Journal of Translational Medicine最新文献

{"title":"ZBTB6 promotes breast cancer progression by inhibiting ARHGAP6 transcription and modulating the STAT3 signaling pathway.","authors":"Xiaojiang Tang, Chaowei Deng, Yang Liu, Shengyu Pu, Qi Zheng, Yudong Zhou, Na Hao","doi":"10.1186/s12967-025-06364-y","DOIUrl":"10.1186/s12967-025-06364-y","url":null,"abstract":"<p><strong>Background: </strong>The ZBTB (zinc finger and BTB domain-containing) protein family comprises a significant class of transcription factors that interact with various corepressors and histone/protein-modifying enzymes. This interaction facilitates chromatin remodeling and the regulation of gene silencing or activation, thereby playing a crucial role in cancer progression. However, the biological effects and molecular mechanisms of ZBTB6, a member of the ZBTB family, in cancer remain unclear.</p><p><strong>Methods: </strong>The expression levels of ZBTB6 in breast cancer (BC) were investigated through public database queries, real-time quantitative PCR (qRT‒PCR), and Western blot analysis. The effects of ZBTB6 on BC cell viability were assessed via MTT assays. Flow cytometry was utilized to analyze the cell cycle distribution and apoptosis. Additionally, cell-derived xenograft experiments were conducted to study the impact of ZBTB6 on BC growth in vivo. The relationship between ZBTB6 and the ARHGAP6 promoter was evaluated via bioinformatics predictions, chromatin immunoprecipitation (ChIP) coupled with qRT‒PCR, and luciferase reporter assays.</p><p><strong>Results: </strong>Our study demonstrated that ZBTB6 is highly expressed in primary BC specimens and cell lines and strongly correlated with tumor grade and poor prognosis. In vitro, ZBTB6 knockdown inhibited cell viability and cell cycle progression while promoting apoptosis; conversely, ZBTB6 overexpression elicited the opposite effects. In vivo, the inhibition of ZBTB6 expression in BC cells significantly suppressed tumor growth. Furthermore, we identified ARHGAP6 as a transcriptional target downstream of ZBTB6, with ZBTB6 binding to the promoter region of ARHGAP6 to repress its transcription. Notably, ARHGAP6 can exert an inhibitory effect on tumors by attenuating STAT3 activity. Our results indicate that ZBTB6 overexpression enhances the STAT3 signaling pathway, whereas ARHGAP6 overexpression counteracts the effects of ZBTB6 overexpression in BC cells.</p><p><strong>Conclusion: </strong>These findings suggest that ZBTB6 promotes breast cancer progression by repressing the transcription of ARHGAP6 and activating the STAT3 signaling pathway. Consequently, ZBTB6 may serve as a potential prognostic biomarker or therapeutic target for breast cancer patients.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"370"},"PeriodicalIF":6.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710383","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":"The emerging role of E3 ubiquitin ligases and deubiquitinases in metabolic dysfunction-associated steatotic liver disease.","authors":"Yu Zhang, Jiahui Yang, Jiali Min, Shan Huang, Yuchen Li, Shanshan Liu","doi":"10.1186/s12967-025-06255-2","DOIUrl":"10.1186/s12967-025-06255-2","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, with a prevalence as high as 32.4%. MASLD encompasses a spectrum of liver pathologies, ranging from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, and, in some cases, progression to end-stage liver disease (cirrhosis and hepatocellular carcinoma). A comprehensive understanding of the pathogenesis of this highly prevalent liver disease may facilitate the identification of novel targets for the development of improved therapies. E3 ubiquitin ligases and deubiquitinases (DUBs) are key regulatory components of the ubiquitin‒proteasome system (UPS), which plays a pivotal role in maintaining intracellular protein homeostasis. Emerging evidence implicates that aberrant expression of E3 ligases and DUBs is involved in the progression of MASLD. Here, we review abnormalities in E3 ligases and DUBs by (1) discussing their targets, mechanisms, and functions in MASLD; (2) summarizing pharmacological interventions targeting these enzymes in preclinical and clinical studies; and (3) addressing challenges and future therapeutic strategies. This review synthesizes current evidence to highlight the development of novel therapeutic strategies based on the UPS for MASLD and progressive liver disease.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"368"},"PeriodicalIF":6.