Cell Reports MedicinePub Date : 2026-04-21Epub Date: 2026-04-06DOI: 10.1016/j.xcrm.2026.102720
Liqiang Guo, Yujia Fan, Huixian Sun, Haoran Du, Hui Xiong, Yilin Li, Xinyan Zhang, Yong Guan, Lingtong Ren, Xuan Wang, Kai Chen, Yachun An, Xiaohui Zhang, Yunuo Mao, Yongfeng Gong, Feng Kong, Jichuan Qiu, Rui Chen, Benkang Shi, Fan Yi, Huili Hu, Shengtian Zhao
{"title":"Patient-derived kidney organoids recapitulate ADPKD and facilitate the identification of Rho pathway inhibitors as candidate therapeutics.","authors":"Liqiang Guo, Yujia Fan, Huixian Sun, Haoran Du, Hui Xiong, Yilin Li, Xinyan Zhang, Yong Guan, Lingtong Ren, Xuan Wang, Kai Chen, Yachun An, Xiaohui Zhang, Yunuo Mao, Yongfeng Gong, Feng Kong, Jichuan Qiu, Rui Chen, Benkang Shi, Fan Yi, Huili Hu, Shengtian Zhao","doi":"10.1016/j.xcrm.2026.102720","DOIUrl":"10.1016/j.xcrm.2026.102720","url":null,"abstract":"<p><p>Autosomal-dominant polycystic kidney disease (ADPKD) remains refractory to curative therapy partly due to the lack of human models that recapitulate its adult-onset nature, genetic context, and multi-segment origin. Here, we established expandable, multi-lineage adult renal organoids (MAROs) directly from surgical specimens of ADPKD patients and healthy donors, creating a three-dimensional (3D) high-content screening platform. Patient-derived MAROs faithfully reproduced hallmark cystogenic features, including elongated primary cilia, polarity disruption, and elevated Rho GTPase/planar cell polarity (PCP) signaling. Single-cell transcriptomics of PKD1/PKD2-mutant organoids revealed genotype-specific alterations. Genetic ablation of IFT88 disrupted cilia and selectively attenuated Rho/PCP activity in mutant backgrounds, supporting a cilia-dependent cyst-activating (CDCA) mechanism in cystogenesis. Microfluidic perfusion accelerated cyst expansion and amplified Rho/PCP signaling. A high-throughput drug screen identified Rho GTPase inhibitors, including ML141, as effective cyst-reducing agents across genotypes without compromising viability. Our findings establish a patient-derived organoid platform that captures ADPKD pathology and nominates Rho pathway modulation as a therapeutic strategy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102720"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632627","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":"Preclinical evaluation of an mRNA vaccine developed from the first human isolate of bovine H5N1.","authors":"Hongli Li, Mengting Huang, Simin Feng, Wansheng Li, Dandan Wei, Xuechun Li, Yun Quan, Hao Gu, Ting Jiang, Yan Liu, Jing Lu, Wenjun Song, Xinkui Zhang, Yujia Yang, Qianyu Pan, LinLei Chen, Jingyou Yu, Hantao Lou, Mengyi Zhang, Youchun Wang, Kelvin Kai-Wang To, Weixin Jia, Jinzhong Lin, Qiong Zhang","doi":"10.1016/j.xcrm.2026.102702","DOIUrl":"10.1016/j.xcrm.2026.102702","url":null,"abstract":"<p><p>Given the global threat posed by H5N1 clade 2.3.4.4b avian influenza, rapid development of effective vaccines is imperative. We design an mRNA vaccine encoding hemagglutinin (HA) from A/Texas/37/2024, the first bovine-to-human strain. In murine models, both wild-type and cleavage-site-modified HA vaccines elicit robust and durable humoral immunity, along with a balanced Th1/Th2 response, conferring complete protection against lethal homologous viral challenge. The vaccine, along with the World Health Organization (WHO)-recommended candidate (A/Astrakhan/3212/2020), elicits cross-clade binding antibody responses and demonstrates improvement against specific clades at a 1 μg dose. Pre-existing H1 immunity does not diminish H5-specific immunogenicity. In avian species, the vaccine also provides full protection against lethal clades (2.3.4.4b and 2.3.4.4h). Formulated with another ionizable lipid, the vaccine elicits responses comparable to benchmark lipid nanoparticles (LNPs) and shows a favorable safety profile in rats. This work establishes a rapidly adaptable mRNA-LNP vaccine prototype for pandemic preparedness against evolving avian influenza threats.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102702"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637529","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 : 2026-04-21Epub Date: 2026-03-30DOI: 10.1016/j.xcrm.2026.102716
