Clinical and translational discovery最新文献

{"title":"Clinical marine biomedicine: An emerging area in clinical and translational medicine","authors":"Xiaojun Yan,&nbsp;Wanxin Duan,&nbsp;Xiangdong Wang","doi":"10.1002/ctd2.70050","DOIUrl":"https://doi.org/10.1002/ctd2.70050","url":null,"abstract":"<p>Marine biomedicine is an important field in oceanology and bio-ecosystem and has evolved significantly alongside advances in biotechnology and growing understanding of marine life. In this perspective, we propose a refined concept of clinical marine biomedicine, with a clear mission to establish an emerging discipline that bridges marine biomedicine and clinical practice. The exploration of marine-origin sources should be emphasised, with a strong focus on the identification, validation and development of human disease-specific diagnostics and target-oriented pharmaceutics. The perspective headlines some of critical components, including marine-oriented human evolution and development, humanised marine-based models, biomarker innovation and validation, marine microbiomes and metabolites, and target nutrition and therapy. We envision that clinical marine biomedicine will become a crucial pillar clinical molecular medicine, contributing to the improvement of human health and the prognosis of patient.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial homeostasis orchestrates the fate of beta-cells and the outcomes of islet transplantation","authors":"Baicheng Kuang,&nbsp;Yuanyuan Zhao,&nbsp;Nianqiao Gong","doi":"10.1002/ctd2.70070","DOIUrl":"https://doi.org/10.1002/ctd2.70070","url":null,"abstract":"&lt;p&gt;In addition to producing energy, mitochondria are also key regulators of cell survival, death and immune signalling. This is particularly evident in the pancreas, where mitochondrial function governs the fate of both acinar cells and insulin-producing beta-cells, especially under inflammatory or stressed conditions. Over recent years, increasing attention has been directed towards investigating the role of mitochondrial dynamics (fusion, fission, mitophagy and biogenesis) in shaping disease outcomes for metabolic diseases, including pancreatitis, autoimmune diabetes and islet transplantation.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; In this regard, the study by Cobo-Vuilleumier et al. provided a valuable new layer of understanding by showing that the nuclear receptor liver receptor homolog-1 (LRH-1/NR5A2) reprograms both macrophages and dendritic cells towards an immune-tolerant phenotype by modulating mitochondrial functionality.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; This research identified mitochondria as a central checkpoint not only for innate immune activation but also for the preservation of beta-cells. The authors demonstrated that pharmacological activation of LRH-1 in myeloid cells triggered mitohormesis, characterised by a suppression of oxidative phosphorylation, slight enhancement of glycolytic activity, and induction of activating transcription factor 4 (ATF4)–growth differentiation factor 15 (GDF15) signalling. Consequently, pro-inflammatory macrophages and dendritic cells were converted into tolerogenic phenotypes that mitigated local immune aggression against islets in models of autoimmune diabetes. These findings suggest that reprogramming immune cell metabolism via mitochondrial remodelling could serve as a novel strategy for the restoration of islet tolerance in type 1 diabetes (T1D). Importantly, this mitochondrial-driven form of immunomodulation may synergise with other interventions that protect the islets.&lt;/p&gt;&lt;p&gt;Of particular interest is the vulnerability of pancreatic beta-cells to mitochondrial stress. These cells are metabolically demanding and rely heavily on mitochondrial ATP production to couple glucose sensing with insulin secretion. Unlike many other cell types, beta-cells exhibit relatively low levels of endogenous antioxidant enzymes, making them especially prone to oxidative damage.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; In a recently published study, Amo-Shiinoki et al. provided compelling evidence that mitochondrial dysfunction is a central driver of beta-cells dedifferentiation in Wolfram syndrome (WS), which is caused by mutations in the endoplasmic reticulum (ER)-resident protein WFS1.