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Imaging Brown Adipose Tissue: Current State and Future Perspective. 褐色脂肪组织成像:现状与未来展望。
IF 13.3 1区 医学
Theranostics Pub Date : 2025-08-16 eCollection Date: 2025-01-01 DOI: 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}
引用次数: 0
Nanotuner targeting mitochondrial redox and iron homeostasis imbalance for the treatment of acute liver injury. 靶向线粒体氧化还原和铁稳态失衡的纳米调谐器治疗急性肝损伤。
IF 13.3 1区 医学
Theranostics Pub Date : 2025-08-16 eCollection Date: 2025-01-01 DOI: 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}
引用次数: 0
RBMS1-mediates the biogenesis of circNFIB promotes perineural invasion of pancreatic ductal adenocarcinoma via the L1CAM/MAPK pathway. rbms1介导circNFIB的生物发生,通过L1CAM/MAPK通路促进胰腺导管腺癌的神经周围侵袭。
IF 13.3 1区 医学
Theranostics Pub Date : 2025-08-16 eCollection Date: 2025-01-01 DOI: 10.7150/thno.112753
Zhuo Wu, Zhou Fang, Liangtang Zeng, Dingwen Zhang, Yu Zhou, Rufu Chen
{"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}
引用次数: 0
Pilot experience of [161Tb]Tb-PSMA-617 RLT in mCRPC patients after conventional PSMA RLT within a prospective registry. [161Tb]Tb-PSMA-617 RLT在mCRPC患者常规PSMA RLT后的前瞻性注册试验经验
IF 13.3 1区 医学
Theranostics Pub Date : 2025-08-16 eCollection Date: 2025-01-01 DOI: 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}
引用次数: 0
Extracellular vehicles-mediated Twsit1 transferred from tumor cells to brain induces depressive-like behaviors via neuronal morphogenesis. 细胞外载体介导的Twsit1从肿瘤细胞转移到大脑通过神经元形态发生诱导抑郁样行为。
IF 13.3 1区 医学
Theranostics Pub Date : 2025-08-16 eCollection Date: 2025-01-01 DOI: 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}
引用次数: 0
Aptamer-based drug delivery for targeted therapy of imatinib-resistant gastrointestinal stromal tumor. 基于适配体的靶向治疗伊马替尼耐药胃肠道间质瘤。
IF 13.3 1区 医学
Theranostics Pub Date : 2025-08-11 eCollection Date: 2025-01-01 DOI: 10.7150/thno.115496
Tao Pan, Ming Wang, Linxi Yang, Yihan Zheng, Yuanding Liu, Yu Xiao, Xudong Qiu, Yanying Shen, Mahan Dawuren, Zhiqiang Ren, Keying Liu, Yang Sun, Lin Tu, Hui Cao, Weihong Tan
{"title":"Aptamer-based drug delivery for targeted therapy of imatinib-resistant gastrointestinal stromal tumor.","authors":"Tao Pan, Ming Wang, Linxi Yang, Yihan Zheng, Yuanding Liu, Yu Xiao, Xudong Qiu, Yanying Shen, Mahan Dawuren, Zhiqiang Ren, Keying Liu, Yang Sun, Lin Tu, Hui Cao, Weihong Tan","doi":"10.7150/thno.115496","DOIUrl":"10.7150/thno.115496","url":null,"abstract":"<p><p><b>Rationale:</b> Gastrointestinal stromal tumors (GIST), the most common mesenchymal tumors of the gastrointestinal tract, are primarily driven by activating mutations in the KIT intracellular segment. The standard treatment with imatinib frequently results in acquired resistance due to secondary mutations. Besides mutations, KIT is also overexpressed in GIST. An aptamer that specifically binds to the extracellular segment of KIT (unaffected by these mutations) was promising in drug delivery and may overcome imatinib resistance. <b>Methods:</b> The microtubule inhibitor VcMMAE (mc-vc-PAB-MMAE) was conjugated with an optimized KIT-targeting aptamer (KIT-d) to generate an aptamer-drug conjugate (ApDC) named KIT-d-MMAE. This ApDC was then evaluated for its binding specificity, internalization via endocytosis, and cytotoxicity towards KIT-positive GIST cells. The therapeutic efficacy of KIT-d-MMAE was evaluated through both <i>in vitro</i> and <i>in vivo</i> experiments. <b>Results:</b> KIT-d-MMAE exhibited specific binding and efficient internalization into KIT-positive GIST cells, including imatinib-resistant lines, inducing targeted cytotoxic effects. In animal studies, KIT-d-MMAE significantly suppressed tumor growth in GIST-T1 subcutaneous and liver metastasis models. Notably, in imatinib-resistant GIST-430/654 and multi-TKI-resistant patient-derived xenograft (PDX) models, KIT-d-MMAE demonstrated superior antitumor efficacy compared to imatinib. Additionally, therapeutic effects were also observed in genetically engineered mouse models, indicating effective inhibition of spontaneous tumor formation and progression. <b>Conclusion:</b> The aptamer-based drug delivery not only provides an innovative approach to overcome drug resistance but also simplifies treatment regimens, offering new therapeutic hope and marking a significant advancement in targeted therapy for GIST patients.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8738-8756"},"PeriodicalIF":13.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081605","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}