Shiyou Wei, Yulan Deng, Jinho Lee, Hongbin Lan, Zhenyu Yang, Marilyne Labrie, Courtney B Betts, Hao Duan, Benjamin Tate, Joanna Pucilowska, Dennie Frederick, Aleigha R Lawless, Tatyana Sharova, Yuanzhong Yang, Wanming Hu, Georgia M Beasley, Lynn M Schuchter, Xiuqi Wang, Wei Xu, Gen Yong, Megan E G Vandenberg, Drew A Torigian, Shamilene Sivagnanam, Kuang Du, Eric Sugarman, Suzanne McGettigan, Cathy Zheng, Rami N Al-Rohil, Maria A Selim, Michael B Datto, Giselle Y López, Smita K Nair, David M Ashley, Xiaowei Xu, Ravi K Amaravadi, Giorgos C Karakousis, Donald M O'Rourke, Steven Brem, Bert W O'Malley, Gokhan Demirkan, Shuangxing Yu, Yiling Lu, Todd Camp, Janice A Patterson, Zhi Wei, Christopher Corless, Dmitry I Gabrilovich, Yonggao Mou, Keith T Flaherty, Lisa M Coussens, Genevieve Boland, Meenhard Herlyn, Gordon Mills, Lunxu Liu, Gao Zhang
{"title":"A longitudinal, multi-omic atlas reveals the emergence of a spatially organized immunosuppressive ecosystem in resistant melanoma.","authors":"Shiyou Wei, Yulan Deng, Jinho Lee, Hongbin Lan, Zhenyu Yang, Marilyne Labrie, Courtney B Betts, Hao Duan, Benjamin Tate, Joanna Pucilowska, Dennie Frederick, Aleigha R Lawless, Tatyana Sharova, Yuanzhong Yang, Wanming Hu, Georgia M Beasley, Lynn M Schuchter, Xiuqi Wang, Wei Xu, Gen Yong, Megan E G Vandenberg, Drew A Torigian, Shamilene Sivagnanam, Kuang Du, Eric Sugarman, Suzanne McGettigan, Cathy Zheng, Rami N Al-Rohil, Maria A Selim, Michael B Datto, Giselle Y López, Smita K Nair, David M Ashley, Xiaowei Xu, Ravi K Amaravadi, Giorgos C Karakousis, Donald M O'Rourke, Steven Brem, Bert W O'Malley, Gokhan Demirkan, Shuangxing Yu, Yiling Lu, Todd Camp, Janice A Patterson, Zhi Wei, Christopher Corless, Dmitry I Gabrilovich, Yonggao Mou, Keith T Flaherty, Lisa M Coussens, Genevieve Boland, Meenhard Herlyn, Gordon Mills, Lunxu Liu, Gao Zhang","doi":"10.1016/j.xcrm.2026.102716","DOIUrl":"10.1016/j.xcrm.2026.102716","url":null,"abstract":"<p><p>Despite advances in immune checkpoint blockade, resistance in metastatic melanoma remains a major challenge. To decode resistance mechanisms, we generate a comprehensive longitudinal, multi-omic, and spatial atlas of 45 tumor samples across 10 patients. Analysis reveals resistant tumors undergo convergent evolution toward a shared, spatially organized immunosuppressive ecosystem. We identify a structural mechanism characterized by spatial partitioning of immune checkpoints, where B7-H3 dominates MITF-high niches while IDO1 characterizes MITF-low zones. Furthermore, integrated single-cell and spatial analysis identifies a specific malignant subclone (c1) and a distinct architectural niche (RCN3), both exhibiting aberrant PI3K-mTOR signaling. Notably, c1 promotes the \"ignored tumor\" phenotype via FN1-ITGB1 and GDF15 signaling. Validated across independent cohorts, these spatial and molecular signatures predict poor survival and point to actionable targets. Ultimately, our study elucidates the spatial logic of resistance and provides a rationale for translating multi-omic discoveries into actionable, personalized therapeutic strategies.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102716"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589838","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":"Development and validation of a 5mC-based prognostic model for lung adenocarcinoma survival.","authors":"Yifan Wu, Zichen Jiao, Jianchao Xue, Xiaoyi Zheng, Zhicheng Huang, Daoyun Wang, Peipei Chen, Tao Wang, Jian-Qun Chen, Naixin Liang, Yao Tang, Qiang Wang, Qihan Chen","doi":"10.1016/j.xcrm.2026.102727","DOIUrl":"10.1016/j.xcrm.2026.102727","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) exhibits marked prognostic heterogeneity. Existing methylation-based prognostic models lack robustness, accuracy, or external validation, limiting their clinical utility. We develop MethPro-LUAD, a prognostic model based on eight 5-methylcytosine features, using TCGA-LUAD data (training, N = 269; testing, N = 180), and validate the model across two independent hospital cohorts (Beijing, N = 195; Nanjing, N = 88) and two external GEO datasets (N = 82 and N = 155) to ensure its generalizability and effectiveness. MethPro-LUAD stratifies patients into high- and low-risk groups, with high-risk individuals consistently showing significantly shorter overall survival across all cohorts. In addition, the model's predictive performance remains robust in subgroups defined by age, sex, stage, and EGFR mutation and in disease-free survival analyses. Compared with other reported LUAD prognostic models, MethPro-LUAD demonstrates better performance across cohorts, which offers valuable support for personalized postoperative treatment and follow-up, and warrants further prospective evaluation, highlighting its strong potential for clinical translation through feasible targeted assays.