Cell Reports MedicinePub Date : 2025-06-17Epub Date: 2025-05-26DOI: 10.1016/j.xcrm.2025.102148
Kai Shang, Deyu Huang, Jun Liu, Zebin Yu, Wei Bian, Jiangqing Chen, Yin Zhao, Lina Liu, Jie Jiang, Yajie Wang, Yanting Duan, Jingyu Ge, Shize Zhang, Chun Zhou, Yingli Han, Yongxian Hu, Weiyan Zheng, Jie Sun, He Huang, Shanshan Pei, Pengxu Qian, Jie Sun
{"title":"CD97-directed CAR-T cells with enhanced persistence eradicate acute myeloid leukemia in diverse xenograft models.","authors":"Kai Shang, Deyu Huang, Jun Liu, Zebin Yu, Wei Bian, Jiangqing Chen, Yin Zhao, Lina Liu, Jie Jiang, Yajie Wang, Yanting Duan, Jingyu Ge, Shize Zhang, Chun Zhou, Yingli Han, Yongxian Hu, Weiyan Zheng, Jie Sun, He Huang, Shanshan Pei, Pengxu Qian, Jie Sun","doi":"10.1016/j.xcrm.2025.102148","DOIUrl":"10.1016/j.xcrm.2025.102148","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-T therapy on acute myeloid leukemia (AML) is hindered by the absence of a suitable tumor-specific antigen. Here, we propose CD97 as a potential target for CAR-T therapy against AML based on its broader and higher expression on AML cells compared to normal hematopoietic stem and progenitor cells (HSPCs). To resolve the fratricide problem caused by CD97 expression on T cells, we knock out CD97 in CAR-T cells using CRISPR-Cas9. Our CD97<sup>KO</sup> CAR-T cells eliminate both AML cell lines and primary AML cells effectively while showing tolerable toxicity to HSPCs. Furthermore, we mutate the CD3ζ domain of the CAR and find that the optimized CD97 CAR-T cells exhibit persistent anti-tumor activity both in vitro and in multiple xenograft models. Mechanistically, transcriptional profiles reveal that the optimized CAR-T cells delay differentiation and resist exhaustion. Collectively, our study supports CD97 as a promising target for CAR-T therapy against AML.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102148"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157012","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}
{"title":"Cross-organ hierarchy of HLA molecular mismatches in donor-specific antibody development in solid organ transplantations.","authors":"Masaaki Hirata, Kazuto Tsukita, Takero Shindo, Shintaro Yagi, Takashi Ito, Satona Tanaka, Ryo Fujimoto, Hidenao Kayawake, Kenji Nakamura, Nobuhiro Fujiyama, Mitsuru Saito, Kimiko Yurugi, Rie Hishida, Arisa Kato, Atsushi Kawaguchi, Tomonori Habuchi, Takashi Kobayashi, Hiroshi Date, Etsuro Hatano","doi":"10.1016/j.xcrm.2025.102153","DOIUrl":"10.1016/j.xcrm.2025.102153","url":null,"abstract":"<p><p>Donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) play a crucial role in antibody-mediated rejection, a major barrier to successful organ transplantation. Donor-recipient HLA molecular incompatibility critically influences DSA susceptibility, commonly assessed by analyzing mismatches in the HLA eplet repertoire. This study, including six distinct liver, lung, and kidney transplant cohorts from two centers (978 donor-recipient pairs), explores associations between individual eplet mismatches and DSA development. Certain mismatched eplets are strongly linked to DSA development, while others show weaker associations, a trend consistent across different organ types. Machine learning leverages these hierarchical associations to develop an eplet risk score (ERS), outperforming traditional eplet mismatch assessments. Furthermore, T cell proliferation in mixed lymphocyte reaction in vitro correlates with the ERS, attenuated by antibody-mediated inhibition of a mismatched DSA-associated eplet. These results establish the differential immunological impacts of mismatched HLA eplets as integral in clinical practice and therapeutic innovation.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102153"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191583","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}
Cell Reports MedicinePub Date : 2025-06-17Epub Date: 2025-06-03DOI: 10.1016/j.xcrm.2025.102160
Anthony Tighe, Louisa Nelson, Robert D Morgan, Bethany M Barnes, I-Hsuan Lin, Samantha Littler, James Altringham, Jean Ling Tan, Joanne C McGrail, Stephen S Taylor
