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Trends in molecular medicine最新文献

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Compartmentalized coenzyme A and ferroptosis vulnerability in PKAN and CoPAN. 分区辅酶A与PKAN和CoPAN的铁下垂易感性。
IF 18.1 1区 医学
Trends in molecular medicine Pub Date : 2026-10-19 DOI: 10.1016/j.molmed.2026.09.016
Chao-Chieh Lin, Jen-Tsan Chi
{"title":"Compartmentalized coenzyme A and ferroptosis vulnerability in PKAN and CoPAN.","authors":"Chao-Chieh Lin, Jen-Tsan Chi","doi":"10.1016/j.molmed.2026.09.016","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.09.016","url":null,"abstract":"<p><p>Ferroptotic vulnerability may arise from the failure of a local antioxidant defense even when whole-cell metabolite abundance appears preserved. Pantothenate kinase-associated neurodegeneration (PKAN) and COASY protein-associated neurodegeneration (CoPAN), two forms of neurodegeneration with brain iron accumulation caused by defects in coenzyme A (CoA) synthesis, provide a genetically defined setting for examining this possibility. We propose that impairment of the mitochondrial CoA pool can weaken a CoA-dependent redox defense without requiring a measurable whole-cell CoA deficit, while regional iron burden and oxidative demand lower the threshold for ferroptotic death. This model could reconcile apparently preserved bulk CoA with selective neuronal vulnerability. It is testable, remains to be validated directly in patient-derived models, and distinguishes mitochondrial CoA availability from total cellular CoA as the disease-relevant variable.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Degradation-coupled antibody conjugates for precision cancer therapy. 用于精确癌症治疗的降解偶联抗体偶联物。
IF 18.1 1区 医学
Trends in molecular medicine Pub Date : 2026-10-16 DOI: 10.1016/j.molmed.2026.09.014
Xinlei Zhuang, Li Lin, Yiyi Zhang, Yifan Wang, Liqiang Pan
{"title":"Degradation-coupled antibody conjugates for precision cancer therapy.","authors":"Xinlei Zhuang, Li Lin, Yiyi Zhang, Yifan Wang, Liqiang Pan","doi":"10.1016/j.molmed.2026.09.014","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.09.014","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are an important class of targeted cancer therapeutics that selectively deliver potent cytotoxic payloads to tumor cells through antibody-mediated targeting. However, the efficacy of some ADCs can be limited by inefficient target protein (e.g., membrane receptor) internalization and lysosomal trafficking, which determine intracellular payload release. In addition, persistent disease-driving proteins sustain oncogenic signaling, promoting tumor progression and therapeutic resistance. Recent advances in targeted protein degradation (TPD) offer a strategy to overcome these limitations by controlling the trafficking and degradation fate of target proteins. Building on the limitations of ADCs and the capabilities of TPD, we propose degradation-coupled antibody conjugates, a conceptual framework that integrates degradation-driven programmable protein fate control with antibody conjugates to enhance payload delivery and expand therapeutic functionality.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in modeling chromosomal aberrations to recapitulate genomic rearrangements. 染色体畸变模型再现基因组重排的研究进展。
IF 18.1 1区 医学
Trends in molecular medicine Pub Date : 2026-10-16 DOI: 10.1016/j.molmed.2026.09.010
Victoria Ginestet, Anna Schwager, Yegor Vassetzky, Anna Shmakova
{"title":"Advances in modeling chromosomal aberrations to recapitulate genomic rearrangements.","authors":"Victoria Ginestet, Anna Schwager, Yegor Vassetzky, Anna Shmakova","doi":"10.1016/j.molmed.2026.09.010","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.09.010","url":null,"abstract":"<p><p>Chromosomal aberrations, including aneuploidies and structural rearrangements, are key drivers of cancer and numerous genetic disorders. Experimental modeling of these alterations is essential for understanding their role in disease initiation and progression. Historically, chromosome engineering relied on methods that lacked precision and could generate off-target genomic damage. Recent advances in genome editing have enabled the precise generation of defined chromosomal abnormalities in human cells. This review summarizes current approaches for modeling numerical and structural chromosomal aberrations, including CRISPR-based chromosome elimination, KaryoCreate, prime editing, programmable recombinases, and RNA-guided bridge recombinases. We also discuss strategies for generating complex chromosomal rearrangements, their applications in studying genome instability, and their limitations. Together, these technologies provide powerful tools to investigate the earliest genomic events underlying cancer and genetic diseases.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Disarming CH25H to clear α-synuclein. 解除CH25H以清除α-synuclein。
