tbuckley/cabot-search huggingface dataset:
Astrocyte-to-neuron H2O2 signalling supports long-term memory formation in Drosophila and is impaired in an Alzheimer’s disease model
Authors: Yasmine Rabah, Jean-Paul Berwick, Nisrine Sagar, Laure Pasquer, Pierre-Yves Plaçais, Thomas Preat
Journal: Nature Metabolism (2025)

Abstract Astrocytes help protect neurons from potential damage caused by reactive oxygen species (ROS). While ROS can also exert beneficial effects, it remains unknown how neuronal ROS signalling is activated during memory formation, and whether astrocytes play a role in this process. Here we discover an astrocyte-to-neuron H 2 O 2 signalling cascade in Drosophila that is essential for long-term memory formation. Stimulation of astrocytes by acetylcholine induces an increase in intracellular calcium ions, which triggers the generation of extracellular superoxide (O 2 • – ) by astrocytic NADPH oxidase. Astrocyte-secreted superoxide dismutase 3 (Sod3) converts O 2 • – to hydrogen peroxide (H 2 O 2 ), which is imported into neurons of the olfactory memory centre, the mushroom body, as revealed by in vivo H 2 O 2 imaging. Notably, Sod3 activity requires copper ions, which are supplied by neuronal amyloid precursor protein. We also find that human amyloid-β peptide, implicated in Alzheimer’s disease, inhibits the nAChRα7 astrocytic cholinergic receptor and impairs memory formation by preventing H 2 O 2 synthesis. These findings may have important implications for understanding the aetiology of Alzheimer’s disease.
TRIM28-dependent developmental heterogeneity determines cancer susceptibility through distinct epigenetic states
Authors: Ilaria Panzeri, Luca Fagnocchi, Stefanos Apostle, Megan Tompkins, Emily Wolfrum, Zachary Madaj, Galen Hostetter, Yanqing Liu, Kristen Schaefer, Chih-Hsiang Yang, Alexis Bergsma, Anne Drougard, Erez Dror, Zachary DeBruine, Mao Ding, Holly Dykstra, Brooke Grimaldi, Tim Gruber, Qingchu Jin, Christine W. Lary, Mitchell J. McDonald, Joseph H. Nadeau, Andrea Parham, Ildiko Polyak, Jillian Richards, Gabriel Seifert, Ember Tokarski, Raimond L. Winslow, Darrell P. Chandler, Daniel Schramek, Timothy J. Triche, John Andrew Pospisilik
Journal: Nature Cancer (2025)
Phase II Trial of Brain MRI Surveillance in Stage IV Breast Cancer
Authors: Kamran A Ahmed, Youngchul Kim, Avan J Armaghani, John A Arrington, Ricardo L Costa, Brian J Czerniecki, Roberto Diaz, Robin A Dowell, Martine Extermann, Peter A Forsyth, Kimberley T Lee, Loretta Loftus, Matthew N Mills, Vania H Phuoc, Marilin Rosa, Hatem H Soliman, Christine S Sam, Iman R Washington, Aixa E Soyano, Hyo S Han
Journal: Neuro-Oncology (2025)

