Theranostics最新文献

{"title":"Dual ROS modulation by MnO₂-integrated collagen hydrogel enhances hiPSC-derived endothelial progenitor cell therapy for critical limb ischemia.","authors":"Zhen Zhang, Liang Huang, Gaocheng Gai, Bingbing Xie, Yijing Zhao, Lei Xu, Qiuling Xiang","doi":"10.7150/thno.127711","DOIUrl":"https://doi.org/10.7150/thno.127711","url":null,"abstract":"<p><strong>Rationale: </strong>Cell therapy shows significant potential in treating ischemic diseases, such as critical limb ischemia. Endothelial progenitor cells (EPCs) are considered ideal candidates, but their clinical efficacy is often limited due to the scarcity of suitable sources and poor post-transplant survival. Human-induced pluripotent stem cell-derived EPCs (hiPSC-EPCs) offer a scalable and promising alternative. Additionally, injectable hybrid hydrogels can enhance cell retention and eliminate harmful components in the microenvironment, such as reactive oxygen species (ROS). However, conventional biomaterials are insufficient in mitigating intracellular oxidative stress induced by ischemia.</p><p><strong>Methods: </strong>hiPSC-EPCs were generated by inducing hiPSC with growth factors and small molecules. Manganese dioxide nanoparticles (MnO₂-NPs) were synthesized by dissolving MnO₂ in an aqueous NaOH solution and neutralizing the mixture under sonication. MnO₂-NPs hybrid hydrogel was prepared by exploiting the thermal-triggered sol-gel transition of collagen. The treatment efficacy of hiPSC-EPCs and MnO₂-NPs hybrid hydrogel was assessed in a hindlimb ischemia mouse model. The protective effect of MnO₂-NPs on hiPSC-EPCs under oxidative stress was explored via immunofluorescence staining, transcriptome sequencing, Western blotting, enzyme-linked immunosorbent assay, mitochondrial function assays, and quantitative polymerase chain reaction.</p><p><strong>Results: </strong>In this study, we developed an injectable collagen hydrogel with high clinical translational potential, incorporated with MnO₂-NPs for the delivery of hiPSC-EPCs. Upon injection, the hydrogel undergoes thermal-triggered gelation, ensuring efficient cell retention at the ischemic site. More importantly, MnO₂-NPs provide a dual protective function by scavenging extracellular ROS and mitigating intracellular ROS via upregulation of MnSOD in transplanted hiPSC-EPCs. This comprehensive modulation of ROS significantly improves cell survival and functionality. Consequently, the protected hiPSC-EPCs robustly promote angiogenesis, restoring blood perfusion and improving limb salvage in critical limb ischemia.</p><p><strong>Conclusions: </strong>This MnO₂-based strategy represents a novel dual-action approach for enhancing cell therapy in ischemic diseases.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 11","pages":"6164-6183"},"PeriodicalIF":13.3,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843188","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 radio-theranostics using a [⁸⁹Zr]Zr-/[¹⁷⁷Lu]Lu-labeled B7-H3 antibody-drug conjugate for prostate cancer.","authors":"Yongkang Qiu, Tingfei Gu, Tianyao Wang, Yelin Mulati, Xinyao Sun, Qi Yang, Lele Song, Tingting Yuan, Yu Fan, Lei Kang, Weibo Cai","doi":"10.7150/thno.125878","DOIUrl":"https://doi.org/10.7150/thno.125878","url":null,"abstract":"<p><strong>Rationale: </strong>Prostate cancer remains a leading cause of cancer-related mortality in men. Although PSMA-directed theranostics have achieved clinical success, heterogeneous expression and therapy-induced downregulation limit their broad applicability. B7-H3 (CD276), which is highly and stably expressed in prostate cancer, represents a promising alternative theranostic target.</p><p><strong>Methods: </strong>A B7-H3 targeted antibody-drug conjugate (ADC) was radiolabeled with [⁸⁹Zr]Zr- for immunoPET imaging and [¹⁷⁷Lu]Lu for radionuclide therapy. <i>In vitro</i> binding specificity, <i>in vivo</i> tumor targeting, biodistribution, therapeutic efficacy, dosimetry, and safety were systematically assessed in prostate cancer xenograft models, with comparisons to radiolabeled antibody, ADC monotherapy, sequential therapy, and vehicle controls.