Clinical and Translational Medicine最新文献

{"title":"Long-term impact of obesity: Unraveling adipose epigenetic memory","authors":"Laura C. Hinte, Daniel Castellano-Castillo, Ferdinand von Meyenn","doi":"10.1002/ctm2.70254","DOIUrl":"https://doi.org/10.1002/ctm2.70254","url":null,"abstract":"<p>Obesity and its associated comorbidities represent a global health burden, with over 1 billion individuals currently living with obesity.<span><sup>1</sup></span> Thus, a primary objective in addressing the obesity pandemic, alongside preventative measures related to lifestyle and environmental factors, is achieving body weight reduction and long-term body weight stability. Therapeutic approaches range from dietary and lifestyle interventions to bariatric surgery and pharmacological treatments, such as incretin mimetics. However, short-term dietary and lifestyle interventions frequently do not achieve sustained weight loss and culminate in weight regain—the so-called yo‒yo effect. Even incretin mimetics (e.g., semaglutide and tirzepatide), which have demonstrated impressive efficacy in body weight reduction and improvement of metabolic health, fail to maintain weight stability following withdrawal in humans. The human body's tendency to defend increased body weight makes weight loss and maintenance challenging, potentially due to a phenomenon akin to a ‘metabolic memory’, reminiscent of the ‘legacy effect’ observed in diabetes. This metabolic memory may be mediated by a plethora of mechanisms such as structural physiological changes, alterations in synaptic plasticity,<span><sup>2</sup></span> gut microbiome,<span><sup>3</sup></span> immune system,<span><sup>4, 5</sup></span> vasculature,<span><sup>6</sup></span> genetic contributions, and notably, epigenome, all of which warrant further investigation.</p><p>Epigenetic mechanisms are essential for cellular development, differentiation and identity maintenance, and they are increasingly implicated as crucial contributors to a memory of obesity.<span><sup>7</sup></span> Yet, it remained unresolved whether individual cells retain a metabolic memory of obesity and whether epigenetic mechanisms are involved in this. To address this question, we focused on the adipose tissue. Adipose tissue, a metabolically active organ, is heavily influenced by obesity and weight loss. As adipocytes are long-lived (approximately 10 years)<span><sup>8</sup></span> and non-dividing cells, they serve as an ideal model for studying epigenetic memory. Additionally, adipose tissue is easily accessible for human biopsies, enabling longitudinal studies not feasible for most other organs.</p><p>We collected human omental and abdominal subcutaneous adipose tissue biopsies from three European study centres in Germany and Sweden. Specifically, we obtained samples from individuals living with obesity but without diabetes, both before and 2 years after bariatric surgery (RYGB or sleeve gastrectomy), as well as from healthy normal-weight donors from the same centres. Only individuals who had lost at least 25% of their body mass index within 2 years were included. Using these biopsies, we performed single nucleus RNA sequencing (snRNA-seq) to obtain transcriptional data for each cell type in the adipose tissue. A comparative analy","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70254","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLINICAL AND TRANSLATIONAL MEDICINE","authors":"","doi":"10.1002/ctm2.70268","DOIUrl":"https://doi.org/10.1002/ctm2.70268","url":null,"abstract":"","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteogenomic characterisation of primary oral cancer unveils extracellular matrix remodelling and immunosuppressive microenvironment linked to lymph node metastasis","authors":"Yu Liu,&nbsp;Zhenyu Yang,&nbsp;Jingya Jane Pu,&nbsp;Jie Zhong,&nbsp;Ui-Soon Khoo,&nbsp;Yu-Xiong Su,&nbsp;Gao Zhang","doi":"10.1002/ctm2.70261","DOIUrl":"https://doi.org/10.1002/ctm2.70261","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Oral squamous cell carcinoma (OSCC) is an increasingly prevalent malignancy worldwide. This study aims to understand molecular alterations associated with lymph node metastasis of OSCC in order to improve treatment strategies. We analysed a cohort of 46 patients with primary OSCC, including 10 with lymph node metastasis and 36 without. Using a comprehensive multi-omics approach – encompassing genomic, transcriptomic, proteomic, epigenetic, single-cell, and spatial analyses – we integrated data to delineate the molecular landscape of OSCC in the context of lymph node metastasis. Our genomic analysis identified significant mutations in key genes within the MAPK, TGF-β