Journal of Translational Medicine最新文献

{"title":"Immunomarker profiling in human chronic wound swabs reveals IL-1 beta/IL-1RA and CXCL8/CXCL10 ratios as potential biomarkers for wound healing, infection status and regenerative stage.","authors":"Julian-Dario Rembe, Waseem Garabet, Matthias Augustin, Joachim Dissemond, Wiebke Ibing, Hubert Schelzig, Ewa K Stuermer","doi":"10.1186/s12967-025-06417-2","DOIUrl":"https://doi.org/10.1186/s12967-025-06417-2","url":null,"abstract":"<p><strong>Background: </strong>Chronic wounds, such as diabetic foot ulcers, venous leg ulcers, and post-surgical wound healing disorders pose a significant challenge due to prolonged healing, risk of infection, and impaired quality of life. Persistent inflammation and impaired tissue remodeling are common in these wounds. Traditional diagnostic methods, including visual inspection and microbiological cultures, offer limited insight into the wound micro-environment. Immunomarker profiling could provide a deeper understanding of the molecular mechanisms underpinning wound healing, offering potential biomarkers for infection status and healing progression.</p><p><strong>Methods: </strong>This observational, multi-center cohort study, part of the 'Wound-BIOME' project, analyzed 110 swab samples from patients with acute and chronic wounds using multiplex immunoassays. Clinical parameters such as wound type, healing status, regeneration stage, and microbial burden were recorded. Total protein concentration was assessed, and 35 key immunomarkers, including cytokines (e.g. IL- 1α, IL- 1β), chemokines (CCL2, CXCL8, CXCL10), growth factors (FGF- 2, VEGF) and matrix metalloproteinases (MMP- 7, MMP- 9, MMP- 13), were quantified. Statistical analyses were performed to correlate immunomarker levels with clinical outcomes.</p><p><strong>Results: </strong>Pro-inflammatory markers, such as IL- 1β, IL- 18 and chemokines like CCL2 and CXCL8, were significantly elevated in non-healing and infected wounds compared to healing wounds. The study identified two new immunomarker ratios - IL- 1β/IL- 1RA and CXCL8/CXCL10 - as potential predictors of wound healing status. The IL- 1β/IL- 1RA ratio showed the highest accuracy for distinguishing healing from non-healing wounds (AUC = 0.6837), while the CXCL8/CXCL10 ratio was most effective in identifying infection (AUC = 0.7669).</p><p><strong>Conclusions: </strong>Immunomarker profiling via wound swabbing offers valuable insights into the wound healing process. Elevated levels of pro-inflammatory cytokines and MMPs are associated with chronic inflammation and impaired healing. The IL- 1β/IL- 1RA and CXCL8/CXCL10 ratios emerge as promising biomarkers to distinguish between infection and inflammation, with potential in targeted wound care. Further studies are needed to validate these findings and implement them in clinical practice.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"407"},"PeriodicalIF":6.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811599","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":"SORBS3-β suppresses lymph node metastasis in cervical cancer by promoting the ubiquitination of β-catenin.","authors":"Huating Sun, Yinghui Zhang, Fang Wang, Zizhao Wang, Yuhong Zhang, Youguo Chen, Li Wang, Jinhua Zhou","doi":"10.1186/s12967-025-06409-2","DOIUrl":"https://doi.org/10.1186/s12967-025-06409-2","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer (CC) is a prevalent gynecological malignancy, with lymph node metastasis (LNM) serving as a critical factor influencing patient prognosis. SORBS3, an adaptor protein with two known isoforms (α and β), has been implicated in tumor suppression, but the specific roles of its isoforms in CC metastasis remains unexplored. This study aimed to identify the functional isoform of SORBS3 driving LNM suppression and elucidate its mechanisms.