia Tang, Yunyun Hu, Weida Shen, Yicheng Xie, Yue Jin, Haifeng Li, Xuekun Li, Yanjun Jiang, Matthew Tak Vai Chan, William Ka Kei Wu, Zhigang Liu, Xiaodong Liu, Yaoqin Hu, Jinpiao Zhu, Daqing Ma","doi":"10.7150/thno.114797","DOIUrl":"10.7150/thno.114797","url":null,"abstract":"<p><p><b>Background:</b> Chronic sleep deprivation (CSD) affects the orchestration of neural networks, leading to cognitive impairment, but the underlying molecular and neural circuitry mechanisms remain unknown. <b>Methods:</b> Mice underwent a two-week CSD regimen, followed by spatial memory assessment using the Y-maze test and EEG gamma oscillation analysis. Dopamine D2 receptor (Drd2) expression in the medial prefrontal cortex (mPFC) was evaluated using transcriptomic and immunofluorescent analysis. The role of Drd2 in CSD-induced memory deficits was examined through local infusion of Drd2 agonists or antagonists into the mPFC. Neural circuit tracing, fiber photometry, and opto-chemogenetic approaches were used to assess Drd2 in the gating of the mPFC-basolateral amygdala (BLA) circuit-mediated memory impairment induced by CSD. <b>Results:</b> CSD disinhibited dopaminergic input to the mPFC and impaired spatial memory in mice. A significant increase in Drd2 expression was found in the layers II/III of the mPFC after CSD. Infusion of Drd2 agonist into the mPFC induced memory deficits in naïve mice, while administration of the Drd2 antagonist reversed memory impairment caused by CSD. Drd2 was found to co-localize with Ca<sup>2+</sup>/calmodulin-dependent protein kinase IIα (CaMKIIα<sup>+</sup>) neurons in the mPFC that project to the basolateral amygdala (BLA). Activation of CaMKIIα<sup>+</sup> neurons restored memory impairment induced by CSD through enhancing mPFC-to-BLA output and reversed memory defects induced by the Drd2 agonist. <b>Conclusion:</b> Our findings demonstrated that excessive Drd2 signaling leads to cognitive impairment following CSD by suppressing mPFC-BLA neurotransmission, suggesting a possible therapeutic value of dopamine D2 receptor antagonists in relieving CSD-induced cognitive decline.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"9073-9090"},"PeriodicalIF":13.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081618","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":"Tumor-responsive cuproptosis nanoinducer realizing efficient PANoptosis for enhanced cancer immunotherapy.","authors":"Kaiqing Yun, Xiaohong Yu, Shuang Liang, Qingling Wang, Ziyi Zhang, Yue Han, Yueyang Zhao, Yuxuan Peng, Lang Rao, Yong Cui, Zhaohui Wang","doi":"10.7150/thno.115275","DOIUrl":"10.7150/thno.115275","url":null,"abstract":"<p><p><b>Rationale:</b> The induction of multiple forms of regulated cell death (RCD) presents a promising approach for antitumor immunotherapy. However, the heterogeneous tumor microenvironment (TME) limits the efficacy of single-mode RCD induction strategies. <b>Methods:</b> We engineered Elesclomol-Cu@PDPA nanoparticles (PEC NPs) designed to induce cuproptosis and subsequent PANoptosis. These NPs remain stable during circulation but rapidly dissociate in the acidic TME, releasing Cu<sup>2+</sup> and Elesclomol to trigger cuproptosis. <b>Results:</b> The cuproptosis induced by PEC NPs resulted in PANoptosis of tumor cells. This process stimulated immunogenic cell death and activated a systemic immune response by promoting immune cell infiltration and reprogramming the immunosuppressive TME. PEC NPs demonstrated potent tumor growth inhibition and exhibited a synergistic antitumor effect when combined with immune checkpoint blockade therapy. <b>Conclusions:</b> This study provides a robust strategy utilizing PEC NPs to induce efficient cuproptosis and PANoptosis for enhanced immunotherapy. It offers new insights into boosting tumor immunogenicity through the activation of multiple RCDs pathways.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"9294-9305"},"PeriodicalIF":13.