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710381","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":"Multi-cohort study in gastric cancer to develop CT-based radiomic models to predict pathological response to neoadjuvant immunotherapy.","authors":"Ze-Ning Huang, Hao-Xiang Zhang, Yu-Qin Sun, Xing-Qi Zhang, Yi-Fen Lin, Cai-Ming Weng, Chao-Hui Zheng, Ping-Li, Jia-Bin Wang, Qi-Yue Chen, Long-Long Cao, Mi Lin, Ru-Hong Tu, Chang-Ming Huang, Jian-Xian Lin, Jian-Wei Xie","doi":"10.1186/s12967-025-06363-z","DOIUrl":"10.1186/s12967-025-06363-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Neoadjuvant immunotherapy has been shown to improve survival in patients with gastric cancer. This study sought to develop and validate a radiomics-based machine learning (ML) model for patients with locally advanced gastric cancer (LAGC), specifically to predict whether patients will achieve a major pathological response (MPR) following neoadjuvant immunotherapy. With its predictive capabilities, this tool shows promise for enhancing clinical decision-making processes in the future.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study utilized a multicenter cohort design, retrospectively gathering clinical data and computed tomography (CT) images from 268 patients diagnosed with advanced gastric cancer who underwent neoadjuvant immunotherapy between January 2019 and December 2023 from two medical centers. Radiomic features were extracted from CT images, and a multi-step feature selection procedure was applied to identify the top 20 representative features. Nine ML algorithms were implemented to build prediction models, with the optimal algorithm selected for the final prediction model. The hyperparameters of the chosen model were fine-tuned using Bayesian optimization and grid search. The performance of the model was evaluated using several metrics, including the area under the curve (AUC), accuracy, and Cohen's kappa coefficient.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Three cohorts were included in this study: the development cohort (DC, n = 86), the internal validation cohort (IVC, n = 59), and the external validation cohort (EVC, n = 52). Nine ML models were developed using DC cases. Among these, an optimized Bayesian-LightGBM model, demonstrated robust predictive performance for MPR following neoadjuvant immunotherapy in LAGC patients across all cohorts. Specifically, within DC, the LightGBM model attained an AUC of 0.828, an overall accuracy of 0.791, a Cohen's kappa coefficient of 0.552, a sensitivity of 0.742, a specificity of 0.818, a positive predictive value (PPV) of 0.586, a negative predictive value (NPV) of 0.867, a Matthews correlation coefficient (MCC) of 0.473, and a balanced accuracy of 0.780. Comparable performance metrics were validated in both the IVC and the EVC, with AUC values of 0.777 and 0.714, and overall accuracies of 0.729 and 0.654, respectively. These results suggested good fitness and generalization of the Bayesian-LightGBM model. Shapley Additive Explanations (SHAP) analysis identified significant radiomic features contributing to the model's predictive capability. The SHAP values of the features wavelet.LLH_gldm_SmallDependenceLowGrayLevelEmphasis, wavelet.HHL_glrlm_RunVariance, and wavelet.LLH_glszm_LargeAreaHighGrayLevelEmphasis were ranked among the top three, highlighting their significant contribution to the model's predictive performance. In contrast to existing radiomic models that exclusively focus on neoadjuvant chemotherapy, our model integrates both neoadjuvant immunotherapy and chemothe","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"362"},"PeriodicalIF":6.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700783","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":"Mfn2 regulates calcium homeostasis and suppresses PASMCs proliferation via interaction with IP3R3 to mitigate pulmonary arterial hypertension.","authors":"Rui Wang, Jie Wang, Jing Yu, Zhiqiang Li, Minfang Zhang, Yuhu Chen, Fen Liu, Dongmei Jiang, Jingfei Guo, Xiaomei Li, Yun Wu","doi":"10.1186/s12967-025-06384-8","DOIUrl":"10.1186/s12967-025-06384-8","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary arterial hypertension (PAH) is a chronic disorder characterized by the excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs). Recent studies indicate that Mitochondrial fusion protein 2 (Mfn2) maintains intracellular calcium (Ca²⁺) homeostasis via the mitochondria-associated endoplasmic reticulum membranes (MAMs) pathway, thereby inhibiting PASMCs proliferation and reducing pulmonary artery pressure. However, the precise mechanisms remain unclear.