tbuckley/cabot-search huggingface dataset:
Free glutaraldehyde gelatin microsphere loaded mesenchymal stem cells alleviate osteoarthritis by promoting <i>Ext1</i> expression
Authors: Ye Yuan, Longsheng Xu, Yu Zhao, Tizhen Yan, Baobiao Zhuo, Fan Bu, Qian Cai, Youjia Xu, Qing Bi, Yu Tong, Dan Xing, Di Sun, Jianhao Lin
Journal: Theranostics (2025)

Rationale: Osteoarthritis (OA) is a chronic joint disorder with limited treatment efficacy, necessitating innovative therapeutic strategies. This study explores one-pot-synthesized gelatin microspheres devoid of glutaraldehyde as a novel biomaterial for OA management. Focusing on the Ext1 gene, critical for cartilage development and downregulated in OA, we investigated its restoration and immune regulation using gelatin microspheres cultured with mesenchymal stem cells (MSCs). Methods: OA patients undergoing knee replacement surgery have their lateral compartment (remote zone) and medial compartment (lesion zone) cartilage collected for transcriptomic testing. The differential gene Ext1 is identified, and the expression of immune regulatory genes is examined. MSCs were cultured with gelatin microspheres to evaluate their compatibility and ability to promote cell attachment. The effects of the gelatin microspheres on Ext1 gene overexpression, immune regulation, and OA symptom mitigation were investigated through in vitro and in vivo experiments. Results: OA patients exhibit decreased expression of the Ext1 gene in the medial compartment (lesion zone) cartilage area, accompanied by abnormal expression of immune regulatory genes. The study demonstrated that the gelatin microspheres exhibited excellent compatibility with MSCs and facilitated their attachment. Culturing MSCs with the microspheres led to enhanced overexpression of the Ext1 gene, which is crucial for cartilage growth and development. Additionally, the microspheres regulated immune responses, contributing to a reduction in OA symptoms. Conclusion: This study introduces an innovative therapeutic strategy for osteoarthritis using gelatin microspheres cultured with MSCs. By promoting Ext1 gene overexpression and regulating immune responses, these microspheres effectively mitigate OA symptoms. The findings highlight the potential of this biomaterial as a promising treatment option for OA.
<i>In vivo</i> molecular imaging of breast cancer metabolic heterogeneity using [1-<sup>13</sup>C]pyruvate-d<sub>3</sub> hyperpolarized by reversible exchange with parahydrogen
Authors: Stefan Petersen, Luca Nagel, Philipp R Groß, Henri de Maissin, Robert Willing, Lisa Heß, Julia Mitschke, Nicole Klemm, Judith Treiber, Christoph A Müller, Stephan Knecht, Ilai Schwartz, Moritz Weigt, Michael Bock, Dominik von Elverfeldt, Maxim Zaitsev, Eduard Y Chekmenev, Jan-Bernd Hövener, André F Martins, Franz Schilling, Thomas Reinheckel, Andreas B Schmidt
Journal: Theranostics (2025)

Metabolic MRI using hyperpolarized (HP) [1-13C]pyruvate is promising for diagnostic medicine, allowing the study of cancer metabolism and early detection of therapy response. However, a possible widespread and routine use requires high-throughput and user-friendly technologies to produce the hyperpolarized media. Methods: Recently, we introduced a fast (6 min) and cost-effective method using Spin-Lock Induced Crossing and Signal Amplification By Reversible Exchange (SLIC-SABRE) at µT fields and a rapid purification to produce biocompatible HP solutions of aqueous pyruvate. In this study, we used SLIC-SABRE to conduct in vivo tumor metabolic imaging in a transgenic breast cancer mouse model (MMTV-PyMT). Results: In agreement with previous HP MRI cancer studies, an elevated lactate metabolism was found in tumors compared to healthy breast tissue, heart, and vasculature, as well as distinct metabolic profiles within different tumor compartments. These findings suggest a potential link between lactate-to-pyruvate ratios and the varying levels of tumor cell proliferation and apoptosis observed by histological analyses. Conclusion: Our results underscore the potential of SABRE to enhance the accessibility and throughput of HP MRI, thereby advancing cancer research and diagnostic oncology.
Designing multifunctional recombinant vaccines: an engineering strategy based on innovative epitope prediction-guided splicing
Authors: Zhidong Wang, Xiaolin Yang, Xiaoyi Wei, Licai Shi, Xuechun Wang, Zhenjian Zhuo, Hailong Su, Wengao Wu, Yu J Cao
Journal: Theranostics (2025)