</p><p><strong>Results: </strong>Histological analysis in prostate cancer patients suggested B7-H3 was consistently and highly expressed in primary and metastatic lesions and remained stable under therapeutic intervention. [⁸⁹Zr]Zr-B7-H3 ADC immunoPET imaging demonstrated high and specific tumor uptake (33.2 ± 1.0 %ID/g at 144 h) and favorable tumor-to-background ratios. Therapeutic studies revealed that [¹⁷⁷Lu]Lu-B7-H3 ADC achieved marked tumor growth inhibition and survival benefit, with comparable efficacy even if reduced the dose of ADC in the treatment system. Integrated [¹⁷⁷Lu]Lu-ADC therapy outperformed radiolabeled antibody, ADC monotherapy, and sequential treatment strategies. No additional organ toxicity was observed compared with ADC alone, and transient hematological changes following [¹⁷⁷Lu]Lu administration were reversible.</p><p><strong>Conclusions: </strong>The [⁸⁹Zr]Zr-/[¹⁷⁷Lu]Lu-B7-H3 ADC theranostic platform enables accurate imaging, precise tumor targeting, and enhanced antitumor efficacy at reduced ADC doses without increasing systemic toxicity, supporting its translational potential for prostate cancer.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 11","pages":"6132-6144"},"PeriodicalIF":13.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843154","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":"Local and systemic cytokine signatures for outcome prediction after transarterial chemoembolization in hepatocellular carcinoma.","authors":"Emine Y Yilmaz, Robin Schmidt, Luisa Heidemann, Yubei He, Yu Liu, Ornela Sulejmani, Dominik N Müller, Andreas Wilhelm, Timo A Auer, Charlie A Hamm, Salma A S Abosabie, Sara A Abosabie, Bernhard Gebauer, Lynn J Savic","doi":"10.7150/thno.130031","DOIUrl":"https://doi.org/10.7150/thno.130031","url":null,"abstract":"<p><strong>Purpose: </strong>Conventional transarterial chemoembolization (cTACE) is a guideline-approved therapy for unresectable hepatocellular carcinoma (HCC). This study aimed to characterize systemic and local cytokine changes induced by cTACE, and to evaluate their correlation with treatment response, Lipiodol deposition, and overall survival (OS).</p><p><strong>Experimental design: </strong>In this prospective single-center study, 46 patients with unresectable HCC underwent either cTACE followed by interstitial brachytherapy (iBT) after 24h (n = 23) or iBT alone (n = 23). Peripheral blood samples were obtained before treatment in both groups and 24h post-cTACE in the cTACE/iBT group. Additionally, tumor interstitial fluid (TIF) was isolated from tumor biopsies that were collected prior to iBT from untreated tumors (iBT group) or 24h post-cTACE (cTACE/iBT group). Serum and TIF cytokines were quantified using multiplex assays and correlated with radiologic response at 8-week MRI, Lipiodol patterns on CT 24h post-cTACE, and OS.</p><p><strong>Results: </strong>Post-cTACE, serum IFN-γ, MCP-1, TNF-α, MIP-1α, IL-17, IL-8, IL-4, and IL-5 significantly decreased, while IL-6 increased (p < 0.005). TIF analysis showed higher IL-17 in untreated tumors compared to post-cTACE (p = 0.038), but differences were modest. In the iBT group, responders had elevated TIF IL-8 (p = 0.0103) and VEGF-A (p = 0.0185) prior to treatment, whereas in the cTACE/iBT group, responders exhibited lower TIF bFGF post-cTACE than non-responders (p = 0.0449). Elevated baseline serum IL-6 (p = 0.052), IL-8 (p = 0.036), and IFN-γ (p = 0.0508) were associated with shorter OS, while higher TIF IFN-γ (p = 0.051) correlated with improved OS. Baseline serum IL-1β (p = 0.0266) and post-cTACE serum level of VEGF-A (p = 0.0318) were higher in patients with homogeneous Lipiodol deposition in tumors, which correlated with longer OS.</p><p><strong>Conclusions: </strong>cTACE induces distinct systemic and local immune alterations that influence patient outcomes. Specifically, elevated serum IL-6 predicted poor survival, while homogeneous Lipiodol deposition marks favorable immune modulation and outcomes. Combining cytokine profiling with imaging biomarkers may enable improved, personalized treatment strategies in HCC.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 11","pages":"6099-6112"},"PeriodicalIF":13.