tbuckley/cabot-search huggingface dataset:
TMTP1-modified nanocarrier boosts cervical cancer immunotherapy by eliciting pyroptosis
Authors: Hanjie Xu, Danya Zhang, Yu Zhang, Yuxin Chen, Yue Sun, Jie Li, Songwei Tan, Ying Zhou, Rui Wei, Fei Li, Ling Xi
Journal: Theranostics (2025)

Rationale: Pyroptosis, an emerging form of programmed cell death, facilitates the release of tumor antigens and inflammatory factors, which can be leveraged to enhance the efficacy of immune checkpoint blockade (ICB) therapy. However, achieving high-efficiency induction of pyroptosis in cancer cells while minimizing toxicity remains a significant challenge. Methods: In this study, we designed a tumor-targeting peptide TMTP1-modified nanostructured lipid carrier (referred to as TP-NLC) with high loading capacities for gambogic acid (GA) and indocyanine green (ICG). The TMTP1, identified by our research team for its tumor-targeting capabilities, was conjugated to the nanocarrier surface using "click chemistry" to improve the drug delivery efficiency to tumor tissues. The TP-NLC nanocarrier was thoroughly characterized with respect to its morphological attributes, photostability, tumor-targeting capabilities, ability to induce pyroptosis, reactive oxygen species (ROS)-responsive behavior, and anti-tumor efficacy both in vitro and in vivo. Results: GA encapsulated within the TP-NLC nanocarrier, induced pyroptosis in tumor cells, and enhanced the efficacy of ICG-induced pyroptosis under laser irradiation by disrupting intracellular antioxidant systems, realizing that the combination of GA and ICG synergistically induced caspase-3/GSDME-mediated pyroptosis in a ROS-dependent manner. Tumor cells of pyroptosis released cellular contents and tumor antigens, which subsequently promoted the maturation of dendritic cells (DCs), enhanced intratumoral infiltration of CD8+ T cells, initiated systemic antitumor immune response, and augmented the efficiency of PD-1 blockade against both primary and metastatic tumors. Conclusion: The combination of GA and ICG therapy utilizing the constructed nanocarriers presents an attractive therapeutic strategy to trigger pyroptosis and potentiate PD-1 blockade therapy for cervical cancer chemo-immunotherapy.
Old players and new insights: unraveling the role of RNA-binding proteins in brain tumors
Authors: Xu Wang, Jiang Li, Chengkai Zhang, Xiudong Guan, Xingang Li, Wang Jia, Anjing Chen
Journal: Theranostics (2025)

