Journal of Translational Medicine最新文献

{"title":"Tilorone suppresses TGF-β-driven fibroblast activation and restores BMP-Smad1/5/8 signaling: implications for laryngotracheal fibrosis.","authors":"Eniko Toth, Kitti Szabo, Attila Gergely Vegh, Agnes Zvara, Laszlo G Puskas, Adam Bach, Ede Migh, Peter Horvath, Laszlo Tiszlavicz, Laszlo Rovo, Aniko Keller-Pinter","doi":"10.1186/s12967-026-08188-w","DOIUrl":"https://doi.org/10.1186/s12967-026-08188-w","url":null,"abstract":"<p><strong>Background: </strong>Laryngotracheal fibrosis is a rare but severe complication of prolonged intubation, leading to airway narrowing, respiratory distress, dysphonia, and, in advanced cases, life-threatening airway obstruction. Current treatments are primarily surgical, while pharmacologic approaches such as mitomycin C, corticosteroids, or 5-fluorouracil show inconsistent efficacy and potential toxicity. Thus, there remains a critical need for safe and effective antifibrotic therapies. Transforming growth factor-beta (TGF-β) is a key mediator of fibrosis, promoting fibroblast activation, migration, and expression of profibrotic markers such as alpha-smooth muscle actin (α-SMA).</p><p><strong>Objectives: </strong>This study aimed to evaluate the antifibrotic potential of tilorone dihydrochloride, a synthetic small molecule, in human respiratory fibroblasts in vitro.</p><p><strong>Methods: </strong>Fibrotic alterations were assessed in human laryngotracheal fibrosis tissue samples. An in vitro model using MRC-5 human lung-derived fibroblasts was employed to investigate the effects of tilorone. Molecular analyses (RT-qPCR, immunocytochemistry, western blotting) quantified mRNA and protein expression of key signaling markers. Cell proliferation and viability were performed to evaluate potential cytotoxic effects of tilorone. Functional assays, including wound scratch and single-cell tracking, assessed fibroblast motility, and atomic force microscopy (AFM) measured extracellular matrix elasticity.</p><p><strong>Results: </strong>Phosphorylation of Smad1/5/8, a key transcription factor in the bone morphogenetic protein (BMP) signaling, was reduced in both human laryngotracheal fibrosis tissue and TGF-β-treated MRC-5 fibroblasts. Tilorone treatment did not affect MRC-5 cell viability or proliferation but increased BMP2, BMP4, BMP7, and BMP14 (GDF5; Growth Differentiation Factor 5) mRNA expression, enhanced Smad1/5/8 phosphorylation, and suppressed TGF-β-induced Smad2/3 phosphorylation. Functionally, tilorone inhibited TGF-β-driven fibroblast migration and α-SMA expression, downregulated collagen I and III mRNA levels, and restored extracellular matrix elasticity, as confirmed by AFM.</p><p><strong>Conclusion: </strong>Tilorone counteracts TGF-β-mediated profibrotic signaling and restores BMP pathway activity in MRC-5 fibroblasts in vitro. These findings identify tilorone as a promising therapeutic candidate for fibrotic airway diseases such as laryngotracheal fibrosis.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional heterogeneity of sperm binding to the ZP2 N terminus across normospermic and infertile phenotypes.","authors":"Manar Ata, Maha A Abdulla, Fadi Choucair, Dania Hamada, Maria Sousa Esteves, Fatima Al Ali, Suma Garibova, Abbirami Sathappan, Johnny T Awwad, Matteo A Avella","doi":"10.1186/s12967-026-08228-5","DOIUrl":"https://doi.org/10.1186/s12967-026-08228-5","url":null,"abstract":"<p><strong>Background: </strong>Human gamete recognition is mediated by the N-terminal domain of the zona pellucida protein ZP2. Conventional semen analysis often fails to identify functional subpopulations within heterogeneous ejaculates, particularly in men with defective spermiogenesis. This study sought to evaluate if a recombinant ZP2^39-154 peptide can serve as a high-stringency selection tool to identify and enrich for morphologically superior and binding competent sperm.</p><p><strong>Methods: </strong>Sperm samples from 10 normospermic and 12 infertile participants (oligozoospermia, asthenozoospermia, and teratozoospermia) were incubated with agarose beads conjugated to recombinant ZP2^39-154. Binding efficiency was quantified using confocal microscopy. Morphometric analysis, including nuclear area and flagellum length, was performed on bound sperm and compared to sperm bound to native human zonae pellucidae.