Cell Proliferation最新文献

{"title":"Co-Culture of Mammalian Cells and Photosynthetic Microorganisms for Oxygen Supply in Engineered Tissues","authors":"Meng Wang,&nbsp;Ahmad Furqan Hala,&nbsp;Vera van der Niet,&nbsp;Sebastian T. Bok,&nbsp;Aylin Kara Özenler,&nbsp;Marcel Janssen,&nbsp;Maria J. Barbosa,&nbsp;Dirk Martens,&nbsp;Rene H. Wijffels,&nbsp;Jos Malda,&nbsp;Mylène de Ruijter","doi":"10.1111/cpr.70224","DOIUrl":"10.1111/cpr.70224","url":null,"abstract":"<p>Ensuring an adequate supply of oxygen remains a significant challenge in the development of large engineered tissue constructs in the field of tissue engineering. To address this, novel strategies have recently been introduced, including the incorporation of photosynthetic microorganisms into engineered tissues. However, to take the full advantage of this co-culture approach, careful selection of photosynthetic microorganisms and a better understanding of their long-term interactions with mammalian cells are required. Here, we first examined the effects of continuous 28-day light exposure on the proliferation and biofunctionality of mammalian cells. We observed that articular cartilage-derived chondroprogenitor cells (ACPCs) did better withstand light exposure under chondrogenic conditions than mesenchymal stromal cells (MSCs). Next, four different photosynthetic microorganisms, capable of growing at 37°C, were co-cultured with cartilage cells. Among them, <i>Leptolyngbya</i> sp. (<i>Leptolyngbya</i>) and <i>Synechococcus</i> sp. (<i>Synechococcus</i>) did not compromise the morphology and chondrogenic capacity of mammalian cells in vitro over 28 days, whereas \u0000 <i>Chlorella sorokiniana</i>\u0000 (<i>Chlorella</i>) inhibited chondrogenesis. This inhibition might due to excessive oxygen release by <i>Chlorella</i> in chondrogenic culture medium, as <i>Leptolyngbya</i> and <i>Synechococcus</i> did not produce detectable oxygen under the same culture conditions. To further explore their potential for oxygen delivery to other tissue-derived cells, we also assessed the growth rate and oxygen production of these four microorganisms in different mammalian cell culture media. We found that the composition, especially the presence of trace elements in tissue medium, critically influenced oxygen production. The tested microorganisms were able to grow and release oxygen in different mammalian cell culture media typically used for the propagation of cardiac, cartilage and liver cells, highlighting their flexible metabolic pathways across the different environments. This study emphasizes the importance of carefully selecting photosynthetic microorganisms for different tissue types, ensuring a balance between oxygen production and the specific nutritional demands of mammalian cells.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"59 10","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13325642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Pancreatic Cancer Organoids","authors":"Aina He,&nbsp;Xiaolin Lin,&nbsp;Xiaozhe Qian,&nbsp;Jiasheng Mu,&nbsp;Zhonghua Tao,&nbsp;Jin Gu,&nbsp;Yonggang Wang,&nbsp;Ting Han,&nbsp;Hongling Zhao,&nbsp;Yalong Wang,&nbsp;Jian Zhang,&nbsp;Zunqiang Zhou,&nbsp;Ligang Xing,&nbsp;Changchun Zhou,&nbsp;Dongyuan Zhu,&nbsp;Zengjun Liu,&nbsp;Gang Chen,&nbsp;Qinghe Zhou,&nbsp;Xiaoguang Wang,&nbsp;Shasha Zhao,&nbsp;Xiao Liu,&nbsp;Dongyan Cao,&nbsp;Bin Yu,&nbsp;Zebing Liu,&nbsp;Jiabei Wang,&nbsp;Gengming Niu,&nbsp;Guiying Wei,&nbsp;Maorong Chen,&nbsp;Weiping Wang,&nbsp;Xiaonan Kang,&nbsp;Junmei Zhou,&nbsp;Shuai Gong,&nbsp;Ying Xie,&nbsp;Jianming Zhang,&nbsp;Xianming Kong,&nbsp;Chunyan Dong,&nbsp;Yanmei Zou,&nbsp;Lina Tang,&nbsp;Aijin Ma,&nbsp;Hua Xiong,&nbsp;Xuemei Liu,&nbsp;Tongbiao Zhao,&nbsp;Jie Hao,&nbsp;Xiuying Xiao,&nbsp;Dongxi Xiang","doi":"10.1111/cpr.70210","DOIUrl":"10.1111/cpr.70210","url":null,"abstract":"<p>This guideline establishes a comprehensive framework for the application of patient-derived pancreatic cancer organoids. It outlines the stringent technical requirements and testing methods necessary to ensure high fidelity to the original tumor tissue, including morphological assessment, pathological biomarker expression (e.g., CK19, CK7), and genetic concordance (e.g., NRG1, KRAS). By standardizing protocols for in vitro culture, microbiological safety, and STR authentication, this consensus aims to ensure the reproducibility, safety, and stability of organoid models, thereby accelerating their integration into basic research, drug discovery, and precision medicine.