Clinical and Translational Medicine最新文献

{"title":"Multi-site sequencing supports dual-track evolution and identifies candidate metastasis-associated factors in gastric cancer ovarian metastasis.","authors":"Peiyu Zhu, Xiaofang Xing, Ke Ji, Lingqian Wang, Zhongwu Li, Shuqin Jia, Longtao Huangfu, Xiaomei Li, Biao Fan, Zhaode Bu, Jiafu Ji","doi":"10.1002/ctm2.70847","DOIUrl":"10.1002/ctm2.70847","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer ovarian metastasis (GCOM) is an aggressive clinical entity whose evolutionary dissemination routes and molecular features remain incompletely defined.</p><p><strong>Methods: </strong>We performed whole-exome sequencing and patient-level phylogenetic reconstruction of 81 spatially distinct tumour specimens from 17 patients with GCOM.</p><p><strong>Results: </strong>Ovarian metastases showed a higher tumour mutational burden than matched primary tumours and substantial inter-lesional genomic heterogeneity. Phylogenetic reconstruction supported two major evolutionary routes of ovarian dissemination: lymph node-dependent evolution, in which ovarian metastases were phylogenetically associated with lymph node-related lineages, and lymph node-independent evolution, in which ovarian and lymph node metastases diverged along separate branches. Putative driver-gene alterations were relatively enriched in the shared/truncal mutational fraction, and SCAF4 emerged as an understudied candidate metastasis-associated factor. In GC cells, SCAF4 depletion was accompanied by widespread alterations in RNA splicing and interferon-related transcriptional programs and enhanced proliferative, migratory, invasive, and clonogenic phenotypes.</p><p><strong>Conclusions: </strong>These findings support a dual-route evolutionary framework for GCOM and nominate SCAF4 as a candidate metastasis-associated factor, providing a genomic basis for understanding the biological heterogeneity of ovarian dissemination in GC.</p><p><strong>Highlights: </strong>A multi-site genomic sequencing and phylogenetic reconstruction in matched gastric primaries and ovarian metastases was performed. Uncovered two distinct evolutionary routes for gastric cancer ovarian metastasis: lymph node-dependent and lymph node-independent evolutionary patterns. Genomic and functional analyses nominate SCAF4 as a candidate metastasis-associated factor.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70847"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012009","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":"From immune checkpoint blockade to metabolic ecosystem intervention: A new perspective on ammonia-mediated remodelling of tumour immunity.","authors":"Yu Li, Yun Zhu, Jian Gu","doi":"10.1002/ctm2.70792","DOIUrl":"10.1002/ctm2.70792","url":null,"abstract":"","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70792"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975842","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":"TMEM59L promotes neuroendocrine differentiation and enzalutamide resistance in prostate cancer by regulating MUC1/β-catenin/MYC axis.","authors":"Xiuchen Guo, Yifan Liu, Jiacheng Huang, Zhiwei Chen, Haihong Liao, Yulin Xu, Xingang Cui, Yongjiang Yu","doi":"10.1002/ctm2.70835","DOIUrl":"10.1002/ctm2.70835","url":null,"abstract":"<p><strong>Background: </strong>Enzalutamide resistance in advanced prostate cancer often leads to treatment-induced neuroendocrine prostate cancer (t-NEPC), characterized by aggressive lineage plasticity. The molecular regulators governing neuroendocrine differentiation and phenotypic transition are not well understood. Here, we characterize the functional role of the transmembrane protein TMEM59L in driving PCa progression, lineage plasticity and therapeutic resistance.</p><p><strong>Methods: </strong>We combined bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics datasets to assess TMEM59L expression patterns and their association with clinical features. We investigated the biological functions of TMEM59L using enzalutamide-resistant (EnzR) PCa cell lines in vitro and corresponding mouse xenograft models in vivo. Mechanistic interactions were elucidated through molecular assays, including co-immunoprecipitation (Co-IP), GST pull-down and molecular docking.