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From seq-ing to modeling: towards a molecular understanding of special properties of immature neurons in the human hippocampus. 从测序到建模:对人类海马体中未成熟神经元特性的分子理解。
IF 6
Life medicine Pub Date : 2025-09-30 eCollection Date: 2025-12-01 DOI: 10.1093/lifemedi/lnaf031
{"title":"From seq-ing to modeling: towards a molecular understanding of special properties of immature neurons in the human hippocampus.","authors":"","doi":"10.1093/lifemedi/lnaf031","DOIUrl":"10.1093/lifemedi/lnaf031","url":null,"abstract":"","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"4 6","pages":"lnaf031"},"PeriodicalIF":6.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12726914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Iron metabolism disorder promotes postovulatory oocyte aging by inducing oxidative stress damage. 铁代谢紊乱通过诱导氧化应激损伤促进排卵后卵母细胞衰老。
IF 6
Life medicine Pub Date : 2025-09-30 eCollection Date: 2025-12-01 DOI: 10.1093/lifemedi/lnaf032
Ziqi Huang, Bicheng Wang, Ying Tian, Xiangning Xu, Jiaqi Zhang, Shuo Lou, Jingyi Kang, Ningning Zhang, Ke Song, Jingyu Li, Jing Weng, Yuanjing Liang, Xiaokui Yang, Wei Ma
{"title":"Iron metabolism disorder promotes postovulatory oocyte aging by inducing oxidative stress damage.","authors":"Ziqi Huang, Bicheng Wang, Ying Tian, Xiangning Xu, Jiaqi Zhang, Shuo Lou, Jingyi Kang, Ningning Zhang, Ke Song, Jingyu Li, Jing Weng, Yuanjing Liang, Xiaokui Yang, Wei Ma","doi":"10.1093/lifemedi/lnaf032","DOIUrl":"10.1093/lifemedi/lnaf032","url":null,"abstract":"<p><p>Reactive oxygen species (ROS) involve in oocyte postovulatory aging, yet the mechanism of ROS accumulation is not fully understood. We explored iron metabolic status and its relationship with ROS in mouse oocytes during postovulatory aging <i>in vivo</i>. We found that heme oxygenase 1 (HO-1) expression was increased in oviduct and iron metabolism was disordered in oocytes with time post-ovulation. The aging oocytes were manifested with high iron content and disturbed expressions of iron metabolic proteins, including ferritin heavy chain (FHC), mitochondrial ferritin (FtMT), divalent metal transporter 1 (DMT1), ferroportin1 (FPN1), iron regulatory protein 2 (IRP2) and transferrin receptor 1 (TFR1), along with increased cytosolic free Fe<sup>2+</sup>, lipid peroxidation, DNA damage, mitochondrial and lysosomal abnormality, and defects in spindle and chromosome alignment. These <i>in vivo</i> aging cells contained stable glutathione peroxidase 4 (GPX4) and 4-hydroxynonenal (4-HNE), unexpectedly, but had more iron and degenerative changes than their <i>in vitro</i> counterparts. The intraperitoneal deferoxamine (DFO) could alleviate all these changes and improve the fertilization competence and preimplantation development. Similarly, the HO-1 inhibitor Zinc Protoporphyrin (ZnPP) also could do this. Together, the iron homeostasis disturbance participates in ROS accumulation and degenerative changes in postovulatory aging oocytes, which can be alleviated by iron chelating.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"4 6","pages":"lnaf032"},"PeriodicalIF":6.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12732666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Peripheral organ crosstalk in the regulation of ovarian endocrine function and reproductive homeostasis. 外周器官串扰在调节卵巢内分泌功能和生殖稳态中的作用。
IF 6
Life medicine Pub Date : 2025-08-28 eCollection Date: 2025-12-01 DOI: 10.1093/lifemedi/lnaf029
Lixuan Huang, Lei Xu, Chuyu Yun, Jie Qiao, Xinyu Qi
