tbuckley/cabot-search huggingface dataset:
Posttranslational Modification in Bone Homeostasis and Osteoporosis
Authors: Yuzhe Lin, Shide Jiang, Yuming Yao, Hengzhen Li, Hongfu Jin, Guang Yang, Bingzhou Ji, Yusheng Li
Journal: MedComm (2025)

ABSTRACT Bone is responsible for providing mechanical protection, attachment sites for muscles, hematopoiesis micssroenvironment, and maintaining balance between calcium and phosphorate. As a highly active and dynamically regulated organ, the balance between formation and resorption of bone is crucial in bone development, damaged bone repair, and mineral homeostasis, while dysregulation in bone remodeling impairs bone structure and strength, leading to deficiency in bone function and skeletal disorder, such as osteoporosis. Osteoporosis refers to compromised bone mass and higher susceptibility of fracture, resulting from several risk factors deteriorating the balanced system between osteoblast‐mediated bone formation and osteoclast‐mediated bone resorption. This balanced system is strictly regulated by translational modification, such as phosphorylation, methylation, acetylation, ubiquitination, sumoylation, glycosylation, ADP‐ribosylation, S‐palmitoylation, citrullination, and so on. This review specifically describes the updating researches concerning bone formation and bone resorption mediated by posttranslational modification. We highlight dysregulated posttranslational modification in osteoblast and osteoclast differentiation. We also emphasize involvement of posttranslational modification in osteoporosis development, so as to elucidate the underlying molecular basis of osteoporosis. Then, we point out translational potential of PTMs as therapeutic targets. This review will deepen our understanding between posttranslational modification and osteoporosis, and identify novel targets for clinical treatment and identify future directions.
Dynamic Alterations in DNA Methylation of CD4<sup>+</sup> T Cells and Macrophages in a Murine Model of Tuberculous Pleural Infection Induced by BCG Vaccination
Authors: Ming‐Ming Shao, Qing‐Yu Chen, Xin Zhang, Shu‐Feng Dong, Rui‐Qi Wei, Huan‐Zhong Shi, Feng‐Shuang Yi
Journal: MedComm (2025)

ABSTRACT Tuberculous pleural effusion (TPE) is a prevalent form of extrapulmonary tuberculosis, and immune abnormalities play a crucial role in promoting its development. However, the dynamic changes and regulatory characteristics of immune cells during TPE progression remain incompletely understood. This study analyzed DNA methylation and transcriptome data from macrophages and CD4 + T cells from pleural lavage fluid of BCG‐induced tuberculous pleurisy mouse models at specific time points (Days 0, 1, 7, and 14). The results revealed substantial alterations in DNA methylation patterns associated with inflammatory factors and interferon genes. Notably, macrophages exhibited the most pronounced differences in DNA methylation profiles on Day 1, while CD4 + T cells demonstrated gradual changes over time. The investigation further indicated that DNA methylation primarily regulated the differentiation of Th1, Th17, and Th22 cells but not Th9 cells. Additionally, single‐cell RNA sequencing analysis revealed an increasing expression of C1q during infection, which was regulated by DNA methylation. Importantly, C1q + and C1q − macrophages demonstrated distinct roles in modulating immune responses during infection. This research provides valuable insights into the DNA methylation profile of immune cells during Mycobacterium bovis infection–induced pleurisy in a mouse model, enhancing our understanding of the upstream regulatory mechanisms underlying immune response development in TPE.
Emerging Therapies and Real-World Application of Metabolic Dysfunction-Associated Steatotic Liver Disease Treatment
Authors: Hee Yeon Kim, Mary E Rinella
Journal: Clinical and Molecular Hepatology (2025)