</p><p><strong>Results: </strong>Normospermic individuals exhibited nearly four-fold inter-individual heterogeneity in ZP2^39-154 binding efficiency (2.88 to 9.04 sperm/bead), which did not correlate with standard concentration, motility, or morphology metrics. In the infertile cohort, ZP2^39-154 beads identified a reservoir of binding-competent sperm even in severe cases of oligoasthenoteratozoospermia. While the global functional reservoir was reduced in defective spermiogenesis, the top-tier binding events frequently overlapped with the normospermic range. Furthermore, the ZP2^39-154 significantly enriched for morphologically normal sperm, increasing the proportion from a 1-5% baseline in raw semen to as high as 90% on the beads. Notably, 70-94% of bound sperm in the infertile group remained structurally atypical, suggesting molecular binding competence can be preserved despite gross morphological defects.</p><p><strong>Conclusion(s): </strong>Recombinant ZP2^39-154 beads provide a standardized, high-throughput functional proxy for the human zona pellucida. This assay transcends the diagnostic limitations of light microscopy by identifying physiologically competent gametes, offering a robust tool for targeted sperm recovery in assisted reproduction.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative single-cell and spatial multi-Omics analyses identify NETs-driven colon cancer subtypes with distinct metabolic features and prognostic implications.","authors":"Xiao-Long Tang, Yi He, Wen-Yu Luan, Kai-Zhen Xu, Zheng Zhang, Zhen-Xi Xu, Yu-Hui Shang, Wen-Jian Hu, Mao-Yin Shan, Jian Gan, Ya-Bo Wang, Yan-Dong Miao","doi":"10.1186/s12967-026-08227-6","DOIUrl":"https://doi.org/10.1186/s12967-026-08227-6","url":null,"abstract":"<p><strong>Background: </strong>Colon cancer remains one of the leading causes of cancer-related deaths worldwide and is associated with high rates of recurrence and metastasis despite advances in therapy. The tumor microenvironment (TME), characterized by complex immune and stromal interactions, plays a pivotal role in tumor progression and treatment resistance. Neutrophil extracellular traps (NETs), an emerging component of the TME, have been implicated in promoting tumor invasion, metastasis, and immune evasion. However, their specific role in colon cancer remains unclear.</p><p><strong>Methods: </strong>Comprehensive transcriptomic analyses were conducted using datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to identify NETs-associated genes involved in colon cancer. Single-cell RNA sequencing (scRNA-seq) was utilized to assess cellular heterogeneity, and spatial transcriptomics mapped NETs activity and cell-cell interactions within the TME. A prognostic model was constructed using multivariate Cox and LASSO regression analyses based on key NETs-related genes. Model performance was validated using internal and external cohorts. Additionally, colocalization analysis between TUBB2A eQTL signals and colorectal cancer overall survival GWAS effects was performed to investigate potential genetic correlations.</p><p><strong>Results: </strong>Two distinct NETs-related molecular subtypes of colon cancer were identified, differing in immune composition, metabolic activity, and gene expression profiles. NETs-high malignant cells demonstrated metabolic reprogramming involving oxidative phosphorylation and cellular respiration, contributing to immune escape and therapeutic resistance. A four-gene prognostic signature (ARRDC1, TUBB2A, DUSP5, and SLC2A3) was developed and showed moderate prognostic discrimination across internal and external cohorts, indicating potential value for risk stratification but limited predictive accuracy at the current stage. Colocalization analysis revealed a modest negative correlation between TUBB2A expression and overall survival and cancer-specific survival, suggesting that increased TUBB2A expression may be associated with adverse clinical outcomes.</p><p><strong>Conclusions: </strong>This study reveals that NETs-associated genes play crucial roles in colon cancer progression, immune modulation, and metabolic reprogramming. The identified four-gene signature may serve as a candidate biomarker for risk stratification in colon cancer, although further validation is needed.