{"title":"Peripheral organ crosstalk in the regulation of ovarian endocrine function and reproductive homeostasis.","authors":"Lixuan Huang, Lei Xu, Chuyu Yun, Jie Qiao, Xinyu Qi","doi":"10.1093/lifemedi/lnaf029","DOIUrl":"10.1093/lifemedi/lnaf029","url":null,"abstract":"<p><p>Ovarian function is increasingly recognized as a systemic process influenced by cross-organ communication, yet knowledge regarding the underlying mechanisms remains fragmented. In addition to the ovary, multiple organs, including the hypothalamus, adipose tissue, gut, liver, thyroid, adrenal gland, and heart, converge to regulate ovarian function. These interactions span endocrine signals (e.g. insulin hormones), immune mediators (e.g. cytokines), and metabolic cues (e.g. adipokines), collectively impacting folliculogenesis, steroidogenesis, and ovulation. Importantly, these interactions suggest novel therapeutic targets to mitigate ovarian dysfunction. However, causal relationships and organ-specific contributions require further mechanistic exploration. This synthesis underscores the necessity of a multisystem perspective in both the research and clinical management of ovarian disorders.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"4 6","pages":"lnaf029"},"PeriodicalIF":6.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12732670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A framework of biomarkers for adipose tissue aging: a consensus statement by the Aging Biomarker Consortium. 脂肪组织老化的生物标志物框架:老化生物标志物联盟的共识声明。
IF 6
Life medicine Pub Date : 2025-07-19 eCollection Date: 2025-10-01 DOI: 10.1093/lifemedi/lnaf027
Jian Yu, Yankang Zhang, Ting Zhang, Yan Bi, Yan Chen, Zheng Chen, Zhe Dai, Feifan Guo, Lixin Guo, Cheng Hu, Xiangqing Kong, Jian Li, Pingsheng Liu, Yong Liu, Jing Qu, Qiqun Tang, Congyi Wang, Liheng Wang, Jiqiu Wang, Jianping Weng, Aimin Xu, Lingyan Xu, Huijie Zhang, Jiajun Zhao, Jingjing Zhang, Weiqi Zhang, Tongjin Zhao, Weiping Zhang, Zhiming Zhu, Guang-Hui Liu, Guang Ning, Gang Pei, Li Qiang, Feng Liu, Xinran Ma
{"title":"A framework of biomarkers for adipose tissue aging: a consensus statement by the Aging Biomarker Consortium.","authors":"Jian Yu, Yankang Zhang, Ting Zhang, Yan Bi, Yan Chen, Zheng Chen, Zhe Dai, Feifan Guo, Lixin Guo, Cheng Hu, Xiangqing Kong, Jian Li, Pingsheng Liu, Yong Liu, Jing Qu, Qiqun Tang, Congyi Wang, Liheng Wang, Jiqiu Wang, Jianping Weng, Aimin Xu, Lingyan Xu, Huijie Zhang, Jiajun Zhao, Jingjing Zhang, Weiqi Zhang, Tongjin Zhao, Weiping Zhang, Zhiming Zhu, Guang-Hui Liu, Guang Ning, Gang Pei, Li Qiang, Feng Liu, Xinran Ma","doi":"10.1093/lifemedi/lnaf027","DOIUrl":"10.1093/lifemedi/lnaf027","url":null,"abstract":"<p><p>Adipose tissue serves as a crucial energy storage and metabolic organ in the human body. With the surging of elderly population in China comes significant challenges in preventing and managing age-associated diseases, while adipose tissue aging represents one of the pivotal initiating events for multi-organ senescence. To address these challenges, the Aging China Biomarkers Consortium (ABC) has established an expert consensus on biomarkers of adipose tissue aging by digesting literature and collecting insights from scientists and clinicians. This consensus provides a comprehensive evaluation of the key changes and characteristics, as well as biomarkers related to adipose tissue aging and proposes a systematic framework categorizing these biomarkers into functional, structural and humoral dimensions. Within each dimension, the ABC recommends clinically and empirically validated biomarkers and parameters for assessing both physiological and pathological changes in adipose tissue during aging, which aims to establish a foundation for future prediction, diagnosis, early warning and treatment for adipose tissue aging and its related diseases, with the ultimate goal of improving adipose tissue health and promoting healthy aging in elderly populations both in China and worldwide.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"4 5","pages":"lnaf027"},"PeriodicalIF":6.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12517170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fat talks first: how adipose tissue sets the pace of aging? 脂肪先说话:脂肪组织如何决定衰老的速度?