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081744","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":"The first abdominal aortic aneurysm organoid model replicates complex microenvironment for <i>in vitro</i> disease study.","authors":"Jiaxuan Feng, Mingjie Rong, Yudong Sun, Guanglang Zhu, Guangkuo Wang, Jiping Liu, Chen Wang, Jian Zhang, Xiaochen Ma, Junyi Yan, Yaojie Wang, Youjin Li, Yu Ning, Chunhui Cai, Xinxin Han","doi":"10.7150/thno.118193","DOIUrl":"10.7150/thno.118193","url":null,"abstract":"<p><p><b>Background:</b> Abdominal Aortic Aneurysm (AAA) is a critical global health issue, affecting an estimated up to 8% of men over 65, with a complex etiology involving smoking, age and gender. However, the lack of specific drug treatments underscores the need for a robust in vitro model to advance our comprehension of AAA pathophysiology and serve as an ex vivo surrogate for drug testing. <b>Methods:</b> This study introduces an innovative AAA patient-derived organoid (PDO) model using a non-enzymatic procedure, a Matrigel-free system, and specialized organoid culture medium, leveraging 3-dimensional (3D) cultures to replicate the disease's microenvironment. The stability of this culture system was assessed through microscopic observation, H&E staining, immunohistochemistry (IHC), viability assays, and whole-genome sequencing (WES). Additionally, we conducted pharmacological assessments to explore the effects of drug treatments on AAA PDO. <b>Results:</b> Our model maintains aortic morphological integrity and pathological phenotypes, incorporates the immune microenvironment (validated by IHC markers for macrophages and lymphocytes), and adjacent tissues (loose connective tissue and vegetative blood vessels). The model demonstrates remarkable stability, confirmed by consistent genetic mutation sites throughout cultivation via WES, and cell survival after five weeks in vitro via live-cell staining. Preliminary pharmacological assessments show promising efficacy, with distinct responses to 1 μM metformin, 1 μM RU.521, or 1 μM STING-IN-2 treatments for 48 h via mass spectrometry. <b>Conclusions:</b> The AAA organoid model, to the best of our knowledge, is the first reported abdominal aortic aneurysm PDO model, and signifies a promising step towards therapeutic treatment options for AAA, potentially complementing existing surgical approaches.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"9029-9046"},"PeriodicalIF":13.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081694","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":"Macrophage-derived KIF13B interacts with USP9X to attenuate abdominal aortic aneurysm development by potentiating TFEB stability.","authors":"Jingxuan Chen, Yitong Xu, Huahui Yu, Yiran Liu, Guolin Miao, Yufei Han, Liwen Zheng, Zeyu Cai, Zihao Zhou, Jinxuan Chen, Sijing Shi, Pingping Lai, Wenxi Zhang, Lianxin Zhang, Si Mei, Yinqi Zhao, Ling Zhang, Wei Huang, Yuhui Wang, Dongyu Zhao, Wei Kong, Yanwen Qin, Erdan Dong, Xunde Xian","doi":"10.7150/thno.118958","DOIUrl":"10.7150/thno.118958","url":null,"abstract":"<p><p><b>Rationale:</b> Abdominal aortic aneurysm (AAA) is a highly lethal cardiovascular disorder for which there is no effective medication to date. Kinesin family member 13b (KIF13B), a vital motor protein, has been recently identified as a novel regulator of lipid metabolism. However, the role of KIF13B in AAA development has not been documented. <b>Methods:</b> We determined the expression of KIF13B in aortic tissues from clinical patients and porcine pancreatic elastase (PPE) or angiotensin II (ANG II)-induced AAA mouse models. To investigate the influence of KIF13B on AAA expansion, we established global, myeloid cell-specific and vascular smooth muscle cell (VSMC)-specific conditional <i>Kif13b</i>-deficient mice in PPE and/or ANG II-induced AAA models. <b>Results:</b> RNA-seq data from GEO database (GSE57691) revealed a significant decrease in <i>KIF13B</i> gene expression within the aortic tissues of patients with AAA. KIF13B protein levels were largely reduced in aortic tissue samples from patients and two mouse models with AAA. Complete inactivation of <i>Kif13b</i> or depleting <i>Kif13b</i> from myeloid cells but not smooth muscle cells (SMCs) exacerbated AAA development. Mechanistic studies identified transcription factor EB (TFEB) as a critical downstream target of KIF13B. KIF13B stabilized and upregulated TFEB by enhancing its deubiquitination through an interaction with deubiquitinase USP9X to maintain the proper function of lysosomes, thus inhibiting the senescence-associated secretory phenotype (SASP) and proinflammatory response of macrophages. Moreover, restoration of macrophage <i>Kif13b</i> or senolytic therapy dramatically mitigated AAA expansion <i>in vivo</i>. <b>Conclusions:</b> In the present study, we provided a new insight into the pathogenesis of AAA and defined a KIF13B-USP9X-TFEB axis that is essential for the regulation of macrophage function, suggesting that macrophage-derived <i>Kif13b</i> is a beneficial regulator of vascular homeostasis and targeting KIF13B could be a potential therapeutic approach for the treatment of human AAA disease in future clinical trial.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"9114-9130"},"PeriodicalIF":13.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081598","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 : 2025-08-16eCollection Date: 2025-01-01DOI: 10.7150/thno.111643
