Journal of Translational Medicine最新文献

{"title":"Editorial Expression of Concern: Safety of targeting tumor endothelial cell antigens.","authors":"Samuel C Wagner, Neil H Riordan, Thomas E Ichim, Julia Szymanski, Hong Ma, Jesus A Perez, Javier Lopez, Juan J Plata-Munoz, Francisco Silva, Amit N Patel, Santosh Kesari","doi":"10.1186/s12967-025-06651-8","DOIUrl":"https://doi.org/10.1186/s12967-025-06651-8","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"607"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208822","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":"ANKHD1 promotes pathogenic proliferation in Autosomal Dominant Polycystic Kidney Disease via the Cyclin D1/CDK4 pathway.","authors":"Maria-Eirini Terzenidou, Foteini Patera, Fiona M Macleod, Albert C M Ong, Maria Fragiadaki","doi":"10.1186/s12967-025-06359-9","DOIUrl":"https://doi.org/10.1186/s12967-025-06359-9","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"612"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208819","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":"Around-the-clock noise exposure induces hippocampus apoptosis and subsequent cognitive impairment via the PI3K/SGK1/Foxo3 signaling pathway.","authors":"Yiming Fu, Pengfang Zheng, Xiaojun She, Yingwen Zhu, Bo Fu, Kefeng Ma, Honglian Yang, Xiujie Gao, Bo Cui","doi":"10.1186/s12967-025-06501-7","DOIUrl":"https://doi.org/10.1186/s12967-025-06501-7","url":null,"abstract":"<p><strong>Background: </strong>Noise exposure is an environmental stressor associated with cognitive impairment. Workers in specific work environments are often exposed to around-the-clock noise and experience severe emotional and cognitive dysfunctions associated with neuropathology similar to Alzheimer's disease. However, the underlying neural mechanisms have not been extensively investigated.</p><p><strong>Methods: </strong>The molecular pathways underlying cognitive impairment following around-the-clock noise exposure were evaluated using male Wistar rats. The open-field and Morris water maze tests were used to assess cognitive performance. RNA sequencing was employed to identify key regulators and pathological pathways of cognitive impairment. Histological changes were observed using hematoxylin and eosin staining, Nissl staining, transmission electron microscopy, and immunofluorescence. Western blotting was performed to detect altered apoptotic markers.</p><p><strong>Results: </strong>Around-the-clock noise exposure significantly induced cognitive decline and neuronal damage in rat. Transcriptome sequencing of hippocampal tissues from control and noise-exposed rats revealed that the expression of the serum/glucocorticoid regulated kinase 1 (SGK1) gene was reduced, with a corresponding decrease in its protein levels. Moreover, this dysregulation led to the inhibition of the intracellular PI3K/SGK1/Foxo3 pathway, triggering the upregulation of the apoptotic proteins Bcl-2, Bax, Fasl, and TRAIL.</p><p><strong>Conclusions: </strong>These findings suggest that around-the-clock noise exposure induces hippocampal neuronal apoptosis, thus exacerbating cognitive impairment. This elucidates the potential role of the PI3K/SGK1/Foxo3 pathway in noise-induced neuronal damage.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"613"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208820","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":"Unraveling the advances of non-coding RNAs on the tumor microenvironment: innovative strategies for cancer therapies.","authors":"Deyang Mu, Bing Han, Hao Huang, Yuchen Zheng, Jungang Zhang, Ying Shi","doi":"10.1186/s12967-025-06629-6","DOIUrl":"https://doi.org/10.1186/s12967-025-06629-6","url":null,"abstract":"<p><p>Non-coding RNAs (ncRNAs) are crucial molecules that do not encode proteins but play roles in regulating various biological processes. Recent research highlights that ncRNAs not only control gene expression within cells but also facilitate intercellular communication via exosomes and other carriers. This function is vital in the tumor microenvironment (TME). Our review covers the structure and functions of different ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). We examine how these ncRNAs influence tumor initiation and progression. Additionally, we explore their role in promoting tumor growth or immune evasion by modulating the TME. The potential of using these ncRNAs as therapeutic targets or biomarkers for clinical use is also discussed. As our understanding of ncRNAs grows, the development of new therapies based on ncRNAs is anticipated to offer improved treatment options for cancer patients.