Theranostics最新文献

{"title":"GPX4 knockdown suppresses M2 macrophage polarization in gastric cancer by modulating kynurenine metabolism.","authors":"Jingli Xu, Chunyan Weng, Yanqiang Zhang, Qianyu Zhao, Jiahui Chen, Siwei Pan, Yan Wang, Ruolan Zhang, Yuqi Wang, Weiwei Zhu, Mengxuan Cao, Dan Zu, Shengjie Zhang, Zhiyuan Xu, Can Hu, Xiangdong Cheng","doi":"10.7150/thno.108817","DOIUrl":"10.7150/thno.108817","url":null,"abstract":"<p><p><b>Background:</b> Glutathione peroxidase 4 (GPX4), an important factor regulating redox homeostasis, plays an important role in tumor microenvironment and progression. However, the role of GPX4 in gastric cancer (GC) is unclear. <b>Methods:</b> Spectral flow cytometry and multiplex immunohistochemistry were employed to assess the correlation between GPX4 expression and immune cell infiltration. Metabolomics analysis of conditioned media from GPX4 knockdown NUGC3 cells identified metabolic alterations. Additionally, both in vitro and in vivo functional studies were conducted to elucidate the mechanistic role of GPX4 in regulating the tumor microenvironment and progression. <b>Results:</b> Knockdown of GPX4 in GC cells inhibited tumor growth, enhanced CD8⁺ T cell infiltration, and suppressed the polarization of tumor-associated macrophages (TAMs) toward the pro-tumor M2 phenotype. Multiplex immunohistochemistry revealed a positive correlation between GPX4 expression and M2 macrophage infiltration in clinical samples from patients with GC. Metabolomics revealed that GPX4 knockdown regulate kynurenine metabolism pathway. Furthermore, mechanistic studies reveal that GPX4 silencing elevates lipid peroxidation, triggering the conversion of KYNU ubiquitin chain modifications from K48 to K63. Such ubiquitination remodeling stabilizes KYNU expression (a key kynurenine-metabolizing enzyme), reduces kynurenine accumulation, and ultimately reprograms TAM polarization to enhance antitumor immunity. We also identified that the K96 and K163 sites are important for KYNU's modification by K48 and K63 ubiquitin chains. <b>Conclusion:</b> Our study not only affirm the role of GPx4 in GC progression but also highlight it as a promising target for reshaping the immune microenvironment.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 12","pages":"5826-5845"},"PeriodicalIF":12.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060941","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":"Fish-derived biomaterials for tissue engineering: advances in scaffold fabrication and applications in regenerative medicine and cancer therapy.","authors":"Seoyul Jo, Hanjun Hwangbo, Nacionales Francis, JaeYoon Lee, Mohan Pei, GeunHyung Kim","doi":"10.7150/thno.109186","DOIUrl":"10.7150/thno.109186","url":null,"abstract":"<p><p>Fish-derived biomaterials, such as collagen, polyunsaturated fatty acids, and antimicrobial peptides, have emerged as promising candidates for scaffold development in stem cell therapies and tissue engineering due to their excellent biocompatibility and low immunogenicity. Although good bioactivity is a prerequisite for biomedical substitutes, scaffold design is necessary for the successful development of bioconstructs used in tissue regeneration. However, the limited processability of fish biomaterials poses a substantial challenge to the development of diverse scaffold structures. In this review, unlike previous reviews that primarily focused on the bioactivities of fish-derived components, we placed greater emphasis on scaffold fabrication and its applications in tissue regeneration. Specifically, we examined various cross-linking strategies to enhance the structural integrity of fish biomaterials and address challenges, such as poor processability, low mechanical strength, and rapid degradation. Furthermore, we demonstrated the potential of fish scaffolds in stem cell therapies, particularly their capacity to support stem cell growth and modulate the cellular microenvironment. Finally, this review provides future directions for the application of these scaffolds in cancer therapy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 12","pages":"5666-5692"},"PeriodicalIF":12.