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"59 10","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13326021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cystic Fibrosis and Colorectal Cancer Risk: Reprogramming of the Intestinal Epithelial Niche and Cell-State Plasticity in the CFTR Modulator Era","authors":"Bala Umashankar,&nbsp;Ines Pankonien,&nbsp;Margarida Amaral,&nbsp;Chee Y. Ooi,&nbsp;Thierry Jardé,&nbsp;Shafagh A. Waters","doi":"10.1111/cpr.70272","DOIUrl":"10.1111/cpr.70272","url":null,"abstract":"<p>Cystic fibrosis (CF) has shifted from a fatal paediatric lung disease to a multi-organ, lifespan-spanning disorder in which gastrointestinal (GI) complications and malignancies are increasingly prominent. With improved survival into mid- and late adulthood, aided by newborn screening, optimised nutrition and the advent of highly effective CF transmembrane conductance regulator (CFTR) modulators, implementation of colonoscopic surveillance has highlighted a several-fold increase in early-onset colorectal cancer (CRC) and a broader spectrum of intestinal pathology. In parallel, work in mouse models, human tissue and patient-derived intestinal organoids now places the CFTR at the centre of a complex epithelial compartment that integrates ion and pH homeostasis, mucus biology, microbiota, redox balance and immune/stromal function. In this review, we advance the hypothesis that CF may be conceptualised as a niche-centric hereditary CRC predisposition syndrome, in which germline CFTR dysfunction chronically destabilises epithelial identity in addition to increasing mutational burden. We synthesise evidence that CFTR loss remodels stem cell regulation, promotes hypoxia and oxidative stress, perturbs microbial ecosystems, drives chronic immune activation and stromal remodelling, and induces epithelial–mesenchymal plasticity (EMP) and DNA-damage vulnerability, collectively creating a pre-neoplastic intestinal ecosystem. We situate this model within contemporary CRC frameworks that emphasise cell-state transitions, hybrid epithelial–mesenchymal (E/M) states and specialised stromal niches, and we distinguish it from oncofoetal reprogramming, an <i>APC</i>-driven programme that CF does not clearly recapitulate. We propose that CF may provide a naturally occurring human context in which chronic epithelial stress sustains EMP-like pressure, a concept that requires direct validation in human CF intestinal tissue. Finally, we consider how CFTR modulators, microbiome-directed therapies and redox-targeted interventions might re-programme the CF intestinal niche and outline experimental and clinical strategies needed to determine whether early, ecosystem-level correction can prevent GI cancers in this high-risk population.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"59 10","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Zeolitic Pyrimidine Framework (ZPF) Nanoplatform Co-Delivers a DNAzyme and a Protein Prodrug for Cascade-Activated Tumour Therapy","authors":"Yan Huang,&nbsp;Xingjie Hu,&nbsp;Jinli Sun,&nbsp;Min Yin,&nbsp;Nan Chen","doi":"10.1111/cpr.70225","DOIUrl":"10.1111/cpr.70225","url":null,"abstract":"<p>The therapeutic application of cytotoxic proteins like ribonuclease A (RNase A) is hindered by their systemic toxicity. Here, we engineer a protein-structure-directed zeolitic pyrimidine framework (ZPF) as a superior nanocarrier that co-encapsulates and stabilizes a ROS-responsive RNase A prodrug (RNBC) and a GPX-1-targeting DNAzyme with high efficiency. This DZ-RNBC@ZPF nanocomplex, camouflaged with a 4T1 cell membrane, ensures tumour-specific delivery and lysosomal degradation. The acidic environment triggers framework dissolution, releasing Zn²⁺ to activate the DNAzyme. The DNAzyme downregulates GPX-1, amplifying intracellular H₂O₂, which in turn cleaves the NBC group to activate the RNase A prodrug precisely within target cells. This coordinated intracellular cascade—from material degradation to enzymatic ROS amplification and prodrug activation—induces significant apoptosis in 4T1 cells and potently suppresses tumour growth in vivo. Our work establishes ZPF as an enabling platform for the co-delivery of bioactive macromolecules and presents a novel therapeutic strategy based on a synergistic protein prodrug-DNAzyme circuit.