Cell Reports Medicine最新文献_第2页

Inhibition of basal IL-6 activity promotes subcutaneous fat retention in humans during fasting and postprandial states.

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-03-22 DOI: 10.1016/j.xcrm.2025.102042

Beckey Trinh, Signe Johanne Rasmussen, Mathilde Ehnhuus Brøgger-Jensen, Christoph Andreas Engelhard, Anton Lund, Ana Rita Tavanez, Alexandra Vassilieva, Susanne Janum, Ulrik Winning Iepsen, Bente Kiens, Kirsten Møller, Bente Klarlund Pedersen, Gerrit Van Hall, Helga Ellingsgaard

{"title":"Inhibition of basal IL-6 activity promotes subcutaneous fat retention in humans during fasting and postprandial states.","authors":"Beckey Trinh, Signe Johanne Rasmussen, Mathilde Ehnhuus Brøgger-Jensen, Christoph Andreas Engelhard, Anton Lund, Ana Rita Tavanez, Alexandra Vassilieva, Susanne Janum, Ulrik Winning Iepsen, Bente Kiens, Kirsten Møller, Bente Klarlund Pedersen, Gerrit Van Hall, Helga Ellingsgaard","doi":"10.1016/j.xcrm.2025.102042","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102042","url":null,"abstract":"Interleukin-6 (IL-6) knockout mice and humans treated with IL-6 receptor blockade gain adipose tissue mass. This study investigates whether basal IL-6 activity (resting IL-6 levels) influences fat storage during fasting and postprandial states. Using stable-isotope tracer techniques and IL-6 receptor blockade with tocilizumab, we examine fat kinetics in humans. Blocking basal IL-6 activity reduces fasting whole-body lipolysis, decreases hormone-sensitive lipase (HSL) phosphorylation and fatty acid release in adipose tissue, and impairs postprandial fatty acid uptake in the leg. These results suggest diminished fatty acid uptake and oxidation in skeletal muscle, along with enhanced fatty acid entrapment in adipose tissue, which may account for the increased adiposity in the absence of IL-6 activity. Additionally, IL-6 blockade increases the escape of meal-derived fatty acids into the bloodstream. Whether this affects fatty acid storage and lipotoxicity in other tissues warrants further investigation. This study was registered at ClinicalTrials.gov (NCT04687540).","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102042"},"PeriodicalIF":11.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A spatially resolved transcriptome landscape during thyroid cancer progression.

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-03-20 DOI: 10.1016/j.xcrm.2025.102043

Tian Liao, Yu Zeng, Weibo Xu, Xiao Shi, Cenkai Shen, Yuxin Du, Meng Zhang, Yan Zhang, Ling Li, Peipei Ding, Weiguo Hu, Zhiheng Huang, Man Him Matrix Fung, Qinghai Ji, Yu Wang, Shengli Li, Wenjun Wei

{"title":"A spatially resolved transcriptome landscape during thyroid cancer progression.","authors":"Tian Liao, Yu Zeng, Weibo Xu, Xiao Shi, Cenkai Shen, Yuxin Du, Meng Zhang, Yan Zhang, Ling Li, Peipei Ding, Weiguo Hu, Zhiheng Huang, Man Him Matrix Fung, Qinghai Ji, Yu Wang, Shengli Li, Wenjun Wei","doi":"10.1016/j.xcrm.2025.102043","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102043","url":null,"abstract":"Tumor microenvironment (TME) remodeling plays a pivotal role in thyroid cancer progression, yet its spatial dynamics remain unclear. In this study, we integrate spatial transcriptomics and single-cell RNA sequencing to map the TME architecture across para-tumor thyroid (PT) tissue, papillary thyroid cancer (PTC), locally advanced PTC (LPTC), and anaplastic thyroid carcinoma (ATC). Our integrative analysis reveals extensive molecular and cellular heterogeneity during thyroid cancer progression, enabling the identification of three distinct thyrocyte meta-clusters, including TG+IYG+ subpopulation in PT, HLA-DRB1+HLA-DRA+ subpopulation in early cancerous stages, and APOE+APOC1+ subpopulation in late-stage progression. We reveal stage-specific tumor leading edge remodeling and establish high-confidence cell-cell interactions, such as COL8A1-ITHB1 in PTC, LAMB2-ITGB4 in LPTC, and SERPINE1-PLAUR in ATC. Notably, both SERPINE1 expression level and SERPINE1+ fibroblast abundance correlate with malignant progression and prognosis. These findings provide a spatially resolved framework of TME remodeling, offering insights for thyroid cancer diagnosis and treatment.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102043"},"PeriodicalIF":11.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Screening of patient-derived organoids identifies mitophagy as a cell-intrinsic vulnerability in colorectal cancer during statin treatment.