Abstract Background Screening of asymptomatic stage IV breast cancer with brain MRIs is currently not recommended by National Comprehensive Cancer Network (NCCN) Guidelines. The incidence of asymptomatic brain metastasis is not well documented. Methods The study is designed as a single arm, phase II trial, with the goal of investigating surveillance brain MRIs in neurologically asymptomatic patients with metastatic breast cancer. Breast cancer patients were classified into triple negative (TN), HER2+, and hormone receptor (HR)+/HER2-. Patients underwent a surveillance brain MRI and a second brain MRI at 6 months if the baseline MRI was negative. Asymptomatic, stage IV breast cancer patients, ECOG ≤2, and life expectancy ≥6 months were eligible. The primary objective was to determine the frequency of asymptomatic brain metastasis in metastatic breast cancer. Clinical trial information: NCT05115474. Results A total of 101 patients completed the surveillance brain MRI including 40 HR+/HER2-, 33 HER2+, and 28 TN patients. The overall frequency of brain metastasis on initial surveillance brain MRI was 14% (n=14) with rates of 18%, 15%, and 10% in TN, HER2+, and HR+/HER2- patients, respectively. Following the 6-month MRI, the cumulative rates of brain metastasis increased to 25% in TN, 24% in HER2+, and 23% in HR+/HER2- patients. Conclusions The highest frequency of brain metastases at baseline was in TN and HER2+ breast cancer. Following the 6-month MRI, the cumulative frequency was approximately a quarter across all subtypes. These results warrant confirmatory trials to refine brain MRI surveillance recommendations for neurologically asymptomatic stage IV breast cancer.
A Mitochondria-Targeted Nanozyme with Enhanced Antioxidant Activity to Prevent Acute Liver Injury by Remodeling Mitochondria Respiratory Chain
Authors: Xin Gao, Xinjian Yang, Chunlin Deng, Yaxiao Chen, Yueying Bian, Xinyu Zhang, Yi Jin, Jinchao Zhang, Xing-Jie Liang
Journal: Biomaterials (2025)
The design of retroviral vectors used in the CAR‐T products, risk management, and future perspective
Authors: Huifang Yin, Xuejing Wei
Journal: MedComm (2025)

Abstract Chimeric antigen receptor T‐cell (CAR‐T) therapy is a revolutionary approach in cancer treatment. More than 10 CAR‐T products have already approved on market worldly wide, and they use either gamma retroviral vectors or lentiviral vectors to deliver the CAR gene. Both vectors have the ability to effectively and persistently integrate the CAR gene into T cells. Despite the advancements in CAR‐T therapy, the potential risks associated with the vectors, particularly the risks of the secondary malignancies, still remain as a concern. This article compares the characteristics of gamma retroviral and lentiviral vectors, discusses the development of vector packaging systems, and examines the design of self‐inactivating (SIN) vectors. It also addresses the risks of secondary malignancies that might possibly be associated with the retroviral vectors, and the strategies to decrease the risks and increase the safer clinical use of the vectors. This article also discusses the current regulatory landscape and management approaches aiming to mitigate these risks through stringent safety measures and ongoing monitoring. Future perspectives focus on improving the safety profiles of the vectors and broadening their scope of use. The article provides a thorough overview of the most recent research discoveries and regulatory updates in the field of CAR‐T therapy, highlighting the significance of a balanced strategy that strikes a balance between innovation and patient safety in the development and implementation of CAR‐T therapy.
Multifunctional Microflowers for Precise Optoacoustic Localization and Intravascular Magnetic Actuation In Vivo
Authors: Daniil Nozdriukhin, Shuxin Lyu, Jérôme Bonvin, Michael Reiss, Daniel Razansky, Xosé Luís Deán‐Ben
Journal: Advanced Healthcare Materials (2025)

Abstract Efficient drug delivery remains a significant challenge in modern medicine and pharmaceutical research. Micrometer‐scale robots have recently emerged as a promising solution to enhance the precision of drug administration through remotely controlled navigation within microvascular networks. Real‐time tracking is crucial for accurate guidance and confirmation of target arrival. However, deep‐tissue monitoring of microscopic structures in vivo is limited by the sensitivity and spatiotemporal resolution of current bioimaging techniques. In this study, biocompatible microrobots are synthesized by incorporating indocyanine green and iron oxide nanoparticles onto copper phosphate microflowers using a layer‐by‐layer approach, enhancing optoacoustic contrast and enabling magnetic navigation. Magnetic control of these particles under optoacoustic guidance is demonstrated in vivo. Furthermore, super‐resolution optoacoustic imaging, achieved through individual particle tracking, is shown to enable the characterization of microvascular structures and quantification of blood flow. The combination of the microflowers' high carrying capacity, in vivo actuation, and high‐resolution tracking capabilities opens new opportunities for precise microvascular targeting and localized administration of theranostic agents via intravascular routes.
At the nucleus of cancer: how the nuclear envelope controls tumor progression
Authors: Francesca Paganelli, Alessandro Poli, Serena Truocchio, Alberto M. Martelli, Carla Palumbo, Giovanna Lattanzi, Francesca Chiarini
Journal: MedComm (2025)