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"59 10","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13325916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin Modifications Orchestrate DNA Repair Pathway Choice: Epigenetics Strategies for Enhancing CRISPR-Cas9-Mediated Knock-In Efficiency.","authors":"Xin Chen, Shan Qin, Ce Yang, Zhiyao Xing, Chong Liu, Xingchen Zhang, Xi Wu, Xueren Li, Yanhua Gong, Zichuan Liu","doi":"10.1111/cpr.70285","DOIUrl":"10.1111/cpr.70285","url":null,"abstract":"<p><p>CRISPR-Cas9-mediated precise gene knock-in relies on homology-directed repair (HDR) at low frequencies in most mammalian cells, limiting precise gene editing in both research and therapeutic applications. Although multiple strategies have been developed to increase knock-in efficiency, their application can be restricted by technical complexity, limited applicability, or potential safety concerns. In this review, we propose a shift in focus from conventional strategies toward epigenetic methods to increase knock-in efficiency. It has been proved that histone modifications such as H3K36me3, H3K9me3, H4K20me2, and H2AK15ub are involved in DNA damage signallings and the recruitment of key HDR and non-homologous end joining (NHEJ) factors. We further discuss conceptual strategies for transient chromatin modulation to bias repair pathway choice and highlight associated technical challenges and safety considerations. Together, these findings and insights highlight the essential role of histone modification in shaping chromatin states and orchestrating DNA repair dynamics. Accordingly, epigenetic regulation emerges as a compelling strategy to facilitate high-fidelity gene knock-in, offering valuable mechanistic clues and actionable epigenetic targets to gene editing for basic research and therapeutic translation.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70285"},"PeriodicalIF":7.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-Printed Bioadhesive Interfaces as Proliferative Niches for Tissue Repair.","authors":"Zhen Gu, Xinyong Su, Guoshi Xu, Yongqiang Wen, Qi Gu","doi":"10.1111/cpr.70286","DOIUrl":"10.1111/cpr.70286","url":null,"abstract":"<p><p>Bioadhesives have traditionally been viewed as materials for wound closure, sealing and haemostasis However, in tissue repair they also create the first engineered interface that influences cell retention, microenvironmental homeostasis and subsequent remodelling Recent advances in 3D printing are shifting bioadhesives from passive, uniform layers to architecturally controlled interfaces with spatially programmable chemistry, mechanics, transport and biological function. In this Review, we propose an interface-centred framework in which qualifying 3D-printed bioadhesive interfaces function as proliferative niches. Such interfaces require stable host-tissue adhesion and a biocompatible, cell-permissive microenvironment. They should also measurably support cell survival, context-appropriate proliferation and constructive remodelling in defined target-cell populations. We summarize the key design principles that govern proliferative-niche formation, with printability-aware fabrication treated as a cross-cutting prerequisite for implementing interfacial adhesion, mechanical matching, mass transport, surface chemistry and temporal evolution. We then discuss the mechanistic basis through which printed bioadhesive interfaces regulate early protein adsorption, immune activation, mechanotransduction, metabolic exchange and long-term remodelling trajectories. Representative application contexts, including sealing and haemostasis musculoskeletal repair, wearable and implantable biointerfaces and organoid-related in vitro models, are examined to highlight application-specific opportunities and trade-offs. We further outline emerging evaluation and modelling frameworks that move beyond adhesion strength towards multidimensional assessment, cross-scale structure-property-function mapping and data-driven predictive design. By reframing bioadhesives as active interfacial regulators rather than passive fixation materials, this Review provides a conceptual framework for engineering 3D-printed bioadhesives that not only adhere and seal, but also actively guide constructive tissue repair.