The human genome harbors >1,600 evolutionarily conserved RNA-binding proteins (RBPs), with extensive multi-omics investigations documenting their pervasive dysregulation in malignancies ranging from glioblastoma to melanoma. These RBPs are integral to the complex regulatory networks governing hallmark cancer processes. Recent studies have investigated the multifaceted contributions of RBPs to tumorigenesis, tumor metabolism, the tumor-immune microenvironment, and resistance to therapy. This complexity is further compounded by the intricate regulation of RNA function at various levels by RBPs, as well as the post-translational modifications of RBPs, which improve their functional capacity. Moreover, numerous RBP-based therapeutics have emerged, each underpinned by distinct molecular mechanisms that extend from genomic analysis to the interference of RBPs' function. This review aims to provide a comprehensive overview of the recent progress in the meticulous roles of RBPs in brain tumors and to explore potential therapeutic interventions targeting these RBPs, complemented by a discussion of innovative techniques emerging in this research field. Advances in deciphering RNA-RBP interactomes and refining targeted therapeutic strategies are revealing the transformative potential of RBP-centric approaches in brain tumor treatment, establishing them as pivotal agents for overcoming current clinical challenges.
Sulforaphane promotes natural killer cell-mediated anti-tumor immune responses partially via cGAS-STING pathway in classical Hodgkin lymphoma
Authors: Ioanna Xagoraris, Ying Yang, Erofili Bougka, Dora Trogrlic, Persa Xyderou, Konstantina Stathopoulou, Nikolas Herold, Andreas Lundqvist, George Z Rassidakis
Journal: Leukemia (2025)
Prognostic impact of clonal representation of myelodysplasia-related gene mutations in acute myeloid leukemia
Authors: Rabea Mecklenbrauck, Nora Borchert, Razif Gabdoulline, Piroska Poll, Carolin Funke, Maximilian Brandes, Louisa-Kristin Dallmann, Walter Fiedler, Jürgen Krauter, Arne Trummer, Bernd Hertenstein, Martin Müller, Michael Lübbert, Monika Schwalenberg, Andreas Voss, Nataliya Di Donato, Anke Bergmann, Verena Gaidzik, Konstanze Döhner, Hartmut Döhner, Arnold Ganser, Florian H Heidel, Felicitas R Thol, Michael Heuser
Journal: Leukemia (2025)
Somatic mutations and outcomes in chronic myeloid leukemia adolescent and young adults compared to children, adults, and BCR::ABL1-positive acute lymphoblastic leukemia
Authors: Jitka Krizkova, Vaclava Polivkova, Adam Laznicka, Nikola Curik, Adela Benesova, Pavla Suchankova, Tomas Smazik, Veronika Vysinova, Dana Mikulenkova, Hana Klamova, Marketa Stastna Markova, Dana Srbova, Jan Zuna, Marketa Zaliova, Jan Trka, Cyril Salek, Katerina Machova Polakova
Journal: Leukemia (2025)
Mild Phototherapy Strategies for Preventing Pathogen Infection and Enhancing Cell Proliferation in Diabetic Wound
Authors: Mingji Jiang, Renhao Nie, Jing Kang, Peng Li, Alideertu Dong
Journal: Advanced Healthcare Materials (2025)

Abstract Excessive inflammation, bacterial infection, and impaired cell proliferation posed significant challenges to diabetic wound healing. There is an urgent need for an effective method that can simultaneously provide antibacterial activity and promote cell proliferation to facilitate the healing of bacteria‐infected diabetic wounds. In this study, a novel nanoplatform, GDYO‐VPIM‐Au is designed, by co‐decorating 1‐vinyl‐3‐pentylimidazolium bromide ([VPIM]Br) and gold nanorods (Au NRs) on graphdiyne oxide (GDYO) nanosheets. GDYO‐VPIM‐Au exhibited excellent antibacterial properties against drug‐resistant bacteria through reactive oxygen species (ROS) generation and electrostatic interactions. Moreover, GDYO‐VPIM‐Au with the synergistic effect of mild phototherapy therapy (mPTT) produced by Au NRs can promote efficient cell proliferation and significantly accelerate the healing of infected diabetic wounds. This work represented a promising therapeutic strategy for addressing drug‐resistant bacterial infections and enhancing diabetic wound healing.
Sequentially conquering transfection obstacles of primary human T cells via non-classical lipid nanoparticles delivering reformative transposon system
Authors: Mengtong Wu, Jingwen Li, Yazhou Xu, Shaoxiong Lv, Guan Wang, Yingshuang Huang, Yu Tao, Caoyun Ju, Can Zhang
Journal: Journal of Controlled Release (2025)
Defect‐Rich MoO<sub>3‐X</sub>@CuO<sub>2</sub> Nanosheets Mediated Ultrasound‐Enhanced Cuproptosis Antibacterial Activity and M2 Macrophage Reprogramming for Optimizing Diabetic Wound Repairment
Authors: Yutang Li, Yi Wang, Yandong Wang, Fenglong Wang, Fei Chang, Yanyan Jiang
Journal: Advanced Healthcare Materials (2025)