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-03-19 DOI: 10.1016/j.xcrm.2025.102039

Zhi-Hang Tao, Ji-Xuan Han, Jia Xu, Enhao Zhao, Ming Wang, Zheng Wang, Xiao-Lin Lin, Xiu-Ying Xiao, Jie Hong, Haoyan Chen, Ying-Xuan Chen, Hui-Min Chen, Jing-Yuan Fang

{"title":"Screening of patient-derived organoids identifies mitophagy as a cell-intrinsic vulnerability in colorectal cancer during statin treatment.","authors":"Zhi-Hang Tao, Ji-Xuan Han, Jia Xu, Enhao Zhao, Ming Wang, Zheng Wang, Xiao-Lin Lin, Xiu-Ying Xiao, Jie Hong, Haoyan Chen, Ying-Xuan Chen, Hui-Min Chen, Jing-Yuan Fang","doi":"10.1016/j.xcrm.2025.102039","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102039","url":null,"abstract":"Statins, commonly used to lower cholesterol, are associated with improved prognosis in colorectal cancer (CRC), though their effectiveness varies. This study investigates the anti-cancer effects of atorvastatin in CRC using patient-derived organoids (PDOs) and PDO-derived xenograft (PDOX) models. Our findings reveal that atorvastatin induces mitochondrial dysfunction, leading to apoptosis in cancer cells. In response, cancer cells induce mitophagy to clear damaged mitochondria, enhancing survival and reducing statin efficacy. Analysis of a clinical cohort confirms mitophagy's role in diminishing statin effectiveness. Importantly, inhibiting mitophagy significantly enhances the anti-cancer effects of atorvastatin in CRC PDOs, xenograft models, and azoxymethane (AOM)-dextran sulfate sodium (DSS) mouse models. These findings identify mitophagy as a critical pro-survival mechanism in CRC during statin treatment, providing insights into the variable responses observed in epidemiological studies. Targeting this vulnerability through combination therapy can elicit potent therapeutic responses.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102039"},"PeriodicalIF":11.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interferon-γ-stimulated antigen-presenting cancer-associated fibroblasts hinder neoadjuvant chemoimmunotherapy efficacy in lung cancer.

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-03-18 Epub Date: 2025-03-07 DOI: 10.1016/j.xcrm.2025.102017

Zhengqi Cao, Zhouwenli Meng, Jian Li, Yu Tian, Li Lu, Anni Wang, Jia Huang, Jingze Wang, Jing Sun, Lixuan Chen, Shun Lu, Ziming Li

{"title":"Interferon-γ-stimulated antigen-presenting cancer-associated fibroblasts hinder neoadjuvant chemoimmunotherapy efficacy in lung cancer.","authors":"Zhengqi Cao, Zhouwenli Meng, Jian Li, Yu Tian, Li Lu, Anni Wang, Jia Huang, Jingze Wang, Jing Sun, Lixuan Chen, Shun Lu, Ziming Li","doi":"10.1016/j.xcrm.2025.102017","DOIUrl":"10.1016/j.xcrm.2025.102017","url":null,"abstract":"Conventional neoadjuvant chemotherapy provides limited benefit for patients with resectable non-small cell lung cancer (NSCLC). Recently, neoadjuvant chemoimmunotherapy (NCIT) has transformed the perioperative management of NSCLC by priming systemic anti-tumor immunity before surgery, yet it remains ineffective for at least 50% of patients. Through single-cell sequencing analysis of our NCIT cohort, we identify that antigen-presenting cancer-associated fibroblasts (apCAFs) can impede the efficacy of NCIT. Using a custom cancer-associated fibroblast biobank, we uncover that interferon (IFN)-γ stimulates apCAF expansion via the JAK1/2-STAT1-IFI6/27 pathway. Mechanistically, apCAFs significantly contribute to PD-L2 expression in the tumor microenvironment (TME), triggering the accumulation of FOXP1+regulatory T cells (Tregs) through the PD-L2-RGMB axis. Reprogramming apCAFs by inhibiting the IFN-γ pathway or blocking the PD-L2-RGMB axis substantially mitigates apCAFs-mediated FOXP1+Tregs' expansion. In summary, we reveal the role of apCAFs in compromising NCIT efficacy and propose applications for anti-PD-L2/RGMB regimens to synergize with anti-PD1 therapies by targeting apCAFs.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102017"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessments of lung nodules by an artificial intelligence chatbot using longitudinal CT images.

