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Decidual macrophages as therapeutic targets in preterm labour. 巨噬细胞作为早产的治疗靶点。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-06-16 DOI: 10.1016/j.molmed.2025.05.013
Emilie O Paterson, Daniel J Short, Victoria Male
{"title":"Decidual macrophages as therapeutic targets in preterm labour.","authors":"Emilie O Paterson, Daniel J Short, Victoria Male","doi":"10.1016/j.molmed.2025.05.013","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.05.013","url":null,"abstract":"<p><p>The initiation of labour in humans remains poorly understood, although there is mounting evidence for a role for decidual macrophages. These may trigger labour by promoting a proinflammatory state, thereby modulating progesterone signalling and weakening fetal membranes. Preclinical work targeting macrophages therapeutically shows promise in preventing preterm labour, underscoring their significance in this process.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317969","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
OTU deubiquitinases in disease: roles and targeting. OTU去泛素酶在疾病中的作用和靶向。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-06-16 DOI: 10.1016/j.molmed.2025.05.006
Yu Deng, Pengda Liu
{"title":"OTU deubiquitinases in disease: roles and targeting.","authors":"Yu Deng, Pengda Liu","doi":"10.1016/j.molmed.2025.05.006","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.05.006","url":null,"abstract":"<p><p>Dysregulation of protein homeostasis contributes to many human diseases and is an emerging therapeutic target. Proteasome-mediated degradation requires ubiquitin tagging, a process regulated by E3 ligases and reversed by deubiquitinases (DUBs). Among DUBs, the ovarian tumor protease (OTU) family exhibits poly-ubiquitin linkage-specific activity and regulates diverse cellular processes. OTU dysregulation has been linked to diseases such as cancer, highlighting their potential as drug targets. This review summarizes current knowledge of OTU functions, regulatory mechanisms, and disease associations, as well as therapeutic strategies targeting OTUs. By examining these aspects, we aim to provide insights into the pathophysiological roles of OTUs and support ongoing efforts to develop OTU-targeted therapies for human diseases.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317970","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
Fibroblasts in AKI: small army, big help. AKI的成纤维细胞：小军队，大帮助。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-06-10 DOI: 10.1016/j.molmed.2025.05.012
Saiya Zhu, Yuan Gui, Jia-Jun Liu, Silvia Liu, Dong Zhou
{"title":"Fibroblasts in AKI: small army, big help.","authors":"Saiya Zhu, Yuan Gui, Jia-Jun Liu, Silvia Liu, Dong Zhou","doi":"10.1016/j.molmed.2025.05.012","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.05.012","url":null,"abstract":"<p><p>Acute kidney injury (AKI), with high morbidity and mortality, stems from tubular injury, vascular damage, and inflammation. Although often overlooked, early fibroblast activation is critical for kidney repair, challenging traditional associations of fibroblasts with fibrosis. Here, we summarize fibroblast origins, heterogeneity, functions, and therapeutics in preventing or mitigating AKI.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276005","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
Targeting FSH for osteoporosis, obesity, and Alzheimer's disease. 针对骨质疏松，肥胖和阿尔茨海默病的FSH。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-06-05 DOI: 10.1016/j.molmed.2025.05.001
Funda Korkmaz, Judit Gimenez-Roig, Farhath Sultana, Victoria Laurencin, Fasilet Sen, Liam Cullen, Steven Sims, Anusha Pallapati, Satish Rojekar, Guzel Burganova, Georgii Pevnev, Uliana Cheliadinova, Darya Vasilyeva, Ofer Moldavski, Tal Frolinger, Anisa Gumerova, Orly Barak, Vitaly Ryu, Daria Lizneva, Keqiang Ye, Anne Schafer, Clifford J Rosen, Tony Yuen, Se-Min Kim, Mone Zaidi
{"title":"Targeting FSH for osteoporosis, obesity, and Alzheimer's disease.","authors":"Funda Korkmaz, Judit Gimenez-Roig, Farhath Sultana, Victoria Laurencin, Fasilet Sen, Liam Cullen, Steven Sims, Anusha Pallapati, Satish Rojekar, Guzel Burganova, Georgii Pevnev, Uliana Cheliadinova, Darya Vasilyeva, Ofer Moldavski, Tal Frolinger, Anisa Gumerova, Orly Barak, Vitaly Ryu, Daria Lizneva, Keqiang Ye, Anne Schafer, Clifford J Rosen, Tony Yuen, Se-Min Kim, Mone Zaidi","doi":"10.1016/j.molmed.2025.05.001","DOIUrl":"10.1016/j.molmed.2025.05.001","url":null,"abstract":"<p><p>Follicle-stimulating hormone (FSH), traditionally known for regulating gonadal development, maturation, and estrogen secretion, has now been implicated in regulating fat and bone metabolism and cognition. Preclinical evidence from genetic and pharmacological studies in rodent models, combined with human data from population-based observations, genetic studies, and a limited number of interventional trials, supports the notion of independent effects of FSH on the skeleton, fat, and brain. This evolving understanding of the nonreproductive roles of FSH presents potential therapeutic opportunities to mitigate age-related health challenges, which include osteoporosis, obesity, cardiovascular risk, and dementia. This review summarizes the current knowledge on the interplay between pituitary-derived FSH and peripheral and central tissues, as well as recent progress in therapeutic development.