Abstract Diabetic wounds are often plagued by persistent bacterial infections, which exacerbate inflammation and impair healing processes such as collagen deposition and fibroblast migration. Conventional antibiotic therapies frequently prove ineffective and can even hinder wound repair. To address these challenges, biodegradable MoO 3‐x @CuO 2 ion disruptors (MCO IDs) that for comprehensive diabetic wound treatment is developed. The MCO IDs generate a burst of multimodal reactive oxygen species (ROS) that effectively penetrate bacterial defenses and disrupt redox homeostasis. Released copper ions induce proteotoxic stress‐like bacterial death by targeting lipoylated and iron–sulfur cluster proteins. Transcriptomic and metabolomic analyses reveal that this mechanism systematically inhibits bacterial energy metabolism and gene expression, effectively suppressing proliferation. Following bacterial eradication, the released copper ions promote macrophage repolarization to the M2 phenotype, mitigating chronic inflammation and stimulating wound healing. Furthermore, to enhance wound management, a portable wound dressing (PVA‐MCO) is fabricated by electrospinning polyvinyl alcohol (PVA) incorporating the MCO IDs. In vivo studies demonstrate that the PVA‐MCO dressing effectively eliminates pathogenic bacteria and promotes collagen deposition, angiogenesis, and epithelialization, thereby accelerating diabetic wound healing. This multifaceted therapeutic strategy offers a promising solution for managing persistent infections and promoting diabetic wound repair.
The Treatment of Large Bone Defects with Atrophic Nonunion by Bioactive Scaffolds Remodeling the Regeneration Microenvironment
Authors: Zhuo Liang, Fei Xue, Jingdi Zhang, Qingqing Pan, Xiaoyang Hu, Yulong Hu, Zhenlin Fan, Weiyun Wang, Xueqiang Guo, Zhuang Qian, Yaping Shen, Wenjuan Song, Lei Wang, Guangdong Zhou, Yong He, Wenjie Ren
Journal: Advanced Healthcare Materials (2025)

Abstract Atrophic nonunion, a particularly challenging complication of diaphyseal bone fractures, arises from a deteriorated regenerative microenvironment characterized by insufficient vascularization and pathological accumulation of reactive oxygen species (ROS). To address this clinical challenge, a dual‐function bioactive scaffolds is developed that simultaneously blocks disease progression and promotes tissue regeneration. The scaffolds design incorporates three key components: First, MnO 2 ‐Cu 2+ (MC) nanoparticles are synthesized to combat the pathological microenvironment through dual mechanisms of ROS scavenging and angiogenesis promotion. Second, circular bone morphogenetic protein 2 (circBMP2) is engineered for sustained BMP2 expression to enhance osteogenic differentiation, with polyethylenimine‐mediated surface conjugation onto MC nanoparticles. Finally, these MC‐circBMP2 (MCB) complexes are integrated into a dopamine‐modified demineralized bone matrix scaffolds to create a hierarchically structured regenerative platform. In vivo experiments showed that the bioactive scaffolds promoted the healing of atrophic nonunion of radial bone defects in rabbits by improving angiogenesis, scavenging ROS, and accelerating the osteogenic differentiation of endogenous cells. The above results indicate that the designed bioactive scaffolds can precisely block the pathology and rapidly initiate the regeneration of damaged tissue, providing theoretical guidance for the regeneration of pathological refractory tissue injuries.
The protein deacetylase HDAC10 controls DNA replication in malignant lymphoid cells
Authors: Andreas O Mieland, Giuseppe Petrosino, Mario Dejung, Jia-Xuan Chen, Amitkumar Fulzele, Fereshteh Mahmoudi, Jia-Wey Tu, Al-Hassan M Mustafa, Yanira Zeyn, Christoph Hieber, Matthias Bros, Tina M Schnöder, Florian H Heidel, Sara Najafi, Ina Oehme, Ilse Hofmann, Mike Schutkowski, Sebastian Hilscher, Christian Kosan, Falk Butter, Sanil Bhatia, Wolfgang Sippl, Oliver H Krämer
Journal: Leukemia (2025)