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047926","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":"A bifunctional fusion membrane-based biocompatible nanovaccine to potentiate cancer immunotherapy.","authors":"Wei Fu, Xing Cai, Jinru Yang, Lian Yang, Yaoyu Pan, Zhan Tuo","doi":"10.7150/thno.106376","DOIUrl":"10.7150/thno.106376","url":null,"abstract":"<p><p><b>Background:</b> Cancer cell membrane-based nanovaccines derived from patients' tumor tissues have shown promising features as a personalized cancer treatment strategy. However, the weak immunogenicity of autologous tumor antigens undermines the therapeutic effects of personalized vaccines. <b>Methods</b>: We synthesized a biomimetic nanovaccine, Bio-HCP@FM-NPs, composed of senescent tumor cell membranes, <i>Escherichia coli</i> cytoplasmic membrane extracts, and granulocyte-macrophage colony-stimulating factor (GM-CSF)-encapsulated biocompatible hypercross-linked polymer nanoparticles. The nanovaccine's antitumor and enhanced immunotherapy effects were demonstrated in multiple tumor models. The tumor prevention effects of nanovaccine were assessed using a postoperative recurrence model. <b>Results:</b> The Bio-FM@HCP-NP vaccine showed promising therapeutic efficacy in the B16-F10 melanoma mouse model and significantly synergized with anti-PD-1 immunotherapy across multiple tumor models. Mechanistically, GM-CSF was promptly released to recruit naïve DCs to the nanovaccine. Thereafter, immature DCs were vigorously activated by FM-NPs, thereby activating the cytotoxic T cells. Furthermore, Bio-HCP@FM-NPs induced robust antigen-specific immune responses, prolonging postoperative survival in mice and providing long-term protection against tumor recurrence. Targeted depletion of immune cell populations revealed that T and B cells were essential for vaccine-induced tumor regression. <b>Conclusion:</b> The Bio-HCP@FM-NPs showed significant promise for immunotherapy and tailored postoperative treatment of cancer, leveraging the strong activation of innate immunity by senescent tumor cell membranes and bacterial cytoplasmic membrane extracts.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 12","pages":"5719-5737"},"PeriodicalIF":12.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033174","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":"Development of a robust BH3 drug toolkit for precision medicine in hematologic malignancies.","authors":"Valentin Jacquier, Andréa Romero, Caroline Molinaro, Ritu Somayaji, Matthieu Abouladze, Ouissem Karmous Gadacha, Sara Ovejero, Hugues de Boussac, Ludovic Gabellier, Matthew S Davids, Jérôme Moreaux, Charles Herbaux","doi":"10.7150/thno.107852","DOIUrl":"10.7150/thno.107852","url":null,"abstract":"<p><p><b>Rationale:</b> In the era of precision medicine, there is a growing need for rapid reliable <i>ex vivo</i> functional assays capable of predicting treatment efficacy. One drug class that may particularly benefit from such assays is BH3 mimetics. These small molecules antagonize anti-apoptotic proteins such as BCL-2, MCL-1, or BCL-XL, on which cancer cells depend for their survival. A functional assay known as BH3 profiling was previously developed to measure those dependencies through the use of specific BH3-only peptides. A variation of this technique, dynamic BH3 profiling (DBP), allows for measuring changes in those dependencies, after <i>ex vivo</i> treatment with a drug of interest. Though well-validated to predict clinical response in hematologic malignancies, BH3 profiling technique requires the use of specialized BH3-only peptides and requires significant optimization to achieve reproducible results. <b>Methods:</b> We used a toolkit of BH3 mimetics drugs as probes instead of BH3-only peptides. This technique reduces the complexity and cost by using Annexin V/7AAD staining instead of cytochrome c release as a functional readout for apoptosis. We also used cell lines as internal controls for a representative response to BH3 mimetics that allow us to easily compare and stratify patients according to their profile. <b>Results:</b> We demonstrate that our new protocol enables apoptotic dependencies to be measured efficiently across different hematologic malignancies. In addition to a detailed description of the assay, we describe the results in several models including cell lines and primary tumor cells, both at baseline and dynamically after <i>ex vivo</i> drug treatments. We also compared BH3 toolkit baseline results on cell lines with those obtained using conventional BH3 profiling. <b>Conclusion:</b> Overall, our data validates this streamlined BH3 drug toolkit, allowing for a more extensive use of the BH3 profiling technique.