Background: Recombinant subunit vaccines leveraging pathogen-derived components are pivotal for disease prevention. Nonetheless, application of these vaccines still faces challenges such as low immunogenicity and a short half-life. Additionally, selecting appropriate antigens presents a significant barrier in recombinant vaccine design. Methods: Here, we applied a novel approach to address these challenges by developing recombinant vaccines targeting LMP2A. We employed in silico epitope prediction and splicing to create epitope enrichment regions (EERs) in conjunction with the TLR4 agonist hEDA to enhance immunogenicity and the immunoglobulin G1 (IgG1) Fc fragment to prolong persistence. Results: This multifaceted strategy enhances antigen uptake by antigen-presenting cells, eliciting major histocompatibility complex (MHC) allele-dependent T-cell responses against targeted epitopes. Compared with split-component candidates, these innovatively designed vaccines demonstrate superiority in inducing the development of IFN-γ+ antigen-specific T cells, along with elevated humoral and cellular immune responses, and exhibit significantly enhanced antitumor efficacy in both preventive and therapeutic models. Furthermore, optimized vaccine treatment synergistically inhibits tumor growth when combined with the administration of immune checkpoint inhibitors, leading to significantly prolonged survival. Conclusion: This novel design strategy offers advances for the development of multifunctional recombinant vaccines and represents a promising platform for cancer immunotherapy and applications in other diseases.
Transcranial ultrasound localization microscopy in moyamoya patients using a clinical ultrasound system
Authors: Louise Denis, Elena Meseguer, Augustin Gaudemer, Georges Jaklh, Sylvain Bodard, Georges Chabouh, Dominique Hervé, Eric Vicaut, Pierre Amarenco, Olivier Couture
Journal: Theranostics (2025)

Background: Deep brain structures are supplied by perforating arteries, which are too thin to be observed with non-invasive and widely available clinical imaging methods. In moyamoya disease, main arteries in the base of the brain progressively narrow, and perforating arteries grow densely and tortuously to compensate the lack of blood supply in deep brain structures. Purpose: The aim of this study is to evaluate the efficacy of transcranial ultrasound localization microscopy (ULM) in visualizing perforating arteries, utilizing a standard low-frame-rate ultrasound clinical scanner and contrast sequences commonly employed in hospital settings. Methods: This prospective single-center study included ischemic stroke patients not related to the study of perforating arteries, and moyamoya disease patients. Contrast-enhanced ultrasound sequences (CEUS) were performed by an experienced neurologist and the images acquired were used to perform post-processing ULM. ULM density maps were compared with conventional 3T TOF MRI and color Doppler imaging in both groups. Results: We included a group of 15 control patients and another group of 9 moyamoya patients between March 2023 and March 2024. The patients had an average age of 45 ± 14 years (65% male). Perforating arteries were captured on all subjects, with a mean diameter of 0.8 ± 0.3 mm in control patients, while it was not possible with TOF MRI or color Doppler (P < 0.05). Moreover, ULM enabled to highlight differences between healthy subjects and those with moyamoya disease through track mean distance (P = 0.05). Conclusions: Using a low-frame-rate ultrasound scanner, CEUS and accessible post-processing tools, we demonstrate that transcranial ULM can facilitate the visualization and characterization of perforating arteries, even in cases where they were previously undetectable using standard non-invasive imaging techniques. We speculate that with the advent of high-frame-rate 3D ULM, this technique may find widespread utility in hospitals.
Hepatic stellate cell-derived microfibrillar-associated protein 2 prevents liver fibrosis by regulating extracellular matrix and inflammation
Authors: Wen Zhang, Wenyue Wu, Ning Zhang, Hong Li, Yameng Sun, Xiaodong Ge, Hui Han, Shuyan Chen, Anjian Xu, Sai Santosh Babu Komakula, Chao Wang, Nithyananthan Subramaniyam, Qi Han, Aiting Yang, Xuzhen Yan, Natalia Nieto, Hong You, Wei Chen
Journal: Theranostics (2025)

