tbuckley/cabot-search huggingface dataset:
Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression: Erratum
Authors: Dong-Liang Chen, Yun-Xin Lu, Jia-Xing Zhang, Xiao-Li Wei, Feng Wang, Zhao-Lei Zeng, Zhi-Zhong Pan, Yun-Fei Yuan, Feng-Hua Wang, Helene Pelicano, Paul J Chiao, Peng Huang, Dan Xie, Yu-Hong Li, Huai-Qiang Ju, Rui-Hua Xu
Journal: Theranostics (2025)

[This corrects the article DOI: 10.7150/thno.20942.].
Histone lactylation-driven B7-H3 expression promotes tumor immune evasion
Authors: Zhibo Ma, Jincui Yang, Wenlong Jia, Le Li, Yixin Li, Junjie Hu, Wei Luo, Ronghui Li, Dawei Ye, Peixiang Lan
Journal: Theranostics (2025)

Rationale: Tumor cells possess sophisticated strategies to circumvent immune detection, including the modulation of endogenous immune checkpoints, particularly those within the B7 family. Elucidating the mechanisms that govern the induction of B7 family molecules is crucial for the advancement of immunotherapy. Lysine lactylation (Kla), a newly identified epigenetic modification, is suggested may play a role in reshaping the tumor microenvironment and facilitating immune evasion. Methods: We analyzed the glycolysis pathway's enrichment in patients with immune-evading tumors and assessed the impact of lactate treatment on the antitumor immunity of CD8+ T cells in the tumor microenvironment. We interrupted glycolysis using lactate dehydrogenase A (LDHA) knockdown and sodium oxamate, and evaluated its effects on CD8+ T cell cytotoxicity. Additionally, we investigated the correlation between B7-H3 expression and the glycolysis pathway, and explored the molecular mechanisms underlying lactate-induced B7-H3 expression. Results: Our findings revealed that the glycolysis pathway was highly enriched in immune-evading tumors. Lactate treatment inhibited the antitumor immunity of CD8+ T cells, whereas interruption of glycolysis via LDHA knockdown or treatment with sodium oxamate augmented the cytotoxicity of CD8+ T cells, effectively counteracting tumor immune evasion. B7-H3 expression was found to be closely linked with the glycolysis pathway. Mechanistically, lactate-upregulated H3K18la directly bound to the B7-H3 promoter in conjunction with the transcription factor Creb1 and its co-activator Ep300, leading to increased B7-H3 expression and contributing to tumor progression by compromising the proportion and cytotoxicity of tumor-infiltrating CD8+ T cells. In mouse tumor bearing models, inhibiting glycolysis and B7-H3 expression suppressed tumor cell growth, activated tumor-infiltrating CD8+ T cells, and demonstrated potent anti-tumor efficacy. Furthermore, this approach enhanced the efficacy of anti-PD-1 treatment. Conclusions: This study uncovers a novel mechanism by which lactate modulates the immune microenvironment through the glycolysis pathway and B7-H3 expression, providing new avenues for lactate metabolism-targeted tumor immunotherapy.
A p-n heterojunction sonosensitizer for improved sono-immunotherapy via induction of multimodal cell death mechanisms
Authors: Sijia Wu, Qian Wang, Jun Du, Qingxuan Meng, Yuhao Li, Yuqing Miao, Qing Miao, Jingxiang Wu
Journal: Theranostics (2025)

Rationale: Activating a robust immune system is a crucial strategy for combating solid tumors and preventing recurrences. Studies have shown that cuproptosis and the resulting increased reactive oxygen species (ROS) can trigger immunogenic cell death (ICD) and modulate the tumor immune microenvironment, thereby activating systemic immunity. Therefore, for this purpose, it is important to design a multifunctional copper-based nanomaterial. Method: In this study, we developed Bi2O3-XSX-CuS p-n heterojunction nanoparticles (BCuS NPs) designed to stimulate systemic immune responses and effectively suppress both dormant and recurrent tumors. BCuS nanoparticles were characterized using transmission electron microscopy, X-ray diffraction, and other methods. In addition, the sonodynamic and chemodynamic properties of BCuS were intensively studied by various experimental methods. We identified the mechanisms by which BCuS induced multiple paths of cell death, by using in vitro experiments, including immunofluorescence assays, western blotting, and cell flow cytometry. In addition, we used mouse orthotopic and distal tumor models and RNA sequencing to evaluate the efficacy of combination therapy. Results: The results showed that BCuS produced a Fenton-like reaction in an acidic environment and induced the production of highly toxic ROS during ultrasound treatment. In vitro studies further showed that BCuS induced the occurrence of cuproptosis and ferroptosis, and stimulated ICD in combination with ROS, thereby effectively reversing the immunosuppression of the tumor microenvironment, and improving the sensitivity of immunotherapy. As demonstrated by in vitro studies, in vivo experiments also confirmed the enhanced effects of combination therapy. Conclusion: The BCuS sonosensitizer showed sonodynamic therapy effects, including inhibition of tumor growth in combination with multiple cell death modalities. These findings provide a novel method for using nanomaterials for multimodal combination cancer therapy.
Renal tubular epithelial-derived follistatin-like 1 protects against UUO-induced renal fibrosis in mice via inhibiting NF-κB-mediated epithelial inflammation
Authors: Zhuan Niu, Jiasen Guo, Xingzu Liu, Mo Chen, Yueyue Jin, Maolin Yao, Xiaoxu Li, Qianqian Che, Shuzi Li, Chenjie Zhang, Kunyue Shangguan, Dekun Wang, Chuan'ai Chen, Wenli Yu, Xiaoyue Tan, Wen Ning, Lian Li
Journal: Theranostics (2025)