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vδ1 T cells exhibit high lactic acid resistance and antitumor activity in solid tumors.","authors":"Yiming Su, Chang Liu, Chenghong Li, Menghua Cai, Yi Xu, Yu Hu, Hui Chen, Jianmin Zhang, Wei He","doi":"10.1186/s12967-026-08234-7","DOIUrl":"https://doi.org/10.1186/s12967-026-08234-7","url":null,"abstract":"<p><strong>Background: </strong>Vδ1 T cells are promising for solid tumor immunotherapy but limited by peripheral rarity and inefficient expansion. This study aimed to establish a scalable expansion protocol and evaluate the therapeutic potential of unmodified and CAR-engineered Vδ1 T cells.</p><p><strong>Method: </strong>Vδ1 T cells were expanded with a patented humanized Vδ1 TCR antibody plus cytokine cocktail (vs. commercial protocols). Transcriptomic profiling, in vitro cytotoxicity assays, in vivo xenograft experiments (vs. Vδ2 T cells), and PARP1-mediated lactate resistance analyses were performed. MSLN/NCL-targeted CAR-Vδ1 T cells were constructed and validated in OVCAR8-baring mice models.</p><p><strong>Results: </strong>Average 1 × 10¹⁰ high-purity Vδ1 T cells were obtained from 10 mL peripheral blood, outperforming commercial protocols. Expanded cells retained a stem-like phenotype, exerted superior antitumor activity vs. Vδ2 T cells, and resisted lactate-induced apoptosis via high PARP1 expression. CAR and IL-15 modified Vδ1 T cells showed potent anti-tumor efficacy.</p><p><strong>Conclusions: </strong>This efficient Vδ1 T cell expansion protocol overcomes key clinical translation barriers. Vδ1 and CAR-Vδ1 T cells represent a novel off-the-shelf immunotherapeutic strategy for solid tumors.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: The ANGPTL3-integrin α5 axis drives retinal vascular leakage in diabetic retinopathy.","authors":"Jing Ke, Yongsong Xu, Yingjun Zhu, Xiaotong Feng, Haodi Cao, Longyan Yang, Dong Zhao","doi":"10.1186/s12967-026-08229-4","DOIUrl":"https://doi.org/10.1186/s12967-026-08229-4","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NCAPD3 promotes osteosarcoma progression by modulating macrophage polarization and tumor cell proliferation.","authors":"Ruiling Xu, Binfeng Liu, Sai Zhu, Lin Qi, Lu Wan, Ruiqi Chen, Lu Wang, Xiaolei Ren, Zhihong Li","doi":"10.1186/s12967-026-08168-0","DOIUrl":"https://doi.org/10.1186/s12967-026-08168-0","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, characterized by aggressive behavior and poor prognosis. Despite advances in multimodal therapies, outcomes for patients with metastatic or recurrent OS remain poor. Non-SMC Condensin II Complex Subunit D3 (NCAPD3) is a core component of the condensin II complex involved in chromosome condensation and segregation; however, its role in OS progression and the tumor immune microenvironment remains unclear.</p><p><strong>Methods: </strong>Publicly available transcriptomic datasets were analyzed to evaluate NCAPD3 expression and prognostic relevance in OS. Using single-cell RNA sequencing (scRNA-seq; n = 6), we characterized tumor cell heterogeneity and NCAPD3-expressing subsets within the osteosarcoma tumor microenvironment. In vitro, NCAPD3 knockdown was performed in RAW264.7 macrophages, primary murine macrophages, and THP-1-derived macrophages to assess changes in macrophage polarization markers at the transcriptional and protein levels. Functional assays, including conditioned-media experiments, evaluated tumor-macrophage crosstalk. The effects of NCAPD3 on osteosarcoma cell proliferation, migration, and tumor growth were assessed in vitro and in vivo. Pathway enrichment analyses were conducted in NCAPD3⁺ macrophages and tumor cells, and in silico drug sensitivity prediction was performed as an exploratory analysis.</p><p><strong>Results: </strong>NCAPD3 was significantly overexpressed in OS tissues and associated with poorer overall survival. scRNA-seq analysis identified distinct tumor cell subsets and a population of NCAPD3⁺ macrophages characterized by reduced inflammatory activity. NCAPD3 knockdown in macrophages consistently upregulated pro-inflammatory markers and downregulated anti-inflammatory markers, indicating a shift toward a pro-inflammatory phenotype. Conditioned-media experiments demonstrated that NCAPD3-dependent tumor-macrophage crosstalk regulates osteosarcoma cell proliferation and migration. Pathway analyses revealed downregulation of IL2/STAT5 and IL6/JAK/STAT3 signaling in NCAPD3⁺ macrophages, while NCAPD3⁺ tumor cells exhibited reduced apoptotic signaling and enhanced DNA repair and PI3K/AKT/mTOR pathway activity. Functional assays confirmed that NCAPD3 promotes osteosarcoma cell growth and tumor progression in vitro and in vivo.