IF 18.1 1区 医学
Trends in molecular medicine Pub Date : 2026-10-14 DOI: 10.1016/j.molmed.2026.09.015
Guangyu Wu, Qin Wang
{"title":"Disarming CH25H to clear α-synuclein.","authors":"Guangyu Wu, Qin Wang","doi":"10.1016/j.molmed.2026.09.015","DOIUrl":"10.1016/j.molmed.2026.09.015","url":null,"abstract":"<p><p>α-Synuclein (α-Syn) accumulation is a defining feature of Parkinson's disease (PD). Zhang et al. identify cholesterol 25-hydroxylase (CH25H) as an astrocytic inhibitor of p62-dependent α-Syn degradation. Disrupting the CH25H-p62 interaction facilitates α-Syn clearance via autophagy and improves PD-like phenotypes, suggesting a previously unrecognized nonenzymatic function for CH25H with therapeutic potential.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184578","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}
引用次数: 0
Mesenchymal stem cells in bone regeneration: an organellar perspective. 间充质干细胞在骨再生中的应用：细胞器视角。
IF 18.1 1区 医学
Trends in molecular medicine Pub Date : 2026-10-13 DOI: 10.1016/j.molmed.2026.09.008
Zong-Yu Zhang, Yue Li, Wei Wang, Bing-Dong Sui, Chen-Xi Zheng
{"title":"Mesenchymal stem cells in bone regeneration: an organellar perspective.","authors":"Zong-Yu Zhang, Yue Li, Wei Wang, Bing-Dong Sui, Chen-Xi Zheng","doi":"10.1016/j.molmed.2026.09.008","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.09.008","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) contribute substantially to bone regeneration, yet osteogenic cues alone do not fully explain how their reparative capacity is established, maintained, or lost. Prior studies show that organelles, especially mitochondria, play critical roles in MSC osteogenesis. Recent advances reveal that individual organelle states, inter-organelle coordination within MSCs, and reciprocal organelle-related intercellular communication together constitute an integrated regulatory network. In this review, we introduce 'organellar governance' as a framework for understanding MSC-mediated bone regeneration. We discuss how adaptive organelle remodeling supports osteogenesis and how organelle regulation is disrupted in disease. We further address reciprocal organelle-related intercellular communication and organelle-directed therapeutics for MSC-mediated bone regeneration. These insights provide a network-level perspective and highlight broader translational significance for regenerative medicine.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
What determines skin wound regeneration or scar healing? 决定皮肤伤口再生或疤痕愈合的因素是什么？
IF 18.1 1区 医学
Trends in molecular medicine Pub Date : 2026-10-10 DOI: 10.1016/j.molmed.2026.09.012
Zhan Su, Ruonan Lu, Xuanfen Zhang
{"title":"What determines skin wound regeneration or scar healing?","authors":"Zhan Su, Ruonan Lu, Xuanfen Zhang","doi":"10.1016/j.molmed.2026.09.012","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.09.012","url":null,"abstract":"<p><p>Skin wound regeneration, scar healing, or scar evolution is a spatiotemporally continuous process with mechanisms that remain unclear. Dynamic interactions between repair cells, including fibroblasts, and the surrounding extracellular matrix scaffold are key determinants. Skin wound models that gradually deepen from the epidermis allow the simultaneous investigation of regeneration and scar-healing processes and their regulation.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
What determines premalignant fate? A tale of stromal-epithelial crosstalk. 是什么决定了癌前病变的命运？一个关于间质-上皮相互作用的故事。
IF 18.1 1区 医学
Trends in molecular medicine Pub Date : 2026-10-10 DOI: 10.1016/j.molmed.2026.09.013
Karolina Chwialkowska
{"title":"What determines premalignant fate? A tale of stromal-epithelial crosstalk.","authors":"Karolina Chwialkowska","doi":"10.1016/j.molmed.2026.09.013","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.09.013","url":null,"abstract":"<p><p>The stroma architects early cancer by building a precancerous niche that supports the expansion of nascent tumors. Disrupting the niche limits tumor growth, and the niche alone may be sufficient to confer tumor-like behavior on otherwise normal epithelial cells. Could mapping the stromal niche transform premalignant risk management?</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Predicting outcomes in oncogenic HPV infection: are we there yet? 预测致癌HPV感染的结果：我们做到了吗？
IF 18.1 1区 医学
Trends in molecular medicine Pub Date : 2026-10-10 DOI: 10.1016/j.molmed.2026.09.009