</p><p><strong>Methods: </strong>This study explored the roles of Mfn2 and IP3R3 in PAH progression by assessing their expression in lung tissues of a monocrotaline (MCT)-induced PAH rat model. Immunoprecipitation assays were performed to confirm the interaction between Mfn2 and IP3R3. PASMCs were treated with either silenced or overexpressed Mfn2 and exposed to TNF-ɑ to observe effects on ER stress, IP3R3 expression, mitochondrial Ca²⁺ transport, and mitochondrial integrity. We also evaluated the effects of 4-phenylbutyric acid (4-PBA) and cistanche phenylethanol glycosides (CPGs) on the Mfn2-IP3R3 interaction in a TNF-α-induced PAH cell model, focusing on Ca²⁺ transport and mitochondrial structure.</p><p><strong>Results: </strong>Mfn2 expression was significantly down-regulated in the MCT-induced PAH rat model. Inhibition of ER stress upregulated Mfn2 expression, downregulated IP3R3 expression, increased mitochondrial Ca²⁺ concentration, and reduced autophagy, improving pulmonary hemodynamics and vascular remodeling. Overexpression of Mfn2 reduced ER stress, decreased IP3R3 expression, decreased mitochondrial Ca²⁺ transport, and restored mitochondrial integrity. Immunoprecipitation assays confirmed the interaction between Mfn2 and IP3R3. Inhibition of IP3R3 elevated Mfn2 levels, yielding similar beneficial effects as Mfn2 overexpression. 4-PBA and CPGs modulated the Mfn2-IP3R3 signaling axis, effectively inhibiting PAH progression.</p><p><strong>Conclusions: </strong>Mfn2 mediates mitochondrial Ca²⁺ transport via IP3R3, suppressing PASMCs proliferation and pulmonary vascular remodeling, underscoring Mfn2's potential in regulating metabolic processes and vascular remodeling in PAH. These findings provide new insights for developing PAH-targeted therapeutics and establish a theoretical basis for traditional Chinese medicine in PAH prevention and treatment.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"366"},"PeriodicalIF":6.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700779","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":"Global research trends in mind body therapies: a bibliometric analysis.","authors":"Yunxiao Zhang, Wenwen Li, Sai Xu, Shudi Li, Zhen Hai Sun, Menghe Zhang, Yaoyao Zuo, Shouqiang Chen","doi":"10.1186/s12967-025-06389-3","DOIUrl":"10.1186/s12967-025-06389-3","url":null,"abstract":"<p><strong>Objectives: </strong>Mind-body therapies are a group of treatments based on the theory of mind-body medicine, which are effective for a wide range of illnesses. However, there are no bibliometric papers that have examined the topic of mind-body therapies. Therefore, it is necessary to review and sort out the current status, hotspots and frontiers of mind-body therapies.</p><p><strong>Methods: </strong>Studies related to mind-body therapies during the period of Web of Science 1999-01/2024-07 were searched, and R language was applied to analyze the data and CiteSpace, Vosviewer software, was used to generate visualization maps.</p><p><strong>Results: </strong>A total of 29,710 relevant articles were included in the study. The country with the highest number of publications was the United States, followed by China and the United Kingdom, and the prolific author was Wang Yuan. Common keywords were acupuncture, quality of life, depression, and pain. The current study focuses on the promotion and application of mind-body therapies in various diseases, the main applicable diseases and the application in special groups.</p><p><strong>Conclusion: </strong>This study presents the current status and trend of research on mind-body therapies, and inflammatory interventions and higher-level research assessment methods are potential hotspots, which can help researchers to clarify hotspots and explore new directions.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"365"},"PeriodicalIF":6.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700770","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":"Multi-omic studies on the pathogenesis of Sepsis.","authors":"Hongjie Tong, Yuhang Zhao, Ying Cui, Jiali Yao, Tianlong Zhang","doi":"10.1186/s12967-025-06366-w","DOIUrl":"10.1186/s12967-025-06366-w","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a life-threatening inflammatory condition, and its underlying genetic mechanisms are not yet fully elucidated. We applied methods such as Mendelian randomization (MR), genetic correlation analysis, and colocalization analysis to integrate multi-omics data and explore the relationship between genetically associated genes and sepsis, as well as sepsis-related mortality, with the goal of identifying key genetic factors and their potential mechanistic pathways.