Rationale: Renal fibrosis is commonly recognized as the ultimate pathway for most chronic kidney diseases (CKD). Renal tubular epithelial inflammation drives the initiation and progression of renal fibrosis. Follistatin-like 1 (FSTL1) is a small matricellular protein, whose expression pattern, function and underlying mechanism in regulating renal inflammation and fibrosis remains largely unknown. Methods: We utilized two Fstl1-deficient genetic mouse models: heterozygous Fstl1+/- mice and whole-body Fstl1 conditional knockout mice, and a mouse model with FSTL1 overexpression via adenoviral vector infection. These mice were subjected to unilateral ureteral obstruction (UUO). We used an Fstl1 lineage tracing mouse to investigate the expression and location of induced FSTL1 in the obstructed kidney. We investigated the effect of FSTL1 on TNF-α induced epithelial inflammation and the NF-κB pathway by overexpression or knockdown of FSTL1 in human kidney epithelial cells (HK2). Results: We observed increased expression of FSTL1 in kidneys from patients with CKD, and UUO mouse model of renal injury and fibrosis. Deletion of Fstl1 in mice aggravated UUO-induced inflammatory kidney injury and subsequent fibrosis. Conversely, overexpression of FSTL1 by adenoviral vector infection in mice mitigated expression of proinflammatory cytokines and the fibrotic phenotype. Mechanistically, we identified that increased FSTL1 was mostly derived from the tubular epithelium of the obstructed mouse kidney. FSTL1 inhibited human renal epithelial cell inflammatory responses, as assessed by reducing the NF-κB pathway, release of IL-1β and IL-6, expression of intercellular adhesion molecule 1 (ICAM-1), and monocyte adhesion to kidney epithelial cells. Conclusions: These findings suggest that FSTL1 plays a protective role against kidney fibrosis by inhibiting renal epithelial inflammation via the NF-κB pathway in epithelium, thereby offering a potential novel strategy for treating progressive CKD.
Vascular regional analysis unveils differential responses to anti-angiogenic therapy in pancreatic xenografts through macroscopic photoacoustic imaging
Authors: Allison Sweeney, Andrew Langley, Marvin Xavierselvan, Ronak T Shethia, Patrick Solomon, Aayush Arora, Srivalleesha Mallidi
Journal: Theranostics (2025)