IF 6
Life medicine Pub Date : 2025-07-19 eCollection Date: 2025-10-01 DOI: 10.1093/lifemedi/lnaf028
Juanhong Liu, Qinlei Huang, Feng Liu
{"title":"Fat talks first: how adipose tissue sets the pace of aging?","authors":"Juanhong Liu, Qinlei Huang, Feng Liu","doi":"10.1093/lifemedi/lnaf028","DOIUrl":"10.1093/lifemedi/lnaf028","url":null,"abstract":"<p><p>Once viewed primarily as an energy reservoir, adipose tissue (AT) is now recognized as a key endocrinal organ in regulating systemic aging. With age, AT undergoes significant remodeling, marked by altered fat distribution, visceral fat expansion, impaired thermogenesis, and chronic low-grade inflammation, which disrupts metabolic and immune homeostasis. Emerging insights from single-cell and spatial transcriptomics highlight the critical roles of adipose progenitors, immune cells, and senescent cells in driving local dysfunction and systemic decline. Through inflammatory and metabolic signaling, dysfunctional AT actively contributes to age-related pathologies. This review explores how AT functions as both an early sensor and driver of aging and discusses therapeutic opportunities targeting adipose dysfunction to promote healthy aging.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"4 5","pages":"lnaf028"},"PeriodicalIF":6.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12517275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
deepBlastoid: a deep learning model for automated and efficient evaluation of human blastoids. deepBlastoid:一个深度学习模型,用于自动和有效地评估人类囊胚。
IF 6
Life medicine Pub Date : 2025-07-11 eCollection Date: 2025-12-01 DOI: 10.1093/lifemedi/lnaf026
Zejun Fan, Zhenyu Li, Yiqing Jin, Arun Pandian Chandrasekaran, Ismail M Shakir, Yingzi Zhang, Aisha Siddique, Mengge Wang, Xuan Zhou, Yeteng Tian, Peter Wonka, Mo Li
{"title":"deepBlastoid: a deep learning model for automated and efficient evaluation of human blastoids.","authors":"Zejun Fan, Zhenyu Li, Yiqing Jin, Arun Pandian Chandrasekaran, Ismail M Shakir, Yingzi Zhang, Aisha Siddique, Mengge Wang, Xuan Zhou, Yeteng Tian, Peter Wonka, Mo Li","doi":"10.1093/lifemedi/lnaf026","DOIUrl":"10.1093/lifemedi/lnaf026","url":null,"abstract":"<p><p>Recent advances in human blastoids have opened new avenues for modeling early human development and implantation. Human blastoids can be generated in large numbers, making them well-suited for high-throughput screening. However, automated methods for evaluating and characterizing blastoid morphology are lacking. We developed a deep-learning model-deepBlastoid-for automated classification of live human blastoids using only brightfield images. The model processes 273.6 images per second with an average accuracy of 87%, which is further improved to 97% by integrating a Confidence Rate metric. deepBlastoid outperformed human experts in throughput while matching accuracy in blastoid classification. We demonstrated the utility of the model in two use cases: (i) systematic assessment of the effect of lysophosphatidic acid (LPA) on blastoid formation and (ii) evaluating the impact of dimethyl sulfoxide (DMSO) on blastoid formation. The evaluation results of deepBlastoid using over 10,000 images were consistent with the known drug effects and showed subtle but significant effects that might have been overlooked in manual assessments. The publicly available deepBlastoid model enables researchers to train customized models based on their imaging and protocols, providing an efficient, automated tool for blastoid classification with broad applications in research, drug screening, and <i>in-vitro</i>-fertilization applications.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"4 6","pages":"lnaf026"},"PeriodicalIF":6.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12732673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Life lies in movement. 生命在于运动。
IF 6
Life medicine Pub Date : 2025-07-02 eCollection Date: 2025-10-01 DOI: 10.1093/lifemedi/lnaf024