</p><p><strong>Methods: </strong>Proteomic analysis of clinical CC tissues and metastatic lymph nodes revealed progressive downregulation of SORBS3. The mRNA and protein levels of SORBS3-α and SORBS3-β were subsequently examined in normal cervical epithelial and CC cell lines. Functional studies, including siRNA-mediated knockdown of SORBS3-α, lentiviral-mediated overexpression and knockdown of SORBS3-β, Transwell migration, lymphangiogenesis assays, and in vivo footpad xenograft models, were conducted to evaluate the role of SORBS3 isoforms in LNM. SORBS3 DNA methylation mechanisms were analyzed by MSP and Targeted Bisulfite sequencing. Mechanistic insights were derived from Co-IP, ubiquitination assays, RNA-seq, and LC-MS/MS.</p><p><strong>Results: </strong>Knockdown of SORBS3-α had no effect on CC cell migration, invasion, or lymphangiogenesis. In contrast, SORBS3-β overexpression markedly suppressed CC cell invasion, lymphangiogenesis, and adhesion to lymphatic endothelial cells, whereas its knockdown significantly promoted these phenotypes. Promoter hypermethylation driven by DNMT-1 inhibited SORBS3 expression in CC. SORBS3- β directly binds to β-catenin and recruits UBA1 to enhance its ubiquitination and degradation, thereby inhibiting Wnt/β-catenin signaling. This inhibition reduced accumulation of β-catenin and downregulated the pro-lymphangiogenic gene VEGFC, ultimately suppressing lymphangiogenesis and LNM. In vivo, SORBS3-β overexpression attenuated lymphatic metastasis in nude mice, whereas its knockdown promoted metastasis.</p><p><strong>Conclusion: </strong>SORBS3-β is the major isoform of SORBS3 that inhibits lymphatic metastasis of cervical cancer by degrading β-catenin through UBA1-mediated ubiquitination, blocking Wnt/β-catenin signaling and downstream lymphangiogenesis pathways, thereby inhibiting lymphatic metastasis. Our findings elucidate key molecular mechanisms underlying cervical cancer lymph node metastasis, offering potential therapeutic targets.metastasis.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"406"},"PeriodicalIF":6.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811600","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":"Editorial Expression of Concern: Ameliorative effect of water spinach, Ipomea aquatica (Convolvulaceae), against experimentally induced arsenic toxicity.","authors":"Tarun K Dua, Saikat Dewanjee, Moumita Gangopadhyay, Ritu Khanra, Muhammad Zia-Ul-Haq, Vincenzo De Feo","doi":"10.1186/s12967-025-06439-w","DOIUrl":"https://doi.org/10.1186/s12967-025-06439-w","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"408"},"PeriodicalIF":6.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811597","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":"Engineering CD5-targeting CAR-NK cells from peripheral blood for the treatment of CD5-positive hematological malignancies.","authors":"Haolong Lin, Lingfeng Zhang, Tong Ge, Ning An, Yongkun Yang, Yicheng Zhang, Wei Mu","doi":"10.1186/s12967-025-06432-3","DOIUrl":"https://doi.org/10.1186/s12967-025-06432-3","url":null,"abstract":"<p><strong>Background: </strong>The therapeutic application of chimeric antigen receptor (CAR) T cells in T-cell malignancies faces substantial limitations owing to fratricide and potential T cell aplasia, primarily attributed to the shared expression of target antigens, such as CD5, between normal and malignant T cells. Although natural killer (NK) cell-based immunotherapy is a promising alternative approach, its efficacy in treating hematologic malignancies remains to be fully elucidated.</p><p><strong>Methods: </strong>CD5-targeted CAR-modified primary NK cells, T cells and NK92 cell lines were generated and comprehensively evaluated for their anti-tumor efficacy through in vitro cytotoxicity assays and xenograft mouse models. Furthermore, preliminary investigation of the herpes simplex virus-1 thymidine kinase (HSV-TK) suicide switch system in CAR-NK cells were conducted using ganciclovir (GCV) as the activating agent.</p><p><strong>Results: </strong>CAR-NK cells exhibited significantly increased cytotoxic activity against CD5-positive cell lines and primary tumor cells, compared to NK, CAR-NK92, and CAR-T cells. Moreover, CAR-NK cells effectively decreased the leukemic burden and extended survival in murine model. Additionally, an off-switch utilizing the HSV-TK switch system successfully eradicated CAR-NK cells for safety considerations.