and WNT signalling pathways, which are essential for tumour development. The proteogenomic analysis highlighted pathways critical for lymph node dissemination and factors contributing to an immunosuppressive tumour microenvironment. Elevated levels of POSTN were found to reorganise the extracellular matrix (ECM), interact with TGF-β, disrupt cell cycle regulation and suppress the immune response by reducing VCAM1 activity. Integrated analyses of single-cell and spatial transcriptome data revealed that cancer-associated fibroblasts (CAFs) secrete TGF-β1/2, promoting cancer cell metastasis through epithelial–mesenchymal transition (EMT). Our integrated multi-omics analysis provides a detailed understanding of molecular mechanisms driving lymph node metastasis of OSCC. These insights could lead to more precise diagnostics and targeted treatments.</p>\u0000 \u0000 <p>This article is protected by copyright. All rights reserved</p>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70261","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SH3GL1-activated FTH1 inhibits ferroptosis and confers doxorubicin resistance in diffuse large B-cell lymphoma","authors":"Zi-Wen Duan,&nbsp;Wei-Ting Wang,&nbsp;Yan Wang,&nbsp;Rong Wang,&nbsp;Wei Hua,&nbsp;Chun-Yu Shang,&nbsp;Rui Gao,&nbsp;Hao-Rui Shen,&nbsp;Yue Li,&nbsp;Jia-Zhu Wu,&nbsp;Hua Yin,&nbsp;Li Wang,&nbsp;Jian-Yong Li,&nbsp;Wei Xu,&nbsp;Jin-Hua Liang","doi":"10.1002/ctm2.70246","DOIUrl":"https://doi.org/10.1002/ctm2.70246","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diffuse large B-cell lymphoma (DLBCL) is predominant subtype of non-Hodgkin lymphoma and can be effectively treated. Nevertheless, a subset of patients experiences refractory or relapsed disease, highlighting the need for new therapeutic strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Depmap database based on CRISPR/Cas9 knock out analysis was employed to identify the essential gene SH3GL1, which encodes endophilin A2, as crucial for the proliferation and survival of DLBCL cells. Immunohistochemistry (IHC) staining was performed on the 126 paraffin-embedded clinical DLBCL samples to investigate the association between SH3GL1 expression levels and the prognosis. To investigate the specific mechanism modulated by SH3GL1 in the progression of DLBCL, an integrative approach was employed. This approach combined high-throughput sequencing technologies, such as Deep-DIA and LC-MS, with functional validation techniques, including CRISPR/Cas9 gene editing, xenograft models, and molecular pathway analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study found that high expression levels of SH3GL1 correlate with poor prognosis in a cohort of 126 newly diagnosed DLBCL patients, underscoring its significance in disease progression. Mechanistically, we found that SH3GL1 deficiency triggers ferritin heavy chain 1 (FTH1)-mediated ferroptosis, specifically ferritinophagy-induced ferroptosis, in DLBCL cells. Additionally, high expression of SH3GL1 suppresses doxorubicin-induced ferroptosis. Cancer cells' resistance to conventional therapies is associated with increased sensitivity to ferroptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings emphasise SH3GL1 as a promising prognostic biomarker and a potential therapeutic target in DLBCL, offering new avenues for treatment strategies aimed at overcoming drug resistance and improving patients' outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Elevated SH3GL1 expression in DLBCL patients was associated with a negative prognosis.</li>\u0000 \u0000 <li>SH3GL1 plays a crucial role in promoting DLBCL cell survival through the regulation of FTH1-mediated ferroptosis and doxorubicin resistance.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical TYK2 inhibitor ameliorates psoriasis-like dermatitis via the AKT-SP1-NGFR-AP1 pathway in keratinocytes","authors":"Zhiqin Fang,&nbsp;Rundong Jiang,&nbsp;Yutong Wang,&nbsp;Wangqing Chen,&nbsp;Xiang Chen,&nbsp;Mingzhu Yin","doi":"10.1002/ctm2.70256","DOIUrl":"https://doi.org/10.1002/ctm2.70256","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Introduction&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Tyrosine kinase 2 (TYK2)-dependent cytokine signalling is integral to the pathogenesis of psoriasis. While BMS-986165, a highly selective TYK2 inhibitor, has recently been approved for oral treatment of psoriasis, its therapeutic potential via topical application remains unexplored.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objectives&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We aim to investigate the efficacy of topically applying TYK2 inhibitor in psoriasis and to elucidate the underlying mechanisms driving the therapeutic effects of this delivery approach.