Junzhu Yi, Yuanyuan Du
{"title":"Life lies in movement.","authors":"Junzhu Yi, Yuanyuan Du","doi":"10.1093/lifemedi/lnaf024","DOIUrl":"10.1093/lifemedi/lnaf024","url":null,"abstract":"","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"4 5","pages":"lnaf024"},"PeriodicalIF":6.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12517164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Heterochronic parabiosis alters the transcriptomic landscape to combat aging and aging-related diseases in aging-accelerated mice. 异慢性异种共生改变了衰老加速小鼠的转录组学景观,以对抗衰老和衰老相关疾病。
IF 6
Life medicine Pub Date : 2025-07-01 eCollection Date: 2025-12-01 DOI: 10.1093/lifemedi/lnaf025
Haochen Wang, Wencong Lyu, Yuzhe Sun, Xinyi Jia, Jinlong Bi, Ran Wei, Zhehao Du, Fanju Meng, Jianuo He, Shiyi Wang, Lijun Zhang, Chao Nie, Wei Tao
{"title":"Heterochronic parabiosis alters the transcriptomic landscape to combat aging and aging-related diseases in aging-accelerated mice.","authors":"Haochen Wang, Wencong Lyu, Yuzhe Sun, Xinyi Jia, Jinlong Bi, Ran Wei, Zhehao Du, Fanju Meng, Jianuo He, Shiyi Wang, Lijun Zhang, Chao Nie, Wei Tao","doi":"10.1093/lifemedi/lnaf025","DOIUrl":"10.1093/lifemedi/lnaf025","url":null,"abstract":"<p><p>Aging is a multifactorial process involving a gradual decline in cellular and tissue functions, making it a major risk factor for aging-related degenerative diseases. In this study, we utilized the senescence-accelerated mouse prone 8 mice model, which mimics pathological characteristics of Alzheimer's disease, fatty liver disease, and cardiac fibrosis, to construct a heterochronic parabiosis model and systematically investigate the rejuvenating effects of heterochronic parabiosis on the brain, liver, and heart. Our findings revealed that heterochronic parabiosis promotes synaptic plasticity and neuronal communication, restores hepatocyte metabolic functions, and reduces chronic inflammation and fibrosis in the heart. Notably, heterochronic parabiosis significantly downregulates the expression of age-related disease risk genes. In addition, endothelial cells, as cell types directly exposed to the circulatory environment, demonstrated the highest sensitivity to heterochronic parabiosis across three organs, and exhibited significantly reduced inflammation after intervention, suggesting that they may play an early and central role in the rejuvenation process. Overall, our study increases the understanding of the molecular and cellular mechanisms of aging and its related diseases, highlights the multiorgan and multitarget potential of heterochronic parabiosis in delaying aging and mitigating aging-related diseases, and provides new therapeutic targets for achieving healthy aging.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"4 6","pages":"lnaf025"},"PeriodicalIF":6.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12732672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A framework of biomarkers for visual system aging: a consensus statement by the Aging Biomarker Consortium. 视觉系统老化的生物标志物框架:老化生物标志物联盟的共识声明。
IF 6
Life medicine Pub Date : 2025-06-28 eCollection Date: 2025-08-01 DOI: 10.1093/lifemedi/lnaf023
Chao Ma, Boxin Geng, Yangqing Zhang, Shan Li, Ruiyang Li, Wenben Chen, Si Wang, Weiqi Zhang, Jing Qu, Yun Feng, Qingfeng Liang, Kangxin Jin, Yonghao Gu, Wenru Su, Xuxiang Zhang, Wenjuan Zhuang, Jihong Wu, Zhaoyang Wang, Shengping Hou, Jiaxu Hong, Honghua Yu, Biao Yan, Mingguang He, Fan Lv, Guang-Hui Liu, Gang Pei, Qingjiong Zhang, Tian Xue, Zi-Bing Jin