Background: Amongst the various imaging techniques that provide surrogate tumor radiographic indications to aid in planning, monitoring, and predicting outcomes of therapy, ultrasound-guided photoacoustic imaging (US-PAI) is a promising non-ionizing modality based on endogenous blood (hemoglobin) and blood oxygen saturation (StO₂) contrast. Adaptation of US-PAI to the clinical realm requires macroscopic system configurations for adequate depth visualization. Methods: Here we present a vascular regional analysis (VRA) methodology of obtaining areas of low and high vessel density regions within the tumor (LVD and HVD respectively) by frequency domain filtering of macroscopic PA images. In this work, we evaluated the various vascular and oxygenation profiles of different murine xenografts of pancreatic cancer (AsPC-1, MIA PaCa-2, and BxPC-3) that have varying levels of angiogenic potentials and investigated the effects of receptor tyrosine kinase inhibitor (sunitinib) on the tumor microvessel density and StO₂. Results: The administration of sunitinib resulted in transient deoxygenation and reduction in vessel density within 72 h in two (AsPC-1 and MIA PaCa-2) of the three tumor types. Utilizing VRA, the regional change in StO2 (∆StO2) revealed the preferential targeting of sunitinib in LVD regions in only the AsPC-1 tumors. We also identified the presence of vascular normalization (validated through immunohistochemistry) in the sunitinib treated AsPC-1 tumors at day 8 post-treatment where a significant increases in HVD ∆StO2 (~20%) were seen following the 72-hour time point, indicative of improved vessel flow and functionality. Treated AsPC-1 vasculature displayed increased maturity and functionality compared to non-treated tumors on day 8, while these same metrics showed no conclusive evidence of vascular normalization in MIA PaCa-2 or BxPC-3 tumors. Conclusion: Overall, VRA as a tool to monitor treatment response allowed us to identify time points of vascular remodeling, highlighting its ability to provide insights into the tumor microenvironment for sunitinib treatment and other anti-angiogenic therapies.
Neurotrophic factor-α1/carboxypeptidase E controls progression and reversal of Alzheimer's disease pathogenesis in mice
Authors: Fang-Cheng Fan, Li-Ming Liu, Mei Guo, Yang Du, Yue-Wen Chen, Y Peng Loh, Yong Cheng
Journal: Theranostics (2025)

Background: Neurotrophic Factor-α1/Carboxypeptidase E (NF-α1/CPE) is a pivotal neuroprotective protein implicated in rescuing cognitive decline associated with Alzheimer's disease (AD). However, its direct role in AD pathogenesis remains unexplored. Methods: We utilized the Cre/LoxP system to diminish NF-α1/CPE expression, and employed AAV-mediated overexpression of NF-α1/CPE. Results: NF-α1/CPE expression was significantly down-regulated in advanced stages of AD and with age in 5xFAD mice. Reduced NF-α1/CPE levels in the hippocampus of 5xFAD mice increased plaque burden, microglial cell count, disrupted synaptogenesis, and intensified cognitive impairments at 5 and 7 months. However, by 9 months, no further progression of detrimental effects was observed. Overexpression of NF-α1/CPE markedly decreased amyloid plaque accumulation, mitigated spatial memory deficits, and normalized hippocampal synaptogenesis and microglial anomalies across early and late stages of the disease. Conclusion: NF-α1/CPE is a critical regulator of AD pathogenesis, offering promising therapeutic potential for reducing amyloid beta deposition and toxicity in AD.
Investigation of the role and mechanism of ARHGAP5-mediated colorectal cancer metastasis: Erratum
Authors: Tian Tian, Zhan-Hong Chen, Zongheng Zheng, Yubo Liu, Qi Zhao, Yuying Liu, Huijun Qiu, Qian Long, Miao Chen, Liren Li, Fangyun Xie, Guangyu Luo, Xiaojun Wu, Wuguo Deng
Journal: Theranostics (2025)

[This corrects the article DOI: 10.7150/thno.43427.].
Construction of human pluripotent stem cell-derived testicular organoids and their use as humanized testis models for evaluating the effects of semaglutide
Authors: Rufei Huang, Huan Xia, Tao Meng, Yufei Fan, Xun Tang, Yifang Li, Tiantian Zhang, Jingxian Deng, Bing Yao, Yadong Huang, Yan Yang
Journal: Theranostics (2025)

Background: The generation of human testicular organoids from human induced pluripotent stem cells (hiPSCs) presents exciting opportunities for gonadal developmental biology, and reproductive disease modeling. However, creating organoids that closely mimic the tissue structure of testes remains challenging. Methods: In this study, we established a method for generating testicular organoids (TOs) from hiPSCs using a stepwise differentiation approach and a combination of hanging drop and rotational culture systems. The capability of hiPSC-derived precursor testicular cells to self-assemble into organoids was confirmed by detection of morphology, single-cell RNA-sequencing, and protein profiles. The reliability of testicular organoids as a drug evaluation model was assessed by the measurements of transcriptome signatures and functional features, including hormone responsiveness and blood-testis barrier (BTB) formation, and drug sensitivity assessment by recording cell viability and BTB integrity in organoids exposed to reproductive toxicants. Finally, we applied testicular organoids to evaluate the effects of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), on testicular function, thereby underscoring their utility as a model for drug evaluation. Results: These organoids exhibited testicular cord-like structures and BTB function. RNA sequencing and functional assays confirmed that testicular organoids possess gene expression profiles and endocrine functions regulated by gonadotropins, closely resembling those of testicular tissue. Notably, these organoids displayed sensitivity to semaglutide. Treatment with semaglutide resulted in reduced testosterone levels and downregulation of INHBB expression, aligning with previous clinical observations. Conclusions: These findings introduced a method for generating testicular organoids from human pluripotent stem cells, highlighting their potential as valuable models for studying testicular function, drug toxicity, and the effects of compounds like semaglutide on testicular health.
OTUD7B is a new deubiquitinase targeting p53
Authors: Caoyuan Ding, Leixi Cao, Ruijie Wang, Qichen Wu, Mengfan Li, Jinjing Zhang, Rick F Thorne, Jinming Li, Jianli Ma, Mian Wu, Shundong Cang
Journal: Theranostics (2025)