</p><p><strong>Methods: </strong>To identify therapeutic targets for sepsis and sepsis-related mortality, we conducted an MR analysis on 11,643 sepsis cases and 1,896 cases of 28-day sepsis mortality from the UK Biobank cohort. The exposure data consisted of 15,944 potential druggable genes (expression quantitative trait loci, eQTL) and 4,907 plasma proteins (protein quantitative trait loci, pQTL). We then performed sensitivity analysis, SMR analysis, reverse MR analysis, genetic correlation analysis, colocalization analysis, enrichment analysis, and protein-protein interaction network analysis on the overlapping genes. Validation was conducted using 17,133 sepsis cases from FinnGen R12. Drug prediction and molecular docking were subsequently used to further assess the therapeutic potential of the identified drug targets, while PheWAS was used to evaluate potential side effects. Finally, mediation analysis was conducted to identify the mediating role of related metabolites.</p><p><strong>Results: </strong>The MR analysis results identified a significant causal relationship between 24 genes and sepsis. The robustness of these causal associations was further strengthened by SMR analysis, sensitivity analysis, and reverse MR analysis. Genetic correlation analysis revealed that only two of these genes were genetically correlated with sepsis. Colocalization analysis showed that only one gene was closely associated with sepsis, while validation using the FinnGen dataset identified three genes. In the MR analysis of 28-day sepsis mortality, seven genes were found to have significant associations, with reverse MR analysis excluding one gene. The remaining genes passed sensitivity analysis, with no significant genes identified in genetic correlation and colocalization analyses. Molecular docking demonstrated excellent binding affinity between drugs and proteins with available structural data. PheWAS at the gene level did not reveal any potential side effects of the related drugs.</p><p><strong>Conclusions: </strong>The identified drug targets, associated pathways, and metabolites have enhanced our understanding of the complex relationships between genes and sepsis. These genes and metabolites can serve as effective targets for sepsis treatment, paving new pathways in this field and laying a foundation for future research.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"361"},"PeriodicalIF":6.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700790","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":"Sodium tanshinone IIA sulfonate promotes proliferation and differentiation of endogenous neural stem cells to repair rat spinal cord injury via the Notch pathway.","authors":"Wenqing Zhong, Luchun Xu, Guozheng Jiang, Yushan Gao, Jiawei Song, Yukun Ma, Guanlong Wang, Jiaojiao Fan, Wenhao Li, Shibo Zhou, Yongdong Yang, Xing Yu","doi":"10.1186/s12967-025-06331-7","DOIUrl":"10.1186/s12967-025-06331-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Interventions that promote the proliferation of endogenous neural stem cells (ENSCs) and induce their differentiation into neurons after spinal cord injury (SCI) hold significant potential for SCI repair. Tanshinone IIA (TIIA) exhibits extensive neuroprotective effects, and its derivative, sodium tanshinone IIA sulfonate (STS), has enhanced water solubility, making it easier to prepare injectable formulations and increasing bioavailability. STS injections have been extensively utilized in the treatment of cardiovascular and cerebrovascular diseases, and their clinical application in SCI shows promising potential. However, it remains unclear whether STS can promote spinal cord injury repair in rats by modulating the proliferation and differentiation of ENSCs, and the underlying regulatory mechanisms are yet to be elucidated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, an incomplete spinal cord injury model was established in rats using the NYU spinal cord impactor. The regulatory effects of STS on ENSCs in rats post-SCI were observed by detecting the NSC marker Nestin, the neuronal marker NeuN, and the astrocyte marker GFAP. Additionally, rat behavioral assessments, histopathology, serum inflammation indices, and Notch signaling pathway activation were evaluated. In vitro experiments utilized an lipopolysaccharide (LPS)-induced rats spinal cord NSCs inflammation model. The effects of STS on the proliferation and viability of rats spinal cord NSCs were assessed using the CCK-8 assay and immunofluorescence cell counting. The mechanisms by which STS regulates NSC proliferation and differentiation via the Notch pathway were verified using immunofluorescence, Western blot, and RT-PCR techniques.