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 12","pages":"5705-5718"},"PeriodicalIF":12.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049056","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":"Inorganic and hybrid nanomaterials for NIR-II fluorescence imaging-guided therapy of Glioblastoma and perspectives.","authors":"Zhigang Li, Lixin Du, Binghua Du, Zia Ullah, Yinghe Zhang, Yanyang Tu, Ying Zhou, Bing Guo","doi":"10.7150/thno.112204","DOIUrl":"10.7150/thno.112204","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most invasive and lethal brain tumor, with limited therapeutic options due to its highly infiltrative nature, resistance to conventional therapies, and blood-brain barriers. Recent advancements in near-infrared II (NIR-II) fluorescence imaging have facilitated greater tissue penetration, improved resolution, and real-time visualization of GBM, providing a promising approach for precise diagnosis and treatment. The inorganic and hybrid NIR-II fluorescent materials have developed rapidly for NIR-II fluorescence imaging-guided diagnosis and therapy of many diseases, including GBM. Herein, we offer a timely update to explore the contribution of inorganic/hybrid NIR-II fluorescent nanomaterials, such as quantum dots, rare-earth-doped nanoparticles, carbon-based nanomaterials, and metal nanoclusters in imaging-guided treatment for GBM. These nanomaterials provide high photostability, strong fluorescence intensity, and tunable optical properties, allowing for multimodal imaging and enhanced therapeutic efficacy. Additionally, their integration with modern therapeutic strategies, such as photothermal therapy, chemodynamic therapy, photodynamic therapy, sonodynamic therapy, and immunotherapy, has shown significant potential in overcoming the limitations of traditional treatments. Looking forward, future advancements including safe body clearance, long-term biocompatibility, efficient BBB penetration, and extended emission wavelengths beyond 1500 nm could enhance the theranostic outcomes. The integration of dual imaging with immunotherapy and AI-driven strategies will further enhance precision and accelerate the clinical translation of smart theranostic platforms for GBM treatment.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 12","pages":"5616-5665"},"PeriodicalIF":12.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064710","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":"Optimizing theranostics chatbots with context-augmented large language models.","authors":"Pia Koller, Christoph Clement, Albert van Eijk, Robert Seifert, Jingjing Zhang, George Prenosil, Mike M Sathekge, Ken Herrmann, Richard Baum, Wolfgang A Weber, Axel Rominger, Kuangyu Shi","doi":"10.7150/thno.107757","DOIUrl":"10.7150/thno.107757","url":null,"abstract":"<p><p><b>Introduction</b>: Nuclear medicine theranostics is rapidly emerging, as an interdisciplinary therapy option with multi-dimensional considerations. Healthcare Professionals do not have the time to do in depth research on every therapy option. Personalized Chatbots might help to educate them. Chatbots using Large Language Models (LLMs), such as ChatGPT, are gaining interest addressing these challenges. However, chatbot performances often fall short in specific domains, which is critical in healthcare applications. <b>Methods</b>: This study develops a framework to examine the use of contextual augmentation to improve the performance of medical theranostic chatbots to create the first theranostic chatbot. Contextual augmentation involves providing additional relevant information to LLMs to improve their responses. We evaluate five state-of-the-art LLMs on questions translated into English and German. We compare answers generated with and without contextual augmentation, where the LLMs access pre-selected research papers via Retrieval Augmented Generation (RAG). We are using two RAG techniques: Naïve RAG and Advanced RAG. <b>Results</b>: A user study and LLM-based evaluation assess answer quality across different metrics. Results show that Advanced RAG techniques considerably enhance LLM performance. Among the models, the best-performing variants are CLAUDE 3 OPUS and GPT-4O. These models consistently achieve the highest scores, indicating