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; The authors demonstrated that &lt;i&gt;Wfs1&lt;/i&gt;-null beta-cells undergo dedifferentiation rather than apoptosis, marked by loss of mature beta-cells markers (e.g., MafA) and re-expression of progenitor genes (e.g., Aldh1a3, Neurog3). Notably, these changes were accompanied by significant metabolic remodelling: impaired glycolysis-TCA coupling, re","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphatidylethanolamine: A key player in lung disease","authors":"Linlin Zhang,&nbsp;Wanxin Duan,&nbsp;Liyang Li","doi":"10.1002/ctd2.70076","DOIUrl":"https://doi.org/10.1002/ctd2.70076","url":null,"abstract":"<p>Phosphatidylethanolamine (PE) is a pivotal glycerophospholipid that constitutes a significant portion of cellular membranes, playing a crucial role in maintaining membrane fluidity, supporting protein integration, and mediating signal transduction. In the lungs, PE is also a key component of pulmonary surfactant, which is essential for preserving alveolar stability and facilitating efficient gas exchange. Recent research has highlighted the association between dysregulated PE metabolism and various lung diseases, such as asthma, pulmonary fibrosis and chronic obstructive pulmonary disease. Nevertheless, the molecular mechanisms underlying these associations remain poorly understood, and the potential of PE as a therapeutic target or biomarker for lung diseases has yet to be fully explored. This review aims to provide a comprehensive overview of the biological functions and biosynthetic pathways of PE, with a particular focus on its roles in pulmonary physiology and pathology. We summarise current findings on PE alterations in different lung diseases and discuss the potential implications of targeting PE metabolism for therapeutic interventions.\u0000\u0000 </p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the potential risks of employing large language models in peer review","authors":"Lingxuan Zhu,&nbsp;Yancheng Lai,&nbsp;Jiarui Xie,&nbsp;Weiming Mou,&nbsp;Lihaoyun Huang,&nbsp;Chang Qi,&nbsp;Tao Yang,&nbsp;Aimin Jiang,&nbsp;Wenyi Gan,&nbsp;Dongqiang Zeng,&nbsp;Bufu Tang,&nbsp;Mingjia Xiao,&nbsp;Guangdi Chu,&nbsp;Zaoqu Liu,&nbsp;Quan Cheng,&nbsp;Anqi Lin,&nbsp;Peng Luo","doi":"10.1002/ctd2.70067","DOIUrl":"https://doi.org/10.1002/ctd2.70067","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to systematically investigate the potential harms of Large Language Models (LLMs) in the peer review process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>LLMs are increasingly used in academic processes, including peer review. While they can address challenges like reviewer scarcity and review efficiency, concerns about fairness, transparency and potential biases in LLM-generated reviews have not been thoroughly investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Claude 2.0 was used to generate peer review reports, rejection recommendations, citation requests and refutations for 20 original, unmodified cancer biology manuscripts obtained from <i>eLife</i>'s new publishing model. Artificial intelligence (AI) detection tools (zeroGPT and GPTzero) assessed whether the reviews were identifiable as LLM-generated.All LLM-generated outputs were evaluated for reasonableness by two expert on a five-point Likert scale.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LLM-generated reviews were somewhat consistent with human reviews but lacked depth, especially in detailed critique. The model proved highly proficient at generating convincing rejection comments and could create plausible citation requests, including requests for unrelated references. AI detectors struggled to identify LLM-generated reviews, with 82.8% of responses classified as human-written by GPTzero.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>LLMs can be readily misused to undermine the peer review process by generating biased, manipulative, and difficult-to-detect content, posing a significant threat to academic integrity. Guidelines and detection tools are needed to ensure LLMs enhance rather than harm the peer review process.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging viral hepatitis and liver cancer: Emerging concepts in pathogenesis and therapeutic innovation","authors":"Keyin Zheng,&nbsp;Aimin Jiang,&nbsp;Zhengrui Li,&nbsp;Li Chen,&nbsp;Kailai Li,&nbsp;Junyi Shen,&nbsp;Hank Z. H. Wong,&nbsp;Quan Cheng,&nbsp;Jian Zhang,&nbsp;Anqi Lin,&nbsp;Peng Luo","doi":"10.1002/ctd2.70063","DOIUrl":"https://doi.org/10.1002/ctd2.70063","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;Viral hepatitis, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, represent the predominant etiological factors for hepatocellular carcinoma (HCC) worldwide. HBV and HCV drive hepatocellular malignant transformation through complex molecular mechanisms that are both distinct and overlapping. Comprehensive elucidation of these mechanisms, particularly the role of viral-mediated remodeling of the tumor microenvironment, is crucial for developing novel preventive and diagnostic strategies as well as personalized therapeutic approaches.