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In vitro, STS significantly reduced the levels of inflammatory indices in the LPS-induced rats NSCs inflammation model and improved the viability of rats NSCs following inflammatory injury. STS also significantly increased the proliferation of NSCs and their differentiation into neurons while reducing their differentiation into astrocytes. Moreover, LPS significantly activated the Notch pathway, similar to the effects of the Notch pathway agonist valproic acid (VPA), whereas STS intervention could inhibit the LPS- or VPA-induced activation of the Notch pathway. In vivo, STS markedly improved the hindlimb motor function of rats with SCI, decreased the levels of pro-inflammatory factors IL-6 and TNF-α, and increased the level of the anti-inflammatory factor IL-10, thereby improving the pathological morphology of the injured spinal cord in rats post-SCI. STS effectively promoted the proliferation of ENSCs post-SCI, facilitated their differentiation into neurons, and inhibited their differentiation into astrocytes. Additionally, STS suppressed the excessive activation of the Notch signaling pathway following SCI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;STS promotes the proliferation of ENSCs post-SCI in ","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"367"},"PeriodicalIF":6.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700793","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":"Mesenchymal stem cells-derived small extracellular vesicles and apoptotic extracellular vesicles for wound healing and skin regeneration: a systematic review and meta-analysis of preclinical studies.","authors":"Yufan Zhu, Han Yang, Zhixin Xue, Haojing Tang, Xihang Chen, Yunjun Liao","doi":"10.1186/s12967-024-05744-0","DOIUrl":"10.1186/s12967-024-05744-0","url":null,"abstract":"<p><strong>Background: </strong>Studies examining the therapeutic potential of Mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) in wound healing and skin regeneration have progressed rapidly. Prior to considering clinical translation, a systematic and comprehensive understanding of these experimental details and the overall impact of MSC-EVs on skin regeneration is necessary.</p><p><strong>Methods: </strong>83 studies were identified in Web of Science, Embase, and PubMed that satisfied a set of prespecified inclusion criteria. A random effects meta-analysis was conducted for wound closure rate, scar width, blood vessel density and collagen deposition.</p><p><strong>Conclusions: </strong>Our findings demonstrate clear potential of MSC-EVs to be developed as therapy for wound healing and skin regeneration both in diabetic and non-diabetic animal models. Moreover, subgroup analyses demonstrated that apoptotic small extracellular vesicles (ApoSEVs) showed better efficacy than apoptotic bodies (ApoBDs) and small extracellular vesicles (sEVs) in wound closure outcome and collagen deposition, while sEVs displayed better than ApoEVs in revascularization. Among frequently used routes of administration, subcutaneous injection displayed a greater improvement to wound closure, collagen deposition and revascularization as compared to dressing/covering. Among easier-access source of MSCs, ADSCs demonstrated the best effect in wound closure rate and collagen deposition, as compared, BMMSCs displayed better in revascularization. Additionally, high heterogeneity observed in collection conditions, separation methods, storage methods, modifications, treatment dose, administration route, and frequency of MSC-EVs underscores the urgent need for standardization in these areas, prior to clinical translation.</p><p><strong>Protocol registration: </strong>PROSPERO CRD42024499172.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"364"},"PeriodicalIF":6.