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;1.5% BMS-986165 ointment was applied topically to the back skin of imiquimod (IMQ)-induced psoriatic mice. To identify potential target cells influenced by the topical TYK2 inhibitor, we performed single cell RNA sequencing (scRNA-seq) and flow cytometry on mouse lesions. The role of TYK2 in vitro was assessed by silencing its expression or administering BMS-986165 in human keratinocytes (KCs). Mechanistic insights into TYK2 function in KCs were further investigated using RNA-seq, dual luciferase reporter assay and ChIP-qPCR.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;External use of 1.5% BMS-986165 ointment significantly ameliorated the IMQ-induced psoriasis-like dermatitis. Importantly, topical TYK2 inhibitor attenuated proinflammatory capability of KCs. In vitro, TYK2 inhibition suppressed the transcription of nerve growth factor receptor (NGFR) by disrupting the AKT-SP1 signalling pathway. This impairment hindered the activation of activator protein 1 (AP1), thereby weakening the proinflammatory potential of KCs.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study reveals a novel therapeutic potential for selective TYK2 inhibitor in topical manner on psoriasis therapy, which might prompt the development of topical treatment for psoriasis. Crucially, our findings provide an underexplored regulatory mechanism of TYK2 inhibitor in psoriasis.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;Topical TYK2 inhibitor alleviates psoriasis-like dermatitis.&lt;/p&gt;\u0000 &lt;/li&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;Topical TYK2 inhibitor reduces psoriasis progression through restraining the inflammat","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the epigenetic role of long non-coding RNAs in mood disorders: Focus on human brain studies","authors":"Bhaskar Roy,&nbsp;Anuj K. Verma,&nbsp;Yu Funahashi,&nbsp;Yogesh Dwivedi","doi":"10.1002/ctm2.70135","DOIUrl":"https://doi.org/10.1002/ctm2.70135","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Epigenetics plays a central role in neuropsychiatric disorders, contributing significantly to their complexity and manifestation. Major depressive disorder (MDD) and bipolar disorder (BD) have profound impact on mood, affect and cognition. Emerging evidence suggests that epigenetic modification of genes plays a pivotal role in the pathogenesis of both MDD and BD. Long non-coding RNAs (lncRNA) constitute a heterogeneous class of transcripts and have emerged as crucial regulators of epigenetic processes, offering promising insights into the pathophysiology of various diseases. Despite their limited coding potential, lncRNAs are known to play a critical role in achieving global transcriptomic regulation in a spatiotemporal fashion, especially in complex tissue like the brain. This review aims to discuss the specific dysregulation of lncRNAs so far observed in the brains of MDD and BD patients and understand their mechanistic contributions to the disease pathogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Brain-centric lncRNAs regulate gene networks, and their disruption is linked to MDD.</li>\u0000 \u0000 <li>In MDD, altered lncRNAs disrupt gene regulation by changing chromatin looping or modifying chromatin accessibility.</li>\u0000 \u0000 <li>These changes lead to neuronal dysfunction, affecting neural circuitry and synaptic plasticity.</li>\u0000 \u0000 <li>The result is impaired brain function, contributing to the symptoms of MDD.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection, molecular function and mechanisms of m5C in cancer","authors":"Linhui Zhang,&nbsp;Yuelong Li,&nbsp;Liqing Li,&nbsp;Fei Yao,&nbsp;Maoping Cai,&nbsp;Dingwei Ye,&nbsp;Yuanyuan Qu","doi":"10.1002/ctm2.70239","DOIUrl":"https://doi.org/10.1002/ctm2.70239","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Interest in RNA posttranscriptional modifications, particularly 5-methylcytosine (m5C), has surged in recent years. Studies have shown that m5C plays a key role in cellular processes and is closely linked to tumourigenesis. This growing focus emphasises the importance of understanding the diverse impacts of m5C modifications in both normal cellular functions and cancer development. Moreover, strides in methodologies for discerning m5C have facilitated intricate transcriptome cartography of RNA methylation at the solitary nucleotide echelon. This technical progress has fueled a surge in m5C-centric investigations, facilitating further exploration of this RNA modification. This review provides a comprehensive analysis of the oncogenic potential of m5C RNA modification, elucidating the precise molecular mechanisms driving its role in cancer development. It consolidates current knowledge regarding the biological consequences of m5C RNA modification in tumour cells. Understanding the role of methylation-related processes in tumourigenesis shows promise for advancing cancer diagnosis and therapeutic strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>\u0000 <p>m5C modifications are dynamically regulated by writers, readers, and erasers, influencing cancer progression, metastasis, and immune evasion.