引用次数: 0
Self-Assembling Hydrogels of Naproxen-Conjugated Peptides for Osteoarthritis Treatment. 萘普生共轭肽自组装水凝胶治疗骨关节炎。
IF 13.3 1区 医学
Theranostics Pub Date : 2025-08-11 eCollection Date: 2025-01-01 DOI: 10.7150/thno.114781
Lulu Yang, Liang Shao, Puhua Hao, Jiaqi Song, Caiting Meng, Bin Zhu, Hongwen Yu, Wanglin Duan, Xiaohua Fang, Guanying Li, Shichang Liu
{"title":"Self-Assembling Hydrogels of Naproxen-Conjugated Peptides for Osteoarthritis Treatment.","authors":"Lulu Yang, Liang Shao, Puhua Hao, Jiaqi Song, Caiting Meng, Bin Zhu, Hongwen Yu, Wanglin Duan, Xiaohua Fang, Guanying Li, Shichang Liu","doi":"10.7150/thno.114781","DOIUrl":"10.7150/thno.114781","url":null,"abstract":"<p><p><b>Rationale</b>: Osteoarthritis (OA), a highly prevalent chronic degenerative joint disease, lacks truly effective therapies. Current approaches are limited by systemic toxicity, short drug half-lives, and insufficient efficacy. To address this, we developed an innovative therapeutic approach integrating the pharmacological benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) with the mechanical support and localized delivery advantages of hydrogels. <b>Methods</b>: Various naproxen-peptide conjugates are designed and synthesized. These candidates were screened based on self-assembly behavior, biocompatibility and cyclooxygenase-2 (COX-2) inhibition. NpxFFK underwent further studies including assessment of anti-inflammatory activities and mechanism of action <i>in vitro</i>. <i>In vivo</i> therapeutic efficacy was evaluated in OA rat model using footprinting assay, micro-CT imaging, MRI imaging, histological staining, and immunohistochemistry. The therapeutic mechanism is explored via RNA sequencing. <b>Results</b>: Among naproxen-peptide conjugates NpxFFX (X = R, H, K, E) tested, NpxFFK demonstrated superior anti-inflammatory efficacy. It self-assembled into a stable hydrogel, exhibiting enhanced retention within the joint cavity and providing sustained anti-inflammatory action. <i>In vitro</i> studies revealed that NpxFFK effectively inhibited COX-2 activity, consequently suppressing key inflammatory factors (IL-1β, IL-6, IL-1, and TNF-α). Furthermore, it reprogramed macrophage polarization from M1 toward M2 and promoted chondrocyte proliferation. <i>In vivo</i> experiments demonstrate the NpxFFK hydrogel significantly mitigated articular degradation in OA rats, outperforming clinical treatments (naproxen treatment or hyaluronic acid treatment), thereby validating its therapeutic potential for OA. <b>Conclusions</b>: By integrating NSAID pharmacology with self-assembling peptide hydrogel delivery platform, we present a multifunctional strategy that significantly improves upon current OA treatments, underscoring its promise for translational healthcare innovation in OA management.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8779-8794"},"PeriodicalIF":13.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081688","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}
引用次数: 0
RIPK3 promotes ASIC1a-mediated fibroblast-like synoviocyte migration and invasion via malate shuttle-driven mitochondrial respiration in rheumatoid arthritis. 在类风湿关节炎中,RIPK3通过苹果酸梭驱动的线粒体呼吸促进asic1a介导的成纤维细胞样滑膜细胞的迁移和侵袭。
IF 13.3 1区 医学
Theranostics Pub Date : 2025-08-11 eCollection Date: 2025-01-01 DOI: 10.7150/thno.113974
Weirong Hu, Ke Wang, Yalu Dong, Yucai Xu, Jing Xing, Jianzhong Zhu, Jie Ding, Yingjie Zhao, Yayun Xu, Yuanzhi Cheng, Xiaoqing Peng, Renpeng Zhou, Wei Hu, Feihu Chen