Abstract Historically considered downstream effects of tumorigenesis—arising from changes in DNA content or chromatin organization—nuclear alterations have long been seen as mere prognostic markers within a genome‐centric model of cancer. However, recent findings have placed the nuclear envelope (NE) at the forefront of tumor progression, highlighting its active role in mediating cellular responses to mechanical forces. Despite significant progress, the precise interplay between NE components and cancer progression remains under debate. In this review, we provide a comprehensive and up‐to‐date overview of how changes in NE composition affect nuclear mechanics and facilitate malignant transformation, grounded in the latest molecular and functional studies. We also review recent research that uses advanced technologies, including artificial intelligence, to predict malignancy risk and treatment outcomes by analyzing nuclear morphology. Finally, we discuss how progress in understanding nuclear mechanics has paved the way for mechanotherapy—a promising cancer treatment approach that exploits the mechanical differences between cancerous and healthy cells. Shifting the perspective on NE alterations from mere diagnostic markers to potential therapeutic targets, this review calls for further investigation into the evolving role of the NE in cancer, highlighting the potential for innovative strategies to transform conventional cancer therapies.
3D Mechanical Response Stem Cell Complex Repairs Spinal Cord Injury by Promoting Neurogenesis and Regulating Tissue Homeostasis
Authors: Jingwei Jiu, Haifeng Liu, Dijun Li, Xiaoke Li, Jing Zhang, Lei Yan, Zijuan Fan, Songyan Li, Guangyuan Du, Jiao Jiao Li, Aimin Wu, Wei Liu, Yanan Du, Bin Zhao, Bin Wang
Journal: Advanced Healthcare Materials (2025)

Abstract Spinal cord injury (SCI) leads to acute tissue damage that disrupts the microenvironmental homeostasis of the spinal cord, inhibiting cell survival and function, and thereby undermining treatment efficacy. Traditional stem cell therapies have limited success in SCI, due to the difficulties in maintaining cell survival and inducing sustained differentiation into neural lineages. A new solution may arise from controlling the fate of stem cells by creating an appropriate mechanical microenvironment. In this study, mechanical response stem cell complex (MRSCC) is created as an innovative therapeutic strategy for SCI, utilizing 3D bioprinting technology and gelatin microcarriers (GM) loaded with mesenchymal stem cells (MSCs). GM creates an optimal microenvironment for MSCs growth and paracrine activity. Meanwhile, 3D bioprinting allows accurate control of spatial pore architecture and mechanical characteristics of the cell construct to encourage neuroregeneration. The mechanical microenvironment created by MRSCC is found to activate the Piezo1 channel and prevent excessive nuclear translocation of YAP, thereby increasing neural‐related gene expression in MSCs. Transplanting MRSCC in rats with spinal cord injuries boosts sensory and motor recovery, reduces inflammation, and stimulates the regeneration of neurons and glial cells. The MRSCC offers a new tissue engineering solution that can promote spinal cord repair.
V3+ extends the V3 framework to ensure user-centricity and scalability of sensor-based digital health technologies
Authors: Jessie P. Bakker, Roland Barge, Jacob Centra, Bryan Cobb, Chas Cota, Christine C. Guo, Bert Hartog, Nathalie Horowicz-Mehler, Elena S. Izmailova, Nikolay V. Manyakov, Samantha McClenahan, Stéphane Motola, Smit Patel, Oana Paun, Marian Schoone, Emre Sezgin, Thomas Switzer, Animesh Tandon, Willem van den Brink, Srinivasan Vairavan, Benjamin Vandendriessche, Bernard Vrijens, Jennifer C. Goldsack
Journal: npj Digital Medicine (2025)