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aim&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This review aims to systematically elucidate the key molecular mechanisms underlying HBV- and HCV-related HCC development and progression (including virus-specific pathways and common pathways), to explore the translational potential of these mechanisms in clinical medicine, and to provide perspectives on future research frontiers.&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;This review systematically elucidates the pathogenic mechanisms of HBV- and HCV-related HCC and provides comprehensive analysis of the common molecular mechanisms underlying viral hepatitis-to-HCC transformation. For HBV-related HCC, we focus on analyzing the following oncogenic mechanisms: genomic instability caused by HBV DNA integration, oncogenic effects of HBV proteins, and the impact of virus infection-mediated tumor microenvironment remodeling on immune responses. For HCV-related HCC, we focus on exploring the following oncogenic mechanisms: oncogenic mechanisms of viral proteins, virus infection-mediated metabolic disorders, functional dysregulation of immune cells in the microenvironment, and virus-induced hepatic fibrosis. Furthermore, we thoroughly investigated the common mechanisms underlying viral hepatitis-to-HCC transformation, including the construction of pro-inflammatory factor networks in chronic inflammatory microenvironments, virus-induced epigenetic alterations, and genomic instability. Based on current research, we further discuss future research directions and perspectives in this field.&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 review systematically elucidates the pathogenic mechanisms of HBV- and HCV-related HCC and provides comprehensive analysis of the common molecular mechanisms underlying viral hepatitis-to-HCC transformation, with particular emphasis on the remodeling effects of viral infection on the HCC microenvironment, which hold significant clinical implications for developing novel preventiv","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of ageing in cancer development and therapeutic response: Translational implications for precision oncology","authors":"Laiba Husain","doi":"10.1002/ctd2.70065","DOIUrl":"https://doi.org/10.1002/ctd2.70065","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The intricate relationship between cellular ageing processes and cancer development represents one of the most significant challenges in contemporary oncology. As populations worldwide experience unprecedented demographic shifts towards advanced age, understanding the molecular mechanisms that link ageing to cancer initiation, progression, and therapeutic response has become essential for developing effective precision medicine approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main body</h3>\u0000 \u0000 <p>This review examines the fundamental molecular pathways through which ageing influences cancer biology, including telomere dysfunction, cellular senescence, DNA damage accumulation, and epigenetic alterations. These age-related changes create a permissive environment for oncogenesis while simultaneously affecting therapeutic efficacy and treatment tolerance. Key ageing-associated molecular signatures include p16^INK4a^ upregulation, shortened telomeres, increased DNA damage response activation, and altered chromatin structure. The accumulation of senescent cells with age contributes to chronic inflammation and tissue dysfunction that promotes tumour development. Additionally, age-related changes in drug metabolism, DNA repair capacity, and immune function significantly impact therapeutic outcomes. Recent advances in molecular ageing biomarkers, including transcriptomic ageing clocks and protein-based signatures, offer promising approaches for personalizing cancer treatment strategies. The integration of ageing biology into precision oncology frameworks presents opportunities for developing age-informed therapeutic protocols that optimize efficacy while minimizing toxicity. Emerging technologies, including artificial intelligence-driven molecular analysis and advanced imaging techniques, enable more precise characterization of ageing-cancer interactions at the cellular and tissue levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The molecular mechanisms underlying ageing-cancer relationships provide critical insights for advancing precision oncology approaches. Understanding these pathways enables the development of targeted interventions that account for age-related biological changes, ultimately improving therapeutic outcomes for older cancer patients. Future research must focus on translating molecular ageing discoveries into clinically actionable tools that enhance treatment personalization and optimize care delivery across the cancer continuum.