Abstract Histone deacetylases (HDACs) comprise a family of 18 epigenetic modifiers. The biologically relevant functions of HDAC10 in leukemia cells are enigmatic. We demonstrate that human cultured and primary acute B cell/T cell leukemia and lymphoma cells require the catalytic activity of HDAC10 for their survival. In such cells, HDAC10 controls a MYC-dependent transcriptional induction of the DNA polymerase subunit POLD1. Consequently, pharmacological inhibition of HDAC10 causes DNA breaks and an accumulation of poly-ADP-ribose chains. These processes culminate in caspase-dependent apoptosis. PZ48 does not damage resting and proliferating human normal blood cells. The in vivo activity of PZ48 against ALL cells is verified in a Danio rerio model. These data reveal a nuclear function for HDAC10. HDAC10 controls the MYC-POLD1 axis to maintain the processivity of DNA replication and genome integrity. This mechanistically defined “HDAC10ness” may be exploited as treatment option for lymphoid malignancies.
Abdominal aortic aneurysm histomorphology shows different inflammatory aspects among patients and is not associated with classic risk factors – the HistAAA study
Authors: Maja Carina Nackenhorst, Felix Menges, Bianca Bohmann, David Zschäpitz, Christine Bollwein, Sven Flemming, Nadja Sachs, Wolf Eilenberg, Christine Brostjan, Christoph Neumayer, Matthias Trenner, Wiebke Ibing, Hubert Schelzig, Christian Reeps, Lars Maegdefessel, Heinz Regele, Markus Udo Wagenhäuser, Claus Jürgen Scholz, Thomas Christian Gasser, Albert Busch
Journal: Cardiovascular Research (2025)

Text Abstract Aims Abdominal aortic aneurysm (AAA) treatment is upon a diameter threshold. Attempts for medical growth abrogation have failed thus far. This study aims to elucidate the heterogeneity of AAA histomorphology in correlation to individual patient and aneurysm metrics. Methods and Results Samples from the left anterior aneurysm wall underwent histologic analysis including angiogenesis, calcification, fibrosis, type and grade of inflammation in adventitia and media. Clinical information and state of aneurysm (intact, symptomatic, ruptured, inflammatory) were retrieved. Semi-automated geometric analysis (Endosize©, Therenva) and finite element methods (A4Clinics© Research Edition, Vascops GmbH) were included. 364 patients’ samples (85.4% male, median age 69 years) were scored for acute or chronic inflammation, both not associated with rupture (52x), symptomatic disease (37x) or diameter (57 [52-69] mm; p = 0.87). The degree of fibrosis and the presence of angiogenesis were significantly higher (both p &amp;lt; 0.001) with increasing inflammation, which in turn significantly decreased with patient age (est = - 0.015/year, p = 0.017). No significant differences were seen for acute (vs. elective), male (vs. female) or diabetic patients. Aneurysm geometry (n=252) or annual growth rate (n=142) were not associated with histologic characteristics. Yet, local luminal thrombus formation was significantly higher with increasing inflammation (p = 0.04). Conclusion Type and degree of inflammation are the most distinguishable histologic characteristics in the AAA wall between individual patients, yet are not associated with diameter or rupture. Local luminal thrombus formation is associated with inflammatory features and suggests a vivid bio-physical compartment with intra-individual age-dependent differences.
SpaNorm: spatially-aware normalization for spatial transcriptomics data
Authors: Agus Salim, Dharmesh D Bhuva, Carissa Chen, Chin Wee Tan, Pengyi Yang, Melissa J Davis, Jean Y H Yang
Journal: Genome biology (2025)

Normalization of spatial transcriptomics data is challenging due to spatial association between region-specific library size and biology. We develop SpaNorm, the first spatially-aware normalization method that concurrently models library size effects and the underlying biology, segregates these effects, and thereby removes library size effects without removing biological information. Using 27 tissue samples from 6 datasets spanning 4 technological platforms, SpaNorm outperforms commonly used single-cell normalization approaches while retaining spatial domain information and detecting spatially variable genes. SpaNorm is versatile and works equally well for multicellular and subcellular spatial transcriptomics data with relatively robust performance under different segmentation methods.
Community dynamics during de novo colonization of the nascent peri-implant sulcus
Authors: Tamires Pereira Dutra, Nicolas Robitaille, Khaled Altabtbaei, Shareef M Dabdoub, Purnima S Kumar
Journal: International Journal of Oral Science (2025)