{"title":"Screening a living biobank identifies cabazitaxel as a strategy to combat acquired taxol resistance in high-grade serous ovarian cancer.","authors":"Anthony Tighe, Louisa Nelson, Robert D Morgan, Bethany M Barnes, I-Hsuan Lin, Samantha Littler, James Altringham, Jean Ling Tan, Joanne C McGrail, Stephen S Taylor","doi":"10.1016/j.xcrm.2025.102160","DOIUrl":"10.1016/j.xcrm.2025.102160","url":null,"abstract":"<p><p>The anti-mitotic agent taxol (paclitaxel) remains a cornerstone of ovarian cancer treatment. To tackle drug resistance and toxicity, second-generation targeted anti-mitotic agents and combination strategies are being explored but have yet to demonstrate meaningful clinical benefits. A limitation is the lack of a platform to compare strategies in models that capture disease heterogeneity. To overcome this, we screen 83 patient-derived ex vivo ovarian cancer models that exhibit extensive intra- and inter-patient heterogeneity, testing four distinct approaches to enhance taxol sensitivity. Inhibitors of the HSET kinesin or the Mps1 spindle assembly checkpoint kinase show minimal impact on the taxol sensitivity landscape. By contrast, Bcl-xL inhibition exerts a global anti-proliferative effect. Inhibition of the MDR1 drug efflux pump restores taxol sensitivity in models characterized by ABCB1 overexpression. These MDR1-driven resistant models also respond to cabazitaxel, which is a poor MDR1 substrate, highlighting a potential therapeutic option for ovarian cancers with acquired taxol resistance.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102160"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224433","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}
{"title":"Felicia Pagliuca.","authors":"Felicia Pagliuca","doi":"10.1016/j.xcrm.2025.102142","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102142","url":null,"abstract":"<p><p>Dr. Felicia Pagliuca is currently Senior Vice President, Cell and Genetic Therapy Research at Vertex Pharmaceuticals. She received a BS from Duke University and a PhD from Cambridge University where she was a Marshall Scholar. She completed her postdoctoral fellowship with Dr. Douglas Melton at the Harvard Stem Cell Institute, where she worked with Dr. Melton to discover how to generate stem cell-derived pancreatic beta cells in the lab. She co-founded Semma Therapeutics with Dr. Melton in 2014. While at Semma, she served as Vice President of Cell Biology Research and Development, where she led the development of investigational cell therapies for the treatment of type 1 diabetes. She joined Vertex Pharmaceuticals in 2019, when Semma was acquired by Vertex, and served as the company's Vice President and Disease Area Executive for type 1 diabetes for 5 years before moving into her current role.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 5","pages":"102142"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118982","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 : 2025-05-20Epub Date: 2025-05-08DOI: 10.1016/j.xcrm.2025.102092
Cheng Gao, Ruifeng Luo, Cheryl H T Kwong, Jinwei Liu, Mian Tang, Beibei Xie, Tianshun Duan, Ruibing Wang
{"title":"Cancer vaccine from intracellularly gelated tumor cells functionalized with CD47 blockage and damage-associated molecular pattern exposure.","authors":"Cheng Gao, Ruifeng Luo, Cheryl H T Kwong, Jinwei Liu, Mian Tang, Beibei Xie, Tianshun Duan, Ruibing Wang","doi":"10.1016/j.xcrm.2025.102092","DOIUrl":"10.1016/j.xcrm.2025.102092","url":null,"abstract":"<p><p>The effectiveness of whole tumor cell vaccines prepared by traditional inactivation methodology is often hindered by insufficient immunogenicity. Here, we report development of a cancer vaccine through the intracellular gelation of tumor cells, combined with CD47 blockade and damage-associated molecular pattern (DAMP) exposure, for effective tumor prevention and treatment. Intracellular hydrogelation preserves the morphology and antigenicity of tumor cells. CD47 blockade and DAMP exposure synergistically enhance the \"eat me\" signals and inhibit the \"don't eat me\" signals on tumor cells, significantly improving their immunogenicity. In the context of tumor prevention and treatment of pre-existing tumors, this vaccine polarizes CD4<sup>+</sup> T cells toward a T<sub>H</sub>1 phenotype, reduces regulatory T cells and T cell exhaustion, and elicits a robust tumor-antigen-specific T cell response. When combined with an immune checkpoint inhibitor, this vaccine demonstrates enhanced efficacy in eradicating established tumors. The successful application of this vaccine using ascites and subcutaneous tumor cells supports the feasibility of developing personalized whole tumor cell vaccines for diverse tumor types.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102092"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974059","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}