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249721","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
Endothelial-to-mesenchymal transition in cardiovascular diseases. 心血管疾病中的内皮细胞向间质细胞转化。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-06-03 DOI: 10.1016/j.molmed.2025.05.002
Zhentao Zhang, Zheyan Fang, Junbo Ge, Hua Li
{"title":"Endothelial-to-mesenchymal transition in cardiovascular diseases.","authors":"Zhentao Zhang, Zheyan Fang, Junbo Ge, Hua Li","doi":"10.1016/j.molmed.2025.05.002","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.05.002","url":null,"abstract":"<p><p>Endothelial-to-mesenchymal transition (EndMT) represents a dynamic process during which endothelial cells (ECs) loosen intercellular interactions, break down the basement membrane and undergo alterations in cell polarity to attain a mesenchymal phenotype. The intermediate stage of EndMT, known as partial EndMT, enables cells to exhibit partial functions and characteristics of both ECs and mesenchymal cells. This endows ECs with a unique physiological function and reflects the potential for reversing the EndMT process. In this article, we review the role of EndMT in diverse organs, the molecular network associated with EndMT, the occurrence of EndMT in cardiac physiological activities and pathophysiological damage, as well as the modulators of EndMT to offer novel perspectives for regulating EndMT-related physiological changes and disease progression.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226807","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
Unveiling the biological functions and therapeutic potentials of LONP1 in the ovary. 揭示LONP1在卵巢中的生物学功能和治疗潜力。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-06-01 Epub Date: 2024-12-07 DOI: 10.1016/j.molmed.2024.11.010
Yi Chen, Weian Mao, Yanting Shen, Honing Huang, Hsun-Ming Chang, Xi Dong, Jingjing Jiang, Liangshan Mu
{"title":"Unveiling the biological functions and therapeutic potentials of LONP1 in the ovary.","authors":"Yi Chen, Weian Mao, Yanting Shen, Honing Huang, Hsun-Ming Chang, Xi Dong, Jingjing Jiang, Liangshan Mu","doi":"10.1016/j.molmed.2024.11.010","DOIUrl":"10.1016/j.molmed.2024.11.010","url":null,"abstract":"<p><p>Recent research highlights that Lon protease 1 (LONP1) regulates steroidogenesis in the ovary and plays a role in oocyte development and quality control. Dysregulation of LONP1 has been observed in polycystic ovary syndrome and ovarian aging. This forum article explores the role of LONP1 in the ovary and its therapeutic potential.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"506-508"},"PeriodicalIF":12.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795180","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
Harnessing IL-22 for metabolic health: promise and pitfalls. 利用 IL-22 促进代谢健康：希望与陷阱。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-06-01 Epub Date: 2024-11-21 DOI: 10.1016/j.molmed.2024.10.016
Haressh Sajiir, Grant A Ramm, Graeme A Macdonald, Michael A McGuckin, Johannes B Prins, Sumaira Z Hasnain
{"title":"Harnessing IL-22 for metabolic health: promise and pitfalls.","authors":"Haressh Sajiir, Grant A Ramm, Graeme A Macdonald, Michael A McGuckin, Johannes B Prins, Sumaira Z Hasnain","doi":"10.1016/j.molmed.2024.10.016","DOIUrl":"10.1016/j.molmed.2024.10.016","url":null,"abstract":"<p><p>Primarily perceived as an anti-inflammatory and antimicrobial mediator in mucosa and skin, interleukin-22 (IL-22) has emerged as a pivotal metabolic regulator. Central to IL-22 signaling is its receptor, IL-22RA1. Through IL-22RA1, IL-22 orchestrates glucose homeostasis by modulating insulin secretion, reducing cellular stress in pancreatic islets, promoting beta-cell regeneration, and influencing hepatic glucose and lipid metabolism. These actions suggest its potential as a therapeutic for metabolic dysfunctions like diabetes, obesity, and steatohepatitis. However, clinical applications of IL-22 face challenges related to off-target effects and safety concerns. This review explores IL-22's physiological roles, regulatory mechanisms, and profound influence on metabolic tissues. It also underscores IL-22's dual role in metabolic health and disease, advocating further research to harness its therapeutic potential.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"574-584"},"PeriodicalIF":12.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693690","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