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102727"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608406","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 : 2026-04-21Epub Date: 2026-03-26DOI: 10.1016/j.xcrm.2026.102719
Shinya Yamanaka
{"title":"Shinya Yamanaka.","authors":"Shinya Yamanaka","doi":"10.1016/j.xcrm.2026.102719","DOIUrl":"10.1016/j.xcrm.2026.102719","url":null,"abstract":"<p><p>Dr. Shinya Yamanaka is recognized for the generation of induced pluripotent stem cells (iPSCs) from fibroblasts by a combination of multiple transcription factors, and he won the Nobel Prize in Physiology or Medicine in 2012 jointly with Sir John B. Gurdon for this discovery. Twenty years after the discovery, the Cell Reports Medicine editorial team discusses with Dr. Yamanaka the scientific, technical, and translational milestones that have shaped the field of regenerative medicine. We also discuss the role of iPSCs in disease modeling and drug discovery, the interplay with genome editing, and ongoing issues that still prevent the widespread clinical application of iPSC-derived therapies. Finally, Dr. Yamanaka reflects on promising, yet underexplored, applications of iPSCs.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102719"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147526598","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 : 2026-04-21Epub Date: 2026-03-26DOI: 10.1016/j.xcrm.2026.102707
Joshua Abd Alla, Alexander Perhal, Xuebin Fu, Andreas Langer, Yasser El Faramawy, Ursula Quitterer
{"title":"Analysis of GRK2 aggregation in the pathology of Alzheimer disease in animal models.","authors":"Joshua Abd Alla, Alexander Perhal, Xuebin Fu, Andreas Langer, Yasser El Faramawy, Ursula Quitterer","doi":"10.1016/j.xcrm.2026.102707","DOIUrl":"10.1016/j.xcrm.2026.102707","url":null,"abstract":"<p><p>The G-protein-coupled receptor kinase 2 (GRK2) exerts essential functions in cell growth and survival. Searching for a connection between GRK2 and the neurodegenerative Alzheimer disease (AD), we find increased aggregated serine-670-phosphorylated GRK2 (phospho-S670-GRK2) in brains of AD mice and patients with dementia likely due to AD. Harmful phospho-S670-GRK2 aggregation is induced by two hallmark proteins of AD: beta-amyloid and the neurofibrillary-tangle-inducing, TAU-P301L. Aggregated phospho-S670-GRK2 triggers aggregation of TOMM6 (translocase of outer mitochondrial membrane 6), promotes mitochondrial dysfunction, and enhances beta-amyloid. Transgenic expression of inactive GRK2-K220R or a GRK-inhibitory peptide proves that neuropathological features are caused by GRK2 inactivation. Restoration of TOMM6 by neuron-specific TOMM6 expression reduces beta-amyloid plaques but enhances soluble beta-amyloid and increases mortality. In contrast, reconstitution of monomeric GRK2 and proteasomal phospho-S670-GRK2 degradation by small molecules counteracts neuropathological AD features, prevents neuronal loss, and improves survival. Thus, targeting of pathological GRK2 aggregation slows aging-induced neurodegeneration.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102707"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147527173","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 : 2026-04-21Epub Date: 2026-03-31DOI: 10.1016/j.xcrm.2026.102712
Zehua Chen, Shengmeng Peng, Shi Fu, Shizhi Lin, Yiwen Su, Xinxin He, Yangjie Zhang, Junlin Lu, Sen Liu, Hengji Zhan, Jianmei Zhong, Baolin Ye, Chengjunyu Zhang, Chu Liu, Bolin Pan, Haonan Dong, Hongqiong Li, Xinni Ye, Jun Wang, Siting Chen, Baoqing He, Jingdie Wu, Hui Li, Qiang Zhang, Haifeng Wang, Xu Chen