{"title":"RIPK3 promotes ASIC1a-mediated fibroblast-like synoviocyte migration and invasion via malate shuttle-driven mitochondrial respiration in rheumatoid arthritis.","authors":"Weirong Hu, Ke Wang, Yalu Dong, Yucai Xu, Jing Xing, Jianzhong Zhu, Jie Ding, Yingjie Zhao, Yayun Xu, Yuanzhi Cheng, Xiaoqing Peng, Renpeng Zhou, Wei Hu, Feihu Chen","doi":"10.7150/thno.113974","DOIUrl":"10.7150/thno.113974","url":null,"abstract":"<p><p><b>Objective:</b> Synovial fibroblast migration and invasion are critical contributors to the progression of rheumatoid arthritis (RA). Acidification of local joint tissue exacerbates RA progression, but the underlying mechanisms remain unclear. This study aimed to investigate the role of acid-sensitive ion channel ASIC1a and its mediator, the RIPK3-MDH1 axis, in regulating the migration and invasion of RA fibroblast-like synoviocytes (RA-FLSs). <b>Methods:</b> The expression of ASIC1a, RIPK3, and MDH1 in synovial tissue from RA patients and arthritic mice was analyzed using immunofluorescence and Western blotting. RA-FLSs were stimulated with extracellular acidification (pH 6.8, mimicking local tissue conditions), and their migration and invasion were assessed via Transwell assays. The interaction between ASIC1a and RIPK3 was predicted using molecular docking and confirmed by co-immunoprecipitation (CO-IP). RIPK3<sup>-/-</sup> mice were used to establish a collagen antibody-induced arthritis (CAIA) model. Pharmacological inhibitors of ASIC1a (PcTX1) and RIPK3 (GSK-872) were employed to evaluate their therapeutic effects on migration and invasion in vitro and arthritis progression in vivo using the collagen-induced arthritis (CIA) model. Bioinformatics analyses, along with glucose, ATP, NAD<sup>+</sup> and NADH assays, and oxygen consumption rate (OCR) measurements, were conducted to investigate the regulation of mitochondrial respiration by the RIPK3-MDH1 axis. <b>Results:</b> Extracellular acidification (pH 6.8) significantly enhanced the migration and invasion of RA-FLSs, effects that were abrogated by ASIC1a knockdown or pharmacological inhibition. ASIC1a activated RIPK3 through its kinase function, independent of its ion channel activity. RIPK3 activation promoted mitochondrial respiration and ATP production via MDH1-mediated malate shuttle activation. Furthermore, inhibition of the malate shuttle using Aminooxyacetic acid (Carboxymethoxylamine) hemihydrochloride (AOA) suppressed ASIC1a-mediated RA-FLSs migration and invasion. The RIPK3-MDH1 axis also maintained malate shuttle activity by enhancing glycolysis and glutamate metabolism through GLS1. Mechanistically, ASIC1a activated RIPK3, which in turn promoted MDH1-mediated malate shuttle activation, enhancing mitochondrial respiration and ATP synthesis, thereby driving RA-FLSs migration and invasion. In vivo, pharmacological inhibition of ASIC1a or RIPK3, as well as RIPK3 knockdown, significantly alleviated arthritis progression in CIA and CAIA mouse models. <b>Conclusion:</b> The RIPK3-MDH1 malate shuttle drives RA-FLSs migration and invasion in RA. Activation of the ASIC1a-RIPK3-MDH1 axis enhances mitochondrial respiration and ATP synthesis in RA-FLSs, highlighting this pathway as a potential therapeutic target for RA.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8719-8737"},"PeriodicalIF":13.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081699","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}
引用次数: 0
Autophagy-driven lipid regulation by an herbal decoction alleviates cardiac lipotoxicity in severe acute pancreatitis. 中药自噬驱动的脂质调节可减轻重症急性胰腺炎的心脏脂肪毒性。
IF 13.3 1区 医学
Theranostics Pub Date : 2025-08-11 eCollection Date: 2025-01-01 DOI: 10.7150/thno.117243
Yue Yang, Qian Hu, Hongxin Kang, Long Xie, Yue Hu, Juan Li, Xianlin Zhao, Lv Zhu, Wenfu Tang, Jingping Liu, Christopher J Lyon, Meihua Wan