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843186","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":"Simultaneous inhibition of ID1 and ID3 mitigates fibroblast activation via cell cycle and MEK/ERK pathways in pulmonary fibrosis.","authors":"Samar A Antar, Eric Mensah, Jacob Dahlka, Mark C Renton, Ahmed A Raslan, Michael Aziz, Aymen Halouani, Seun Imani, Aanandi Parashar, Scott R Johnstone, Robert Benezra, Diego Fraidenraich, Giovanni Ligresti, Yassine Sassi","doi":"10.7150/thno.127118","DOIUrl":"https://doi.org/10.7150/thno.127118","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease for which novel therapeutic approaches are urgently needed. Transforming Growth Factor-β (TGF-β) plays a central role in IPF pathogenesis by activating lung fibroblasts. Inhibitor of DNA binding (ID) proteins are regulated by TGF-β; however, their role in IPF remains poorly understood. We aimed to evaluate the regulation of ID proteins in IPF and to determine their functional role in human lung fibroblasts (HLF) <i>in vitro</i> and pulmonary fibrosis <i>in vivo</i>.</p><p><strong>Methods: </strong>ID protein expression was assessed in lungs and lung fibroblasts from mice and patients with pulmonary fibrosis. <i>In vitro</i>, the effects of ID1/ID3 inhibition and overexpression on HLF proliferation, migration and differentiation into myofibroblasts were evaluated. Genetic and pharmacological approaches were used <i>in vivo</i> to determine the role of ID1/ID3 in pulmonary fibrosis.</p><p><strong>Results: </strong>ID1/ID3 levels were elevated in lungs and lung fibroblasts from mice and patients with pulmonary fibrosis, as well as in HLFs treated with TGF-β. ID1/ID3 knockdown reduced proliferation, migration and differentiation of healthy and IPF-derived HLFs. Bleomycin-exposed ID1/ID3 double KO mice exhibited improved lung function and reduced fibrosis compared with WT mice. Pharmacological inhibition of ID1/ID3 decreased HLF proliferation, migration and differentiation <i>in vitro</i> and attenuated pulmonary fibrosis <i>in vivo</i>. Lung-specific inhibition of ID1/ID3 using adeno-associated viruses expressing short hairpins targeting ID1 and ID3 also reversed pulmonary fibrosis in mice. Mechanistically, ID1/ID3 inhibition reduced fibroblast proliferation through regulation of cell cycle genes and attenuated fibroblast differentiation via the MEK/ERK pathway.</p><p><strong>Conclusions: </strong>Simultaneous inhibition of ID1 and ID3 attenuates pulmonary fibrosis. Targeting ID1/ID3 represents a potential novel therapeutic strategy for IPF.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 11","pages":"6081-6098"},"PeriodicalIF":13.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843081","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 MAM-targeting therapeutic peptide restores autophagy homeostasis and ameliorates atherosclerosis.","authors":"Jungmin Ha, Minjeong Ko, Yong-Beom Lim, Ho Jeong Kwon","doi":"10.7150/thno.132357","DOIUrl":"https://doi.org/10.7150/thno.132357","url":null,"abstract":"<p><strong>Rationale: </strong>Mitochondria-associated ER membranes (MAMs) are critical hubs for Ca²⁺ signaling, energy homeostasis, and autophagy. Their dysregulation contributes to lipid-driven cardiovascular diseases; however, selective and reversible strategies to modulate MAM-associated protein-protein interactions (PPIs) remain limited. This study aimed to develop a targeted peptide to disrupt the IP₃R-GRP75-VDAC1 complex and evaluate its therapeutic efficacy in atherosclerosis.</p><p><strong>Methods: </strong>Based on structural and interface analyses of the IP₃R-GRP75 complex, we designed cell-permeable MAM-targeting peptides. The activity of the lead candidate, Peptide 4, was assessed using proximity ligation assays, microscale thermophoresis (MST) analysis, cellular thermal shift assays, co-immunoprecipitation, live-cell Ca²⁺ imaging, and autophagy flux analyses in endothelial cells and macrophages under basal and oxidized low-density lipoprotein (oxLDL)-induced stress. The therapeutic efficacy was further evaluated in Western diet-fed ApoE^-/- mice.</p><p><strong>Results: </strong>Peptide 4 bound to GRP75, disrupted the IP₃R-GRP75 interaction, and selectively attenuated ER-to-mitochondria Ca²⁺ transfer. This controlled Ca²⁺ modulation modestly reduced cellular ATP levels, activated the AMPK-TFEB axis, and restored functional autophagic flux. These effects were preserved under oxLDL-induced lipid stress. Restoration of MAM architecture closely correlated with autophagy recovery and lipid clearance, indicating its potential utility as a pharmacodynamic indicator. <i>In vivo</i>, systemic administration of Peptide 4 significantly improved serum lipid profiles, attenuated aortic plaque formation, reduced cardiac lipid deposition, and normalized MAM architecture in ApoE^-/- mice.