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"614"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208869","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":"IL-6R blockade combined with immunosuppressants alleviates adult-onset Still's disease through immune remodeling: a mass cytometry study.","authors":"Ruru Guo, Ting Zhang, Yixuan Li, Xuesong Liu, Xinyu Meng, Lei Tong, Xiaoxiang Chen, Xianting Ding, Liangjing Lu","doi":"10.1186/s12967-025-06597-x","DOIUrl":"https://doi.org/10.1186/s12967-025-06597-x","url":null,"abstract":"<p><strong>Background: </strong>Early administration of IL-6R blockade is effective in adult-onset Still's disease (AOSD), but the underlying immune alterations during combined immunotherapy remain unclear.</p><p><strong>Methods: </strong>We employed high-dimensional single-cell mass cytometry and an unbiased bioinformatics pipeline to characterize the immune landscape in treatment-naïve AOSD patients, stable AOSD patients after 24 weeks of IL-6R blockade plus methotrexate and prednisone, and matched healthy controls. Cytokine profiling was conducted using a high-throughput cytometric bead array, and potential regulatory networks were identified using the PerformanceAnalytics package. Validation was performed via flow cytometry and mRNA sequencing.</p><p><strong>Results: </strong>We identified 22 peripheral immune cell populations and characterized their composition and phenotypic markers. Treatment-naïve AOSD patients exhibited significant depletion of CD4⁺ T cells and B cells, along with excessive activation of CD8⁺ T cells and a previously unreported CD45⁺CD3^-CD19^-CD10^-CD66a⁺ population, findings that were validated in an independent AOSD cohort. mRNA sequencing revealed the proinflammatory role of CD8⁺ T cells. Notably, these dysregulated immune profiles were markedly restored following immunotherapy. IL-18, IL-21, and IFN-γ demonstrated strong associations with adaptive immune cells and AOSD clinical indices.</p><p><strong>Conclusions: </strong>Combined IL-6R blockade effectively modulates immune dysregulation in refractory AOSD, reversing key pathological immune alterations and highlighting its therapeutic potential.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"610"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208824","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":"Mitochondrial dynamics reveal potential to facilitate axonal regeneration after spinal cord injury.","authors":"Kaixuan Wang, Xi Chen, Mengmin Liu, Yunjuan Li, Yihua Zhu, Tiantong Zhou, Weiwei Tao, Yong Ma, Yang Guo, Lining Wang, Yue Hu","doi":"10.1186/s12967-025-06611-2","DOIUrl":"https://doi.org/10.1186/s12967-025-06611-2","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord injury (SCI) arises from traumatic damage to the spinal cord, resulting in varying degrees of sensory, motor, and autonomic dysfunction. Mitochondria, as the primary energy-producing organelles within cells, have garnered increasing attention for their critical role in promoting axonal regeneration following SCI.</p><p><strong>Aim of review: </strong>This review aims to systematically examine the alterations in mitochondrial dynamics post-SCI and to elucidate their influence on axonal regeneration. Furthermore, the review evaluates the current challenges associated with SCI treatment and proposes potential therapeutic strategies for future research.</p><p><strong>Key scientific concepts of review: </strong>The review comprehensively addresses mitochondrial dynamics, with a focus on key processes such as biogenesis, fusion and fission, mitophagy, trafficking, and anchoring. It delves into the molecular mechanisms by which signaling pathways within neurons and glial cells regulate these mitochondrial processes to facilitate axonal regeneration. Additionally, the review identifies existing challenges in SCI treatment and advocates for targeted interventions in mitochondrial dynamics as a promising therapeutic avenue, offering significant potential for advancing future research and treatment of SCI.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"617"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208867","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":"Inhibition of histone deacetylases 3 attenuates imiquimod-induced psoriatic dermatitis via targeting cGAS-STING signaling in keratinocytes.","authors":"Chong Zeng, Xiujuan Wen, Zibo Wei, Xinhuai Dong","doi":"10.1186/s12967-025-06544-w","DOIUrl":"https://doi.org/10.1186/s12967-025-06544-w","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a common chronic inflammatory skin disease characterized by epidermal keratinocyte hyperproliferation and persistent immune activation. Histone deacetylase 3 (HDAC3), a member of the class I HDAC family, plays critical roles in regulating immunity and inflammation. However, its precise expression profile and functional contribution to psoriasis pathogenesis remain poorly defined.