Microfibrillar-associated protein 2 (MFAP-2) is a crucial component of the extracellular matrix (ECM) microfibrils, yet its role in liver fibrosis remains elusive. Methods: Human tissue arrays and mouse models of fibrosis progression and resolution were used to investigate MFAP-2 expression patterns. Mfap2 deficiency (Mfap2 -/-) or overexpression (ovMfap2) mice were subjected to carbon tetrachloride (CCl4) injection or bile duct ligation (BDL) to induce liver fibrosis. Histological, biochemical, bulk, or single-cell RNA-sequencing (scRNA-seq), proteomics to analyze the matrisome, and in vitro studies were conducted. Results: MFAP-2 was predominantly enriched in activated hepatic stellate cells (HSCs) and upregulated in advanced liver fibrosis. Although Mfap2 ablation had minimal impact on collagen deposition during CCl4 injection, it significantly delayed fibrosis regression after CCl4 cessation. The delayed fibrosis regression due to Mfap2 deficiency was likely linked to aggravated intrahepatic inflammation, ECM stabilization, and activated focal adhesion signaling in HSCs. Mechanically, inhibiting HSC-derived Mfap2 enhanced HSC interactions and increased matrisome protein production, while reducing the interaction between HSCs and liver-resident macrophages by decreasing macrophage migration inhibitory factor secretion from HSCs. Additionally, we validated the role of Mfap2 deletion in liver fibrosis using the BDL mouse model, demonstrating a more pronounced effect on fibrosis progression. Adeno-associated virus vector (serotype 6)-mediated Mfap2 overexpression in HSCs conferred protection against liver fibrosis in both models. Conclusion: This study reveals the compensatory protective effects of HSC-derived MFAP-2 on liver fibrosis and its underlying mechanisms. Enhancing MFAP-2 in HSCs may therefore benefit patients with liver fibrosis.
Neural-enhancing PRP/Alg/GelMA triple-network hydrogel for neurogenesis and angiogenesis after spinal cord injury via PI3K/AKT/mTOR signaling pathway
Authors: Zhihe Yun, Jiuping Wu, Xinzhi Sun, Tao Yu, Wu Xue, Anyuan Dai, Tianyang Yuan, Xuhao Yang, Inbo Han, Yanting Liu, Wenlong Song, Qinyi Liu
Journal: Theranostics (2025)