</p><p><strong>Conclusions: </strong>Our findings identify peptide-mediated targeting of the IP₃R-GRP75 interaction as a promising strategy to modulate MAM structure, activate adaptive autophagy, and alleviate atherosclerotic pathology. This study supports organelle contact site modulation as both a therapeutic mechanism and a measurable disease-responsive feature, highlighting peptide-based modulation of protein-protein interactions as a promising approach for metabolic and cardiovascular diseases.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 11","pages":"6113-6131"},"PeriodicalIF":13.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843203","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":"Bioinspired Nanoplatform Potentiates Sonodynamic Immunotherapy by Remodeling the Antioxidant Tumor Microenvironment and Activating STING pathway.","authors":"Yuanyuan Zhang, Wenxiang Zhu, Kaimin Li, Yun Xie, Zhichao Deng, Yuanyuan Zhu, Bowen Gao, Chenxi Xu, Junlong Fu, Mingzhen Zhang, Xiaoliang Zheng, Haifeng Zhang","doi":"10.7150/thno.129765","DOIUrl":"https://doi.org/10.7150/thno.129765","url":null,"abstract":"<p><strong>Background: </strong>Sonodynamic therapy (SDT) has emerged as a promising modality for treating deep-seated tumors. It has been demonstrated that SDT effectively induces immunogenic cell death (ICD), thereby initiating a systemic anti-tumor immune response - a process known as sonodynamic immunotherapy. However, its efficacy is severely limited by the hypoxic tumor microenvironment (TME) and elevated glutathione (GSH) levels, which together scavenge reactive oxygen species (ROS) and create a potent antioxidant barrier.</p><p><strong>Methods: </strong>Ultra-small Mn₃O₄ nanoparticles with multi-enzyme mimicking activity were synthesized, and co-encapsulated with the sound sensitizer Ag₂S quantum dot (Ag₂S QD) in cell membrane hybrid liposomes to construct a biomimetic nanoplatform (Mn₃O₄/QD@LM). The Catalase and glutathione peroxidase activities of Mn₃O₄/QD@LM were evaluated. Its antitumor efficacy <i>in vitro</i> was evaluated by measuring ROS levels, mitochondrial membrane potential staining, live/dead cell staining, and apoptosis analysis. By recording tumor growth and performing histological and immunohistochemical examinations, its antitumor effects <i>in vivo</i> were investigated in a mouse model of colon cancer. Flow cytometry analysis was used to analyze the tumor immune microenvironment.</p><p><strong>Results: </strong>Mn₃O₄/QD@LM functioned as a \"ROS amplifier\" by exhibiting catalase-like and glutathione peroxidase-like activities, which alleviated tumor hypoxia and depleted GSH, thereby markedly enhancing SDT efficacy. Moreover, released Mn²⁺ ions generated highly cytotoxic hydroxyl radicals via a Fenton-like reaction, further augmenting tumor cell killing. <i>In vitro</i> experiments confirmed that Mn₃O₄/QD@LM effectively induced ICD and activated the STING pathway. Benefiting from homologous targeting, the nanoplatform achieved efficient accumulation in tumor tissue <i>in vivo</i>. Upon ultrasound activation, Mn₃O₄/QD@LM significantly inhibited tumor growth both <i>in vitro</i> and <i>in vivo</i>. Notably, it remodeled the tumor immune microenvironment by promoting CD8⁺ T cell infiltration, enhancing the secretion of IFN-γ and TNF-α, and reducing the populations of regulatory T cells and myeloid-derived suppressor cells.</p><p><strong>Conclusions: </strong>Mn₃O₄/QD@LM confirms the synergistic role of multi-enzyme activities and STING pathway activation in potentiating sonodynamic immunotherapy, and provides an innovative strategy to overcome TME-mediated therapy resistance.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 11","pages":"6145-6163"},"PeriodicalIF":13.