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of the annexin A family in atherosclerosis","authors":"Suha Jarad,&nbsp;Da-wei Zhang","doi":"10.1002/ctd2.70064","DOIUrl":"https://doi.org/10.1002/ctd2.70064","url":null,"abstract":"<p>Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality and morbidity worldwide despite advancements in therapeutic options for the management of atherosclerosis (AS). Treatments that lower low-density lipoprotein (LDL) cholesterol levels, such as statins or proprotein convertase subtilisin/kexin type 9 inhibitors, have effectively reduced ASCVD risk. However, residual CVD risk remains high, highlighting the need for additional effective therapies. Recently, colchicine has been approved for managing AS, introducing new avenues for targeting inflammation, a key process in AS.</p><p>Various factors contribute to AS progression, such as endothelial dysfunction, leukocyte transmigration, vascular smooth muscle cell migration and phenotype-switching, increased lipid retention, production of pro-inflammatory cytokines and regulated cell death processes such as apoptosis. The annexin A (AnxA) family of proteins is well-known for their ability to bind Ca²⁺ and phospholipids, and they play diverse roles in inflammation, cell proliferation, migration, differentiation and signalling. Several AnxA proteins have been implicated in essential processes involved in AS development, including endothelial dysfunction, leukocyte transmigration and apoptosis.</p><p>In this mini-review, we highlight the roles of AnxA1, AnxA2, AnxA5, AnxA6, AnxA7 and AnxA8 in AS development and progression and their therapeutic potential in AS management.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial single-cell sequencing: A new way to understand endothelial biomedicine","authors":"Zehua Shao,&nbsp;Hao Tang,&nbsp;Wanxin Duan,&nbsp;Hongwei Guo","doi":"10.1002/ctd2.70062","DOIUrl":"https://doi.org/10.1002/ctd2.70062","url":null,"abstract":"&lt;p&gt;Vascular endothelial cells (ECs) are critical guardians of vascular homeostasis, regulating angiogenesis, inflammation, and barrier integrity. However, their phenotypic and functional heterogeneity across vascular beds has posed challenges to traditional bulk analysis methods. Single-cell RNA sequencing (scRNA-seq) has emerged as a transformative tool, offering unparalleled resolution at the individual cell level. This technology has revolutionized our ability to dissect endothelial diversity and function and unveiled novel endothelial subtypes, unexpected signaling pathways, and dynamic responses to environmental stimuli (Figure 1). scRNA-seq now stands at the forefront of endothelial biology research, providing insights into both physiological and pathological processes.&lt;/p&gt;&lt;p&gt;In vascular inflammation, scRNA-seq has transformed our ability to dissect endothelial plasticity and pathological transitions. For instance, McQueen et al. demonstrated how scRNA-seq in atherosclerotic lesions identified distinct endothelial subsets specializing in lipid handling, oxidative stress response, and leukocyte recruitment.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Bondareva and Sheikh further highlighted that scRNA-seq platforms uncover vascular zonation patterns and region-specific endothelial responses to inflammation, thereby redefining our understanding of vascular homeostasis.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; In human heart failure, Rao et al. mapped fibrotic and non-fibrotic myocardial tissues, revealing that fibrotic-region ECs could upregulate adhesion molecules and foster leukocyte infiltration.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Notably, tools for single-cell trajectory inference allowed dynamic modeling of endothelial activation, illustrating a continuum from quiescence to inflammation rather than discrete states.&lt;/p&gt;&lt;p&gt;In oncology, scRNA-seq has improved the concept of tumour-associated ECs (TECs). Shiau et al. performed single-nucleus RNA-seq on pancreatic ductal adenocarcinoma samples and identified a “reactive EndMT” program enriched in hypoxia-driven signaling and mesenchymal traits, which correlates with poor outcomes.