</p><p><strong>Results: </strong>TMEM59L expression is negatively regulated by androgen receptor (AR) signalling and markedly elevated in EnzR PCa tissues. In PCa cells, ectopic TMEM59L expression induced a neuroendocrine-like phenotype, enhanced stemness, promoted epithelial-mesenchymal transition (EMT) and conferred enzalutamide resistance. Conversely, TMEM59L depletion restored drug sensitivity and significantly suppressed EnzR tumour growth in vivo. Mechanistically, TMEM59L directly interacts with MUC1 to facilitate its nuclear accumulation, thereby activating the downstream β-catenin/MYC signalling axis. Importantly, pharmacological inhibition or genetic silencing of MUC1 effectively reversed TMEM59L-induced neuroendocrine differentiation, stemness and enzalutamide resistance.</p><p><strong>Conclusions: </strong>Our findings uncover a previously unrecognized TMEM59L/MUC1/β-catenin/MYC signalling cascade associated with neuroendocrine differentiation and enzalutamide resistance in PCa. Targeting this regulatory axis presents a promising therapeutic strategy to circumvent resistance to next-generation AR signalling inhibitors.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70835"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975850","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":"Towards universal deconvolution of tissue-level multiomics for translational medicine.","authors":"Renjie Liu, Tianyi Zhao, Yadong Wang","doi":"10.1002/ctm2.70826","DOIUrl":"10.1002/ctm2.70826","url":null,"abstract":"","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70826"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954980","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":"CPT1A through succinylation regulates the CTCF/LINC01503‒91aa feedback loop to promote gemcitabine resistance in pancreatic ductal adenocarcinoma","authors":"De-Liang Fang,&nbsp;Si-Yuan Lu,&nbsp;Zhi-De Liu,&nbsp;Qiong-Cong Xu,&nbsp;Yang-Yinhui Yu,&nbsp;Ying-Qin Zhu,&nbsp;Ming-Jian Ma,&nbsp;Jing-Yuan Ye,&nbsp;Xiao-Yu Yin","doi":"10.1002/ctm2.70776","DOIUrl":"10.1002/ctm2.70776","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant solid tumors, characterized by strong invasiveness and poor clinical prognosis. Recent studies have revealed that long non-coding RNAs (lncRNAs) can serve as translational templates to produce functional microproteins, which further participate in the regulation of cellular metabolism.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To investigate the function and detailed mechanism of the novel protein 1503–91aa encoded by LINC01503 in gemcitabine-resistant PDAC, and explore the possibility of clinical translation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The differentially expressed lncRNAs in gemcitabine-resistant PDAC cells with coding potential were screened by whole transcriptome sequencing and coding prediction from database. A series of cellular, molecular and in vivo assays were performed to characterize the novel microprotein 1503–91aa, its upstream transcriptional regulation, and its role in mediating PDAC gemcitabine resistance. A series of molecular assays clarified the interaction between 1503–91aa and carnitine palmitoyl transferase 1A (CPT1A). Finally, the clinical translational potential of the CPT1A inhibitor etomoxir in combination with gemcitabine was validated using our center's gemcitabine-resistant patient-derived xenograft (PDX) model.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Here, we revealed that LINC01503 had coding potential in drug-resistant PDAC and encoded a novel 91–amino acid protein, which designated as 1503–91aa. Simultaneously, LINC01503's transcriptional regulation is mediated by CTCF and then 1503–91aa expression levels were significantly upregulated in PDAC. Functionally, 1503–91aa, instead of LINC01503 confers gemcitabine resistance in vitro and in vivo. Mechanistically, 1503–91aa targeted the CPT1A, and up-regulated CPT1A activity through antagonizing the association of malonyl-CoA (MCoA), the best known metabolic intermediate inhibiting CPT1A, to promote fatty acid oxidation (FAO) and thereby facilitate gemcitabine resistance. We discovered that CPT1A functions as a succinyltransferase to regulate the succinylation level of CTCF, thereby controlling its stability. This establishes a positive feedback loop that continuously sustains 1503–91aa protein levels to regulate CPT1A activity. Consequently, this induces persistent FAO in PDAC cells, ensuring a continuous energy source that facilitates gemcitabine resistance in pancreatic cancer. Notably, the combined application of the etomoxir and g","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":""},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873288","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":"Systematic evaluation of whole exome sequencing for copy number variation detection in prenatal diagnosis.","authors":"Lihua Yu, Rong Hu, Xingwang Wang, Yongchu Liu, Haowen Tan, Haoyu Dou, Yi Kong, Jian Lu, Hongke Ding, Yimo Zeng, Cuize