</p><p><strong>Conclusions: </strong>NCAPD3 promotes osteosarcoma progression through coordinated effects on tumor cell proliferation and suppression of macrophage-mediated inflammatory responses. These findings identify NCAPD3 as a context-dependent regulator of tumor-immune interactions in OS and support its potential as a prognostic biomarker and therapeutic target.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal training grounds: the developmental origins of chronic immune disease.","authors":"Sameeksha Chopra, Naomi Madokoro, Mya Bal, Kelly M McNagny","doi":"10.1186/s12967-026-08213-y","DOIUrl":"https://doi.org/10.1186/s12967-026-08213-y","url":null,"abstract":"<p><strong>Background: </strong>Immune cells seed tissues in orchestrated waves beginning in utero. While the impact of prenatal environmental exposures is well-documented in neuroimmunology, the influence of maternal-fetal interactions on systemic immune development and its contribution to lifelong chronic inflammatory disease remains underappreciated.</p><p><strong>Main body: </strong>This narrative review synthesizes recent ontogeny data to demonstrate how diverse prenatal cues, ranging from maternal infection to microbial-derived metabolites, function as a \"prenatal training ground\" for the developing fetal immune system. These maternal signals interact with specific waves of hematopoiesis to shape long-lived tissue-resident immune cells. In many tissues, these prenatally programmed populations persist into adulthood, acting as lifelong immunological rheostats that dictate the type and intensity of local inflammatory responses. Furthermore, we critically evaluate the translational gaps in the field, highlighting fundamental species-specific differences in developmental timelines that necessitate careful alignment between preclinical animal models and human biology.</p><p><strong>Conclusions: </strong>We propose that many chronic immune conditions are not strictly adult-onset in their etiology, but rather adult-manifesting, making prenatal immune seeding a critical, yet overlooked, determinant of long-term health. Current interventions largely focus postnatally, but reorienting research and clinical focus toward prenatal factors provides new insights into the developmental origins of chronic inflammation and offers a novel therapeutic window to optimize the health trajectory of the next generation.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of bladder cancer in patients with microscopic hematuria using Oncuria-Detect: results of a prospective, multicenter international study.","authors":"Yair Lotan, Satoshi Anai, Howard Kim, Greg Gin, Arash Akhavein, Makito Miyake, Michael Luu, Michael Ahdoot, Edward Messing, Garry Peers, Andrew Chen, Ariel Moradzadeh, Arnold I Chin, Menghan Liu, Sunao Tanaka, Sergei Tikhonekov, Ian Pagano, Yingye Zheng, Zhen Zhang, Hideki Furuya, Charles J Rosser","doi":"10.1186/s12967-026-08245-4","DOIUrl":"https://doi.org/10.1186/s12967-026-08245-4","url":null,"abstract":"<p><strong>Background: </strong>Microscopic hematuria occurs in up to 10% of the general population and initiates costly evaluation to ensure no bladder cancer exists. Oncuria-Detect is a 10-plex immunoassay that detects de novo bladder cancer by generating a protein biomarker signature from a single voided urine sample. This report details the analysis of our prospective study that compares the diagnostic performance of the multiplex Oncuria-Detect assay to that of the single-analyte (i.e., NMP22) BladderChek™ urine assay and urine cytology for identifying bladder/urothelial cancer in patients with microscopic hematuria.</p><p><strong>Methods: </strong>From September 2018 through July 2025, 9 medical facilities in the US and Japan prospectively enrolled 321 participants of whom 292 were deemed eligible. The bladder cancer diagnostic reference standard was cystoscopy with biopsy. Pre-cystoscopy, patients provided a urine sample for analysis by Oncuria-Detect and BladderChek™ (analyzed in a blinded manner) as well as urine cytology.