Metabolic dysfunction-associated steatotic liver disease, formerly referred to as non-alcoholic fatty liver disease, is the most common liver disease in Western countries and has emerged as the leading indication for liver transplantation. Metabolic dysfunction-associated steatohepatitis (MASH), a more advanced stage, carries a high risk of progression to liver fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. Until recently, lifestyle intervention remained the mainstay of MASH management, with no pharmacological treatments specifically approved. However, advances in understanding its pathophysiological mechanisms have fueled numerous clinical trials, culminating in the FDA's approval of resmetirom as the first treatment for MASH in 2024. Additionally, many investigational drugs are nearing FDA approval or progressing through late-stage clinical trials. This review examines the current therapeutic landscape, highlights strategies for identifying patients suitable for liver-directed therapies in real-world settings, and discusses the challenges that remain.
FGFR2 Abrogation Intercepts Pancreatic Ductal Adenocarcinoma Development
Authors: Claudia Tonelli, Astrid Deschênes, Victoria A. Gaeth, Amanda Jensen, Nandan Vithlani, Melissa A. Yao, Zhen Zhao, Youngkyu Park, David A. Tuveson
Journal: Cancer Research (2025)

Abstract Activating KRAS mutations are a key feature of pancreatic ductal adenocarcinoma (PDA) and drive tumor initiation and progression. However, mutant KRAS by itself is weakly oncogenic. Defining the pathways that cooperate with mutant KRAS to induce tumorigenesis could identify prevention and treatment strategies. Analyzing organoids and murine and human pancreatic specimens, we found that the receptor tyrosine kinase FGFR2 was progressively up-regulated in mutant KRAS-driven metaplasia, pre-cancerous lesions and classical PDA. In genetic mouse models, FGFR2 inactivation impeded mutant KRAS-driven transformation of acinar cells by reducing proliferation and MAPK pathway activation. FGFR2 abrogation significantly delayed tumor formation and extended the survival of these mice. Furthermore, FGFR2 collaborated with EGFR and dual blockade of these receptor signaling pathways significantly reduced mutant KRAS-induced pre-cancerous lesion formation. Together, these data have uncovered a pivotal role for FGFR2 in the early phases of pancreatic tumorigenesis, paving the way for future therapeutic applications of FGFR2 inhibitors for pancreatic cancer interception.
Response to “Comment on ‘IARC Workshop on the Key Characteristics of Carcinogens: Assessment of End Points for Evaluating Mechanistic Evidence of Carcinogenic Hazards’”
Authors: David M. DeMarini, Weihsueh A. Chiu, Kathryn Z. Guyton, William Gwinn, Brad Reisfeld, Amy Wang, Aline de Conti, Mary K. Schubauer-Berigan, Federica Madia
Journal: Environmental Health Perspectives (2025)
Targeted therapies overcome the poor prognosis of stereotyped Subset#2 chronic lymphocytic leukemia : a real-world multicentric study
Authors: Lucile Bussot, Stéphanie Poulain, Morgane Nudel Ortmans, Frédéric Davi, Damien Roos-Weil, Stéphane Lepretre, Doriane Richard, Cédric Pastoret, Anne Desmares, Emmanuelle Ferrant, Sarah Huet, Pierre Sujobert, Eric Delabesse, Loïc Ysebaert, Grégory Lazarian, Anne-Sophie Michallet, Audrey Bidet, Marie Sarah Dilhuydy, Marie-Hélène Delfau-Larue, Jehan Dupuis, Aline Clavert, Bernard Drenou, Elsa Maitre, Xavier Troussard, Edouard Cornet, Yannick Le Bris, Anne Lok, Bruno Villemagne, Hélène Barbier, Marie C Béné, Cécile Tomowiak, Stéphanie Tardy, Pascale Cornillet-Lefebvre, Anne Quinquenel, Romain Guièze, Sarah Barbieux, Isabelle Plantier, Julia Hieulle, Pascale Flandrin Gresta, Jérôme Cornillon, Sophie Dupire, Kamel Laribi, Pierre Feugier, Caroline Algrin, Florence Lachenal, Adrien Caillet, Anne Murati, Luca Inchiappa, Céline Lechat, Caroline Dartigeas, Émilie Montaut, Lysiane Molina, Sylvain Carras