{"title":"Targeting TPX2-dependent lineage plasticity by CDK4/6 inhibition reverses therapy resistance in neuroendocrine bladder carcinoma.","authors":"Zehua Chen, Shengmeng Peng, Shi Fu, Shizhi Lin, Yiwen Su, Xinxin He, Yangjie Zhang, Junlin Lu, Sen Liu, Hengji Zhan, Jianmei Zhong, Baolin Ye, Chengjunyu Zhang, Chu Liu, Bolin Pan, Haonan Dong, Hongqiong Li, Xinni Ye, Jun Wang, Siting Chen, Baoqing He, Jingdie Wu, Hui Li, Qiang Zhang, Haifeng Wang, Xu Chen","doi":"10.1016/j.xcrm.2026.102712","DOIUrl":"10.1016/j.xcrm.2026.102712","url":null,"abstract":"<p><p>Neuroendocrine bladder carcinoma (NEBC) is an aggressive and therapy-resistant cancer with poor prognosis. Although lineage plasticity drives urothelial-to-neuroendocrine transdifferentiation, intermediate states remain poorly characterized. Through transcriptomic profiling of public datasets, we define a lineage plasticity-associated signature in bladder cancer. We analyze 64,756 in-house and 201,720 public single-cell transcriptomes from NEBC and urothelial carcinoma (UC), identifying TPX2<sup>high</sup> bladder cancer cell subpopulation with increased lineage plasticity, supported by multi-cohort histological validation. TPX2<sup>high</sup> cells lack canonical neuroendocrine markers and are associated with adverse clinical outcomes. TPX2<sup>high</sup> cells exhibit dysregulated cell cycle progression and occupy a suppressive niche associated with CD8<sup>+</sup> T cell exhaustion. In vitro and in vivo, TPX2 promotes lineage plasticity and induces T cell exhaustion. In preclinical patient-derived organoids (PDOs) and patient-derived xenograft (PDX) models, CDK4/6 inhibition plus immune checkpoint blockade demonstrates potent antitumor efficacy. Overall, our findings suggest this combination therapy as a promising therapeutic strategy for TPX2<sup>high</sup> and NEBC patients.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102712"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590369","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 : 2026-04-21Epub Date: 2026-03-31DOI: 10.1016/j.xcrm.2026.102715
Michael Mints, Reilly A Sample, Anuraag S Parikh, Jesse M Zaretsky, Zongtai Qi, Travis Law, Fudong Wang, Thomas F Barrett, Riley Mullins, Ashley Reeb, Alissa C Greenwald, Emily Stoller, Salma Ramadan, Sophie Gerndt, Peter Oppelt, Jessica Ley, Wade Thorstad, Randal C Paniello, Jason T Rich, Richard A Harbison, Paul A Zolkind, Ryan S Jackson, Patrik Pipkorn, Douglas R Adkins, Ravindra Uppaluri, Itay Tirosh, Sidharth V Puram
{"title":"Single-cell analysis highlights the significance of malignant cell IFN/MHC-II for immunotherapy response in head and neck squamous cell carcinoma.","authors":"Michael Mints, Reilly A Sample, Anuraag S Parikh, Jesse M Zaretsky, Zongtai Qi, Travis Law, Fudong Wang, Thomas F Barrett, Riley Mullins, Ashley Reeb, Alissa C Greenwald, Emily Stoller, Salma Ramadan, Sophie Gerndt, Peter Oppelt, Jessica Ley, Wade Thorstad, Randal C Paniello, Jason T Rich, Richard A Harbison, Paul A Zolkind, Ryan S Jackson, Patrik Pipkorn, Douglas R Adkins, Ravindra Uppaluri, Itay Tirosh, Sidharth V Puram","doi":"10.1016/j.xcrm.2026.102715","DOIUrl":"10.1016/j.xcrm.2026.102715","url":null,"abstract":"<p><p>In head and neck squamous cell carcinoma (HNSCC), immunotherapy response rates remain modest, with difficulty predicting responders. Previous studies characterizing immunotherapy-associated cellular changes in HNSCC focus on immune cells, providing limited insight into malignant cell responses. Here, we perform single-cell RNA sequencing (RNA-seq) on 16 HNSCC patients pre- and post-neoadjuvant pembrolizumab treatment. We identify an interferon (IFN)/major histocompatibility complex class II (MHC-II) expression program in malignant cells, characterized by MHC-II and IFN-response genes, which is associated with response to pembrolizumab. We validate malignant cell MHC-II expression at the protein level via multiplexed immunofluorescence. In a murine HNSCC model, IFN-γ-induced malignant cell MHC-II expression marks immunotherapy-sensitive tumors with favorable immune microenvironments. Finally, we confirm that pre-treatment malignant-IFN/MHC-II is a marker of response through deconvolution of bulk RNA-seq data from an independent cohort. Beyond identifying the malignant IFN/MHC-II program as a potential biomarker for immunotherapy response in HNSCC, our work elucidates the important role of malignant cells in immunotherapy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102715"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590377","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 : 2026-04-21Epub Date: 2026-03-30DOI: 10.1016/j.xcrm.2026.102714