robust integration and utilization of contextual information. The most notable improvements between Naive RAG and Advanced RAG are observed in the GEMINI 1.5 and COMMAND R+ variants. <b>Conclusion</b>: This study demonstrates that contextual augmentation addresses the complexities inherent in theranostics. Despite promising results, key limitations include the biased selection of questions focusing primarily on PRRT, the need for comprehensive context documents. Future research should include a broader range of theranostics questions, explore additional RAG methods and aim to compare human and LLM evaluations more directly to enhance LLM performance further.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 12","pages":"5693-5704"},"PeriodicalIF":12.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035756","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":"Comparative study of [¹⁸F]AlF-NOTA-FAPI-RGD and [¹⁸F]FDG/[¹⁸F]AlF-NOTA-FAPI-04 PET/CT in renal cell carcinoma.","authors":"Haiyan Gao, Zhiwei Ma, Ziyang Zhu, Zhichuan Yang, Bo Chen, Xiaoming Wu, Vivianne Jakobsson, Yujiao Deng, Hao Wang, Wei Zhang, Jingjing Zhang","doi":"10.7150/thno.113070","DOIUrl":"10.7150/thno.113070","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Renal cell carcinoma (RCC) is a significant global health concern, and the early diagnosis and accurate staging of clear cell renal cell carcinoma (ccRCC) remain major challenges. [&lt;sup&gt;18&lt;/sup&gt;F]FDG PET/CT is not ideal for diagnosing ccRCC due to the low glucose metabolism potential of cancer cells. Both fibroblast activation protein (FAP) and the angiogenic integrin α&lt;sub&gt;v&lt;/sub&gt;β&lt;sub&gt;3&lt;/sub&gt; receptor are closely linked to the pathogenesis and progression of ccRCC. The aim of this study is to evaluate a novel radiopharmaceutical [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-FAPI-RGD (denoted as [&lt;sup&gt;18&lt;/sup&gt;F]AlF-LNC1007), a dual-targeting heterodimer tracer targeting both FAP and integrin α&lt;sub&gt;v&lt;/sub&gt;β&lt;sub&gt;3&lt;/sub&gt;, and to compare the diagnostic value of [&lt;sup&gt;18&lt;/sup&gt;F]AlF-LNC1007 with [&lt;sup&gt;18&lt;/sup&gt;F]FDG and [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-FAPI-04 PET/CT in RCC. &lt;b&gt;Materials and Methods&lt;/b&gt;: A total of 35 participants, highly suspected to have RCC, were recruited. [&lt;sup&gt;18&lt;/sup&gt;F]AlF-LNC1007 and [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-FAPI-04/[&lt;sup&gt;18&lt;/sup&gt;F]FDG scans were performed at least one day apart, and both were completed within one week. The Wilcoxon signed-rank test or paired t-test was used to assess differences in tumor uptake and TBR (tumor-to-background ratio) between [&lt;sup&gt;18&lt;/sup&gt;F]AlF-LNC1007 and the other two imaging agents. The Spearman correlation coefficient was used to evaluate the correlation between tumor uptake and the expression of FAP and α&lt;sub&gt;v&lt;/sub&gt;β&lt;sub&gt;3.&lt;/sub&gt; &lt;b&gt;Results:&lt;/b&gt; The detection rate, sensitivity, and positive predictive value (PPV) of [&lt;sup&gt;18&lt;/sup&gt;F]AlF-LNC1007 for RCC primary lesions were significantly higher than those of [&lt;sup&gt;18&lt;/sup&gt;F]FDG, at 91% vs. 76%, 100% vs. 85%, and 91% vs. 87%, respectively. Obvious advantages were also seen in metastatic lesions at 94% vs. 34%, 94% vs. 29%, and 100% vs. 100%. Compared to [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-FAPI-04, the corresponding detection rate, sensitivity, and PPV were 98% vs. 90%, 100% vs. 92%, and 98% vs. 98% for primary lesions, and 89% vs. 78%, 89% vs. 93%, and 100% vs. 82% for metastatic lesions. The uptake and TBR of [&lt;sup&gt;18&lt;/sup&gt;F]AlF-LNC1007 in both primary and metastatic lesions were significantly higher than those of [&lt;sup&gt;18&lt;/sup&gt;F]FDG (all P &lt; 0.001). The uptake of [&lt;sup&gt;18&lt;/sup&gt;F]AlF-LNC1007 showed a moderate to high positive correlation with the expression levels of α&lt;sub&gt;v&lt;/sub&gt;β&lt;sub&gt;3&lt;/sub&gt; and the combined expression of FAP and α&lt;sub&gt;v&lt;/sub&gt;β&lt;sub&gt;3&lt;/sub&gt; (r = 0.756, P = 0.0003; r = 0.678, P = 0.0002) and a low positive correlation with FAP expression alone (r = 0.389, P = 0.014). The uptake of [&lt;sup&gt;18&lt;/sup&gt;F]AlF-NOTA-FAPI-04 showed a low to moderate positive correlation with FAP expression and the combined expression of FAP and α&lt;sub&gt;v&lt;/sub&gt;β&lt;sub&gt;3&lt;/sub&gt; (r = 0.570, P = 0.0002; r = 0.408, P = 0.010), and no correlation with α&lt;sub&gt;v&lt;/sub&gt;β&lt;sub&gt;3&lt;/sub&gt; expression alone (r = 0.262, P = 0.107). &lt;b&gt;Conclusion:&lt;/b&gt; [&lt;sup&gt;18&lt;/sup&gt;F]AlF-LNC1007 demonstrated significantly higher d","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 12","pages":"5790-5800"},"PeriodicalIF":12.