Targeting CDK2 to circumvent treatment resistance in HR+ breast cancer. 靶向CDK2以规避HR+乳腺癌的治疗耐药。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-06-01 Epub Date: 2024-12-27 DOI: 10.1016/j.molmed.2024.12.009
Leire Arrizabalaga, Esmeralda García-Torralba, Lorenzo Galluzzi, Aitziber Buqué
{"title":"Targeting CDK2 to circumvent treatment resistance in HR<sup>+</sup> breast cancer.","authors":"Leire Arrizabalaga, Esmeralda García-Torralba, Lorenzo Galluzzi, Aitziber Buqué","doi":"10.1016/j.molmed.2024.12.009","DOIUrl":"10.1016/j.molmed.2024.12.009","url":null,"abstract":"<p><p>Genetic and epigenetic defects of the p53 system have previously been associated with resistance to CDK4/6 inhibitors in women with HR<sup>+</sup> breast cancer. Recent data from Kudo et al. demonstrate that CDK2-targeting agents may offer an effective strategy to circumvent such resistance by enforcing cellular senescence downstream of RBL2 dephosphorylation.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"495-497"},"PeriodicalIF":12.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898449","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
Tertiary lymphoid structures in the central nervous system. 中枢神经系统的三级淋巴结构。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-06-01 Epub Date: 2024-11-21 DOI: 10.1016/j.molmed.2024.10.014
Chao Yang, Yu-Xiang Cai, Ze-Fen Wang, Su-Fang Tian, Zhi-Qiang Li
{"title":"Tertiary lymphoid structures in the central nervous system.","authors":"Chao Yang, Yu-Xiang Cai, Ze-Fen Wang, Su-Fang Tian, Zhi-Qiang Li","doi":"10.1016/j.molmed.2024.10.014","DOIUrl":"10.1016/j.molmed.2024.10.014","url":null,"abstract":"<p><p>Tertiary lymphoid structures (TLSs) frequently occur at sites of chronic inflammation. A more advanced stage of multiple sclerosis (MS) has been associated with certain TLSs. However, tumor-associated TLSs have been shown to correlate with a greater treatment response rate and a better prognosis in glioma mouse models. In this review, we evaluate the clinical significances of TLSs in prognosis and treatment response, as well as the status of TLS-directed therapies targeting alternative biochemical pathways in various central nervous system (CNS) disorders. Potential molecular mechanisms underlying the development of TLSs are also discussed. Exploring these areas may provide an essential understanding of the processes behind disease advancement, uncover new therapeutic objectives, and detect biomarkers that forecast disease progression and treatment efficacy.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"509-521"},"PeriodicalIF":12.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693692","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
m6A and beyond: RNA modifications shaping angiogenesis. m6A及以上：形成血管生成的RNA修饰。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-06-01 Epub Date: 2024-11-29 DOI: 10.1016/j.molmed.2024.11.001
Yu Luan, Renbing Jia, Peiwei Chai, Xianqun Fan
{"title":"m<sup>6</sup>A and beyond: RNA modifications shaping angiogenesis.","authors":"Yu Luan, Renbing Jia, Peiwei Chai, Xianqun Fan","doi":"10.1016/j.molmed.2024.11.001","DOIUrl":"10.1016/j.molmed.2024.11.001","url":null,"abstract":"<p><p>RNA modifications are crucial post-transcriptional processes that significantly influence gene expression, RNA stability, nuclear transport, and translational capacity. Angiogenesis, the formation of new blood vessels, is a physiological process that is dysregulated in many pathological conditions, including ocular diseases, immune disorders, and cancer. In this review, we compile the current understanding of the intricate relationship between various RNA modifications and angiogenic mechanisms, spotlighting emerging evidence that underscore their pivotal regulatory roles in both physiological and pathological angiogenesis. Furthermore, we delve into recent advances in innovative therapeutic approaches that target RNA modifications to modulate angiogenesis, offering insights into their potential as novel treatment modalities.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"559-573"},"PeriodicalIF":12.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751766","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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