Journal: Leukemia (2025)
Genome-wide CRISPR/Cas9 screen reveals factors that influence the susceptibility of tumor cells to NK cell-mediated killing
Authors: Sophie Guia, Aurore Fenis, Camille Baudesson De Chanville, Justine Galluso, Hakim Medjouel, Bertrand Escaliere, Angelika Modelska, Margaux Vienne, Noella Lopes, Amelie Pouchin, Benjamin Rossi, Laurent Gauthier, Sandrine Roulland, Eric Vivier, Emilie Narni-Mancinelli
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Natural killer (NK) cells exhibit potent cytotoxic activity against various cancer cell types. Over the past five decades, numerous methodologies have been employed to elucidate the intricate molecular mechanisms underlying NK cell-mediated tumor control. While significant progress has been made in elucidating the interactions between NK cells and tumor cells, the regulatory factors governing NK cell-mediated tumor cell destruction are not yet fully understood. This includes the diverse array of tumor ligands recognized by NK cells and the mechanisms that NK cells employ to eliminate tumor cells. Methods In this study, we employed a genome-wide CRISPR/Cas9 screening approach in conjunction with functional cytotoxicity assays to delineate the pathways modulating the susceptibility of colon adenocarcinoma HCT-116 cells to NK cell-mediated cytotoxicity. Results Analysis of guide RNA distribution in HCT-116 cells that survived co-incubation with NK cells identified ICAM-1 as a pivotal player in the NKp44-mediated immune synapse, with NKp44 serving as an activating receptor crucial for the elimination of HCT-116 tumor cells by NK cells. Furthermore, disruption of genes involved in the apoptosis or interferon (IFN)-γ signaling pathways conferred resistance to NK cell attack. We further dissected that NK cell-derived IFN-γ promotes mitochondrial apoptosis in vitro and exerts control over B16-F10 lung metastases in vivo. Conclusion Monitoring ICAM-1 levels on the surface of tumor cells or modulating its expression should be considered in the context of NK cell-based therapy. Furthermore, promoting FasL expression on the NK cell surface is reaffirmed as an important strategy to enhance NK cell-mediated tumor killing, offering an additional avenue for therapeutic optimization. Additionally, considering the diffusion properties of IFN-γ, our findings highlight the potential of leveraging NK cell-derived IFN-γ to enhance direct tumor cell killing and facilitate bystander effects via cytokine diffusion, warranting further investigation.
C3G promotes bone marrow adipocyte expansion and hematopoietic regeneration after myeloablation by enhancing megakaryocyte niche function
Authors: Óscar Herranz, Pablo Berrocal, Carmen Sicilia-Navarro, Cristina Fernández-Infante, Luis Hernández-Cano, Almudena Porras, Carmen Guerrero
Journal: Journal of Hematology & Oncology (2025)
Saturated fatty acid-induced neutrophil extracellular traps contribute to exacerbation and biologic therapy resistance in obesity-related psoriasis
Authors: Yuting Xia, Jiajia Lan, Jing Yang, Shijie Yuan, Xiaorong Xie, Qiuyang Du, Hongyao Du, Wenjia Nie, Biling Jiang, Liang Zhao, Zhen Cai, Xin Zhang, Yan Xiong, Yan Li, Ran He, Juan Tao
Journal: Cellular and Molecular Immunology (2025)
Ambient formaldehyde combined with high temperature exposure and respiratory disease admissions among children: a time-series study across multiple cities
Authors: Yuting Cheng, Mingzhi Zhang, Hao Zheng, Qiurun Yu, Hongcheng Wei, Ruibin Xue, Shanshan Wang, Bo Hang, Atsuko Ikeda, Yuming Guo, Yankai Xia
Journal: Thorax (2025)