Li Lu, Yuan Xiong, Jiewen Liao, Juan Zhou, Guangji Wang, Yating Qin, Shengming Zhang, Yanzhi Zhao, Xiaodan Zhong, Mengwen Wang, Kangkang Zha, Fawwaz Al-Smadi, Guohui Liu, Yanli Zhao, Bobin Mi
{"title":"Enalaprilat reverses neutrophil polarization imbalance via targeting taurine-STING axis for treatment of diabetic wounds.","authors":"Li Lu, Yuan Xiong, Jiewen Liao, Juan Zhou, Guangji Wang, Yating Qin, Shengming Zhang, Yanzhi Zhao, Xiaodan Zhong, Mengwen Wang, Kangkang Zha, Fawwaz Al-Smadi, Guohui Liu, Yanli Zhao, Bobin Mi","doi":"10.1016/j.xcrm.2026.102714","DOIUrl":"10.1016/j.xcrm.2026.102714","url":null,"abstract":"<p><p>Persistent inflammation derived from neutrophil activation drives delayed healing of diabetic wounds. Herein, a dissolvable alginate methacryloyl-based microneedle patch functionalized with polypeptide CFLFLFK-NH<sub>2</sub>-coupled manganese/zinc ion metal-organic framework (MnZn-MOF) loading enalaprilat (Ena) (TMZE@A-MN) is developed. Ena promotes neutrophil repolarization from pro-inflammatory N1 to anti-inflammatory N2 state by inhibiting nuclear factor (NF)-κB axis and activating Smad3 pathway, attributed to Ena-induced level elevation of taurine and subsequently STING signaling cascade suppression, thus causing macrophage phenotype switching and endothelial cell ferroptosis repression. Due to identifiable property of CFLFLFK-NH2 on neutrophil membrane receptors, the delivery system endows Ena with targeting inhibitory roles in neutrophil activation. In addition, MnZn-MOFs possess free radical-eliminating performance and can effectively combat the growth of methicillin-resistant Staphylococcus aureus and Escherichia coli. In vivo evaluation on diabetic murine and porcine wounds also demonstrates that the TMZE@A-MN accelerates wound healing process. Consequently, the targeted microneedle delivery system holds great promise for diabetic wound treatment.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102714"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147589972","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 : 2026-04-21Epub Date: 2026-03-31DOI: 10.1016/j.xcrm.2026.102723
Maximilian Bellut, Alexander M Kollikowski, Marius L Vogt, Lukas Rossnagel, Ibrahim Hawwari, Bernardo S Franklin, Mirko Pham, Guido Stoll, Michael K Schuhmann
{"title":"Identifying the role of NLRP3 inflammasome in stroke progression and outcome before recanalization.","authors":"Maximilian Bellut, Alexander M Kollikowski, Marius L Vogt, Lukas Rossnagel, Ibrahim Hawwari, Bernardo S Franklin, Mirko Pham, Guido Stoll, Michael K Schuhmann","doi":"10.1016/j.xcrm.2026.102723","DOIUrl":"10.1016/j.xcrm.2026.102723","url":null,"abstract":"<p><p>Acute ischemic stroke (AIS) induces a rapid inflammatory response that partly counteracts the beneficial effects of recanalization by endovascular thrombectomy (EVT). The molecular triggers of inflammation in AIS are still elusive. We analyze the role of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome before recanalization. NLRP3-mRNA levels increase rapidly in the ischemic brain following permanent middle cerebral artery occlusion in mice. NLRP3 protein is primarily expressed by intravascular neutrophils and cerebral endothelium. Blocking NLRP3 activation with the small molecule MCC950 reduces infarct progression and inflammation significantly already during large vessel occlusion. In human AIS, we find similarly increased NLRP3 expression in accumulating leukocytes within pial blood samples taken from the secluded ischemic brain territory immediately before recanalization. The number of NLRP3-positive cells before EVT predicts stroke outcome after 3 months. Our results identify NLRP3 as a promising therapeutic target to attenuate rapid infarct progression prior to recanalization.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102723"},"PeriodicalIF":10.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590144","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}
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