Cell Reports MedicinePub Date : 2025-03-18Epub Date: 2025-03-04DOI: 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":"<p><p>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.</p>","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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell Reports MedicinePub Date : 2025-03-18Epub Date: 2025-03-07DOI: 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":"<p><p>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.</p>","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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting pathogenic interferon-stimulated gene RSAD2 improves pregnancy outcomes in systemic lupus erythematosus models.","authors":"Seble G Negatu, Kellie A Jurado","doi":"10.1016/j.xcrm.2025.102034","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102034","url":null,"abstract":"<p><p>Excessive type I interferons during pregnancy are associated with poor pregnancy outcomes. Ding et al.<sup>1</sup> demonstrate the pathogenic effects of the interferon-stimulated gene RSAD2 that drives adverse pregnancy outcomes through placental lipid accumulation, and further identify a promising therapeutic candidate.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 3","pages":"102034"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662639","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}
{"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":"<p><p>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.</p>","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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell Reports MedicinePub Date : 2025-03-18Epub Date: 2025-03-06DOI: 10.1016/j.xcrm.2025.101982
Kenneth J O'Riordan, Gerard M Moloney, Lily Keane, Gerard Clarke, John F Cryan
{"title":"The gut microbiota-immune-brain axis: Therapeutic implications.","authors":"Kenneth J O'Riordan, Gerard M Moloney, Lily Keane, Gerard Clarke, John F Cryan","doi":"10.1016/j.xcrm.2025.101982","DOIUrl":"10.1016/j.xcrm.2025.101982","url":null,"abstract":"<p><p>The microbiota-gut-brain axis has major implications for human health including gastrointestinal physiology, brain function, and behavior. The immune system represents a key pathway of communication along this axis with the microbiome implicated in neuroinflammation in health and disease. In this review, we discuss the mechanisms as to how the gut microbiota interacts with the brain, focusing on innate and adaptive immunity that are often disrupted in gut-brain axis disorders. We also consider the implications of these observations and how they can be advanced by interdisciplinary research. Leveraging an increased understanding of how these interactions regulate immunity has the potential to usher in a new era of precision neuropsychiatric clinical interventions for psychiatric, neurodevelopmental, and neurological disorders.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101982"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584178","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}
{"title":"Histamine 2 receptor: Emerging target for the treatment of attention-deficit/hyperactivity disorder.","authors":"Ling Shan, Dick F Swaab","doi":"10.1016/j.xcrm.2025.102023","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102023","url":null,"abstract":"<p><p>A study by An et al. sheds a novel light on the potential role of histamine 2 receptor (H<sub>2</sub>R) deficiency in attention-deficit/hyperactivity disorder (ADHD), which could be a future therapeutic target of ADHD. This spotlight provides an overview of the current knowledge of the histaminergic system and proposes future directions.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 3","pages":"102023"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662632","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}
Ivan Jelcic, Reza Naghavian, Imran Fanaswala, Will Macnair, Cinzia Esposito, Daniela Calini, Yanan Han, Zoe Marti, Catarina Raposo, Jacobo Sarabia Del Castillo, Pietro Oldrati, Daniel Erny, Veronika Kana, Galina Zheleznyakova, Faiez Al Nimer, Björn Tackenberg, Ina Reichen, Mohsen Khademi, Fredrik Piehl, Mark D Robinson, Ilijas Jelcic, Mireia Sospedra, Lucas Pelkmans, Dheeraj Malhotra, Richard Reynolds, Maja Jagodic, Roland Martin
{"title":"T-bet+ CXCR3+ B cells drive hyperreactive B-T cell interactions in multiple sclerosis.","authors":"Ivan Jelcic, Reza Naghavian, Imran Fanaswala, Will Macnair, Cinzia Esposito, Daniela Calini, Yanan Han, Zoe Marti, Catarina Raposo, Jacobo Sarabia Del Castillo, Pietro Oldrati, Daniel Erny, Veronika Kana, Galina Zheleznyakova, Faiez Al Nimer, Björn Tackenberg, Ina Reichen, Mohsen Khademi, Fredrik Piehl, Mark D Robinson, Ilijas Jelcic, Mireia Sospedra, Lucas Pelkmans, Dheeraj Malhotra, Richard Reynolds, Maja Jagodic, Roland Martin","doi":"10.1016/j.xcrm.2025.102027","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102027","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Self-peptide-dependent autoproliferation (AP) of B and T cells is a key mechanism in MS. Here, we show that pro-inflammatory B-T cell-enriched cell clusters (BTECs) form during AP and mirror features of a germinal center reaction. T-bet+CXCR3+ B cells are the main cell subset amplifying and sustaining their counterpart Th1 cells via interferon (IFN)-γ and are present in highly inflamed meningeal tissue. The underlying B cell activation signature is reflected by epigenetic modifications and receptor-ligand interactions with self-reactive T cells. AP+ CXCR3+ B cells show marked clonal evolution from memory to somatically hypermutated plasmablasts and upregulation of IFN-γ-related genes. Our data underscore a key role of T-bet+CXCR3+ B cells in the pathogenesis of MS in both the peripheral immune system and the CNS compartment, and thus they appear to be involved in both early relapsing-remitting disease and the chronic stage.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 3","pages":"102027"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662640","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}