We propose the addition of usability validation to the extended V3 framework, now "V3+", and describe a pragmatic approach to ensuring that sensor-based digital health technologies can be used optimally at scale by diverse users. Alongside the original V3 components (verification; analytical validation; clinical validation), usability validation will ensure user-centricity of digital measurement tools, paving the way for more inclusive, reliable, and trustworthy digital measures within clinical research and clinical care.
A novel framework for assessing causal effect of microbiome on health: long-term antibiotic usage as an instrument
Authors: Nele Taba, Krista Fischer, None Estonian Biobank Research Team, Elin Org, Oliver Aasmets
Journal: Gut Microbes (2025)

Assessing causality is undoubtedly one of the key questions in microbiome studies for the upcoming years. Since randomized trials in human subjects are often unethical or difficult to pursue, analytical methods to derive causal effects from observational data deserve attention. As simple covariate adjustment is not likely to account for all potential confounders, the idea of instrumental variable (IV) analysis is worth exploiting. Here we propose a novel framework of antibiotic instrumental variable regression (AB-IVR) for estimating the causal relationships between microbiome and various diseases. We rely on the recent studies showing that antibiotic treatment has a cumulative long-term effect on the microbiome, resulting in individuals with higher antibiotic usage to have a more perturbed microbiome. We apply the AB-IVR method on the Estonian Biobank data and show that the microbiome has a causal role in numerous diseases including migraine, depression and irritable bowel syndrome. We show with a plethora of sensitivity analyses that the identified causal effects are robust and propose ways for further methodological developments.
Association of age, race, and ethnicity with access, response, and toxicities from CAR-T therapy in children and adults with B-cell malignancies: a review
Authors: Guido Ghilardi, Zainul S Hasanali, Sandra P Susanibar-Adaniya, Lena E Winestone, Marco Ruella, Alfred L Garfall
Journal: Journal for ImmunoTherapy of Cancer (2025)

Chimeric antigen receptor T cell (CAR-T) therapies are now standard-of-care for several B-cell malignancies, and additional indications are being evaluated. In this review, we survey data on how outcomes after CAR-T therapies vary according to age, race, and ethnicity. We also review the representation of age, racial, and ethnic groups in key CAR-T clinical trials. We focus on B-cell acute lymphoblastic leukemia, B-cell non-Hodgkin’s lymphoma, and multiple myeloma.
Neoadjuvant anti-PD-1-based immunotherapy: evolving a new standard of care
Authors: Suzanne L Topalian, Drew M Pardoll
Journal: Journal for ImmunoTherapy of Cancer (2025)