{"title":"AI-powered integration of multimodal imaging in precision medicine for neuropsychiatric disorders.","authors":"Weijie Huang, Ni Shu","doi":"10.1016/j.xcrm.2025.102132","DOIUrl":"10.1016/j.xcrm.2025.102132","url":null,"abstract":"<p><p>Neuropsychiatric disorders have complex pathological mechanism, pronounced clinical heterogeneity, and a prolonged preclinical phase, which presents a challenge for early diagnosis and development of precise intervention strategies. With the development of large-scale multimodal neuroimaging datasets and advancement of artificial intelligence (AI) algorithms, the integration of multimodal imaging with AI techniques has emerged as a pivotal avenue for early detection and tailoring individualized treatment for neuropsychiatric disorders. To support these advances, in this review, we outline multimodal neuroimaging techniques, AI methods, and strategies for multimodal data fusion. We highlight applications of multimodal AI based on neuroimaging data in precision medicine for neuropsychiatric disorders, discussing challenges in clinical adoption, their emerging solutions, and future directions.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 5","pages":"102132"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118964","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}
Cell Reports MedicinePub Date : 2025-05-20Epub Date: 2025-04-29DOI: 10.1016/j.xcrm.2025.102098
Yong Liu, Zefan Du, Lindi Li, Junbin Huang, Su Liu, Bo Lu, Yifei Duan, Yucai Cheng, Tianwen Li, Jing Zhang, Jiani Mo, Yalin Yang, Wengqing Wang, Hailin Zou, Tianqi Liang, Meng Jiang, Mo Yang, Yun Chen, Cheng Ouyang, Chun Chen
{"title":"scRNA-seq reveals an immune microenvironment and JUN-mediated NK cell exhaustion in relapsed T-ALL.","authors":"Yong Liu, Zefan Du, Lindi Li, Junbin Huang, Su Liu, Bo Lu, Yifei Duan, Yucai Cheng, Tianwen Li, Jing Zhang, Jiani Mo, Yalin Yang, Wengqing Wang, Hailin Zou, Tianqi Liang, Meng Jiang, Mo Yang, Yun Chen, Cheng Ouyang, Chun Chen","doi":"10.1016/j.xcrm.2025.102098","DOIUrl":"10.1016/j.xcrm.2025.102098","url":null,"abstract":"<p><p>T cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease characterized by a high relapse rate. By single-cell transcriptome analysis, we characterize the bone marrow immune microenvironment in patients with T-ALL, identifying 13 major cell clusters. These patients exhibited abnormally expanded hematopoietic stem cells (HSCs) and granulocyte-monocyte progenitors (GMPs), immunosuppressive traits in CD4<sup>+</sup> T, CD8<sup>+</sup> T, and natural killer (NK) cells. Subdividing CD4<sup>+</sup> T cells reveal two subsets transitioning between T helper (Th)1/Th2, Annexin-A1 (ANXA1)<sup>-</sup>GATA3<sup>-</sup>CD4<sup>+</sup> T, and ANXA1<sup>+</sup>GATA3<sup>+</sup>CD4<sup>+</sup> T. Additionally, NK cells demonstrate exhaustion in the tumor microenvironment of patients with relapsed T-ALL, with JUN identified as a critical factor. Additionally, JUN is also highly expressed in T-ALL and is crucial for maintaining its proliferation. The JUN inhibitor exhibited successful lethality toward leukemia cells and ameliorated NK cell exhaustion in relapsed T-ALL cell line, as well as in cell-derived tumor xenograft (CDX), patient-derived tumor xenograft (PDX), and NOTCH1-mutant mouse models. In summary, our findings enhance the understanding of T-ALL relapse mechanisms and support the development of innovative immunotherapies for patients with relapsed T-ALL.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102098"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992557","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}
Cell Reports MedicinePub Date : 2025-05-20Epub Date: 2025-04-14DOI: 10.1016/j.xcrm.2025.102078
Chen Xu, Liting Chen, Guangna Liu, Jiaqi Xu, Wei Lv, Xiaoyu Gao, Peijun Xu, Ming Tang, Yaohe Wang, Xiao Zhao, Guangjun Nie, Keman Cheng, Funan Liu
{"title":"Tailoring an intravenously injectable oncolytic virus for augmenting radiotherapy.","authors":"Chen Xu, Liting Chen, Guangna Liu, Jiaqi Xu, Wei Lv, Xiaoyu Gao, Peijun Xu, Ming Tang, Yaohe Wang, Xiao Zhao, Guangjun Nie, Keman Cheng, Funan Liu","doi":"10.1016/j.xcrm.2025.102078","DOIUrl":"10.1016/j.xcrm.2025.102078","url":null,"abstract":"<p><p>Oncolytic viruses (OVs) combined with radiotherapy (RT) show promise but are limited by challenges such as poor intravenous delivery and insufficient RT-induced DNA damage. In this study, an oncolytic adenovirus (AD) formulation, RadioOnco (AD@PSSP), is developed to improve delivery, infectivity, immune response, and RT efficacy. The multifunctional polyethylenimine (PEI)-selenium-polyethylene glycol (PEG) (PSSP) enhances intravenous delivery, shields the virus from rapid clearance, and enables targeted delivery to tumor sites after RT. The exposed PEI enhances the infectivity of AD through electrostatic interactions, thereby increasing DNA damage after RT by inhibiting the expression of DNA repair proteins, such as CHEK1 and CDK1. Furthermore, AD-PEI captures and delivers RT-induced tumor-released antigens to lymph nodes, activating robust anti-tumor immune responses. Animal model data demonstrate that RadioOnco overcomes RT resistance, targets distant metastases, and promotes long-term immunity, addressing metastasis and recurrence. In summary, this intravenously injectable OV enhances RT synergy through surface modification with multifunctional materials.