Abstract Dental implants have restored masticatory function to over 100 000 000 individuals, yet almost 1 000 000 implants fail each year due to peri-implantitis, a disease triggered by peri-implant microbial dysbiosis. Our ability to prevent and treat peri-implantitis is hampered by a paucity of knowledge of how these biomes are acquired and the factors that engender normobiosis. Therefore, we combined a 3-month interventional study of 15 systemically and periodontally healthy adults with whole genome sequencing, fine-scale enumeration and graph theoretics to interrogate colonization dynamics in the pristine peri-implant sulcus. We discovered that colonization trajectories of implants differ substantially from adjoining teeth in acquisition of new members and development of functional synergies. Source-tracking algorithms revealed that this niche is initially seeded by bacteria trapped within the coverscrew chamber during implant placement. These pioneer species stably colonize the microbiome and exert a sustained influence on the ecosystem by serving as anchors of influential hubs and by providing functions that enable cell replication and biofilm maturation. Unlike the periodontal microbiome, recruitment of new members to the peri-implant community occurs on nepotistic principles. Maturation is accompanied by a progressive increase in anaerobiosis, however, the predominant functionalities are oxygen-dependent over the 12-weeks. The peri-implant community is easily perturbed following crown placement, but demonstrates remarkable resilience; returning to pre-perturbation states within three weeks. This study highlights important differences in the development of the periodontal and peri-implant ecosystems, and signposts the importance of placing implants in periodontally healthy individuals or following the successful resolution of periodontal disease.
The Severity of Pollen‐Induced Allergic Rhinitis at 16 Years of Age: Data From the Population‐Based <scp>BAMSE</scp> Birth Cohort
Authors: Magnus Lindqvist, Marit Westman, Allan Linneberg, Inger Kull, Anna Bergström, Marianne van Hage, Erik Melén, Katja Biering Leth‐Møller
Journal: Allergy (2025)
Kinesin-like protein KIFC2 stabilizes CDK4 to accelerate growth and confer resistance in HR+/HER2- breast cancer
Authors: Shao-Ying Yang, Ming-Liang Jin, Lisa Andriani, Qian Zhao, Yun-Xiao Ling, Cai-Jin Lin, Min-Ying Huang, Jia-Yang Cai, Yin-Ling Zhang, Xin Hu, Zhi-Ming Shao, Fang-Lin Zhang, Xi Jin, A Yong Cao, Da-Qiang Li
Journal: Journal of Clinical Investigation (2025)

Hormone receptor-positive and human epidermal growth factor receptor 2-negative breast cancer (HR+/HER2- BC) is the most common subtype, with high risk of long-term recurrence and metastasis. Endocrine therapy (ET) combined with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors is a standard treatment for advanced/metastatic HR+/HER2- BC, but resistance remains a major clinical challenge. We report that kinesin family member C2 (KIFC2) was amplified in approximately 50% HR+/HER2- BC, and its high expression was associated with poor disease outcome, increased tumor protein p53 (TP53) somatic mutation, and active pyrimidine metabolism. Function assays revealed that depletion of KIFC2 suppressed growth and enhanced sensitivity of HR+/HER2- BC cells to tamoxifen and CDK4/6 inhibitors. Mechanistically, KIFC2 stabilized CDK4 by enhancing its interaction with ubiquitin specific peptidase 9 X-linked (USP9X). Importantly, re-expression of CDK4 in KIFC2-depleted cells partially rescued the decreased growth and increased sensitivity to tamoxifen and CDK4/6 inhibitors caused by KIFC2 depletion. Clinically, high KIFC2 mRNA expression was negatively associated with survival rate of HR+/HER2- BC patients received adjuvant ET alone or in combination with CDK4/6 inhibitors. Collectively, these findings identify an important role for KIFC2 in HR+/HER2- BC growth and therapeutic resistance, and support its potential as a therapeutic target and predictive biomarker.
DNA demethylating agents suppress preclinical models of synovial sarcoma
Authors: Nobuhiko Hasegawa, Nezha S Benabdallah, Kyllie Smith-Fry, Li Li, Sarah McCollum, Jinxiu Li, Caelen A Jones, Lena Wagner, Vineet Dalal, Viola Golde, Anastasija Pejkovska, Lara Carroll, Malay Haldar, Seth M Pollack, Scott W Lowe, Torsten O Nielsen, Ana Banito, Kevin B Jones
Journal: Journal of Clinical Investigation (2025)