</p>\u0000 </li>\u0000 \u0000 <li>\u0000 <p>Distinct m5C regulatory networks exist across cancers, modulating oncogenic pathways and therapy responses.</p>\u0000 </li>\u0000 \u0000 <li>\u0000 <p>m5C signatures serve as biomarkers for cancer prognosis and treatment stratification, highlighting their role in precision oncology.</p>\u0000 </li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced human adipose-derived stem cells with VEGFA and bFGF mRNA promote stable vascular regeneration and improve cardiac function following myocardial infarction","authors":"Kaixiang Li,&nbsp;Runjiao Luo,&nbsp;Xindi Yu,&nbsp;Wei Dong,&nbsp;Guoliang Hao,&nbsp;Dan Hu,&nbsp;Ziyou Yu,&nbsp;Minglu Liu,&nbsp;Tingting Lu,&nbsp;Xiangying Wang,&nbsp;Xin Tang,&nbsp;Xinjun Lin,&nbsp;Huijing Wang,&nbsp;Wei Wang,&nbsp;Wei Fu","doi":"10.1002/ctm2.70250","DOIUrl":"https://doi.org/10.1002/ctm2.70250","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Mesenchymal stem cell therapy involves the secretion of various factors to regulate the local microenvironment in various of diseases. This therapy offers hope for treating acute myocardial infarction (MI), which poses a serious threat to human health. However, challenges such as low paracrine efficiency and poor cell survival persist due to the harsh post-infarction conditions, such as hypoxia. Recently, enhanced cell therapy, in which vascular endothelial growth factor A (VEGFA) and basic fibroblast growth factor (bFGF) are used as therapeutic agents to limit myocardial injury and simultaneously induce neovascularisation, has been recognised as a promising new strategy to improve the efficacy of cell therapy. Chemically synthetic modified messenger RNA (modRNA), a novel protein expression technology, enables safe, rapid, efficient and pulsatile expression of target proteins in vivo and in vitro settings. It has been widely applied in the fields of vaccine research and tissue regeneration. In this study, human adipose-derived stem cells (hADSCs) were transfected with VEGFA and bFGF modRNA to transiently overexpress these proteins before transplantation. This modification enhanced the paracrine effect of transplanted hADSCs and promoted stability in the vascular network at the transplantation site. Overexpression of VEGFA and bFGF in hADSCs not only inhibited apoptosis but also reduced ventricular remodelling and improved cardiac function and left ventricular conduction. Overall, the additive effects of VEGFA modRNA, bFGF modRNA and hADSCs hold promise for comprehensive cardiac repair post-MI and show substantial potential for treating ischemic heart diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>ModRNAs-transfected hADSCs exhibit pulsed and transient expression, enabling efficient production of functional VEGFA and bFGF proteins.</li>\u0000 \u0000 <li>Intracardiac injection of these engineered hADSCs leads to the enhancement of cardiac function and the improvement of electrical conduction.</li>\u0000 \u0000 <li>The hADSCs^dual mainly exerts its effect on myocardial infarction by promoting stable vascular regeneration and suppressing cell apoptosis.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Irisin-mediated muscle-renal crosstalk as a protective mechanism against contrast-induced acute kidney injury via cGAS-STING signalling inhibition","authors":"Long Peng,&nbsp;Suhua Li,&nbsp;Qiang Huang,&nbsp;Yuxiang Sun,&nbsp;Juan Sun,&nbsp;Ting Luo,&nbsp;Yanlin Wang,&nbsp;Zhaoyong Hu,&nbsp;Weiyan Lai,&nbsp;Hui Peng","doi":"10.1002/ctm2.70235","DOIUrl":"https://doi.org/10.1002/ctm2.70235","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Contrast-induced acute kidney injury (CI-AKI) continues to pose a pressing clinical challenge during invasive cardiovascular procedures due to the limited availability of preventative strategies. We aimed to demonstrate that irisin, a myokine induced by exercise, protects against CI-AKI by inhibiting the cGAS-STING inflammatory pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>We explored the relationship between serum irisin levels and CI-AKI