</p><p><strong>Conclusions: </strong>This study developed a controllable CD5 CAR-NK cells that exhibit high efficacy against T-cell malignancies, although further validation is necessary to assess their clinical potential.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"409"},"PeriodicalIF":6.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811598","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":"Tobacco smoke exposure is a driver of altered oxidative stress response and immunity in head and neck cancer.","authors":"Yang Li, Pedram Yadollahi, Fonma N Essien, Vasanta Putluri, Chandra Shekar R Ambati, Karthik Reddy Kami Reddy, Abu Hena Mostafa Kamal, Nagireddy Putluri, Lama M Abdurrahman, Maria E Ruiz Echartea, Keenan J Ernste, Akshar J Trivedi, Jonathan Vazquez-Perez, William H Hudson, William K Decker, Rutulkumar Patel, Abdullah A Osman, Farrah Kheradmand, Stephen Y Lai, Jeffrey N Myers, Heath D Skinner, Cristian Coarfa, Kwangwon Lee, Antrix Jain, Anna Malovannaya, Mitchell J Frederick, Vlad C Sandulache","doi":"10.1186/s12967-025-06258-z","DOIUrl":"10.1186/s12967-025-06258-z","url":null,"abstract":"<p><strong>Background: </strong>Exposomes are critical drivers of carcinogenesis. However, how they modulate tumor behavior remains unclear. Extensive clinical data show cigarette smoke to be a key exposome that promotes aggressive tumors, higher rates of metastasis, reduced response to chemoradiotherapy, and suppressed anti-tumor immunity. We sought to determine whether smoke itself can modulate aggressive tumor behavior in head and neck squamous cell carcinoma (HNSCC) through reprogramming of the cellular reductive state.</p><p><strong>Methods: </strong>Using established human and murine HNSCC cell lines and syngeneic mouse models, we utilized conventional western blotting, steady state and flux metabolomics, RNA sequencing, quantitative proteomics and flow cytometry to analyze the impact of smoke exposure on HNSCC tumor biology and anti-tumor immunity.</p><p><strong>Results: </strong>Cigarette smoke persistently activated Nrf2 target genes essential for maintenance of the cellular reductive state and survival under conditions of increased oxidative stress in HNSCC regardless of human papillomavirus (HPV) association. In contrast to e-cigarette vapor, conventional cigarette smoke mobilizes cellular metabolism toward oxidative stress adaptation, resulting in development of cross-resistance to cisplatin. In parallel, smoke exposure modulates expression of PDL1 and the secretory phenotype of HNSCC cells resulting in an altered tumor immune microenvironment (TIME) in syngeneic mouse models and downregulated expression of antigen presentation and costimulatory genes in myeloid cells.</p><p><strong>Conclusion: </strong>The cigarette smoke exposome is a potent activator of the Nrf2 pathway and appears to be the primary trigger for a tripartite phenotype of aggressive HNSCC consisting of: (1) reduced chemotherapy sensitivity, (2) enhanced metastatic potential and (3) suppressed anti-tumor immunity.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"403"},"PeriodicalIF":6.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GEM-CRAP: a fusion architecture for focal seizure detection.","authors":"Jianwei Shi, Yuanyuan Zhang, Ziang Song, Hang Xu, Yanfeng Yang, Lei Jin, Hengxin Dong, Zhaoying Li, Penghu Wei, Yongzhi Shan, Guoguang Zhao","doi":"10.1186/s12967-025-06414-5","DOIUrl":"10.1186/s12967-025-06414-5","url":null,"abstract":"<p><strong>Background: </strong>Identification of seizures is essential for the treatment of epilepsy. Current machine-learning and deep-learning models often perform well on public datasets when classifying generalized seizures with prominent features. However, their performance was less effective in detecting brief, localized seizures. These seizure-like patterns can be masked by fixed brain rhythms.