Junhao Li, Li Wang, Shiyao Wu, Guifen Yang, Long Jiang Zhang
{"title":"Imaging Brown Adipose Tissue: Current State and Future Perspective.","authors":"Junhao Li, Li Wang, Shiyao Wu, Guifen Yang, Long Jiang Zhang","doi":"10.7150/thno.111643","DOIUrl":"10.7150/thno.111643","url":null,"abstract":"<p><p>Brown adipose tissue (BAT) is a specialized type of fat tissue that utilizes various nutrients and is considered a novel therapeutic target for metabolic, disorders, cardiovascular diseases, and certain types of cancer. However, the current standard imaging method for BAT, <sup>18</sup>F-flurodeoxyglucose positron emission tomography computed tomography ([<sup>18</sup>F] FDG PET-CT), fails to meet clinical demands due to its prohibitive costs, prolonged imaging times, and radiation exposure, which are significant concerns for longitudinal studies. To overcome these limitations, emerging imaging modalities are being explored, aiming to address these challenges by focusing on alternative biomarkers of BAT, such as lipid content, perfusion, density, thermal emissions, and mitochondrial activity. Advanced imaging methods have been developed for precise imaging, facile operation, and broad applicability. In this review, we provide a brief overview of BAT physiology and function, as well as current advancements in BAT imaging methods, including positron emission tomography, single photon emission computed tomography, magnetic resonance imaging, computed tomography, infrared thermography, optoacoustic imaging, and Xenon-enhanced imaging. Future perspectives, such as the application of artificial intelligence to BAT imaging, are also discussed.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"9001-9018"},"PeriodicalIF":13.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081657","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 : 2025-08-16eCollection Date: 2025-01-01DOI: 10.7150/thno.119357
Minghao Li, Qiwei Yang, Jie Gao, Xudong Liu, Jihua Shi, Wenzhi Guo, Yi Zhang, Qiwen Yu, Xinzhi Sun, Shuijun Zhang
{"title":"Nanotuner targeting mitochondrial redox and iron homeostasis imbalance for the treatment of acute liver injury.","authors":"Minghao Li, Qiwei Yang, Jie Gao, Xudong Liu, Jihua Shi, Wenzhi Guo, Yi Zhang, Qiwen Yu, Xinzhi Sun, Shuijun Zhang","doi":"10.7150/thno.119357","DOIUrl":"10.7150/thno.119357","url":null,"abstract":"<p><p><b>Background</b>: Acute liver injury (ALI), a highly perilous clinical condition triggered by diverse etiological factors, frequently progresses to acute liver failure with life-threatening consequences. However, due to the limited intervention time window for ALF, donor shortages, challenges in utilizing marginal grafts, surgical complexity and risks, and the high economic burden, developing novel therapeutic strategies targeting ALI-induced ALF has become imperative. <b>Methods</b>: Through transcriptome analysis, we determined that ferroptosis is a key driver in the pathogenesis of ALI. To combat hepatocyte ferroptosis, we designed a novel mitochondria-targeted nanotuner (CPTD) for regulating mitochondrial oxidative stress and iron homeostasis imbalance during ALI. This nanotuner features a cerium oxide (CeO₂) nanozyme core with a polydopamine (PDA) coating, functionalized with triphenylphosphonium (TPP) for mitochondrial targeting and deferoxamine (DFO) for iron chelation. In vitro and in vivo experiments evaluated CPTD's ability to target mitochondria and the labile iron pool (LIP). <b>Results</b>: The nanotuner demonstrates dual regulatory capacity by effectively accumulating in hepatic mitochondria to concurrently scavenge reactive oxygen species (ROS) and sequester labile iron ions, thereby rectifying mitochondrial oxidative stress and iron dyshomeostasis. Comprehensive evaluations across multiple ALI models, mainly including hepatic ischemia-reperfusion injury and acetaminophen-induced hepatotoxicity, revealed that CPTD robustly inhibits ferroptosis, mitigates oxidative damage, attenuates inflammatory responses, and preserves hepatic function. <b>Conclusions</b>: Our findings establish this dual-targeting nanotuner as a promising therapeutic strategy for ALI, providing novel insights into mitochondrial redox and iron homeostasis modulation.