</p><p><strong>Results: </strong>Bladder cancer was diagnosed in 22 patients (7.5%). The Oncuria-Detect assay had the following performance characteristics 82.0% sensitivity and 97.5% negative predictive value (NPV) compared to BladderChek™ (9.3% sensitivity and 95.4% NPV) and cytology (44.8% sensitivity and 97.2% NPV). Oncuria-Detect displayed favorable sensitivity for identifying early- and late-stage cancer. Oncuria-Detect had a favourable performance in detecting high-grade and MIBC (i.e., aggressive cancers); high-grade sensitivity was 93.5% (95%CI: 0.783-1.000) and MIBC sensitivity was 100.0% (95%CI: 1.000-1.000) compared to BladderChek™ high-grade sensitivity of 13.8% (95%CI: 0.000-0.370) and MIBC sensitivity was 0.0% (95%CI: 0.000-0.000) and cytology high-grade sensitivity was 60.1% (95%CI: 0.333-0.852) and MIBC sensitivity was 73.9% (95%CI: 0.000-1.000).</p><p><strong>Conclusions: </strong>In this analysis of an international prospective trial, Oncuria-Detect performed favorably in the non-invasive evaluation of bladder cancer presence in patients presenting with microscopic hematuria.</p><p><strong>Clinical trial number: </strong>Clinicaltrials.gov NCT03193541.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duration-dependent hippocampal structural changes in focal epilepsy: multicenter neuroimaging evidence.","authors":"Yuxin Wu, Zaiyu Zhang, Baohui Yang, Junyi Tan, Yue Qin, Chenyang Li, Yujie Zhu, Xinping Luan, Hongmei Han, Yasi Yang, Zi Yang, Shihang Chen, Hui Gan, Jing Zhao, Xuan Zhai","doi":"10.1186/s12967-026-08230-x","DOIUrl":"https://doi.org/10.1186/s12967-026-08230-x","url":null,"abstract":"<p><strong>Background: </strong>Hippocampal sclerosis (HS) represents a higher proportion of surgical pathology in adult epilepsy patients compared to pediatric surgical cohorts. We hypothesized that while HS may serve as an initial pathological substrate, hippocampal abnormalities in epilepsy may also represent a duration-related structural change process that evolves with disease progression. To test this duration-dependent hypothesis, we investigated associations between disease duration and hippocampal morphological features using advanced neuroimaging in a large multicenter cohort.</p><p><strong>Methods: </strong>This study included 705 patients with unilateral focal epilepsy (age 25.4 ± 14.9 years, disease duration 14.8 ± 13.6 years) and 424 healthy controls from three centers in China. Global hippocampal features (volume, thickness, gyrification, mean curvature, intrinsic curvature) and subfield volumes were extracted using HippUnfold and AID-HS. Z-scores were calculated using normative models controlling for age, sex, total intracranial volume, and site. Associations between disease duration and hippocampal features were assessed using Spearman correlations and duration-stratified group comparisons. Longitudinal changes were evaluated in 80 patients with serial MRI scans using linear mixed-effects models.</p><p><strong>Results: </strong>Patients with epilepsy showed significant bilateral hippocampal abnormalities compared to controls, with more severe changes ipsilateral to the seizure focus. Disease duration significantly correlated with all ipsilateral hippocampal metrics: negatively with volume (ρ = -0.181, p < 0.001), thickness (ρ = -0.135, p < 0.001), and gyrification (ρ = -0.141, p < 0.001), and positively with mean curvature (ρ = 0.121, p = 0.003) and intrinsic curvature (ρ = 0.171, p < 0.001). Contralateral associations were observed for volume (ρ = -0.085, p = 0.044), thickness (ρ = -0.082, p = 0.049), and intrinsic curvature (ρ = 0.080, p = 0.049). Longitudinal analysis revealed significant annual decline in ipsilateral hippocampal volume (β = -0.21 Z-score units/year, p = 0.042).</p><p><strong>Conclusions: </strong>We provide novel neuroimaging evidence supporting the duration-related structural alteration hypothesis of hippocampal structural changes in focal epilepsy. These findings may help explain the higher proportion of HS observed in adult surgical cohorts compared to pediatric surgical cohorts and enhance understanding of epilepsy pathophysiology, suggesting that disease duration is significantly associated with hippocampal structural abnormalities, indicating that it may serve as an important reference indicator for clinical monitoring and therapeutic decision-making.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: System analysis based on the cuproptosis-related genes identifies LIPT1 as a novel therapy target for liver hepatocellular carcinoma.","authors":"Cheng Yan, Yandie Niu, Liukai Ma, Lifang Tian, Jiahao Ma","doi":"10.1186/s12967-025-07008-x","DOIUrl":"https://doi.org/10.1186/s12967-025-07008-x","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}