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055127","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":"Investigating post-infection anxiety- and depression-like behaviors in a SARS-CoV-2 mouse model.","authors":"Qian Ge, Shan Zhou, Jose Porras, Panfeng Fu, Ting Wang, Jianyang Du, Kun Li","doi":"10.7150/thno.102752","DOIUrl":"10.7150/thno.102752","url":null,"abstract":"<p><p><b>Rationale:</b> The COVID-19 pandemic, driven by SARS-CoV-2, has resulted in a wide range of neuropsychiatric symptoms associated with post-acute sequelae (PASC). However, the mechanisms by which SARS-CoV-2 impacts the brain and leads to persistent behavioral changes remain poorly understood. We hypothesize that SARS-CoV-2 exposure induces neuroinflammation and microglial activation, leading to anxiety- and depression-like behaviors in mice. <b>Methods:</b> We established a SARS-CoV-2 mouse model using the virulent SARS2-N501Y_MA30 strain to investigate its impact on the central nervous system (CNS). We assessed neuroinvasion via immunostaining of dsRNA and markers for neuronal, astrocyte, and microglia in brain slices. Behavioral changes were evaluated at 2 weeks, 2 months, and 4 months post-infection. Molecular and cellular analyses included bulk RNA-seq, Golgi-Cox staining, field excitatory postsynaptic potential (fEPSP) recordings, immunofluorescence, and quantitative real-time PCR (qRT-PCR) to assess gene expression, neuronal morphology, and microglial activation in the brain. <b>Results</b>: We demonstrated that intranasal inoculation of SARS2-N501Y_MA30 results in viral dissemination to multiple brain regions, including the amygdala and the prefrontal cortex (PFC). Behavioral assays indicated a marked elevation in anxiety- and depression-like behaviors post-infection. A comparative analysis of RNA expression profiles disclosed alterations in the post-infected brains. Additionally, we observed dendritic spine remodeling on neurons within the amygdala after infection. Infection with SARS2-N501Y_MA30 was associated with microglial activation and a subsequent increase in microglia-dependent neuronal activity in the amygdala. Transcriptomic analysis of infected brains revealed the upregulation of inflammatory and cytokine-related pathways, implicating neuroinflammation in the pathogenesis of neuronal hyperactivity and behavioral abnormality. <b>Conclusion:</b> Our findings provide evidence that SARS-CoV-2 neuroinvasion plays a critical role in the development of lasting behavioral sequelae observed in PASC. These data provide critical insights into the neurological consequences of SARS-CoV-2 infection and underscore microglia as a potential therapeutic target for ameliorating virus-induced neurobehavioral abnormalities.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 12","pages":"5738-5755"},"PeriodicalIF":12.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049170","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":"Integrated cascade antioxidant nanozymes-Cu_5.4O@CNDs combat acute liver injury by regulating retinol metabolism.","authors":"Jiayu Chen, Yujie Zhang, Zhichao Deng, Yuanyuan Zhu, Chenxi Xu, Bowen Gao, Wenlong Wang, Jie Xiao, Zhengtao Xiao, Mingzhen Zhang, Kangsheng Tu","doi":"10.7150/thno.106811","DOIUrl":"10.7150/thno.106811","url":null,"abstract":"<p><p><b>Background:</b> Acute liver failure (ALF) represents a critical medical condition marked by the abrupt onset of hepatocyte damage, commonly induced by etiological factors such as hepatic ischemia/reperfusion injury (HIRI) and drug-induced hepatotoxicity. Across various types of liver injury, oxidative stress, heightened inflammatory responses, and dysregulated hepatic retinol metabolism are pivotal contributors, particularly in the context of excessive reactive oxygen species (ROS). <b>Methods:</b> C-dots were combined with Cu_5.4O USNPs to synthesize a cost-effective nanozyme, Cu_5.4O@CNDs, which mimics the