Yao, Li'ai Pan, Shuqi Chen, Yan Zhang, Aihua Yin","doi":"10.1002/ctm2.70761","DOIUrl":"10.1002/ctm2.70761","url":null,"abstract":"","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70761"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910936","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":"Circulating tumour DNA to guide rechallenge with cetuximab plus irinotecan in RAS/BRAF wild-type metastatic colorectal cancer: A nonrandomised clinical trial.","authors":"De-Shen Wang, Wen-Chuan Chen, Chao Ren, Feng-Hua Wang, Zhi-Qiang Wang, Hui-Yan Luo, Feng Wang, Qiong Tan, Yu-Hong Li","doi":"10.1002/ctm2.70827","DOIUrl":"10.1002/ctm2.70827","url":null,"abstract":"<p><strong>Background: </strong>Mutant subclones driving anti-EGFR resistance may progressively decline after therapy cessation, potentially reversing resistance to EGFR-targeted treatment. We therefore examined whether rechallenge with cetuximab plus irinotecan is active and tolerable in patients selected by circulating tumour DNA (ctDNA) testing, focusing on metastatic colorectal cancer (mCRC) with RAS/BRAF wild-type (WT) status.</p><p><strong>Methods: </strong>This single-arm, Phase II clinical trial enrolled patients between November 2019 and February 2025. Eligible patients had histologically confirmed RAS/BRAF WT mCRC at diagnosis, prior cetuximab-based first-line therapy with clinical benefit, radiographic progression while on cetuximab or within 3 months after stopping it, subsequent progression after at least 1 additional systemic therapy, a cetuximab washout period of at least 4 months, and ctDNA-confirmed RAS/BRAF WT status before rechallenge. Each 2-week cycle delivered intravenous cetuximab (500 mg/m²) together with irinotecan (180 mg/m²). The primary endpoint was the objective response rate (ORR). We additionally assessed progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs).</p><p><strong>Results: </strong>This study enrolled 36 patients. Partial response was seen in 6 patients (16.7%), stable disease in 10 (27.8%), and progressive disease in 16 (44.4%); the remaining 4 patients were unevaluable due to early loss to follow-up. The ORR reached 16.7% (95% CI: 7.9-31.9), with a disease control rate of 44.4% (95% CI: 29.5-60.4). The median PFS and OS were 3.9 months (95% CI: 3.1-4.7) and 13.0 months (95% CI: 8.1-17.9). Multivariate Cox regression analyses identified screening time interval (STI) as an independent predictor of PFS (HR = 0.93 per additional month; 95% CI: 0.88-0.99). TRAEs of grade 3-4 were uncommon and clinically manageable.</p><p><strong>Conclusions: </strong>These findings suggest that ctDNA-guided rechallenge with cetuximab plus irinotecan may offer benefit in RAS/BRAF WT mCRC, with STI potentially informing patient selection. Nevertheless, further validation in larger randomised trials is warranted.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04224415.</p><p><strong>Graphical headlights: </strong>RAS/BRAF wild-type status confirmed by ctDNA may identify candidates for cetuximab rechallenge. A longer screening time interval was associated with improved progression-free survival. These hypothesis-generating findings warrant validation in larger randomised trials.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70827"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929097","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":"Organoids as an emerging platform for osteoarthritis drug development.","authors":"Xukun Lyu, Jianhua Wang, Jiacan Su","doi":"10.1002/ctm2.70806","DOIUrl":"10.1002/ctm2.70806","url":null,"abstract":"","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70806"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886526","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":"ACP5-positive macrophages contribute to cerebral oedema and neuroinflammation after traumatic brain injury.","authors":"Dang Hanhan, He Kun, Zhang Yulian, Zhang Chuanpeng, Zhang Yunsheng, Wang Zixi, Yang Xu, Chen Pengyu, Zhang Li, Yu Yanbing","doi":"10.1002/ctm2.70845","DOIUrl":"10.1002/ctm2.70845","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) is a leading cause of death and long-term disability worldwide. Secondary cerebral oedema, driven by neuroinflammation and blood-brain barrier (BBB) disruption, critically determines poor outcomes, yet effective targeted therapies remain absent. This study aimed to identify immune cell subsets associated with post-TBI cerebral oedema and to explore their functional contributions in preclinical models.