Synovial sarcoma is an aggressive soft tissue cancer driven by the chimeric SS18::SSX fusion oncoprotein, which disrupts chromatin remodeling by combining two antagonistic transcriptional regulators. SS18 participates in BAF complexes that open chromatin, while the SSX genes are cancer-testis antigens that interface with chromatin decorated with monoubiquitinated histone H2A placed by Polycomb repressive complexes (PRCs) activity. Because KDM2B brings PRC to unmethylated CpG islands, it is plausible that methylation directly determines the distribution of SS18::SSX to target loci. Given that synovial sarcoma is also characterized by a peculiarly low DNA hypomethylation profile, we hypothesized that further disturbance of DNA methylation would have a negative impact on synovial sarcoma growth. DNMT1 disruption by CRISPR/Cas9 targeting or pharmacologic inhibition with cytidine analogs 5-aza-2'-deoxycytidine (decitabine) and 5-azacytidine led to decreased genome-wide methylation, redistribution of SS18::SSX, and altered gene expression profiles, most prominently including upregulation of tumor suppressor genes, immune-related genes, and mesenchymal differentiation-related genes. These drugs suppressed growth of synovial sarcoma cell lines and drove cytoreduction in mouse genetic models. DNMT1 inhibitors, already approved for treating myelodysplastic syndromes, warrant further clinical investigation for synovial sarcoma as repurposed, targeted treatments exploiting a vulnerability in the intrinsic biology of this cancer.
OCA-B promotes pathogenic maturation of stem-like CD4+ T cells and autoimmune demyelination
Authors: Erik P Hughes, Amber R Syage, Elnaz Mirzaei Mehrabad, Thomas E Lane, Benjamin T Spike, Dean Tantin
Journal: Journal of Clinical Investigation (2025)

Stem-like T cells selectively contribute to autoimmunity, but the activities that promote their pathogenicity are incompletely understood. Here, we identify the transcription coregulator OCA-B as a driver of the pathogenic maturation of stem-like CD4+ T cell to promote autoimmune demyelination. Using two human multiple sclerosis (MS) datasets, we show that POU2AF1, the gene encoding OCA-B, is elevated in CD4+ T cells from MS patients. We show that T cell-intrinsic OCA-B loss protects mice from experimental autoimmune encephalomyelitis (EAE) while preserving responses to viral CNS infection. In EAE models driven by antigen reencounter, OCA-B deletion nearly eliminates CNS infiltration, proinflammatory cytokine production and clinical disease. OCA-B-expressing CD4+ T cells of mice primed with autoantigen express an encephalitogenic gene program and preferentially confer disease. In a relapsing-remitting EAE model, OCA-B loss protects mice specifically at relapse. During remission, OCA-B promotes the expression of Tcf7, Slamf6, and Sell in proliferating CNS T cell populations. At relapse timepoints, OCA-B loss results in both the accumulation of an immunomodulatory CD4+ T cell population expressing Ccr9 and Bach2, and loss of pro-inflammatory gene expression from Th17 cells. These results identify OCA-B as a driver of pathogenic CD4+ T cells.