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843228","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":"Future opportunities and nuances with the use of PSMA PET in prostate cancer (MD PET 1).","authors":"Alicia K Morgans, Christopher M Pieczonka, Evan Y W Yu, Himanshu Nagar, Leonard G Gomella, Medhat M Osman, Phillip J Koo, Steven E Finkelstein","doi":"10.7150/thno.132930","DOIUrl":"https://doi.org/10.7150/thno.132930","url":null,"abstract":"<p><p>Imaging with prostate-specific membrane antigen (PSMA) PET has significantly improved prostate cancer staging with superior diagnostic performance compared to conventional methods. Although it is increasingly adopted in clinical practice, several barriers hinder its full integration into routine workflows. This review highlights the existing knowledge gaps, infrastructure limitations, and inconsistencies in interpretation that affect the utility of PSMA PET across healthcare settings. We examine the potential reasons behind variability in scan performance, including scanner design, detector technology, sensitivity, and resolution, as well as the accreditation status of the facilities and reader expertise. We also highlight the inconsistent understanding of PSMA PET ordering practices, particularly among urologists, and the influence of ownership-driven utilization, both of which contribute to underuse and overuse. Radiology reporting that lacks sufficient detail and a shortage of trained nuclear medicine specialists may present additional challenges to effective treatment planning, although diagnostic radiologists also contribute to PET scan interpretation. This review highlights the potential role of standardized reporting protocols, accreditation, expanded education, and integration of AI tools in enhancing diagnostic accuracy and consistency. Additionally, we examine the impact of PSMA PET on clinical decision-making in unfavorable intermediate-, high risk-, and biochemically recurrent prostate cancer, as well as the emerging role of PSMA PET-derived metrics in staging, biopsy guidance, and treatment planning. While PSMA PET has shown value in modifying management strategies, its clinical benefit requires validation through future, prospective, outcome-driven studies. In addition, emerging applications of PSMA PET in non-prostate malignancies hold the potential to transform diagnostic and therapeutic approaches beyond prostate cancer.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 11","pages":"5816-5829"},"PeriodicalIF":13.3,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843183","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":"Multi-functional Small Molecule for Regenerative Healing of Avascular Meniscus Tears: Modulation of Inflammation, Differentiation, and Multi-Tissue Crosstalk.","authors":"Meng Feng, David D Pellei, Ming Wang, Angelyn Nguyen, Sarah Ginsberg, Hun Jin Jeong, Chang H Lee","doi":"10.7150/thno.132326","DOIUrl":"https://doi.org/10.7150/thno.132326","url":null,"abstract":"<p><p>Avascular meniscus tears are a major contributor to mechanical joint locking, compromised gait and function, and the initiation and progression of post-traumatic osteoarthritis. Unfortunately, the avascular meniscus tears hardly heal. Here, we report a novel small molecule, 4-PPBP, a sigma-1 receptor (σ1R) agonist, exhibiting significant potential to promote avascular meniscus healing by activating synovial mesenchymal stem cells (syMSCs) and modulating macrophage-regulated inflammation via multi-tissue crosstalk. <i>In vitro,</i> 4-PPBP promoted the proliferation and migration of meniscus cells and syMSCs, exhibited anti-inflammatory effects, and induced fibrochondrogenic differentiation. 4-PPBP significantly promoted the healing of avascular meniscus tears <i>ex vivo</i>. <i>In vivo</i>, a single injection of 4-PPBP-loaded bioglue minimized meniscal gapping, with improved meniscus healing and gait performance. In contrast to the degenerative changes in the untreated control, 4-PPBP/bioglue application resulted in integrated fibrocartilaginous tissues. scRNA-seq and CellChat analyses revealed 4-PPBP-activated cell-cell communications leading to inflammatory regulation and cell differentiation. Macrophages showed a robust reduction in pro-inflammatory genes, and fibroblasts, chondrocytes, and fibrochondrocytes increased genes associated with differentiation and matrix synthesis in response to 4-PPBP. Anti-inflammatory cell-cell communication signals were significantly elevated between adipocytes and macrophages. Together, this study demonstrates the notable potential of 4-PPBP as a multi-functional therapeutic for avascular meniscus tears.