</p><p><strong>Methods: </strong>Our study proposes a supervised multilayer hybrid model called GEM-CRAP (gradient-enhanced modulation with CNN-RES, attention-like, and pre-policy networks), with three parallel feature extraction channels: a CNN-RES module, an amplitude-aware channel with attention-like mechanisms, and an LSTM-based pre-policy layer integrated into the recurrent neural network. The model was trained on the Xuanwu Hospital and HUP iEEG dataset, including intracranial, cortical, and stereotactic EEG data from 83 patients, covering over 8500 labeled electrode channels for hybrid classification (wakefulness and sleep). A post-SVM network was used for secondary training on channels with classification accuracy below 80%. We introduced an average channel deviation rate metric to assess seizure detection accuracy.</p><p><strong>Results: </strong>For public datasets, the model achieved over 97% accuracy for intracranial and cortical EEG sequences in patients, and over 95% for mixed sequences, with deviations below 5%. In the Xuanwu Hospital dataset, it maintained over 94% accuracy for wakefulness seizures and around 90% during sleep. SVM secondary training improved average channel accuracy by over 10%. Additionally, a strong positive correlation was found between channel accuracy distribution and the temporal distribution of seizure states.</p><p><strong>Conclusions: </strong>GEM-CRAP enhances focal epilepsy detection through adaptive adjustments and attention mechanisms, achieving higher precision and robustness in complex signal environments. Beyond improving seizure interval detection, it excels in identifying and analyzing specific epileptic waveforms, such as high-frequency oscillations. This advancement may pave the way for more precise epilepsy diagnostics and provide a suitable artificial intelligence algorithm for closed-loop neurostimulation.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"405"},"PeriodicalIF":6.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomics guiding personalized first-line immunotherapy response in lung and bladder tumors.","authors":"Jenifer Brea-Iglesias, María Gallardo-Gómez, Ana Oitabén, Martin E Lázaro-Quintela, Luis León, Joao M Alves, Manuel Pino-González, Laura Juaneda-Magdalena, Carme García-Benito, Ihab Abdulkader, Laura Muinelo, Jesús M Paramio, Mónica Martínez-Fernández","doi":"10.1186/s12967-025-06323-7","DOIUrl":"10.1186/s12967-025-06323-7","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment, particularly in advanced non-small cell lung cancer (NSCLC) and muscle-invasive bladder cancer (MIBC). However, identifying reliable predictive biomarkers for ICI response remains a significant challenge. In this study, we analyzed real-world cohorts of advanced NSCLC and MIBC patients treated with ICI as first-line therapy.</p><p><strong>Methods: </strong>Tumor samples underwent Whole Genome Sequencing (WGS) to identify specific somatic variants and assess tumor mutational burden (TMB). Additionally, mutational signature extraction and pathway enrichment analyses were performed to uncover the underlying mechanisms of ICI response. We also characterized HLA-I haplotypes and investigated LINE-1 retrotransposition.</p><p><strong>Results: </strong>Distinct mutation patterns were identified in patients who responded to treatment, suggesting potential biomarkers for predicting ICI effectiveness. In NSCLC, tumor mutational burden (TMB) did not differ significantly between responders and non-responders, while in MIBC, higher TMB was linked to better responses. Specific mutational signatures and HLA haplotypes were associated with ICI response in both cancers. Pathway analysis showed that NSCLC responders had active inflammatory and immune pathways, while pathways enriched in non-responders related to FGFR3 and neural crest differentiation, associated to resistance mechanisms. In MIBC, responders had alterations in DNA repair, leading to more neoantigens and a stronger ICI response. Importantly, for the first time, we found that LINE-1 activation was positively linked to ICI response, especially in MIBC.