{"title":"Potentiating anti-tumor immunity by re-engaging immune synapse molecules.","authors":"Xindi Zhou, Tian Xu, Changhe Li, Yufeng He, Yuanzhi Hu, Hao Gong, Jiahui Li, Haitao Jiang, Liang Wen, Yangxin Fu, Zexian Zeng, Deng Pan","doi":"10.1016/j.xcrm.2025.101975","DOIUrl":"10.1016/j.xcrm.2025.101975","url":null,"abstract":"<p><p>The formation of immune synapses (ISs) between cytotoxic T cells and tumor cells is crucial for effective tumor elimination. However, the role of ISs in immune evasion and resistance to immune checkpoint blockades (ICBs) remains unclear. We demonstrate that ICAM-1, a key IS molecule activating LFA-1 signaling in T and natural killer (NK) cells, is often expressed at low levels in cancers. The absence of ICAM-1 leads to significant resistance to T and NK cell-mediated anti-tumor immunity. Using a CRISPR screen, we show that ICAM-1 is epigenetically regulated by the DNA methylation pathway involving UHRF1 and DNMT1. Furthermore, we engineer an antibody-based therapeutic agent, \"LFA-1 engager,\" to enhance T cell-mediated anti-tumor immunity by reconstituting LFA-1 signaling. Treatment with LFA-1 engagers substantially enhances immune-mediated cytotoxicity, potentiates anti-tumor immunity, and synergizes with ICB in mouse models of ICAM-1-deficient tumors. Our data provide promising therapeutic strategies for re-engaging immune stimulatory signals in cancer immunotherapy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101975"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499514","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}
{"title":"Unveiling familial aggregation of nasopharyngeal carcinoma: Insights from oral microbiome dysbiosis.","authors":"Ying Liao, Xia-Ting Tong, Ting Zhou, Wen-Qiong Xue, Tong-Min Wang, Yong-Qiao He, Mei-Qi Zheng, Yi-Jing Jia, Da-Wei Yang, Yan-Xia Wu, Xiao-Hui Zheng, Zhi-Xiang Zuo, Ming-Yuan Chen, Na Liu, Wei-Hua Jia","doi":"10.1016/j.xcrm.2025.101979","DOIUrl":"10.1016/j.xcrm.2025.101979","url":null,"abstract":"<p><p>Familial aggregation is common in nasopharyngeal carcinoma (NPC), yet the impact of oral microbiome dysbiosis on this occurrence remains largely unexplored. We recruit 127 families (649 members, 1-5 patients each) and a case-control cohort of 337 individuals, validating findings in an additional cohort of 995 individuals. Significant microbial similarity is observed among family members, with family factors contributing most to microbiome variation, followed by cigarette smoking, age, and gender. Among multi-NPC families, especially those with three or more patients, we identify three NPC-enriched taxa with notable heritability, including Gemella sp. (heritability, h<sup>2</sup> = 53.1%), Lautropia mirabilis (h<sup>2</sup> = 38.8%), and Streptococcus sp. (h<sup>2</sup> = 38.0%). Heritable bacteria present a markedly higher heritability in families with increased clustering of NPC and form closely interacting networks, suggesting their role in NPC familial aggregation. These findings open up possibilities for identifying high-risk individuals, enhancing clinical surveillance, and developing personalized prevention and treatment approaches of NPC through microbiome-based strategies.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101979"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499542","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}
Cell Reports MedicinePub Date : 2025-03-18Epub Date: 2025-03-07DOI: 10.1016/j.xcrm.2025.101996
Valdemar Brimnes Ingemann Johansen, Anna Katrina Jógvansdóttir Gradel, Stephanie Kjærulff Holm, Joyceline Cuenco, Christoffer Merrild, Natalia Petersen, Damien Demozay, Bharath Kumar Mani, Malte Palm Suppli, Magnus F G Grøndahl, Asger Bach Lund, Filip Krag Knop, Cesar A Prada-Medina, Wouter Frederik Johan Hogendorf, Jens Lykkesfeldt, Myrte Merkestein, Kei Sakamoto, Birgitte Holst, Christoffer Clemmensen
{"title":"Regulation of LEAP2 by insulin and glucagon in mice and humans.","authors":"Valdemar Brimnes Ingemann Johansen, Anna Katrina Jógvansdóttir Gradel, Stephanie Kjærulff Holm, Joyceline Cuenco, Christoffer Merrild, Natalia Petersen, Damien Demozay, Bharath Kumar Mani, Malte Palm Suppli, Magnus F G Grøndahl, Asger Bach Lund, Filip Krag Knop, Cesar A Prada-Medina, Wouter Frederik Johan Hogendorf, Jens Lykkesfeldt, Myrte Merkestein, Kei Sakamoto, Birgitte Holst, Christoffer Clemmensen","doi":"10.1016/j.xcrm.2025.101996","DOIUrl":"10.1016/j.xcrm.2025.101996","url":null,"abstract":"<p><p>Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous antagonist and inverse agonist of the ghrelin receptor, countering ghrelin's effects on cell signaling and feeding. However, despite an emerging interest in LEAP2's physiology and pharmacology, its endocrine regulation remains unclear. Here, we report that plasma LEAP2 levels decrease significantly upon glucagon infusions during somatostatin clamps in humans. This effect is preserved in patients with obesity and type 2 diabetes while diminished following a hypercaloric diet and a sedentary lifestyle for 2 weeks. Additionally, insulin receptor antagonism offsets the upregulation of LEAP2 during the postprandial state in mice. Finally, insulin and glucagon receptor-expressing hepatocytes are the primary source of hepatic LEAP2 expression, coinciding with a putative enhancer-like signature bound by insulin- and glucagon-regulated transcription factors at the LEAP2 locus. Collectively, our findings implicate insulin and glucagon in regulating LEAP2 and warrant further investigations into the exact mechanisms orchestrating this endocrine axis.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101996"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582220","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}