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700774","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":"DMC-BH derivative DMC-GF inhibits the growth of glioma stem cells by targeting the TRIM33/SLC25A1/mitochondrial oxidative phosphorylation pathway.","authors":"Lei Shi, Xifeng Fei, Jian Huang, Bao He, Zhixiang Sun, Guan Sun","doi":"10.1186/s12967-025-06355-z","DOIUrl":"10.1186/s12967-025-06355-z","url":null,"abstract":"<p><p>Glioma stem cells (GSCs) exhibit significant resistance to conventional radiotherapy and chemotherapy, contributing to high recurrence rates in gliomas. Addressing this critical clinical need, we developed DMC-GF, a novel GLUT1-based curcumin derivative, to enhance brain specificity and metabolic stability compared to its predecessor DMC-BH. Pharmacokinetic studies in rats demonstrated that DMC-GF achieved an 8.5-fold increase in brain-to-blood concentration ratio two hours post-intravenous administration, markedly superior to the 0.2-fold increase observed with DMC-BH. In vitro assays showed that DMC-GF exerted a more substantial inhibitory effect on GSC proliferation than DMC-BH (p < 0.01), as assessed by Cell Counting Kit-3D and EdU assays. Mechanistic analysis via the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway indicated that DMC-GF's anti-GSC activity is associated with disruption of mitochondrial oxidative phosphorylation. Treatment with DMC-GF at a concentration of 4 µM caused a notable decrease in mitochondrial membrane potential and maximal mitochondrial oxygen consumption. Additionally, exposure to 8 µM DMC-GF led to a marked (> 70%) reduction in SLC25A1, a mitochondrial citrate transporter, protein levels (p < 0.01). Overexpression of SLC25A1 attenuated both the decreased proliferation and enhanced apoptosis caused by DMC-GF (p < 0.01). Furthermore, the proteasome inhibitor MG132 (10 µM) and TRIM33, an E3 ubiquitin ligase involved in proteasome-mediated protein degradation, knockdown via shRNA both abrogated the DMC-GF-mediated decrease in SLC25A1 protein levels (p < 0.05). These findings underscore the potential of DMC-GF as an efficacious targeted therapeutic against GSCs, offering enhanced brain specificity and stability, and elucidating its mechanism involving mitochondrial dysfunction and SLC25A1 degradation.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"363"},"PeriodicalIF":6.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700724","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":"Distinct immune responses to proton and photon radiotherapy: implications for anti-PD-L1 combination therapy in colorectal cancer.","authors":"Hélène Burckel, Anaïs Nicol, Carole Mura, Marc Rousseau, Jolie Bou-Gharios, Lisa Froidurot, Corentin Richard, Véronique Morgand, Pierre-Antoine Laurent, Emeric Limagne, Romain Boidot, Georges Noël, Céline Mirjolet","doi":"10.1186/s12967-025-06377-7","DOIUrl":"10.1186/s12967-025-06377-7","url":null,"abstract":"<p><strong>Background: </strong>Ionizing radiation can influence the antitumor immune response, either activating or suppressing the immune system depending on the tumor type and radiotherapy modality. While photon radiation (RT) combined with immunotherapy (IT) is widely studied in clinical trials, proton radiation (PT) combined with IT has not been thoroughly investigated in clinical or preclinical studies despite its radiobiological advantages. This study aims to explore the immune effects of a hypofractionated PT scheme compared to RT and its efficacy with anti-PD-L1 immunotherapy.</p><p><strong>Methods: </strong>Balb/c mice bearing subcutaneous CT26 colon tumors were treated with RT or PT, delivered with 3 × 8 Gy. Seven days post-treatment, transcriptomic analysis and immune response assessments to characterize lymphoid cells, myeloid cells, and PD-L1 expression were performed. Tumor growth was monitored to evaluate the efficacy of combining RT or PT with anti-PD-L1 IT.</p><p><strong>Results: </strong>The RNA sequencing analysis demonstrated an overexpression of genes involved in the interferon type I pathway after both RT and PT. Tumor microenvironment analysis showed enhanced immune cell infiltration in tumors after both treatments. Immunoactivating cells infiltration was observed, with LT CD8 + cells infiltration after both RT and PT, more significantly after RT. NK and TAM1 cells infiltrated only after RT. Immunosuppressive cell populations were induced by PT, including MDSCs, while Tregs infiltrated both RT and PT treated tumors. PD-L1 expression was significantly induced only by RT. The combination of anti-PD-L1 with RT or PT resulted in tumor growth delay compared to RT or PT alone, with a significant survival benefit observed only after the combination of RT and IT.</p><p><strong>Conclusions: </strong>This study demonstrates that hypofractionated RT and PT induced both similar and significantly distinct immune responses. PT triggers a stronger immunosuppressive response than RT. Optimizing the combination of PT with IT, including dose, fractionation, and sequencing is crucial for improving treatment efficacy.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"360"},"PeriodicalIF":6.1,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692436","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}