{"title":"Autophagy-driven lipid regulation by an herbal decoction alleviates cardiac lipotoxicity in severe acute pancreatitis.","authors":"Yue Yang, Qian Hu, Hongxin Kang, Long Xie, Yue Hu, Juan Li, Xianlin Zhao, Lv Zhu, Wenfu Tang, Jingping Liu, Christopher J Lyon, Meihua Wan","doi":"10.7150/thno.117243","DOIUrl":"10.7150/thno.117243","url":null,"abstract":"<p><p><b>Rationale:</b> Myocardial injury is a common and life-threatening complication of severe acute pancreatitis (SAP) and is driven primarily by metabolic disturbances. This study aimed to elucidate the pathogenesis of SAP-induced cardiac injury (SACI) and to identify effective therapeutic strategies. <b>Methods:</b> Untargeted metabolomics and proteomics analyses were employed to identify metabolic pathways and proteins associated with myocardial injury in SACI mouse model. Histological and Western blot assays were used to assess lipid droplet (LD) accumulation, the expression of autophagy markers, and LD-autophagosome colocalization. The traditional Chinese medicine formula Taohong Siwu Decoction (THSWD) was tested for its therapeutic potential in a SACI mouse model and a SACI cardiomyocyte model established by incubating primary mouse cardiomyocytes with serum from the SACI mouse model. These SACI cardiomyocytes cultures were then treated with serum from control or THSWD-treated mice, with or without autophagy inhibitors, and analyzed for effects on lipophagy, mitochondrial structure and function, long-chain fatty acid metabolism, and oxidative stress. <b>Results:</b> SAP-induced myocardial injury was characterized by disrupted lipid metabolism, leading to abnormal cardiomyocyte LD accumulation and structural and functional deficiencies in their mitochondria. THSWD treatment reduced LD accumulation, restored LD-autophagosome colocalization, and increased mitochondrial structural integrity, membrane potential, and fatty acid β-oxidation. However, these THSWD effects were abolished in the presence of an autophagy inhibitor, implying they occur via a lipophagy-dependent mechanism. <b>Conclusion:</b> Excessive LD accumulation drives mitochondrial dysfunction, contributing to SAP-induced myocardial lipotoxicity. THSWD promotes lipophagy to mitigate lipid accumulation and restore mitochondrial function, and may serve as an effective therapeutic strategy for SAP-induced cardiac metabolic disorders and mitochondrial dysfunction.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8822-8839"},"PeriodicalIF":13.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081642","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}
引用次数: 0
Modulation of Stem Cell Survival and Engraftment: Implications for Stem Cell-Based Therapy. 干细胞存活和植入的调节:对干细胞治疗的启示。
IF 13.3 1区 医学
Theranostics Pub Date : 2025-08-11 eCollection Date: 2025-01-01 DOI: 10.7150/thno.120805
Qingwen Xu, Chaochao Zhang, Xinyu Liu, Yuyao Sun, Bowei Li, Sihui Nian, Yan Wang, Chenggong Yu
{"title":"Modulation of Stem Cell Survival and Engraftment: Implications for Stem Cell-Based Therapy.","authors":"Qingwen Xu, Chaochao Zhang, Xinyu Liu, Yuyao Sun, Bowei Li, Sihui Nian, Yan Wang, Chenggong Yu","doi":"10.7150/thno.120805","DOIUrl":"10.7150/thno.120805","url":null,"abstract":"<p><p>Stem cell transplantation holds promise for the treatment of degenerative diseases, tissue injuries, and malignancies. Despite this potential, clinical outcomes have often fallen short, largely due to limited survival and engraftment of transplanted cells at target sites. Recent research efforts have focused on optimizing cell-based therapies through improved understanding of stem cell biology and responsiveness to environmental cues. Emerging evidence indicates that the hostile post-transplantation microenvironment contributes to irreversible cellular damage and death, driven by metabolic dysfunction, immune-mediated responses, reactive oxygen species (ROS), altered biomechanical rigidity, and disrupted intercellular communication. To address these challenges, various strategies have been explored, including supplementation with exogenous metabolic substrates, enhancement of vascular remodeling, administration of antioxidants, and the application of three-dimensional (3D) stem cell spheroids. This review synthesizes current approaches aimed at improving cell viability and therapeutic efficacy in regenerative medicine.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8840-8856"},"PeriodicalIF":13.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081652","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}
引用次数: 0
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