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-03-18 Epub Date: 2025-03-04 DOI: 10.1016/j.xcrm.2025.101988

Yuqiang Mao, Nan Xu, Yanan Wu, Lu Wang, Hongtao Wang, Qianqian He, Tianqi Zhao, Shuangchun Ma, Meihong Zhou, Hongjie Jin, Dongmei Pei, Lina Zhang, Jiangdian Song

{"title":"Assessments of lung nodules by an artificial intelligence chatbot using longitudinal CT images.","authors":"Yuqiang Mao, Nan Xu, Yanan Wu, Lu Wang, Hongtao Wang, Qianqian He, Tianqi Zhao, Shuangchun Ma, Meihong Zhou, Hongjie Jin, Dongmei Pei, Lina Zhang, Jiangdian Song","doi":"10.1016/j.xcrm.2025.101988","DOIUrl":"10.1016/j.xcrm.2025.101988","url":null,"abstract":"Large language models have shown efficacy across multiple medical tasks. However, their value in the assessment of longitudinal follow-up computed tomography (CT) images of patients with lung nodules is unclear. In this study, we evaluate the ability of the latest generative pre-trained transformer (GPT)-4o model to assess changes in malignancy probability, size, and features of lung nodules on longitudinal CT scans from 647 patients (547 from two local centers and 100 from a public dataset). GPT-4o achieves an average accuracy of 0.88 in predicting lung nodule malignancy compared to pathological results and an average intraclass correlation coefficient of 0.91 in measuring nodule size compared with manual measurements by radiologists. Six radiologists' evaluations demonstrate GPT-4o's ability to capture changes in nodule features with a median Likert score of 4.17 (out of 5.00). In summary, GPT-4o could capture dynamic changes in lung nodules across longitudinal follow-up CT images, thus providing high-quality radiological evidence to assist in clinical management.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101988"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The expanding role of the receptor tyrosine kinase MET as a therapeutic target in non-small cell lung cancer.

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-03-18 Epub Date: 2025-02-27 DOI: 10.1016/j.xcrm.2025.101983

Martin Sattler, Ravi Salgia

引用次数: 0

Outer radial glia promotes white matter regeneration after neonatal brain injury.

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-03-18 Epub Date: 2025-02-28 DOI: 10.1016/j.xcrm.2025.101986

Hideo Jinnou, Lauren M Rosko, Satoshi Yamashita, Soichiro Henmi, Jaya Prasad, Van K Lam, Artur Agaronyan, Tsang-Wei Tu, Yuka Imamura, Kazuya Kuboyama, Kazunobu Sawamoto, Kazue Hashimoto-Torii, Nobuyuki Ishibashi, Vittorio Gallo

{"title":"Outer radial glia promotes white matter regeneration after neonatal brain injury.","authors":"Hideo Jinnou, Lauren M Rosko, Satoshi Yamashita, Soichiro Henmi, Jaya Prasad, Van K Lam, Artur Agaronyan, Tsang-Wei Tu, Yuka Imamura, Kazuya Kuboyama, Kazunobu Sawamoto, Kazue Hashimoto-Torii, Nobuyuki Ishibashi, Vittorio Gallo","doi":"10.1016/j.xcrm.2025.101986","DOIUrl":"10.1016/j.xcrm.2025.101986","url":null,"abstract":"The developing gyrencephalic brain contains a large population of neural stem cells in the ventricular zone and outer subventricular zone (OSVZ), the latter populated by outer radial glia (oRG). The role of oRG during postnatal development is not well understood. We show that oRG cells increase proliferative capacity and contribute to oligodendrocyte precursor cell (OPC) production following brain injury in human infants and neonatal piglets, whose brains resemble the human brain in structure and development. RNA sequencing revealed oRG-specific transcriptional responses to injury in piglets and showed that the activating transcription factor 5 (ATF5) pathway positively regulates oRG proliferation. Intranasal activation of ATF5 using salubrinal enhanced OSVZ-derived oligodendrogenesis in the injured periventricular white matter and improved functional recovery. These results reveal a key role for postnatal oRG in brain injury recovery and identify ATF5 as a potential therapeutic target for treating white matter injury in infants.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101986"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineered human myogenic cells in hydrogels generate innervated vascularized myofibers within dystrophic mouse muscle on long-term engraftment.