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102078"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973963","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}
{"title":"Targeting mitochondrial complex I of CD177<sup>+</sup> neutrophils alleviates lung ischemia-reperfusion injury.","authors":"Junqi Wu, Peigen Gao, Chenlu Yang, Fenghui Zhuang, Yunzhe Luo, Feng Wen, Panyu Zhang, Long Wang, Huikang Xie, Chenyang Dai, Deping Zhao, Chongwu Li, Haohao Deng, Ziqing Deng, Chang Chen","doi":"10.1016/j.xcrm.2025.102140","DOIUrl":"10.1016/j.xcrm.2025.102140","url":null,"abstract":"<p><p>Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality following lung transplantation, with neutrophils playing a central role in its inflammatory pathology. Here, we employ single-cell RNA sequencing and spatial transcriptomics to investigate neutrophil subtypes in the lung ischemia-reperfusion injury (IRI) model. We identify CD177<sup>+</sup> neutrophils as an activated subpopulation that significantly contributes to lung injury and serves as an early biomarker for predicting severe PGD in human lung transplant recipients (area under the curve [AUC] = 0.871). CD177<sup>+</sup> neutrophils exhibit elevated oxidative phosphorylation and increased mitochondrial complex I activity, driving inflammation and the formation of neutrophil extracellular traps. Targeting mitochondrial function with the complex I inhibitor IACS-010759 reduces CD177<sup>+</sup> neutrophil activation and alleviates lung injury in both mouse IRI and rat left lung transplant models. These findings provide a comprehensive landscape of CD177<sup>+</sup> neutrophil-driven inflammation in lung IRI and highlight its potential value for future early diagnosis and therapeutic interventions.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 5","pages":"102140"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118999","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}
Cell Reports MedicinePub Date : 2025-05-20Epub Date: 2025-04-25DOI: 10.1016/j.xcrm.2025.102093
Teng Ma, Yalin Li, Ni Yang, Huan Wang, Xuan Shi, Yanfang Liu, Hao Jin, Lai-Yu Kwok, Zhihong Sun, Heping Zhang
{"title":"Efficacy of a postbiotic and its components in promoting colonic transit and alleviating chronic constipation in humans and mice.","authors":"Teng Ma, Yalin Li, Ni Yang, Huan Wang, Xuan Shi, Yanfang Liu, Hao Jin, Lai-Yu Kwok, Zhihong Sun, Heping Zhang","doi":"10.1016/j.xcrm.2025.102093","DOIUrl":"10.1016/j.xcrm.2025.102093","url":null,"abstract":"<p><p>This study evaluates the efficacy of the postbiotic Probio-Eco in alleviating constipation in humans and mice. A randomized, double-blind, placebo-controlled crossover trial involving 110 adults with chronic constipation (Rome IV criteria) demonstrates that a 3-week Probio-Eco intervention significantly improves constipation symptoms, stool straining, and worry scores. Gut microbiota and metabolomic analyses reveal modulations in specific gut microbiota, succinate, tryptophan derivatives, deoxycholate, propionate, butyrate, and cortisol, correlating with symptom relief. A loperamide-induced mouse model confirms that Probio-Eco and its bioactive components (succinate, 3-indoleacrylic acid, and 5-hydroxytryptophan) alleviate constipation by stimulating mucin-2 secretion, regulating intestinal transport hormones, and promoting anti-inflammatory responses. Multi-omics integration identifies key pathways, including succinate-short-chain fatty acid, tryptophan-5-hydroxytryptophan-serotonin, and tryptophan-3-indoleacrylic acid, driving intestinal homeostasis and motility. These findings highlight the comprehensive efficacy of Probio-Eco and provide robust evidence for its clinical application in constipation management. This study was registered at Chinese Clinical Trial Registry (ChiCTR2100054376).</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102093"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983642","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}