Rational: Spinal cord injury (SCI) is among the most devastating conditions affecting the central nervous system. Nerve regeneration and vascular regeneration are two important strategies for SCI. While platelet-rich plasma (PRP) gel is a bio-hydrogel enriched with a large number of growth factors. It has an excellent ability to promote blood vessel regeneration, but its role in nerve repair needs to be further enhanced. In addition, its weak mechanical properties and rapid release of components have limited its efficacy. Method: In this study, we cleverly applied the dual effects of activation and cross-linking of calcium ions to construct a novel PRP/ sodium alginate (Alg)/ gelatin methacrylate (GelMA) triple-networked hydrogel and enhanced the hydrogel's function in promoting nerve regeneration using brain-derived neurotrophic factor (BDNF). Results: In vitro experiments, we verified the biomimetic, injectable, biodegradable, biocompatible, vascular regenerative and neural regenerative properties of the neural-enhancing triple-network hydrogel by involving endothelial cells and neural stem cells (NSCs). When implanted into SCI rats, this hydrogel significantly improved its motor function. It promotes neuronal differentiation, inhibits astrocyte differentiation, supports axonal regeneration, and enhances the migration of endogenous NSCs and vascular regeneration. In addition, this hydrogel may facilitate neurogenesis and angiogenesis via activating the PI3K/AKT/mTOR signaling pathway. Conclusions: The neural regeneration-enhanced triple-network hydrogel we developed has excellent dual biological functions of neural regeneration and angiogenesis, and it is a straightforward, viable, and promising therapeutic strategy for SCI regeneration.
Hybrid NIR-responsive liposome/hydrogel platform mediating chemo-photothermal therapy of retinoblastoma enhanced by quercetin as an adjuvant
Authors: Min Lin, Xiumei Liu, Jing Li, Hong Zou, Jie Wang, Zi Yan, Ying Liu, Yaqi Lyu, Nianping Feng
Journal: Theranostics (2025)

Rationale: Retinoblastoma is one of the most aggressive paediatric cancers originating from retina and finally invades vitreous humour or other tissues if treated improperly. Current interventions often fail due to the complexities of tumour progression and drug resistance driven by frequent intravitreal injection and epithelial-mesenchymal transition (EMT). Consequently, there is an unmet need for more effective, less invasive treatments. Methods: A near-infrared (NIR)-responsive liposome/hydrogel platform that incorporates quercetin (QUE) and doxorubicin (DOX) co-loaded liposomes (QD Lipo), and indocyanine green (ICG) in a low-gelling temperature agarose hydrogel (LAgel) was developed to improve efficacy through localized, on-demand delivery of chemo-photothermal therapy directly at the site of tumour. The initial phase of the study examined the injectability, reversibility and stability of QD Lipo/ICG/LAgel under NIR using cryo-SEM technique and rheological measurement. Following this, photothermal conversion capability and controlled release of QD Lipo, alongside the mobility and penetration of QD Lipo was investigated using infrared thermal imaging, nanoparticle tracking analysis and fluorescence microscope. Moreover, retinoblastoma orthotopic model was established to corroborate the anti-tumour effectiveness in vivo. Flow cytometry, H&E, immunohistochemical staining, animal imaging and western blotting were performed to identify the underling mechanism of QD Lipo/ICG/LAgel to improve the treatment. Results: The thermosensitivity and photothermal conversion capabilities of QD Lipo/ICG/LAgel enable precise, on-demand drug delivery in vitreous, significantly reducing the need for frequent intravitreal injections. In vitro and in vivo evaluation demonstrated that with facilitation of QUE, our platform effectively targets the rapid tumour progression and overcome therapeutic resistance of mild photothermal therapy (PTT), by modulating EMT process and inhibiting heat shock protein (HSP) level. Conclusions: This innovative approach not only mitigates the current challenges of repeated invasive medication, but also sets new strategies for treating complex ocular diseases.
Augmented expression of superoxide dismutase 2 mitigates progression and rupture of experimental abdominal aortic aneurysm
Authors: Huimin Yan, Ying Hu, Yang Lyu, Antonina Akk, Angela C Hirbe, Samuel A Wickline, Hua Pan, Elisha D O Roberson, Christine T N Pham
Journal: Theranostics (2025)