Introduction Ambient formaldehyde (HCHO) is globally distributed, posing significant exposure to vast populations, particularly vulnerable demographics such as children. Investigations into the correlation between ambient HCHO exposure and children’s respiratory ailments are deficient. Methods Ambient HCHO exposure was retrieved from the TROPOspheric Monitoring Instrument. A two-stage time-series analysis was conducted to examine the relationship between HCHO exposure and hospital admission of respiratory diseases among 198 704 children in Jiangsu Province, China, from 2019 to 2021. Additionally, 12 exposure patterns were defined to further discern potential synergistic effects of HCHO and high temperature combined exposure. Results After controlling for relevant covariates, our findings revealed HCHO exposure was associated with respiratory-related hospital admissions. Specifically, we identified a pronounced effect at lag 3 day, demonstrating a 1.14% increase (95% CI: 0.60%, 1.69%). Subgroup analyses further identified that warm season, 3–7 years old group and disadvantaged economic areas showed higher admission risk. Moreover, we found HCHO combined with high temperature exposure would trigger the elevated risk of hospital admission. Notably, in specific exposure scenarios, the cumulative relative risk reached up to 1.051 (95% CI: 1.025, 1.078), highlighting the synergistic effect of combined exposure on the respiratory health of children. Conclusions Ambient HCHO exposure increased hospital admission risks for respiratory diseases in children, and high temperature could trigger the elevated risk. To have an in-depth understanding of ambient HCHO health impact is critical for intervention strategies aimed at mitigating ambient HCHO pollution and regarding adverse impacts on children under a changing climate.
Genomic and functional co-diversification imprint African Hominidae microbiomes to signal dietary and lifestyle adaptations
Authors: Saria Otani, Marie Louise Jespersen, Christian Brinch, Frederik Duus Møller, Bo Pilgaard, Emilie Egholm Bruun Jensen, Pimlapas Leekitcharoenphon, Christina Aaby Svendsen, Amalie H. Aarestrup, Tolbert Sonda, Teresa J. Sylvina, Jeff Leach, Alexander Piel, Fiona Stewart, Panagiotis Sapountzis, Paul E. Kazyoba, Happiness Kumburu, Frank M. Aarestrup
Journal: Gut Microbes (2025)

In the diverse landscape of African hominids, the obligate relationship between the host and its microbiome narrates signals of adaptation and co-evolution. Sequencing 546 African hominid metagenomes, including those from indigenous Hadza and wild chimpanzees, identified similar bacterial richness and diversity surpassing those of westernized populations. While hominids share core bacterial communities, they also harbor distinct, population-specific bacterial taxa tailored to specific diets, ecology and lifestyles, differentiating non-indigenous and indigenous humans and chimpanzees. Even amongst shared bacterial communities, several core bacteria have co-diversified to fulfil unique dietary degradation functions within their host populations. These co-evolutionary trends extend to non-bacterial elements, such as mitochondrial DNA, antimicrobial resistance, and parasites. Our findings indicate that microbiome-host co-adaptations have led to both taxonomic and within taxa functional displacements to meet host physiological demands. The microbiome, in turn, transcends its taxonomic interchangeable role, reflecting the lifestyle, ecology and dietary history of its host.
Tumor‐Targeted Exosome‐Based Heavy Atom‐Free Nanosensitizers With Long‐Lived Excited States for Safe and Effective Sono‐Photodynamic Therapy of Solid Tumors
Authors: Van‐Nghia Nguyen, Thuy Giang Nguyen Cao, Hyunsun Jeong, Quan Truong Hoang, Binh T. T. Pham, Jieun Bang, Chang Woo Koh, Ji Hee Kang, Jeong Hyun Lee, Xiaofeng Wu, Won Jong Rhee, Young Tag Ko, K. M. K. Swamy, Sungnam Park, JaeHong Park, Min Suk Shim, Juyoung Yoon
Journal: Advanced Healthcare Materials (2025)