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70286"},"PeriodicalIF":7.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting a Novel AREG⁺ Dendritic Cell Alleviates Renal Fibrosis Induced by Ischemia-Reperfusion Injury.","authors":"Xin Luo, Longbin Xiong, Zhaohui Zhou, Lihao Zhang, Yulu Peng, Xiangpeng Zou, Yixin Huang, Yisong Lin, Xiaofeng Yang, Zhanji Zhan, Fangjian Zhou, Youhua Liu, Chunping Yu, Baokui Ye, Zhiling Zhang","doi":"10.1111/cpr.70287","DOIUrl":"https://doi.org/10.1111/cpr.70287","url":null,"abstract":"<p><p>Renal ischemia-reperfusion injury (RIRI) is a major cause of acute tubular damage and a key driver of maladaptive repair and fibrosis. However, the cellular initiators that connect early immune activation to tubular epithelial-mesenchymal transition (EMT) during RIRI remain poorly defined. Here, we established a human RIRI model by modifying the surgical procedures in patients undergoing radical nephrectomy and confirmed successful injury induction by tubular dilation, severe mitochondrial swelling and increased apoptosis in renal tissues. Using single-cell RNA sequencing, we uncovered an underappreciated dendritic cell (DC) subset, CD11c⁺AREG⁺ DCs, that expands after RIRI, coinciding with EMT activation in tubular epithelial cells at early stages. Notably, ligand-receptor inference revealed markedly enhanced communication between CD11c⁺AREG⁺ DCs and tubular epithelial cells after RIRI, suggesting the AREG-EGFR as a dominant axis. Mechanistically, CD11c⁺AREG⁺ DCs initiate and promote tubular EMT via AREG-dependent EGFR signalling, establishing a direct causal link between this DC population and injured tubular epithelial cells. Importantly, Areg knockdown or DC depletion significantly alleviated tubular damage and fibrosis and preserved kidney function in the IRI mouse model, which highlights these cells could be potential therapeutic targets for mitigating RIRI.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70287"},"PeriodicalIF":7.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AFF4 Loss Compromises Osteogenesis of Orofacial Mesenchymal Stem Cells During Alveolar Bone Repair via AMPK-Mediated Mitophagy.","authors":"Li Zhu, Shuo Chen, Guowen Luo, Tingyue Zhang, Hengyi Lin, Yiling Chen, Chenchen Zhou, Shujuan Zou","doi":"10.1111/cpr.70284","DOIUrl":"10.1111/cpr.70284","url":null,"abstract":"<p><p>Repair of maxillofacial bone defects presents significant clinical challenges. Orofacial mesenchymal stem cells (OMSCs) mediate maxillofacial bone repair, while the molecular mechanisms governing osteogenic commitment of OMSCs remain incompletely understood. Here, we investigate the function of AF4/FMR2 family member 4 (AFF4) in OMSCs osteogenesis and maxillofacial bone healing. By using a tamoxifen-inducible Aff4 knockout mouse model, we demonstrate that AFF4 depletion significantly delays the alveolar bone repair post-tooth extraction. OMSCs of Aff4 knockout mice exhibit decreased expression of osteogenic markers (RUNX2, ALPL, OSX, COL1A1) and reduced mineralization in vitro. Mechanistically, AFF4 loss suppresses AMPK signalling and downstream mitophagy, manifested by reduced Parkin translocation and LC3B recruitment to mitochondria, and impaired mitophagosome-lysosome fusion. Notably, the rescue of mitophagy and the osteogenic capacity of Aff4-deficient OMSCs by AICAR (an AMPK activator) was abolished by Compound C (an AMPK inhibitor). Collectively, our findings establish the critical role of AFF4 in maxillofacial bone regeneration and demonstrate that it functions through the AMPK-mitophagy axis in OMSCs. This study provides a novel insight into the function of AFF4 in maxillofacial bone biology.