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Yang et al. integrated scRNA-seq-derived TEC markers into a liver cancer prognostic model and then linked endothelial gene signatures to immune infiltration and therapy response.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; In gastric cancer, Chen et al. used longitudinal scRNA-seq to reveal endothelial expansion and pro-angiogenic activation following neoadjuvant chemotherapy,&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; suggesting that endothelial remodeling is highly dynamic and therapy-responsive.&lt;/p&gt;&lt;p&gt;Recent studies further highlight the critical role of vascular ECs in cancer progression. Using single-cell RNA sequencing, Zhang et al. characterized endothelial heterogeneity in colorectal cancer liver metastases and identified specific subpopulations that actively engage with immune cells.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; In gastric cancer, Yang et al. demonstrated that chemot","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current advances in the role of classical non-homologous end joining in hematologic malignancies","authors":"Pengcheng Liu,&nbsp;Zizhen Xu","doi":"10.1002/ctd2.70053","DOIUrl":"https://doi.org/10.1002/ctd2.70053","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Double-strand breaks (DSBs) are universally acknowledged as the most detrimental type of DNA damage, and their effective repair primarily depends on the non-homologous end joining (NHEJ) pathway. Such DSBs, which require NHEJ for resolution, can arise from intrinsic and extrinsic DNA-damaging factors or emerge naturally during essential biological processes like V(D)J recombination and antibody class switch recombination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main Body</h3>\u0000 \u0000 <p>Failure to properly repair DSBs may lead to genomic instability, disruption of cellular functions, and immunodeficiency, thereby promoting the development of hematologic malignancies. Conversely, overexpression of NHEJ-related genes can enhance resistance to DNA-damaging therapies in these cancers. Analyzing mutations in key classical NHEJ (cNHEJ) components and understanding their mechanisms could provide valuable biomarkers for predicting therapeutic outcomes and guiding treatment decisions. Consequently, defects in cNHEJ may offer insights into the development of novel drugs targeting DNA repair pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We focus on genetic changes and alterations in gene regulation, while also providing an overview of cNHEJ.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A snapshot of the role of estrogen-regulated divergent non-coding transcripts","authors":"Barbara Yang,&nbsp;Melina J. Sedano,&nbsp;Kimberly Diwa,&nbsp;Johnathan Dominguez,&nbsp;Gabriela Boisselier,&nbsp;Alana L. Harrison,&nbsp;Victoria A. Reid,&nbsp;Enrique I. Ramos,&nbsp;Maria V. Jimenez,&nbsp;Laura A. Sanchez-Michael,&nbsp;Shreya Kolli,&nbsp;Jai Patel,&nbsp;Debra Lee,&nbsp;Mahalakshmi Vijayaraghavan,&nbsp;Jessica Chacon,&nbsp;Subramanian Dhandayuthapani,&nbsp;Shrikanth S. Gadad","doi":"10.1002/ctd2.70055","DOIUrl":"https://doi.org/10.1002/ctd2.70055","url":null,"abstract":"<p>Recent high-throughput sequencing technologies have discovered various polymerase II transcribed transcripts. The majority of them are non-protein-coding, understudied and poorly conserved. Non-coding transcripts are categorised based on their location in the genome and the direction in which they are transcribed; these categories classify a non-coding transcript as either antisense, intergenic or divergent. The RNAs belonging to divergent classes consist of two transcripts, transcribed in sense and antisense direction, generated from the same promoter or locus. Multiple environmental and genetic cues can determine the regulation of these transcripts. One of the well-known signalling molecules, estrogen, has been shown to play a vital role in the activation and regulation of divergent transcripts by mediating effects through the estrogen receptors. Emerging studies have shown a strong causative effect between estrogen-regulated divergent transcripts and diseases such as cancer. However, few, viz., <i>lncRNA67</i>, <i>CUPID1</i> and <i>CUPID2</i>, show a causal relationship with estrogen-dependent biology. This mini-review summarises their role in estrogen-dependent processes that may drive the research to identify novel estrogen-signalling regulators.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}