Neoadjuvant (presurgical) anti-programmed cell death protein-1 (PD-1)-based immunotherapy as a new approach to cancer treatment has been developing on an accelerated trajectory since the seminal clinical trial results from studies in lung cancer and melanoma were published in 2018. Groundbreaking regulatory approvals in triple-negative breast cancer, non-small cell lung cancer and melanoma will certainly be followed by additional approvals in other disease indications, as clinical and basic research are burgeoning globally in hundreds of clinical trials across dozens of cancer types. As this field is evolving, it is addressing gaps in our understanding of biological mechanisms underlying PD-1 pathway blockade and their synergy with other antineoplastic drugs, probing mechanisms of response and resistance to neoadjuvant immunotherapy, optimizing efficacious clinical strategies, and analyzing commonalities and differences across cancer types. Knowledge gained thus far provides a firm foundation from which to launch the next phase of translational research in this expanding arena of biomedical investigation.
A multimodal transformer system for noninvasive diabetic nephropathy diagnosis via retinal imaging
Authors: Zheyi Dong, Xiaofei Wang, Sai Pan, Taohan Weng, Xiaoniao Chen, Shuangshuang Jiang, Ying Li, Zonghua Wang, Xueying Cao, Qian Wang, Pu Chen, Lai Jiang, Guangyan Cai, Li Zhang, Yong Wang, Jinkui Yang, Yani He, Hongli Lin, Jie Wu, Li Tang, Jianhui Zhou, Shengxi Li, Zhaohui Li, Yibing Fu, Xinyue Yu, Yanqiu Geng, Yingjie Zhang, Liqiang Wang, Mai Xu, Xiangmei Chen
Journal: npj Digital Medicine (2025)
Chronic kidney disease–mineral and bone disorder: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference
Authors: Markus Ketteler, Pieter Evenepoel, Rachel M Holden, Tamara Isakova, Hanne Skou Jørgensen, Hirotaka Komaba, Thomas L Nickolas, Smeeta Sinha, Marc G Vervloet, Michael Cheung, Jennifer M King, Morgan E Grams, Michel Jadoul, Rosa M A Moysés
Journal: Kidney International (2025)
Biology of extracellular vesicles and the potential of tumor-derived vesicles for subverting immunotherapy of cancer
Authors: Theresa L Whiteside
Journal: Journal for ImmunoTherapy of Cancer (2025)

Extracellular vesicles (EVs) are produced by all living cells and are present in all body fluids. EVs are heterogeneous in size, biogenesis, molecular/genetic content and functions. They constitute a part of the intercellular communication system. Among them, a subset of small EVs (sEVs) (30–150 nm) originating in the tumor cell endosomes and often referred to as “tumor cell-derived exosomes” have been of special interest. Tumors have adapted sEV they produce to promoting their own survival. Plasma of patients with cancer contains variably elevated numbers of tumor-derived sEV called “TEX,” which differ from circulating sEV produced by non-malignant cells by the immunosuppressive phenotype and the molecular/genetic content. Immunosuppressive molecular profiles and abilities to signal, enter and functionally reprogram a variety of recipient cells enable TEX to exert pro-tumor effects that promote tumor resistance to immunotherapy. This review describes phenotypic and functional attributes of TEX that underline their reprogramming capabilities. It also considers mechanisms responsible for TEX pro-tumor activities and the potential significance of TEX signaling for responses of patients with cancer to immune therapies.
Corrigendum to “Shield and sword nano-soldiers ameliorate rheumatoid arthritis by multi-stage manipulation of neutrophils” [Journal of Controlled Release, Volume 335 (2021), Pages 38–48]
Authors: Jiaxin Li, Yang Long, Rong Guo, Kebai Ren, Zhengze Lu, Man Li, Xuhui Wang, Jiaxin Li, Yashi Wang, Zhirong Zhang, Qin He
Journal: Journal of Controlled Release (2025)
Self-assembled HO-1i-Pt(IV) nanomedicine targeting p38/MAPK and MDR pathways for cancer chemo-immunotherapy
Authors: Xiao-Meng Liu, Zhe Li, Xiao-Ya Wang, Bo-Wen Ding, Jia-Qian Wang, Xin Qiao, Yu-Kuan Feng, Ji-Hui Hao, Jing-Yuan Xu
Journal: Journal of Controlled Release (2025)
Decoding the Therapeutic Target SVEP1: Harnessing Molecular Trait GWASs to Unravel Mechanisms of Human Disease
Authors: Jared S. Elenbaas, Paul C. Lee, Ved Patel, Nathan O. Stitziel
Journal: The Annual Review of Pharmacology and Toxicology (2025)