Abstract Theranostic nanosensitizers with combined near‐infrared (NIR) fluorescence imaging and sono‐photodynamic effects have great potential for use in the personalized treatment of deep‐seated tumors. However, developing effective nanosensitizers for NIR fluorescence image‐guided sono‐photodynamic therapy remains a considerable challenge, including the low generation efficacy of reactive oxygen species (ROS), poor photostability, and the absence of cancer specificity. Herein, a novel heavy atom‐free nanosensitizer is developed, which exhibits intense NIR fluorescence, high ROS generation efficiency, and improved aqueous stability. By conjugating a bulky and electron‐rich group, 4‐(1,2,2‐triphenylvinyl)‐1,1′‐biphenyl (TPE), to the IR820 backbone, the resulting IR820 bearing TPE (IR820‐TPE) effectively generates ROS via type I and II photochemical mechanisms under 808 nm laser irradiation. Moreover, TPE conjugation considerably increases the sono‐photodynamic performance of IR820. To improve the intracellular delivery and tumor‐targeting ability of IR820‐TPE, biotin‐conjugated exosome (B‐Exo) is used as a natural nanocarrier. In vitro studies demonstrate the outstanding therapeutic performance of IR820‐TPE‐loaded B‐Exo (IR820‐TPE@B‐Exo) in synergistic sono‐photodynamic cancer therapy. In vivo studies reveal that IR820‐TPE@B‐Exo shows enhanced tumor accumulation, strong fluorescence signals, and effective sono‐photodynamic therapeutic activity with high biosafety. This work demonstrates that IR820‐TPE@B‐Exo is a promising sono‐phototheranostic agent for safe and targeted cancer therapy and NIR fluorescence imaging.
L-Kynurenine activates the AHR-PCSK9 pathway to mediate the lipid metabolic and ovarian dysfunction in polycystic ovary syndrome
Authors: Yujiao Wang, Yifan Wu, Hongwei Jiang, Shang Li, Jingjing Li, Cong Wang, Lexin Yang, Xiying Zhou, Juanjuan Yu, Junyu Zhai, Zi-Jiang Chen, Yanzhi Du
Journal: Metabolism (2025)
Lung cancer detection by electronic nose analysis of exhaled breath: a multi-center prospective external validation study
Authors: A I G Buma, M Benthe Muntinghe-Wagenaar, V van der Noort, R de Vries, M M F Schuurbiers, P J Sterk, S Schipper, J Meurs, S M Cristescu, T J N Hiltermann, M M van den Heuvel
Journal: Annals of Oncology (2025)

Electronic nose (eNose) analysis of exhaled breath shows potential for accurate and timely lung cancer diagnosis, yet prospective external validation studies are lacking. Our study primarily aimed to prospectively and externally validate a published eNose model for lung cancer detection in COPD patients and assess its diagnostic performance alongside a new eNose model, specifically tailored to the target population, in a more general outpatient population. This multi-center prospective external validation study included adults with clinical and/or radiological suspicion of lung cancer who were recruited from thoracic oncology outpatient clinics of two sites in The Netherlands. Breath profiles were collected using a cloud-connected eNose (SpiroNose®). The diagnostic performance of the original and new eNose model was assessed in various population subsets based on ROC-AUC, specificity, positive predictive value (PPV), and negative predictive value (NPV), targeting 95% sensitivity. For the new eNose model, a training and validation cohort were used. Between March 2019 and November 2023, 364 participants were included. The original eNose model detected lung cancer with a ROC-AUC of 0.92 (95% CI: 0.85-0.99) in COPD patients (n=98/116; 84%) and 0.80 (95% CI: 0.75-0.85) in all participants (n=216/364; 59%). At 95% sensitivity, the specificity, PPV, and NPV, were 72% and 51%, 95% and 74%, and 72% and 88%, respectively. In the validation cohort, the new eNose model identified lung cancer across all participants (n=72/121; 60%) with a ROC-AUC of 0.83 (95% CI: 0.75-0.91), 94% sensitivity, 63% specificity, PPV of 79%, and NPV of 89%. Notably, accurate detection was consistent across tumour characteristics, disease stage, diagnostic centers, and clinical characteristics. This multi-center prospective external validation study confirms that eNose analysis of exhaled breath enables accurate lung cancer detection at thoracic oncology outpatient clinics, irrespective of tumour characteristics, disease stage, diagnostic center, and clinical characteristics.
STopover captures spatial colocalization and interaction in the tumor microenvironment using topological analysis in spatial transcriptomics data
Authors: Sungwoo Bae, Hyekyoung Lee, Kwon Joong Na, Dong Soo Lee, Hongyoon Choi, Young Tae Kim
Journal: Genome Medicine (2025)