</p><p><strong>Conclusion: </strong>These findings reveal promising biomarkers and mechanistic insights, offering a new perspective on predicting ICI response and opening up exciting possibilities for more personalized immunotherapy strategies in NSCLC and MIBC.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"404"},"PeriodicalIF":6.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human neural stem cell-derived exosomes activate PINK1/Parkin pathway to protect against oxidative stress-induced neuronal injury in ischemic stroke.","authors":"Mengke Zhao, Jiayi Wang, Shuaiyu Zhu, Shensen Zhang, Chao Han, Chengcheng Tan, Yubing Huang, Zhaokai Sun, Liang Wang, Jing Liu","doi":"10.1186/s12967-025-06283-y","DOIUrl":"10.1186/s12967-025-06283-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Mitochondria play a critical role in oxidative stress (OS)-induced neuronal injury during ischemic stroke (IS), making them promising therapeutic targets. Mounting evidence underscores the extraordinary therapeutic promise of exosomes derived from human neural stem cells (hNSCs) in the management of central nervous system (CNS) diseases. Nonetheless, the precise mechanisms by which these exosomes target mitochondria to ameliorate the effects of IS remain only partially elucidated. This study investigates the protective effects of hNSC derived exosomes (hNSC-Exos) on neuronal damage.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Using a rat model of middle cerebral artery occlusion (MCAO) in vivo and OS-induced HT22 cells in vitro. Firstly, our research group independently isolated human neural stem cells (hNSCs) and subsequently prepared hNSC-Exos. In vivo, MCAO rats were restored to blood flow perfusion to simulate ischemia-reperfusion injury, and hNSC-Exos were injected through stereotaxic injection into the brain. Subsequently, the protective effects of hNSC-Exos on MCAO rats were evaluated, including histological studies, behavioral assessments. In vivo, H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; was used in HT22 cells to simulate the OS environment in MCAO, and then its protective effects on HT22 were evaluated by co-culturing with hNSC-Exos, including immunofluorescence staining, western blotting (WB), quantitative real time PCR (qRT-PCR). In the process of exploring specific mechanisms, we utilized RNA sequencing (RNA-seq) to detect the potential induction of mitophagy in OS-induced HT22 cells. Afterwards, we employed a series of mitochondrial function assessments and autophagy related detection techniques, including measuring mitochondrial membrane potential, reactive oxygen species (ROS) levels, transmission electron microscopy (TEM) imaging, monodansylcadaverine (MDC) staining, and mCherry-GFP-LC3B staining. In addition, we further investigated the regulatory pathway of hNSC-Exos by using autophagy inhibitor mdivi-1 and knocking out PTEN induced kinase 1 (PINK1) in HT22 cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Administration of hNSC-Exos significantly ameliorated brain tissue damage and enhanced behavioral outcomes in MCAO rats. This treatment led to a reduction in brain tissue apoptosis and facilitated the normalization of impaired neurogenesis and neuroplasticity. Notably, the application of hNSC-Exos in vitro resulted in an upregulation of mitophagy in HT22 cells, thereby remedying mitochondrial dysfunction. We demonstrate that hNSC-Exos activate mitophagy via the PINK1/Parkin pathway, improving mitochondrial function and reducing neuronal apoptosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;These findings suggest that hNSC-Exos alleviate OS-induced neuronal damage by regulating the PINK1/Parkin pathway. These reveals a novel role of stem cell-derived mitochondrial therapy in promoting neuroprotection and suggest their potential as a thera","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"402"},"PeriodicalIF":6.