Rationale: Oxidative stress is implicated in the pathogenesis and progression of abdominal aortic aneurysm (AAA). It is suggested that an excess in reactive oxygen species (ROS) over endogenous antioxidant activities can lead to endothelial and mitochondrial dysfunction, which promotes tissue inflammation, extracellular matrix degradation, and cellular apoptosis, all pathologic features characteristic of AAA. While elevated levels of ROS in human and experimental AAA appear well established, the contribution of endogenous antioxidant systems to aneurysm formation and progression remains controversial. We demonstrate that the antioxidant enzyme superoxide dismutase 2 (SOD2), the resident mitochondrial form of SODs that protects against mitochondrial damage, is relatively deficient in established preclinical AAA. We hypothesize that augmented expression of SOD2 will protect against oxidative stress and mitigate aneurysm progression. Methods: Herein, we employ a peptide-based nanoplatform to overexpress a key modulator of oxidative stress, SOD2. The efficacy of systemic delivery of murine SOD2 mRNA as an antioxidant nanotherapeutic agent was studied in two different murine AAA models. Unbiased mass spectrometry-enabled proteomics and high-dimensional bioinformatics were used to examine pathways modulated by SOD2 overexpression. Results: Using two different murine models of AAA, we show that in vivo augmentation of SOD2 expression via mRNA-based nanotherapy mitigates the expansion of small aneurysms and largely prevents rupture. Mitigation of AAA is accompanied by concomitant suppression of ROS, ROS surrogate markers, and apoptotic cell death. Proteomic profiling of AAA tissue and gene set enrichment analysis show that SOD2 overexpression is associated with modulation of oxidative phosphorylation, respiratory electron transport, and fatty acid metabolism. In addition, SOD2 overexpression inhibits platelet activation, downregulates mitogen-activated protein kinase signaling, and augments levels of microRNAs miR-181a-5p and miR17-5p targets that regulate vascular inflammation and cell apoptosis, respectively. Conclusions: These results confirm that SOD2 plays a pivotal role in the pathogenesis of experimental AAA and identify its potential as a therapeutic target.
A <i>“</i>CPApoptosis<i>”</i> nano-actuator switches immune-off solid tumors to immune-on for fueling T-cell- based immunotherapy
Authors: Ying Luo, Yi Wang, Bo Liu, Yun Liu, Wenli Zhang, Sijin Chen, Xiyue Rong, Lian Xu, Qianying Du, Jia Liu, Jie Xu, Haitao Ran, Zhigang Wang, Dajing Guo
Journal: Theranostics (2025)

Background: Most anticancer agents induce tumor apoptosis, but they often lack immunogenicity and display limited success when combined with mainstream immunotherapies, thus killing cancer cells through multiple cell death modalities as well as switching immune-off tumors to immune-on is a strategy with great promise. To this end, we developed a CPApoptosis (cuproptosis, pyroptosis, apoptosis) nano-actuator for immunologically cold solid tumors. Methods: In this study, elesclomol (ES), a mitochondrial targeting copper transporter, was encapsulated within bacterial outer membrane vesicles (OMVs). These OMVs were then surface-modified via metal-phenolic self-assembly using Cu2+ and tannic acid (TA). Results: The Cu2+ and ES were released from the OMVs in a pH-dependent manner. OMV activated the non-canonical pyroptotic pathway, leading to cell membrane rupture. Cu2+ on the one hand was transported to the mitochondria for cuproptosis facilitated by ES, on the other hand, Cu2+ was reduced into Cu+ by TA, which catalyzed ROS production to induce oxidative apoptosis. Simultaneously, TA degraded glutathione (GSH), sensitizing cells to cuproptosis. The multifactorial cell death mechanisms led to the release of immunogenic factors from lysed tumor cells, stimulating dendritic cell maturation and recruiting cytotoxic T cells. This immune response was further amplified by αPD-L1 antibody treatment. Conclusion: The CPApoptosis nano-actuator represents a promising approach to enhance current cancer therapies, inducing both tumor cell death and a robust immune response, with the potential for long-lasting protective effects.
Comparison of 5-aminolevulinic acid and MMP-14 targeted peptide probes in preclinical models of GBM
Authors: Benjamin B Kasten, Tingting Dai, Ke Jiang, Jennifer Coleman Clements, Kaixiang Zhou, Carlos A Gallegos, Seth N Lee, Anna G Sorace, Hailey A Houson, Logan D Stone, James M Markert, Jianghong Rao, Jason M Warram
Journal: Theranostics (2025)