Abstract Unraveling the spatial configuration of the tumor microenvironment (TME) is crucial for elucidating tumor-immune interactions based on immuno-oncology. We present STopover, a novel approach utilizing spatially resolved transcriptomics (SRT) data and topological analysis to investigate the TME. By gradually lowering the feature threshold, connected components (CCs) are extracted based on spatial distance and persistence, with Jaccard indices quantifying their spatial overlap, and transcriptomic profiles are permutated to assess statistical significance. Applied to lung and breast cancer SRT, STopover revealed immune and stromal cell infiltration patterns, predicted key cell–cell communication, and identified relevant regions, shedding light on cancer pathophysiology (URL: https://github.com/bsungwoo/STopover ).
Immune Escape of Acute Myeloid Leukemia after Transplantation
Authors: Nguyen Huong Jenny Giang Ho, Nana Talvard-Balland, Natalie Köhler, Robert Zeiser
Journal: Blood Cancer Discovery (2025)

Abstract Acute myeloid leukemia (AML) is the main indication for allogeneic hematopoietic cell transplantation, but relapse is common because of chemotherapy resistance and immune escape. We discuss the mechanisms of AML immune evasion including loss or downregulation of MHC class I and II, reduced tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptor expression, inhibitory metabolite production, inhibitory ligand expression, impaired proinflammatory cytokine production, and AML niche alterations. Understanding and targeting these mechanisms could enhance outcomes for patients with AML undergoing allogeneic hematopoietic cell transplantation and immunotherapies. Significance: We discuss the mechanisms of AML immune evasion including loss or downregulation of MHC class I and II, reduced TRAIL receptor expression, inhibitory metabolite production, inhibitory ligand expression, impaired proinflammatory cytokine production, and AML niche alterations.
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Authors: Martina Živná, Gabriela Dostálová, Veronika Barešová, Dita Mušálková, Klára Svojšová, Doria Meiseles, Sara Kinstlinger, Ladislav Kuchař, Befekadu Asfaw, Helena Poupětová, Hana Vlášková, Tereza Kmochová, Petr Vyleťal, Hana Hartmannová, Kateřina Hodaňová, Viktor Stránecký, Lenka Steiner-Mrázová, Aleš Hnízda, Jan Živný, Martin Radina, Miroslav Votruba, Jana Sovová, Helena Trešlová, Larisa Stolnaja, Petra Reková, Lenka Roblová, Eva Honsová, Ivan Rychlík, Moran Dvela-Levitt, Anthony J. Bleyer, Aleš Linhart, Jakub Sikora, Stanislav Kmoch
Journal: Journal of the American Society of Nephrology (2025)
The Hallmarks of Cancer as Eco-Evolutionary Processes
Authors: Ranjini Bhattacharya, Stanislav S. Avdieiev, Anuraag Bukkuri, Christopher J. Whelan, Robert A. Gatenby, Kenneth Y. Tsai, Joel S. Brown
Journal: Cancer Discovery (2025)

Abstract The “Hallmarks of Cancer” represent characteristics of neoplastic cells. Hanahan and Weinberg noted that the acquisition of these hallmarks mimics Darwinian evolution. In this study, we deconstruct the hallmarks “color wheel” into linear, parallel, and interlinked stages: cancer initiation, evolving evolvability, niche construction, adaptations for safety, and emergent phenomenon. During carcinogenesis, a cell evolves from being part of the organism into an autonomous unit subject to natural selection. The hallmark traits enable this transition, representing adaptations for survival within their tumor ecosystem. Unwinding the hallmarks color wheel and viewing them as eco-evolutionary processes provide a unifying framework for defining, understanding, and treating cancer. Significance: Viewing the hallmarks as a sequence of adaptations captures the “why” behind the “how” of the molecular changes driving cancer. This eco-evolutionary view distils the complexity of cancer progression into logical steps, providing a framework for understanding all existing and emerging hallmarks of cancer and developing therapeutic interventions.