Rationale: The tumor suppressor p53 safeguards against cellular transformation, with its expression regulated by diverse post-translational modifications (PTMs). While polyubiquitination by Mdm2 principally drives its proteasomal degradation, the identity of p53 deubiquitinases (DUBs) remains less well defined. This study investigates the role of the deubiquitinase enzyme OTUD7B in hepatocellular carcinoma (HCC), where it is notably downregulated and proposed to function as a tumor suppressor. Methods: Mass spectrometry screening of immunoprecipitates from HCC cells was used to identify OTUD7B-binding proteins. Co-immunoprecipitation assays with endogenous, ectopic, and mutant forms of OTUD7B and p53 assessed binding interactions and p53 polyubiquitination levels, respectively. Regulatory mechanisms were explored via luciferase reporter and chromatin immunoprecipitation (ChIP) assays. OTUD7B function was evaluated in vitro and in xenograft models using shRNA knockdown, overexpression, and CRISPR-Cas9 knockout. OTUD7B expression in normal and HCC tissues was analyzed by immunohistochemistry and immunoblotting. Results: We identified p53 as a binding partner of OTUD7B, confirming interactions with both wild-type and mutant p53 in HCC cells. OTUD7B was shown to remove lysine-linked polyubiquitin chains in p53, including those mediated by Mdm2, thereby stabilizing p53 by inhibiting its proteasomal degradation. Overexpression of OTUD7B suppressed growth in HCC cultures and xenografts through p53-dependent mitochondrial apoptosis, marked by PUMA and BAX induction. Conversely, OTUD7B knockdown promoted tumor growth. These effects were absent in p53-null or CRISPR-knockout cells, underscoring p53 as a key OTUD7B substrate. Additionally, OTUD7B expression was found to be transcriptionally repressed via p53-dependent mechanisms. Bioinformatics and ex vivo analysis revealed a positive correlation between OTUD7B and p53 protein levels in HCC tissues. Conclusion: OTUD7B plays a critical role in stabilizing both wild-type and mutant p53 in HCC cells, with its expression regulated through a mutual feedback loop involving p53. By inhibiting cell growth, OTUD7B exhibits tumor-suppressive properties, underscored by its atypical downregulation in patient tissues and its positive correlation with p53 expression. These findings highlight the clinical significance of OTUD7B and position it as a promising therapeutic target for modulating the p53 pathway in HCC.
Enhancing Immunomodulation and Osseointegration of Bone Implants via Thrombin‐Activated Platelet‐Rich Plasma Self‐Assembly
Authors: Xiaotong Shi, Zongliang Wang, Zhiguo Bi, Jianguo Liu, Peibiao Zhang
Journal: Advanced Healthcare Materials (2025)

Abstract Platelet‐rich plasma (PRP) is characterized by elevated concentrations of growth factors that facilitate bone repair. Nonetheless, the effective integration of PRP with bone implants and the sustained release of its active constituents pose significant challenges. In this study, thrombin is grafted onto the surface of polyetheretherketone (PEEK) via an N,N'‐Disuccinimidyl Carbonate (DSC) linker and the retained enzymatic activity of thrombin enables the controlled activation of PRP self‐assembly, resulting in the formation of a functional bio‐gel layer. The optimal thrombin concentration to be 100 U/ mL −1 is determined, at which point both the grafting amount and enzymatic activity of thrombin reaches their peak, with no further increases observed at higher concentrations. PRP solutions with varying platelet enrichment ratios are subsequently activated on the thrombin‐grafted PEEK surface, yielding self‐assembled bio‐gels capable of sustained growth factor release for up to 16 days. The thrombin‐activated PRP bio‐gel on PEEK surface not only enhances in vitro cell adhesion, proliferation, osteogenic differentiation, vascularization and specific polarization of macrophages, but also effectively facilitates in vivo angiogenesis, immunomodulation and bone formation in a platelet dose‐dependent manner. Consequently, the thrombin‐activated PRP gel presents a promising strategy for the biological functionalization of PEEK implants in orthopedic applications.
<i>Fusobacterium nucleatum</i> upregulates the immune inhibitory receptor <i>PD-L1</i> in colorectal cancer cells via the activation of ALPK1
Authors: Coco Duizer, Moniek Salomons, Merel van Gogh, Sanne Gräve, Freke A. Schaafsma, Maaike J. Stok, Merel Sijbranda, Raghuvandhanan Kumarasamy Sivasamy, Rob J. L. Willems, Marcel R. de Zoete
Journal: Gut Microbes (2025)