Rationale: Developing novel pre-operative and intraoperative imaging approaches for glioblastoma multiforme (GBM) could aid therapeutic intervention while sparing healthy normal brain, which remains a significant clinical challenge. 5-aminolevulinic acid (5-ALA) is the only intraoperative imaging agent approved to aid the resection of GBM. Matrix metalloproteinase 14 (MMP14), which is overexpressed in GBM, is an attractive target for preoperative and intraoperative imaging of GBM. Prior studies have shown the feasibility of near-infrared fluorescence (NIRF) imaging and positron emission tomography (PET) imaging of GBM xenografts in mice using MMP-14 targeted peptide probes. The present studies assessed the tumor-specific localization and contrast of these MMP-14 targeted peptides relative to 5-ALA in GBM models. Methods: Fluorescence and PET imaging was performed after i.v. injection of 5-ALA and the MMP-14 targeted peptide probes (non-labeled or radiolabeled with 64Cu) in mice bearing human GBM orthotopic xenografts (U87, D54). Imaging signals were correlated to MMP-14 expression determined by immunofluorescence. Tumor-to-normal brain ratio (TBR) and Dice similarity coefficient (DSC) relative to tumor defined by ex vivo pathology or in vivo magnetic resonance imaging were determined for each imaging agent. Results: NIRF signals from the MMP-14 targeted peptide probes showed comparable TBR (p < 0.05) but significantly higher DSC (p < 0.05) relative to 5-ALA. NIRF signals from the peptide probes significantly correlated with MMP-14 expression (p < 0.05). MMP-14 binding peptide labeled with 64Cu showed moderate DSC (0.45) while PET signals significantly correlated (p < 0.05) with NIRF signals from a co-injected MMP-14 substrate peptide. NIRF and PET signals localized in residual tumor regions in the resection cavity during in situ resection. Conclusions: MMP-14 targeted peptides showed favorable TBR and higher tumor localization than 5-ALA in GBM orthotopic models. Further development of MMP-14 targeted peptide probes could lead to improved pre-operative and intraoperative management of GBM.
Visceral metastases, platelet dynamics, and PSA decline: from biomarkers to better outcomes in [<sup>177</sup>Lu]Lu‑PSMA‑617 therapy in metastatic castration-resistant prostate cancer
Authors: Nathan Poterszman, Cécile Hammer-Lefevre, Clémence Porot, Julien Salvadori, Philippe Barthélémy, François Somme
Journal: Theranostics (2025)

Radioligand therapy with [177Lu]Lu-PSMA-617 constitutes a significant breakthrough in the management of metastatic castration-resistant prostate cancer (mCRPC). However, clinical outcomes remain variable due to the heterogeneity of patient profiles and limitations in current selection criteria. This study aims to identify simple and reproducible predictive factors to optimize therapy and improve patient stratification. Methods: A retrospective analysis was conducted on 109 mCRPC patients treated with [177Lu]Lu-PSMA-617 at the Institut de Cancérologie Strasbourg Europe. Clinical, biological, and imaging parameters were collected, including early biological changes after the first cycle. Survival analyses and regression models were employed to identify prognostic and predictive factors. Results: Visceral metastases (p < 0.001) and a decrease in platelet count above 25% (p = 0.004) between the first and second cycles were significantly associated with reduced overall survival. Furthermore, a decline in PSA levels above 30% following two cycles emerged as a robust predictor of treatment response, markedly affecting both biochemical progression-free survival (p < 0.001) and radiological progression-free survival (p = 0.002). Conclusion: By combining three factors-visceral metastases, platelet count variation, and PSA reduction-patients could be stratified into distinct prognostic groups as early as after the first cycle. These findings pave the way for personalized management and enhanced clinical outcomes for mCRPC patients receiving [177Lu]Lu-PSMA-617.