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"9131-9158"},"PeriodicalIF":13.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081678","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":"RBMS1-mediates the biogenesis of circNFIB promotes perineural invasion of pancreatic ductal adenocarcinoma via the L1CAM/MAPK pathway.","authors":"Zhuo Wu, Zhou Fang, Liangtang Zeng, Dingwen Zhang, Yu Zhou, Rufu Chen","doi":"10.7150/thno.112753","DOIUrl":"10.7150/thno.112753","url":null,"abstract":"<p><p><b>Background:</b> Circular RNAs (circRNAs) play a key regulatory role in various functional characteristics of pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms underlying circRNA's involvement in the occurrence of perineural invasion (PNI) in PDAC remain unclear and require further investigation. <b>Methods:</b> Through circRNA sequencing, we identified the circNFIB (hsa_circ_0086376) that is highly associated with PNI in PDAC tissues. We then evaluated the promoting effect of circNFIB on PNI using various assays, including the Matrigel/dorsal root ganglia (DRG) model, DRG-matrix assay, transwell assay, orthotopic xenograft model, and in vivo model of neural infiltration. The interaction mechanism between circNFIB and IGF2BP3, which enhances L1CAM mRNA stability, was explored using RNA pulldown, mass spectrometry, RNA Immunoprecipitation (RIP), and actinomycin D assays. Additionally, the role of RBMS1 in promoting the biogenesis of circNFIB was investigated using RIP and Western blotting. <b>Results:</b> This study confirmed that circNFIB is significantly upregulated in PDAC samples and samples with high PNI. Both in vitro and in vivo experiments demonstrated its role in promoting PNI in PDAC. Mechanistically, circNFIB binds with IGF2BP3 in PDAC cells to enhance the stability of L1CAM mRNA, activating the ERK/MAPK signaling pathway, and facilitating PNI in PDAC. Additionally, we found that RBMS1 binds to the NFIB pre-mRNA and promotes the biogenesis of circNFIB. Finally, we verified circNFIB as a potential therapeutic target that can mitigate the anti-tumor effects of SCH772984 in vivo. <b>Conclusion:</b> RBMS1-mediated circNFIB interacts with IGF2BP3 to stabilize L1CAM mRNA, thereby activating the ERK/MAPK signaling pathway and promoting PNI in PDAC. This study provides a novel perspective on the molecular mechanisms underlying PNI in PDAC and lays the theoretical foundation for circNFIB as a potential therapeutic target for PDAC.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"9261-9278"},"PeriodicalIF":13.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081705","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 : 2025-08-16eCollection Date: 2025-01-01DOI: 10.7150/thno.115831
Florian Rosar, Caroline Burgard, Christine Petrescu, Arne Blickle, Mark Bartholomä, Stephan Maus, Moritz B Bastian, Tilman Speicher, Andrea Schaefer-Schuler, Samer Ezziddin
{"title":"Pilot experience of [<sup>161</sup>Tb]Tb-PSMA-617 RLT in mCRPC patients after conventional PSMA RLT within a prospective registry.","authors":"Florian Rosar, Caroline Burgard, Christine Petrescu, Arne Blickle, Mark Bartholomä, Stephan Maus, Moritz B Bastian, Tilman Speicher, Andrea Schaefer-Schuler, Samer Ezziddin","doi":"10.7150/thno.115831","DOIUrl":"10.7150/thno.115831","url":null,"abstract":"<p><p><i>Rationale:</i> The radionuclide <sup>161</sup>Tb is an increasingly discussed potential candidate for radioligand therapy (RLT). Through the considerable emitted amount of low-energy Auger and conversion electrons, <sup>161</sup>Tb offers physical advantages over the commonly used <sup>177</sup>Lu, resulting in higher locally absorbed doses. In this study, we present initial experience with [<sup>161</sup>Tb]Tb-PSMA-617 RLT across different clinical settings following initial PSMA RLT. <i>Methods:</i> The study involved n=18 patients with metastasized castration-resistant prostate cancer (mCRPC) participating in a prospective registry (NCT04833517) and receiving [<sup>161</sup>Tb]Tb-PSMA-617 after initial PSMA RLT with established radionuclides (<sup>177</sup>Lu, <sup>225</sup>Ac). In total 47 cycles of [<sup>161</sup>Tb]Tb-PSMA-617 RLT were administered with a median of 3 cycles (1 - 4 cycles) per patient. The mean administered activity of <sup>161</sup>Tb per cycle was 6.2 ± 0.8 GBq, the mean cumulative activity was 16.1 ± 4.9 GBq. Outcome was evaluated by biochemical and molecular imaging response, progression-free survival (PFS), and overall survival (OS). Adverse events were assessed by '<i>Common Terminology Criteria for Adverse Events</i>' (CTCAE v.5.0) grading system. <i>Results:</i> In the heterogeneous cohort of patients previously experiencing insufficient response or progression post RLT with [<sup>177</sup>Lu]Lu-PSMA-617, or even after <sup>225</sup>Ac augmentation, biochemical and molecular imaging response rates were 38.9% and 44.4%, median PFS and OS 3.5 and 11.3 months, respectively. The best response and outcome were observed in patients who initially responded to [<sup>177</sup>Lu]Lu-PSMA-617 RLT. The majority of all post therapeutically recorded adverse events were mild or moderate (CTCAE °1 or °2); higher grades (CTCAE °3 or °4) were rarely observed (2 cases of thrombocytopenia, 4 cases of anemia and 4 cases of renal impairment). No treatment discontinuation due to therapy related adverse events was recorded. <i>Conclusion:</i> These pilot results confirm <sup>161</sup>Tb as a promising radionuclide for PSMA RLT and suggest [<sup>161</sup>Tb]Tb-PSMA-617 as a potential effective and safe treatment option even in the advanced mCRPC setting after multi-line systemic therapies including standard PSMA RLT. Larger studies are warranted to confirm and extend this initial experience and clinical trials even in earlier CRPC settings appear promising based on our initial impression of this radionuclide-based novelty in PSMA RLT.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"9019-9028"},"PeriodicalIF":13.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081708","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 : 2025-08-16eCollection Date: 2025-01-01DOI: 10.7150/thno.112238
Ruo-Si Zou, Jin-Gang He, Yang Zhao, Bing Zhou, Si-Long Deng, Jian-Guo Chen, Fang Wang
{"title":"Extracellular vehicles-mediated Twsit1 transferred from tumor cells to brain induces depressive-like behaviors via neuronal morphogenesis.","authors":"Ruo-Si Zou, Jin-Gang He, Yang Zhao, Bing Zhou, Si-Long Deng, Jian-Guo Chen, Fang Wang","doi":"10.7150/thno.112238","DOIUrl":"10.7150/thno.112238","url":null,"abstract":"<p><p><b>Rationale:</b> Depression is commonly comorbid with cancer and affects therapeutic efficacy and outcome-of-disease. However, the molecular mechanism underlying cancer-induced depression (CID) remains poorly understood. Twist1 is a proto-oncogene driving tumor progression and metastasis, and chronic stress induces Twist1 expression in the medial prefrontal cortex (mPFC). This study aims to investigate the role and mechanisms of tumor-derived Twist1 in CID. <b>Methods:</b> shTwist1 stably expressing 4T1 cells were obtained through lentivirus transduction and puromycin selection. Tumor cells were subcutaneously inoculated into mice to establish a tumor-bearing mice model. Behavioral assays were used to assess depressive-like behaviors in mice. Ultra-high-speed centrifugation was employed to extract extracellular vehicles (EVs) in 4T1 cell medium or serum from tumor-bearing mice. Quantitative polymerase chain reaction and western blot were used to detect the levels of Twist1 mRNA and protein from tumor-derived EVs or mPFC tissue. Lentivirus was injected into the mPFC to knock down Twist1. Intravenous or intranasal administration of tumor or serum-derived EVs were used to investigate the role of EVs-packaged Twist1 in depressive-like behaviors in mice. <b>Results:</b> The present study demonstrated that tumor-derived EVs mediated the inter-organ communication between tumor cells and brain. Pharmacological inhibition of EVs secretion mitigated depressive-like behaviors in tumor-bearing mice. Intravenous or intranasal injection of EVs from tumor cells or serum from tumor-bearing mice into naïve mice induced a depressive-like phenotype. Further investigation identified tumor-derived EVs Twsit1 as a crucial mediator of cancer-induced dendritic atrophy and depressive-like behaviors in tumor-bearing mice. Knockdown of Twist1 in tumor cells significantly alleviated the detrimental effects of tumor-derived EVs on neuronal morphogenesis and prevented their pro-depressant effects. <b>Conclusions:</b> This study demonstrates that tumor-derived EVs containing Twist1 constitute a key pathological driver of cancer-induced depression, revealing a potential therapeutic target for clinical intervention.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8985-9000"},"PeriodicalIF":13.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081620","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}