Fusobacterium nucleatum is a Gram-negative oncobacterium that is associated with colorectal cancer. The molecular mechanisms utilized by F. nucleatum to promote colorectal tumor development have largely focused on adhesin-mediated binding to the tumor tissue and on the pro-inflammatory capacity of F. nucleatum. However, the exact manner in which F. nucleatum promotes inflammation in the tumor microenvironment and subsequent tumor promotion remains underexplored. Here, we show that both living F. nucleatum and sterile F. nucleatum-conditioned medium promote CXCL8 release from the intestinal adenocarcinoma HT-29 cell line. We determined that the observed pro-inflammatory effect was ALPK1-dependent in both HEK293 and HT-29 cells and that the released F. nucleatum molecule had characteristics that match those of the pro-inflammatory ALPK1 ligand ADP-heptose or related heptose phosphates. In addition, we determined that not only F. nucleatum promoted an ALPK1-dependent pro-inflammatory environment but also other Fusobacterium species such as F. varium, F. necrophorum and F. gonidiaformans generated similar effects, indicating that ADP-heptose or related heptose phosphate secretion is a conserved feature of the Fusobacterium genus. By performing transcriptional analysis of ADP-heptose stimulated HT-29 cells, we found several inflammatory and cancer-related pathways to be differentially regulated, including DNA mismatch repair genes and the immune inhibitory receptor PD-L1. Finally, we show that stimulation of HT-29 cells with F. nucleatum resulted in an ALPK1-dependent upregulation of PD-L1. These results aid in our understanding of the mechanisms by which F. nucleatum can affect tumor development and therapy and pave the way for future therapeutic approaches.
Hierarchical DNA Octahedral Nanoplatform for in Situ Biosensing and Clinical Monitoring of Acute Lymphoblastic Leukemia
Authors: Qian Liu, Man Shen, Hanqing Xu, Jingxue Wang, Ruoding Wang, Ting Xiao, Shuang Wang, Jiao Chen, Lu Liu, Ligai Zhang, Yang Zhou, Xianlan Wu, Yingchun Huang, Zhangyin Ren, Jing Bao, Ming Chen, Mingxuan Gao
Journal: Advanced Healthcare Materials (2025)

Abstract Developing nanoscale platforms with high integration, assembly efficiency, and structural stability for performing complex computations in specific cells remains a significant challenge. To address this, the Three‐dimensional Hierarchical Octahedral Robotic (THOR) DNA nanoplatform is introduced, which integrates targeting, logic computation, and sensing modules within a single framework. This nanoplatform specifically binds to cancer cell surface proteins, releasing aptamer‐linked fuel chains to initiate subsequent computational processes. Three logic gates efficiently compute any arbitrary binary combination of target proteins. The sensing module employs catalytic hairpin assembly for detecting specific miRNAs with high sensitivity. THOR demonstrates robust functionality both in vitro and in situ. As a proof‐of‐concept, this nanoplatform to distinguish acute lymphoblastic leukemia (ALL) patients from other leukemia subtypes and healthy participants, achieving 100% accuracy is applied. Additionally, this approach reliably monitored the therapeutic progress of ALL patients, showing strong concordance with bone marrow smear results. The THOR platform highlights the feasibility of constructing a reliable, hierarchical, and multifunctional analytical system based on a single DNA polyhedron. It offers a promising auxiliary tool for clinical diagnostics and therapeutic monitoring.
Final Overall Survival and Molecular Data Associated with Clinical Outcomes in Patients Receiving Ipatasertib and Abiraterone in the Phase 3 IPATential150 Trial
Authors: Johann S de Bono, Meng He, Zhen Shi, Malgorzata Nowicka, Sergio Bracarda, Cora N Sternberg, Kim N Chi, David Olmos, Shahneen Sandhu, Christophe Massard, Nobuaki Matsubara, Geng Chen, Nives Selak Bienz, Daniel Canter, Matthew Wongchenko, Christopher Sweeney
Journal: European Urology (2025)