Diane Bruyere, Romane Geuzaine, Michael Herfs
{"title":"Predicting outcomes in oncogenic HPV infection: are we there yet?","authors":"Diane Bruyere, Romane Geuzaine, Michael Herfs","doi":"10.1016/j.molmed.2026.09.009","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.09.009","url":null,"abstract":"<p><p>Although most human papillomavirus (HPV) infections are transient, a small fraction persist and eventually progress to invasive cancer. Predicting the outcome of an HPV infection remains a major unresolved challenge. Despite decades of intensive research, no single viral, host, or molecular biomarker has demonstrated sufficient accuracy to reliably identify HPV infections and associated preneoplastic lesions at increased risk of persistence or progression. We argue that this limitation reflects the dynamic and multifactorial nature of HPV-associated carcinogenesis rather than a lack of candidate biomarkers. Recent advances in high-throughput molecular analysis, artificial intelligence, and integrative risk modeling provide new opportunities to capture this complexity. Such approaches may ultimately improve clinical decision-making and reduce reliance on prolonged surveillance as a surrogate for accurate prediction.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The unfolded protein response in precision oncology: from mechanisms to therapeutic opportunities. 精确肿瘤学中的未折叠蛋白反应：从机制到治疗机会。
IF 18.1 1区 医学
Trends in molecular medicine Pub Date : 2026-10-06 DOI: 10.1016/j.molmed.2026.09.005
Quentin Bourgery, Dimitrios Doultsinos, Antoine Galmiche, Eric Chevet, Olivier Pluquet
{"title":"The unfolded protein response in precision oncology: from mechanisms to therapeutic opportunities.","authors":"Quentin Bourgery, Dimitrios Doultsinos, Antoine Galmiche, Eric Chevet, Olivier Pluquet","doi":"10.1016/j.molmed.2026.09.005","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.09.005","url":null,"abstract":"<p><p>The unfolded protein response (UPR) is a fundamental stress pathway coopted in cancer, and it is thought to drive adaptation, tumor progression, and therapeutic resistance. While the analysis of 'single-effector' biomarkers within the tumor microenvironment often fails to capture its spatial, temporal, and cellular complexity, recent advances in high-resolution spatial transcriptomics and single-cell multiomics may enable a shift from static readouts toward more comprehensive multigene UPR signatures. This could help resolve proteostatic heterogeneity at unprecedented resolution. In this review, we provide a pan-cancer perspective on using these quantitative signatures to map proteostatic states. By combining cell biology, mechanobiology, and computational pathology, our proposed translational framework blends morphological hallmarks with multiomic UPR signatures. Although still requiring prospective clinical validation, this approach could improve patient stratification and treatment decisions, advancing the field of precision oncology.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vascular-device suit concordance: a tri-ecological framework for eco-rebalancing. 血管装置套装协调：生态再平衡的三生态框架。
IF 18.1 1区 医学
Trends in molecular medicine Pub Date : 2026-10-02 DOI: 10.1016/j.molmed.2026.09.007
Lingsen You, Yaxuan Li, Yuchen Luo, Qiang Cheng, Liuliu Feng, Li Shen, Junbo Ge
{"title":"Vascular-device suit concordance: a tri-ecological framework for eco-rebalancing.","authors":"Lingsen You, Yaxuan Li, Yuchen Luo, Qiang Cheng, Liuliu Feng, Li Shen, Junbo Ge","doi":"10.1016/j.molmed.2026.09.007","DOIUrl":"https://doi.org/10.1016/j.molmed.2026.09.007","url":null,"abstract":"<p><p>Panvascular intervention can restore lumen patency, exclude structural defects, or replace diseased valves, but procedural success does not reestablish ecological stability within the treated vessel. We propose eco-rebalancing as a tri-ecological framework in which durable device performance depends on coordinated recovery across three domains: the mechanical, cellular, and physicochemical-immune ecologies. Vascular-device suitcordance denotes the spatiotemporal match between a device's mechanical behavior, biological interface, and material persistence, and the healing trajectory of a specific vascular bed, lesion, and patient; we introduce the Suitcordance Score (Su-Score) as a conceptual metric of that match. This perspective reinterprets restenosis, thrombosis, fibrosis, calcification, and structural degeneration as signatures of incomplete eco-rebalancing, providing a translational basis for device design and patient-device matching.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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