</p><p><strong>Methods: </strong>We first performed bioinformatics analysis of HDAC3 expression using the Gene Expression Omnibus (GEO) database. Subsequently, we employed a combination of cellular and molecular techniques, including hematoxylin and eosin (H&E) staining, immunohistochemistry, flow cytometry, quantitative real-time PCR (qRT-PCR), western blotting, and transmission electron microscopy (TEM), to analyze the role of HDAC3 in IMQ-induced psoriasis-like inflammation in mice and in vitro psoriasis models.</p><p><strong>Results: </strong>HDAC3 expression was significantly upregulated in psoriasis lesions of patients and in both in vitro and in vivo models of psoriasis. Pharmacological inhibition of HDAC3 using the specific inhibitor RGFP966 alleviated IMQ-induced skin inflammation in mice and suppressed psoriasis-like phenotypes in vitro. Mechanistically, HDAC3 upregulation in an inflammatory microenvironment promoted oxidative stress, disrupted mitochondrial structural integrity, and triggered mitochondrial DNA leakage into the cytosol, thereby activating the cGAS-STING pathway in keratinocytes.</p><p><strong>Conclusion: </strong>Our findings establish HDAC3 as a pivotal mediator of psoriasis pathogenesis through the cGAS-STING pathway via mitochondrial dysfunction. The role of HDAC3 in exacerbating epidermal hyperproliferation and inflammation highlights its potential as a therapeutic target. Targeting HDAC3 in keratinocytes may offer a novel strategy for preventing and treating psoriasis by modulating epigenetic regulation, mitochondrial homeostasis, and innate immune responses.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"609"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208825","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":"Macrophages in prostate cancer: dual roles in tumor progression and immune evasion.","authors":"Ruihong Liu, Jianxin Lu, Jun Liu, Yilei Liao, Yinuo Guo, Peiqi Shi, Ziqiang Wang, Han Wang, Jingling Lai","doi":"10.1186/s12967-025-06519-x","DOIUrl":"https://doi.org/10.1186/s12967-025-06519-x","url":null,"abstract":"<p><p>Prostate malignant tumors are notably common within the male urinary tract and present significant challenges in medical treatment. A crucial aspect of understanding the progression of these tumors involves examining the immune microenvironment, particularly the multifaceted role played by macrophages. These immune cells have dual functions: on the one hand, they can inhibit tumor growth, while on the other hand, they can also facilitate and accelerate the progression of prostate cancer. Investigations have shed light on the mechanisms through which macrophages contribute to cancer promotion. These mechanisms include their involvement in mediating inflammatory responses, the secretion of chemokines that attract other immune cells, and the production of macrophage extracellular traps (METs), all of which may create favorable environments for tumor development. In the context of advanced prostate cancer, immunotherapy has emerged as the primary treatment modality. However, the effectiveness of this approach often falls short, leading to disheartening prognoses for patients undergoing such therapies. The suboptimal efficacy and poor outcomes associated with immunotherapy may be correlated with the activity of macrophages within the tumor microenvironment (TME). Specifically, the infiltration of macrophages into tumor tissues, along with elevated levels of these cells in the peripheral blood, has been identified as an indicator of a poor prognosis for individuals with prostate cancer. This study provides a deeper understanding of the cancer-promoting effects of macrophages and the various mechanisms by which they operate, including the roles of chemokines and the production of macrophage extracellular traps in both the onset and progression of prostate cancer. Furthermore, we explored how these factors are related to local tumor infiltration and systemic macrophage counts, which are associated with unfavorable survival outcomes for patients with this disease.