{"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}
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":"https://doi.org/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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"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}
{"title":"IL-6: a pivotal molecule for tumor-brain dysfunction interaction.","authors":"Yuan-Yuan Wang, Yong-Fei Wang, Wei-Lin Jin","doi":"10.1016/j.molmed.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.05.004","url":null,"abstract":"<p><p>Neuropsychiatric complications of cancer cachexia include apathy. Zhu et al. identified a brain circuit sensitive to tumor-driven interleukin-6 (IL-6) signaling that directly reduces motivation by suppressing dopaminergic activity. Targeted circuit-based and pharmacologic interventions, including systemic anti-IL-6 antibodies, reversed motivational deficits and point to new therapeutic avenues for apathy.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217019","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}
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}
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}
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}
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}
{"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}
{"title":"Bursts of brain erosion: seizures and age-dependent neurological vulnerability.","authors":"Noemie Cresto, Laurent Givalois, Jerome Badaut, Alicia Janvier, Athenais Genin, Etienne Audinat, Amy L Brewster, Nicola Marchi","doi":"10.1016/j.molmed.2024.11.003","DOIUrl":"10.1016/j.molmed.2024.11.003","url":null,"abstract":"<p><p>Hypersynchronous and exaggerated neuronal firing, exemplified by epileptiform activity and seizures, are disruptors of brain function across acute and chronic neuropathological conditions. Here, we focus on how seizure activity, whether as a primary symptom or a secondary comorbid event within a complex pathological setting, adversely impacts neurological trajectories. We discuss experimental and clinical evidence illustrating the participation of neurodegenerative and senescence-like adaptations. Paroxysmal neuronal events, through bidirectional causality, are linked with immune and microvascular changes, disrupting cellular homeostasis and creating a feed-forward loop that intertwines with age-related frailty to deteriorate mental health. We emphasize the clinical significance of early detection of these brain vulnerabilities through biomarkers, monitoring neurodevelopmental risks in children, and tracking neurodegenerative disease progression in aging populations.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"535-547"},"PeriodicalIF":12.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814299","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}