activity of cascade enzymes. The <i>in vitro</i> evaluation demonstrated the ROS scavenging and anti-inflammatory capacity of Cu_5.4O@CNDs. The therapeutic potential of Cu_5.4O@CNDs was evaluated <i>in vivo</i> using mouse models of hepatic ischemia/reperfusion injury and LPS/D-GalN induced hepatitis, with transcriptome analysis conducted to clarify the mechanism underlying hepatoprotection. <b>Results:</b> The Cu_5.4O@CNDs demonstrated superoxide dismutase (SOD) and catalase (CAT) enzyme activities, as well as hydroxyl radical (·OH) scavenging capabilities, effectively mitigating ROS <i>in vitro</i>. Furthermore, the Cu_5.4O@CNDs exhibited remarkable targeting efficacy towards inflammation cells induced by H₂O₂ and hepatic tissues in murine models of hepatitis, alongside exhibiting favorable biocompatibility in both <i>in vitro</i> and <i>in vivo</i> settings. Moreover, it has been demonstrated that Cu_5.4O@CNDs effectively scavenged ROS, thereby enhancing cell survival <i>in vitro</i>. Additionally, Cu_5.4O@CNDs exhibited significant therapeutic efficacy in mice models of HIRI and lipopolysaccharide-induced acute lung injury (LPS-ALI). This efficacy was achieved through the modulation of the ROS response and hepatic inflammatory network, as well as the amelioration of disruptions in hepatic retinol metabolism. <b>Conclusions:</b> In summary, this study demonstrates that Cu_5.4O@CNDs exhibit significant potential for the treatment of various acute liver injury conditions, suggesting their promise as an intervention strategy for clinical application.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 12","pages":"5592-5615"},"PeriodicalIF":12.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052522","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":"Apolipoprotein E promotes primary resistance to AR-targeted therapy via inducing TRIM25-mediated AR ubiquitination and sensitizes immunotherapy in prostate cancer.","authors":"Chaofan Liu, Xi Wang, Qinyu Li, Xintao Gao, Kai Zeng, Beining Li, Jianping Miao, Bolong Zheng, Jihong Liu, Zhihua Wang, Xianglin Yuan, Bo Liu","doi":"10.7150/thno.109994","DOIUrl":"10.7150/thno.109994","url":null,"abstract":"<p><p><b>Rationale:</b> Prostate cancer (PCa) growth is facilitated by the androgen receptor (AR) and its downstream signaling pathways, making AR-targeted therapy crucial for treating advanced stages. Despite this, the response to AR-targeted therapies is inconsistent, with a significant proportion of patients even exhibiting unresponsiveness to therapy from the outset, known as primary resistance. Therefore, a refined categorization framework is imperative for the timely detection of resistant phenotypes and the exploration of novel therapeutic avenues. <b>Methods:</b> Tissue microarrays and clinical cohorts were employed to delineate the impact of APOE on the prognostic outcomes and therapeutic resistance in PCa patients. Employing flow cytometry, immunoprecipitation, and mass spectrometry, we dissected the molecular underpinnings of APOE's role in conferring resistance to AR-targeted interventions. Single-cell RNA sequencing elucidated the intricate transcriptomic profiles of PCa with elevated APOE expression. Additionally, the therapeutic potential of anti-PD-L1 agents in treating PCa with APOE induction was rigorously assessed. <b>Results:</b> In this study, we elucidated the pivotal role of APOE in mediating primary resistance to AR-targeted therapy in PCa through the suppression of AR signaling pathways. Mechanistically, APOE was found to enhance the ubiquitination and subsequent degradation of AR by mediating the interaction between the E3-ligase TRIM25 and AR, concurrently dampening the transcriptional activity of AR. Additionally, elevated APOE expression was correlated with an augmented response to anti-PD-L1 treatment, hinting at the therapeutic advantage of immunotherapy in APOE-high PCa contexts. <b>Conclusions:</b> APOE expression could serve as a prognostic biomarker, pivotal for forecasting responses to both AR-targeted therapy and immunotherapy, thereby offering an innovative strategy for the personalized selection of treatment modalities in PCa.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 12","pages":"5572-5591"},"PeriodicalIF":12.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043442","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}