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"615"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208827","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":"Engineered macrophage membrane-coated dihydroartemisinin nanoparticles with enhanced CCR2 expression improved symptoms in MRL/LPR mice by metabolic reprogramming of proinflammatory macrophages.","authors":"Li Zhao, Yanlong Zhang, Rongrong Wang, Jiaqi Yang, Ruonan Wu, Zewen Wu, Jie Hu, Shuqiu Zhang, Liyun Zhang","doi":"10.1186/s12967-025-06574-4","DOIUrl":"https://doi.org/10.1186/s12967-025-06574-4","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is a debilitating autoimmune condition characterized by limited therapeutic options. Dihydroartemisinin (DHA), an antimalarial compound, exhibits promising immunomodulatory effects against SLE; however, its clinical application is limited by poor bioavailability.</p><p><strong>Methods: </strong>This study presented an innovative DHA delivery system based on macrophage membrane-coated nanoparticles (CCR2-MM@PEG-PCL/DHA), engineered to target SLE and its severe renal manifestation, lupus nephritis (LN). CCL2, a central mediator of leukocyte chemotaxis, contributes significantly to SLE pathogenesis. The targeting ability of nanoparticles to inflammatory sites is enhanced by genetically modifying the membrane of macrophages to over-express CCR2, and the nanoparticles can act as \"nanobait\" to capture CCL2 in the inflammatory microenvironment, thereby inhibiting macrophage-mediated inflammation. Efficacy was evaluated in vitro and in vivo using the MRL/lpr murine model.</p><p><strong>Results: </strong>The findings showed that this nanosystem effectively alleviated symptoms in the MRL/lpr mouse model of SLE. Furthermore, CCR2-MM@PEG-PCL/DHA modulated the renal immune microenvironment by reducing monocyte/macrophage infiltration and reprogramming the M1/M2 macrophage balance, thus mitigating kidney damage in SLE mice.</p><p><strong>Conclusions: </strong>The study establishes a mechanistically informed strategy for SLE intervention, substantiated by robust in vitro and in vivo data. These findings lay the foundation for translational research and potential clinical advancement in SLE therapy.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"608"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208823","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":"Scutellarin prevents obesity-induced renal fibrosis via reduced activation of AP-1.","authors":"Haoan Yi, Yibing Jiang, Wei Li, Ling Shen, Wei Zhang, Shude Li, Yushan Xu, Fei Li","doi":"10.1186/s12967-025-06616-x","DOIUrl":"https://doi.org/10.1186/s12967-025-06616-x","url":null,"abstract":"<p><strong>Background: </strong>Renal fibrosis is characterized by the formation of scar tissue in the kidney parenchyma. Obesity, with its rising global incidence, has become a significant cause of renal fibrosis. This study investigates the effect of Scutellarin (SCU) on obesity-induced renal fibrosis.</p><p><strong>Methods: </strong>Rats were fed a high-fat and high-sugar diet (HFSD) for 40 weeks. SCU was administered orally at doses of 25, 50, and 100 mg/kg/day during the last 8 weeks. Metabolic function was assessed by measuring serum triglycerides (TG), total cholesterol (TC), and glucose levels. Renal function was evaluated by analyzing serum uric acid (UA), creatinine (CRE), and blood urea nitrogen (BUN). RNA-seq was used to evaluate transcriptome changes in the kidney. Histopathological changes were examined using HE and Masson staining. Protein expressions and localization of FOS, JUN, FN, and TGF-β1 were analyzed by western blot, immunohistochemistry, and immunofluorescence.</p><p><strong>Results: </strong>HFSD-fed rats exhibited significant increases in body weight, serum TG, TC, and glucose levels, alongside elevated UA, CRE, and BUN levels, indicating metabolic and renal dysfunction. SCU treatment significantly improved these metabolic and renal parameters across all doses. Biochemical analyses and RNA-seq results confirmed the absence of dose-dependency in the effects of SCU. Histopathological analysis showed a reduction in glomerular hypertrophy and collagen deposition in the SCU-treated groups. RNA-seq data indicated a downregulation of Activator Protein 1 (AP-1), composed of FOS and JUN, at the transcriptional level. Western blot analysis confirmed that SCU treatment reduced both the expression and phosphorylation levels of FOS and JUN. Additionally, SCU downregulated the expression of fibrosis-related proteins TGF-β1 and FN, contributing to a reduction in renal fibrosis.</p><p><strong>Conclusion: </strong>SCU alleviates obesity-induced renal fibrosis through the downregulation of AP-1 activity and the expression level of fibrosis-related proteins TGF-β1 and FN.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"611"},"PeriodicalIF":6.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208868","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}