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCL12/CXCR4 axis mediates CD8 ⁺ T cell overactivation in the progression of viral myocarditis.","authors":"Li Zhang, Keyu Liu, Xiuyun Duan, Shan Zhou, Hailin Jia, Yingnan You, Bo Han","doi":"10.1186/s12967-025-06394-6","DOIUrl":"10.1186/s12967-025-06394-6","url":null,"abstract":"<p><strong>Background: </strong>Myocarditis is a common inflammatory heart disease in children and young adults, with fulminant myocarditis (FM) being the most severe form due to its rapid onset and high mortality rate. However, the precise pathological immune subsets and molecular change in myocarditis, particularly FM, remain unknown.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing of pediatric peripheral blood mononuclear cells during the acute and recovery phases of FM. A viral myocarditis (MC) mouse model was established using CVB3. Deletion and adoptive transfer of CD8⁺T cells, as well as blockade of CXCR4, were conducted in vivo. CD8⁺T cells were sorted and cultivated in vitro, then stimulated with CXCL12 and CXCR4 antagonists to investigate the mechanism of CD8⁺T cell overactivation.</p><p><strong>Results: </strong>CD8⁺T cells show significant activation, amplification, enhanced cytotoxicity, and increased chemotactic ability in FM. Deletion of CD8⁺T cells alleviates myocardial injury and improves cardiac function in MC mice, while adoptive transfer of CD8⁺T cells from MC mice aggravates myocardial inflammation and injury. The transcriptomic analysis reveals elevated CXCR4 expression in CD8⁺T cells in acute FM. In vitro experiments demonstrate that the CXCL12/CXCR4 axis drives the overactivation and cytotoxicity of CD8⁺T cells. In vivo treatment with a CXCR4 antagonist effectively reduces CD8⁺T cell accumulation in the heart, alleviates myocardial inflammation, and improves cardiac function in MC mice.</p><p><strong>Conclusions: </strong>These findings provide deeper insights into the immune landscape of pediatric FM, uncovering a novel role of the CXCL12/CXCR4 axis in driving CD8⁺T cell responses in myocarditis. Furthermore, they highlight the CXCL12/CXCR4 axis as a promising therapeutic target for myocarditis treatment.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"399"},"PeriodicalIF":6.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epicardial fat thickness is increased in menopausal patients in comparison with premenopausal patients with similar excess weight: a cross-sectional study.","authors":"Elena Gangitano, Giuseppe Barbaro, Lucio Gnessi, Gianluca Iacobellis, Carla Lubrano","doi":"10.1186/s12967-025-06335-3","DOIUrl":"10.1186/s12967-025-06335-3","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of excess weight and ageing is notably high in contemporary Western societies. The effectiveness of body mass index (BMI) and waist circumference as tools for identifying excess weight and ectopic fat deposition, both associated with an increased cardiovascular risk, is questionable.</p><p><strong>Methods: </strong>Our objective is to compare women affected by overweight and obesity during fertile years and menopausal time and identify easily accessible clinical parameters associated with ectopic fat deposition, providing valuable insights into cardiovascular risk. Over 1300 female patients with excess weight referred to the CASCO Centre (High Specialization Centre for the Care of Obesity) at Umberto I Polyclinic in Rome, Italy, were included. Each participant underwent a DXA scan and a cardiac ultrasound, and blood tests to verify menopausal status and evaluate metabolic profile and hepatic steatosis through indirect measurements.</p><p><strong>Results: </strong>775 patients were in the pre-menopausal phase and 617 in the post-menopausal phase. The two cohorts did not differ in BMI, total body fat and lean mass, or waist circumference. However, the post-menopausal group showed an increased visceral fat deposition, evaluated by waist-to-hip ratio and epicardial fat thickness (EFT), and a worse metabolic profile.</p><p><strong>Conclusion: </strong>Menopause is associated with a worsening of the metabolic features observed in obesity, with an increase in visceral fat deposition. Of note, these alterations are more pronounced despite similar BMI and waist circumference.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"401"},"PeriodicalIF":6.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}