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70284"},"PeriodicalIF":7.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ammonia Accumulation Drives Intervertebral Disc Degeneration by Triggering Ammonia-Induced Cell Death Through Lysosome-Mitochondria Crosstalk.","authors":"Yang Zhang, Yucheng Gao, Shuhang Dong, Shuanggong Liu, Lei Liu, Ziyi Song, Jie Xu, Yijun Rong, Guangxu Song, Yingze Zhang, Dongjin Wu, Zengxin Gao","doi":"10.1111/cpr.70283","DOIUrl":"10.1111/cpr.70283","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IVDD) is a major cause of low back pain and is closely associated with metabolic imbalance within the disc microenvironment, yet the underlying mechanisms remain poorly understood. Here, we identify ammonia accumulation as a metabolically relevant stressor that promotes nucleus pulposus cell injury and death and characterise ammonia-induced cell death (AICD) as a non-canonical, metabolite-driven pathological process in IVDD. Through a combination of clinical cohort-based analyses of human samples, multi-omics profiling, in vitro experiments, and in vivo models, we demonstrate that ammonia stress induces AICD characterised by coordinated disruption of organelle homeostasis. Mechanistically, ammonia accumulation initially impairs lysosomal integrity, which subsequently triggers mitochondrial dysfunction and oxidative stress, accompanied by a metabolic shift from oxidative phosphorylation towards glycolysis, ultimately leading to suppressed mitophagy and activation of cell death pathways. Notably, AICD exhibits crosstalk with multiple programmed cell death pathways, highlighting its integration within the broader cell death network. Importantly, modulation of ammonia levels or restoration of organelle homeostasis effectively alleviates NP cell injury and attenuates IVDD progression. Collectively, these findings support AICD as a previously underappreciated, metabolite-driven process contributing to IVDD and highlight the ammonia metabolism-organelle axis as a potential target for future metabolism- and organelle-directed therapeutic strategies.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70283"},"PeriodicalIF":7.6,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methyl 4-O-Demethylbarbatate Destabilises HIF-1α and Enhances Temozolomide Sensitivity in Glioma Cells.","authors":"Rui Zhou, Mücahit Varlı, Rundong Liu, Jieun Yu, Hyung-Ho Ha, Jae-Seoun Hur, Sang Kyum Kim, Hahyun Park, Hangun Kim","doi":"10.1111/cpr.70279","DOIUrl":"10.1111/cpr.70279","url":null,"abstract":"<p><p>Gliomas remain among the most lethal brain tumours, driven by aggressive invasion, stem-like properties, metabolic plasticity, and frequent resistance to temozolomide (TMZ). Hypoxia-inducible factor-1α (HIF-1α) is a central regulator of these malignant traits. In this study, we identify methyl 4-O-demethylbarbatate (Me-4-O-DBA), a biosynthetically produced lichen-derived metabolite, as a potential modulator of HIF-1α signaling. Molecular docking analysis suggested a possible interaction between Me-4-O-DBA and HIF-1α near the Lys304 ubiquitination site, which may contribute to reduced HIF-1α stability and suppression of downstream EMT and stemness signaling. This inhibition simultaneously attenuated both glycolytic activity and mitochondrial respiration, indicating a broad suppression of metabolic reprogramming. Network pharmacology and molecular docking further indicated HIF-1α-associated signaling as a potential regulatory hub, while in vitro assays demonstrated marked reductions in glioma cell viability, invasion, migration, and clonogenicity. Notably, Me-4-O-DBA synergised with TMZ to enhance suppression of motility, stemness, and metabolic activity, resulting in profound impairment of tumourigenic potential. In vivo zebrafish assays also indicated a favourable safety profile at the tested concentrations. Together, these findings suggest that Me-4-O-DBA suppresses HIF-1α-associated malignant phenotypes and enhances TMZ responsiveness in glioma cells, highlighting its potential as a natural product-derived modulator of glioma progression.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70279"},"PeriodicalIF":7.6,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}