{"title":"A framework of biomarkers for visual system aging: a consensus statement by the Aging Biomarker Consortium.","authors":"Chao Ma, Boxin Geng, Yangqing Zhang, Shan Li, Ruiyang Li, Wenben Chen, Si Wang, Weiqi Zhang, Jing Qu, Yun Feng, Qingfeng Liang, Kangxin Jin, Yonghao Gu, Wenru Su, Xuxiang Zhang, Wenjuan Zhuang, Jihong Wu, Zhaoyang Wang, Shengping Hou, Jiaxu Hong, Honghua Yu, Biao Yan, Mingguang He, Fan Lv, Guang-Hui Liu, Gang Pei, Qingjiong Zhang, Tian Xue, Zi-Bing Jin","doi":"10.1093/lifemedi/lnaf023","DOIUrl":"10.1093/lifemedi/lnaf023","url":null,"abstract":"<p><p>The visual system is essential for human perception, converting light signals into electrical impulses and transmitting them to the brain to process environmental information. As individuals age, their physiological functions gradually decline, leading to age-related vision impairment that significantly impacts the quality of life in elderly individuals. China is home to the world's largest aging population and faces significant challenges in combating visual system aging through effective treatments and interventions. In response to this challenge, the Aging Biomarker Consortium (ABC) of China has developed a consensus statement on biomarkers of visual system aging by integrating cutting-edge global research and synthesizing evidence-based medicine with clinical expertise. This consensus provides a multi-dimensional evaluation framework encompassing functional, morphological, and molecular biomarkers. Validated biomarkers for each domain are recommended not only to facilitate the early detection of vision changes but also to provide insights into the progression of age-related ocular diseases. By advancing this initiative, ABC aims to revolutionize visual health management in aging societies, ultimately improving outcomes for elderly populations in China and globally.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"4 4","pages":"lnaf023"},"PeriodicalIF":6.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Whole-process 3D ECM-encapsulated organoid-based automated high-throughput screening platform accelerates drug discovery for rare diseases. 全流程3D ecm封装类器官自动化高通量筛选平台加速罕见疾病药物的发现。
IF 6
Life medicine Pub Date : 2025-06-14 eCollection Date: 2025-10-01 DOI: 10.1093/lifemedi/lnaf021
Zhaoting Xu, Hui Yang, Yuru Zhou, Emmanuel Enoch Dzakah, Bing Zhao
{"title":"Whole-process 3D ECM-encapsulated organoid-based automated high-throughput screening platform accelerates drug discovery for rare diseases.","authors":"Zhaoting Xu, Hui Yang, Yuru Zhou, Emmanuel Enoch Dzakah, Bing Zhao","doi":"10.1093/lifemedi/lnaf021","DOIUrl":"10.1093/lifemedi/lnaf021","url":null,"abstract":"<p><p>Organoid-based high-throughput screening (HTS) is revolutionizing pharmaceutical development. However, the complexity of handling extracellular matrix (ECM) components with traditional HTS devices leads to the use of suspension cultures for organoids during HTS, which alters their transcriptomic landscape and drug responses. Although automated generation techniques for 3D ECM-encapsulated organoids have been established, limitations in operational simplicity and time efficiency remain barriers to achieving high throughput. Here, we develop a whole-process 3D ECM-encapsulated organoid-based automated HTS (wp3D-OAHTS) platform, which achieves superior throughput compared to existing reported systems for 3D organoid drug screening. Utilizing this automated platform, we generated more than 10,000 homogeneous 3D organoid domes of neuroendocrine cervical cancer (NECC) and evaluated their drug responses to 2802 compounds in 13 days. This highly efficient and reproducible approach finally enabled the identification of 5 top hits that significantly inhibited NECC organoids <i>in vitro</i> with half-maximal inhibitory concentration (IC<sub>50</sub>) of lower than 10 nM. The representative candidate, Quisinostat 2HCl, demonstrated significantly stronger anti-tumor efficacy than clinically used agents <i>in vivo</i>. This platform significantly improves the rapidity and efficiency of 3D ECM-encapsulated organoid drug screening and facilitates new drug discovery for rare diseases.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"4 5","pages":"lnaf021"},"PeriodicalIF":6.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12517169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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