incidence in patients administered the contrast media iohexol. Notably, lower serum irisin levels were strongly associated with an increased incidence of CI-AKI following contrast media administration. To establish a causal link between serum irisin levels and CI-AKI, we utilised a mouse model that simulates exercise by overexpressing muscle-specific PGC-1α. This approach showed a significant reduction in tubular injury and mitochondrial dysfunction induced by iohexol via cGAS/STING suppression, thereby diminishing inflammation. Mechanistically, irisin was found to inhibit the activation of cGAS/STING, preventing double stranded DNA (dsDNA) leakage and reducing inflammation in tubular epithelial cells (TECs). Pharmacological inhibition of STING further corroborated these observations. Moreover, we identified integrin complex αV/β5 as the irisin receptor on TECs, which is essential for irisin-mediated suppression of cGAS-STING signalling and resolution of inflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data position irisin as a crucial factor in muscle‒kidney crosstalk, inhibiting cGAS-STING signalling and preventing dsDNA leakage via integrin αV/β5 in TECs, thus mitigating tubular injury and inflammation. These data underscore the potential of irisin as both a predictive biomarker for CI-AKI and a promising candidate for preventative strategies against CI-AKI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Irisin mediated muscle-kidney crosstalk mitigated tubular injury and inflammation.</li>\u0000 \u0000 <li>Irisin inhibited the cGAS-STING signalling activation via integrin αV/β5 in tubular epithelial cells.</li>\u0000 \u0000 <li>Irisin was a predictive biomarker and a promising candidate for CI-AKI.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive circulating biomarkers of the response to anti-PD-1 immunotherapy in advanced HER2 negative breast cancer","authors":"Yuhan Wei,&nbsp;Hewei Ge,&nbsp;Yalong Qi,&nbsp;Cheng Zeng,&nbsp;Xiaoying Sun,&nbsp;Hongnan Mo,&nbsp;Fei Ma","doi":"10.1002/ctm2.70255","DOIUrl":"https://doi.org/10.1002/ctm2.70255","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Immunotherapy shows promise for treating advanced breast cancer, but only a few patients could respond. Predictive biomarkers from peripheral blood are urgently needed.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We designed a comprehensive 42-marker mass cytometry panel to profile the peripheral blood samples from 57 patients diagnosed with advanced HER2-negative breast cancer receiving anti-PD-1 combination therapy. Patients were categorized as responders and non-responders according to 6-month progression-free survival (PFS), followed by phenotypic and functional comparations to identify candidate predictive biomarkers. Longitudinal analysis of paired samples further revealed dynamic changes in these specific subpopulations.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Non-responders exhibited significantly higher frequencies of CD39+ Tregs (adjusted &lt;i&gt;p&lt;/i&gt; = .031) in the T-cell milieu at baseline, which exhibited a positive correlation with PD-1+ T cells in the NR group. Longitudinal assessment indicated a significant decrease of PD-1+ T cells and an increase of CD39+ Tregs following anti-PD-1 treatment, suggesting their potential role in immunotherapy resistance. In the myeloid compartment, responders showed significantly higher CCR2+ monocyte-derived dendritic cell frequencies than non-responders (adjusted &lt;i&gt;p&lt;/i&gt; = .037). These cells were positively correlated with other dendritic cells in responders but negatively with naïve T cells in non-responders. Based on these two efficacy-related biomarkers, we developed an immunotherapy prognostic prediction model and confirmed its superiority in distinguishing patient PFS (&lt;i&gt;p&lt;/i&gt; &lt; .001).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Peripheral CD39+ Tregs and monocyte-derived dendritic cells are correlated with immunotherapy response, serving as potential biomarkers to guide therapeutic choices in immunotherapy.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;CD39+ Tregs in peripheral blood are associated with poor response to anti-PD-1 immunotherapy in advanced breast cancer.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Higher frequencies of CCR2+ monocyte-derived dendritic cells correlate with better immunotherapy outcomes.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;A predictive model based on CD39+ Tregs and monocyte-derived dendritic cells effectively ","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 3","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}