Although human genetics has substantial potential to illuminate novel disease pathways and facilitate drug development, identifying causal variants and deciphering their mechanisms remain challenging. We believe these challenges can be addressed, in part, by creatively repurposing the results of molecular trait genome-wide association studies (GWASs). In this review, we introduce techniques related to molecular GWASs and unconventionally apply them to understanding SVEP1, a human coronary artery disease risk locus. Our analyses highlight SVEP1's causal link to cardiometabolic disease and glaucoma, as well as the surprising discovery of SVEP1 as the first known physiologic ligand for PEAR1, a critical receptor governing platelet reactivity. We further employ these techniques to dissect the interactions between SVEP1, PEAR1, and the Ang/Tie pathway, with therapeutic implications for a constellation of diseases. This review underscores the potential of molecular GWASs to guide drug discovery and unravel the complexities of human health and disease by demonstrating an integrative approach that grounds mechanistic research in human biology.
Pharmacogenetics: Opportunities for the All of Us Research Program and Other Large Data Sets to Advance the Field
Authors: Philip E. Empey, Jason H. Karnes, Julie A. Johnson
Journal: The Annual Review of Pharmacology and Toxicology (2025)

Pharmacogenetic variation is common and an established driver of response for many drugs. There has been tremendous progress in pharmacogenetics knowledge over the last 30 years and in clinical implementation of that knowledge over the last 15 years. But there have also been many examples where translation has stalled because of the lack of available data sets for discovery or validation research. The recent availability of data from very large cohorts with linked genetic, electronic health record, and other data promises new opportunities to advance pharmacogenetics research. This review presents the stages from pharmacogenetics discovery to widespread clinical adoption using prominent gene-drug pairs that have been implemented into clinical practice as examples. We discuss the opportunities that the All of Us Research Program and other large biorepositories with genomic and linked electronic health record data present in advancing and accelerating the translation of pharmacogenetics into clinical practice.
G Protein–Coupled Receptor Heteromers in Brain: Functional and Therapeutic Importance in Neuropsychiatric Disorders
Authors: Yalin Sun, Ahmed Hasbi, Susan R. George
Journal: The Annual Review of Pharmacology and Toxicology (2025)

G protein-coupled receptors (GPCRs) represent the largest family of plasma membrane proteins targeted for therapeutic development. For decades, GPCRs were investigated as monomeric entities during analysis of their pharmacology or signaling and during drug development. However, a considerable body of evidence now indicates that GPCRs function as dimers or higher-order oligomers. Greater acceptance of oligomerization occurred with the recognition that GPCR interactions form heteromeric receptor complexes, which was validated in vivo, often with pharmacologic, signaling, and functional properties distinct from the constituent protomers. GPCR heteromerization is reviewed in the context of brain disorders, with examples illustrating their functional implication in diverse neuropsychiatric and neurodegenerative disorders, making them an enormous unexploited resource for selective pharmacotherapy target identification. The strategies for development of heteromer-selective ligands are discussed as a new opportunity to precisely target the function of a receptor complex with greater specificity, in contrast to the classical ligands targeting individual receptors.
Toluene Toxicity in the Brain: From Cellular Targets to Molecular Mechanisms
Authors: Andrew A. Shaw, Jeffery D. Steketee, Anna N. Bukiya, Alex M. Dopico
Journal: The Annual Review of Pharmacology and Toxicology (2025)

Toluene intoxication constitutes a persistent public health problem worldwide. While most organs can be damaged, the brain is a primary target whether exposure is accidental, occupational, or recreational. Interventions to prevent/revert brain damage by toluene are curtailed by the scarce information on the molecular targets and mechanisms mediating toluene's brain toxicity and the common exposure to other neurotoxins and/or coexistence of neurological/psychiatric disorders. We examine (a) the physicochemical properties of toluene that allow this inhalant to primarily target the lipid-rich brain; (b) the cell types targeted by toluene (neurons, different types of glia), while considering a cerebrovascular component; and (c) putative molecular mechanisms by which toluene may modify receptor function while analyzing structural features that allow toluene to directly interact with membrane lipids or specific proteins. This information constitutes a stepping stone to design pharmacotherapies that counteract toluene brain intoxication.