</p><p><strong>Methods: </strong>We integrated single-cell transcriptomic datasets from a mouse TBI model (GSE175430) and human intracerebral haemorrhage (ICH) perihaematomal oedema samples (GSE266873) with our previously published temporal bulk RNA-seq profiling data. Through cross-species comparative analysis, Mfuzz clustering, AUCell scoring and gene set enrichment analysis (GSEA), Acp5 was identified as an oedema-associated signature gene, and its macrophage-enriched expression pattern was supported by single-cell profiling and immunofluorescence colocalisation. Using the controlled cortical impact (CCI) model, we validated Acp5 expression dynamics across injury severities. Pharmacological inhibition (AubipyOMe) and genetic knockout of Acp5 were employed to assess brain oedema, neuroinflammation, neurological function and long-term cognitive recovery.</p><p><strong>Results: </strong>A previously unrecognised population of ACP5-positive monocytes/macrophages infiltrated the brain parenchyma within 1-3 days post-injury, coinciding with peak oedema severity and neurological deficits. Inhibiting ACP5 significantly reduced brain water content, BBB leakage and proinflammatory cytokines, while improving sensorimotor function. Mechanistically, ACP5-positive macrophages were associated with CSF2-related JAK/STAT and NF-κB signalling. Genetic Acp5 ablation attenuated acute macrophage infiltration and neuroinflammation, and was associated with improved long-term behavioural outcomes.</p><p><strong>Conclusions: </strong>ACP5-positive macrophages represent an injury-associated myeloid population that contributes to neuroinflammatory and oedema-related phenotypes after experimental TBI. Pharmacological and genetic findings provide preclinical evidence supporting further investigation of ACP5 and CSF2-related signalling in secondary TBI injury.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70845"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036545","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":"Cascade-targeted intervention of the NLRP3 inflammasome and downstream angiogenesis by curcumin nanoparticles for ocular neovascularization therapy.","authors":"Siyu Jiang, Ziwei Cheng, Yujuan Cai, Yanji Zhu, Nyamjargal Nyambayar, Ruijie Lin, Li Zhang, Jian Chen, Bing Xie, Xiuping Chen","doi":"10.1002/ctm2.70846","DOIUrl":"10.1002/ctm2.70846","url":null,"abstract":"<p><strong>Background: </strong>Retinal neovascularization (RNV) causes irreversible vision loss. Despite the benefits of anti-VEGF therapy, incomplete responses and persistent inflammation necessitate complementary treatments. Curcumin has anti-inflammatory and anti-angiogenic activity, but its poor solubility and bioavailability limit ocular application.</p><p><strong>Methods: </strong>PLGA-encapsulated curcumin nanoparticles (Cur-NPs; approximately 125 nm) were produced using an ultrasound-microreactor platform. Therapeutic efficacy was assessed in oxygen-induced retinopathy (OIR) and Rho/VEGF transgenic mouse models following intravitreal administration. Neovascularization, vascular leakage, retinal structure, apoptosis, retinal distribution, and intraocular retention were evaluated using histology, fluorescence imaging, and longitudinal in vivo imaging. Mechanisms were investigated using single-cell transcriptomics, untargeted metabolomics, genetic loss-of-function, and pharmacological perturbation. Conbercept monotherapy and Cur-NP combination treatment were also evaluated.</p><p><strong>Results: </strong>Cur-NPs reduced pathological neovascularization in both models and improved vascular integrity, decreased vascular leakage, preserved retinal architecture, and attenuated apoptosis in OIR mice. Compared with free curcumin, Cur-NPs showed broader retinal fluorescence distribution and prolonged intraocular fluorescence retention. Cur-NPs suppressed the NLRP3ASCCaspase-1 inflammasome and associated VEGF/VEGFR2 signaling. Genetic and pharmacological experiments supported a functional contribution of NLRP3 signaling to the anti-angiogenic effects of Cur-NPs. Multi-omics analyses revealed treatment-associated changes in retinal immune-cell states and metabolic pathways. ConberceptCur-NP combination therapy reduced neovascularization more than either treatment alone.</p><p><strong>Conclusions: </strong>Cur-NPs inhibit pathological RNV through modulation of NLRP3-associated inflammatoryangiogenic signaling while improving retinal protection and intraocular retention. These findings support further evaluation of Cur-NPs as a potential upstream anti-inflammatory adjunct to VEGF-directed therapy.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70846"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015667","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}