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 11","pages":"5911-5925"},"PeriodicalIF":13.3,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842650","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":"Enzyme-responsive hydrogel coating for <i>in situ</i> re-endothelialization of bioprosthetic heart valves.","authors":"Xuyue Liang, Qi Tong, Zhongwu Bei, Tianying Luo, Lin Ye, Meng Pan, Yun Yang, Bingyang Chu, Yongjun Qian, Zhiyong Qian","doi":"10.7150/thno.131155","DOIUrl":"https://doi.org/10.7150/thno.131155","url":null,"abstract":"<p><strong>Background: </strong>Bioprosthetic heart valves (BHVs) replacement serves as a critical treatment for severe valvular heart disease. However, it often faces irreversible damage caused by thrombosis, inflammation, and calcification, severely limiting its therapeutic value for younger patients.</p><p><strong>Methods: </strong>Herein, we construct a biomimetic hydrogel coating loaded with cerium dioxide nanoparticles and vascular endothelial growth factor on the surface of BHVs material. This design aims to suppress material-induced thrombosis and inflammation, modulate the local microenvironment, achieve <i>in situ</i> re-endothelialization, and enhance the therapeutic potential of BHVs.</p><p><strong>Results: </strong>The findings demonstrate that the hydrogel coating improved the antithrombotic and anti-inflammatory properties of the BHVs material. Furthermore, i<i>n vivo</i> implantation in a rat abdominal aorta model exhibited effective <i>in situ</i> re-endothelialization.</p><p><strong>Conclusion: </strong>The hydrogel coating system developed in this study promoted <i>in situ</i> re-endothelialization of BHVs material and holds promise for extending its service lifespan. This work provides a strategy for enhancing the therapeutic potential of BHVs for younger patients.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 11","pages":"6032-6050"},"PeriodicalIF":13.3,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843197","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":"EGFR-19del nuclear translocation increases HDAC7 expression inhibiting the Hippo pathway and exacerbating TKI resistance in lung adenocarcinoma.","authors":"Yuheng Feng, Minghao Wang, Yang Liu, Xinhao Wu, Xuyong Lin, Qiang Han, Xuezhu Rong","doi":"10.7150/thno.128873","DOIUrl":"https://doi.org/10.7150/thno.128873","url":null,"abstract":"<p><strong>Rationale: </strong>Epidermal growth factor receptor (EGFR) \"membrane-cytoplasmic-nuclear translocation\" occurs in EGFR-19del lung adenocarcinoma (LUAD) following resistance to tyrosine kinase inhibitors (TKIs). This study aimed to elucidate the mechanism of TKI resistance conferred by nuclear EGFR-19del.</p><p><strong>Methods: </strong>RNA sequencing and immunohistochemistry were performed to assess histone deacetylase 7 (HDAC7) expression in LUAD with TKI resistance. Functional assays were performed both <i>in vitro</i> and <i>in vivo</i> to assess the effects of changes in HDAC7 expression on the malignant phenotype of LUAD cells and drug sensitivity to TKIs. Mass spectrometry and dual-luciferase assays were performed to verify the effect of changes in HDAC7 expression on the Hippo pathway. Chromatin immunoprecipitation and coimmunoprecipitation assays were conducted to clarify the potential role of EGFR-19del in the cell nucleus.</p><p><strong>Results: </strong>EGFR-19del nuclear translocation correlated with elevated HDAC7 expression in TKI-resistant cells. HDAC7 overexpression promoted malignancy and reduced TKI sensitivity, whereas HDAC7 knockdown or TSA treatment suppressed tumour growth and enhanced TKI sensitivity <i>in vivo</i>. Mechanistically, HDAC7 interacts with large tumour suppressor kinase 1 (LATS1) and promotes its deacetylation at K688, which reduced T1079 phosphorylation, thereby inhibiting the Hippo pathway. Concurrently, nuclear EGFR-19del acts as a coactivator to accelerate HDAC7 transcription through signal transducer and activator of transcription 3 (STAT3).</p><p><strong>Conclusions: </strong>We elucidated the underlying mechanism by which nuclear EGFR-19del inhibits the Hippo pathway; these results indicate that TKIs and HDAC inhibitors may serve as a potential therapeutic strategy to reduce drug resistance in LUAD with EGFR-19del.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 11","pages":"5992-6010"},"PeriodicalIF":13.3,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843200","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}