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-03-18 Epub Date: 2025-03-07 DOI: 10.1016/j.xcrm.2025.102019

Anna Kowala, James Boot, Jinhong Meng, Charles A Mein, Olivier Pourquié, John T Connelly, Jennifer E Morgan, Yung-Yao Lin

{"title":"Engineered human myogenic cells in hydrogels generate innervated vascularized myofibers within dystrophic mouse muscle on long-term engraftment.","authors":"Anna Kowala, James Boot, Jinhong Meng, Charles A Mein, Olivier Pourquié, John T Connelly, Jennifer E Morgan, Yung-Yao Lin","doi":"10.1016/j.xcrm.2025.102019","DOIUrl":"10.1016/j.xcrm.2025.102019","url":null,"abstract":"Transplantation of human myogenic progenitor cells (MPCs) is a promising therapeutic strategy for treating muscle-wasting diseases, e.g., Duchenne muscular dystrophy (DMD). To increase engraftment efficiency of donor stem cells, modulation of host muscles is required, significantly limiting their clinical translation. Here, we develop a clinically relevant transplantation strategy synergizing hydrogel-mediated delivery and engineered human MPCs generated from CRISPR-corrected DMD patient-derived pluripotent stem cells. We demonstrate that donor-derived human myofibers produce full-length dystrophin at 4 weeks and 5-6 months (long-term) after transplantation in the unmodulated muscles of the dystrophin-deficient mouse model of DMD. Remarkably, human myofibers are innervated by mouse motor neurons forming neuromuscular junctions and supported by vascularization after long-term engraftment in dystrophic mice. PAX7+ cells of human origin populate the satellite cell niche. There was no evidence of tumorigenesis in mice engrafted with hydrogel-encapsulated human MPCs. Our results provide a proof of concept in developing hydrogel-based cell therapy for muscle-wasting diseases.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102019"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting pathogenic interferon-stimulated gene RSAD2 improves pregnancy outcomes in systemic lupus erythematosus models.

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-03-18 DOI: 10.1016/j.xcrm.2025.102034

Seble G Negatu, Kellie A Jurado

引用次数: 0

RSAD2: A pathogenic interferon-stimulated gene at the maternal-fetal interface of patients with systemic lupus erythematosus.

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-03-18 Epub Date: 2025-02-20 DOI: 10.1016/j.xcrm.2025.101974

Xiaoyu Ding, Yonggang Zhou, Xiaofeng Qiu, Xiuxiu Xu, Xinyu Hu, Jingkun Qin, Yulan Chen, Min Zhang, Jieqi Ke, Zhenbang Liu, Ying Zhou, Chen Ding, Nan Shen, Zhigang Tian, Binqing Fu, Haiming Wei

{"title":"RSAD2: A pathogenic interferon-stimulated gene at the maternal-fetal interface of patients with systemic lupus erythematosus.","authors":"Xiaoyu Ding, Yonggang Zhou, Xiaofeng Qiu, Xiuxiu Xu, Xinyu Hu, Jingkun Qin, Yulan Chen, Min Zhang, Jieqi Ke, Zhenbang Liu, Ying Zhou, Chen Ding, Nan Shen, Zhigang Tian, Binqing Fu, Haiming Wei","doi":"10.1016/j.xcrm.2025.101974","DOIUrl":"10.1016/j.xcrm.2025.101974","url":null,"abstract":"Pregnancy disorders in patients with autoimmune diseases or viral infections are often associated with an excessive response of type I interferons. We identify radical S-adenosyl methionine domain containing 2 (RSAD2) as a pathogenic interferon-stimulated gene (ISG) associated with pregnancy complications in systemic lupus erythematosus (SLE). The increased expression of RSAD2 mainly occurs in macrophages and structural cell populations at the maternal-fetal interface of pregnant patients with SLE. The elevation of RSAD2 leads to the accumulation of diacylglycerol lipids in the placenta, impairing the necessary vascular development for the fetus. Depletion of Rsad2 in pregnant mice models exposed to type I interferon inducers significantly reduces lipid accumulation, vascular injury, and embryo development disorders. An RSAD2 inhibitor, L-chicoric acid (LCA), alleviates lipid accumulation and vascular damage, improving pregnancy outcomes in SLE-induced and spontaneous mouse models. This study proposes the potential of targeting RSAD2 to improve pregnancy outcomes in individuals with heightened type I interferon response.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101974"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0