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The molecular underpinnings of female predominance in lupus. 狼疮女性优势的分子基础。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-05-01 Epub Date: 2024-12-02 DOI: 10.1016/j.molmed.2024.11.002
Despoina Kosmara, Elpida Neofotistou-Themeli, Maria Semitekolou, George Bertsias
{"title":"The molecular underpinnings of female predominance in lupus.","authors":"Despoina Kosmara, Elpida Neofotistou-Themeli, Maria Semitekolou, George Bertsias","doi":"10.1016/j.molmed.2024.11.002","DOIUrl":"10.1016/j.molmed.2024.11.002","url":null,"abstract":"<p><p>Most people affected by systemic lupus erythematosus (SLE) are women. Although the role of sex hormones has been appreciated, we discuss emerging evidence that links X-linked genes escaping from dosage compensation to female predisposition to lupus. This is exemplified by TLR7 and CXorf21 whose female-biased expression may converge to enhance interferon responses and promote autoantibody-producing B cells, which are hallmarks of SLE. Notably, autosomal transcription factors with female overexpression may regulate molecular programs in the skin that are sufficient to induce lupus. These findings indicate a multifactorial basis for female vulnerability; however, several areas remain elusive, including the epigenetic landscape of X-chromosome inactivation (XCI) in SLE, the interplay with environmental factors, and the role of male-specific factors such as Y-linked genes.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"438-451"},"PeriodicalIF":12.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772685","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 dual role of the TSC complex in cancer. TSC 复合物在癌症中的双重作用。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-05-01 Epub Date: 2024-11-01 DOI: 10.1016/j.molmed.2024.10.009
Josephine Hartung, Christine Müller, Cornelis F Calkhoven
{"title":"The dual role of the TSC complex in cancer.","authors":"Josephine Hartung, Christine Müller, Cornelis F Calkhoven","doi":"10.1016/j.molmed.2024.10.009","DOIUrl":"10.1016/j.molmed.2024.10.009","url":null,"abstract":"<p><p>The tuberous sclerosis complex (TSC1/TSC2/TBC1D7) primarily functions to inhibit the mechanistic target of rapamycin complex 1 (mTORC1), a crucial regulator of cell growth. Mutations in TSC1 or TSC2 cause tuberous sclerosis complex (TSC), a rare autosomal dominant genetic disorder marked by benign tumors in multiple organs that rarely progress to malignancy. Traditionally, TSC proteins are considered tumor suppressive due to their inhibition of mTORC1 and other mechanisms. However, more recent studies have shown that TSC proteins can also promote tumorigenesis in certain cancer types. In this review, we explore the composition and function of the TSC protein complex, the roles of its individual components in cancer biology, and potential future therapeutic targeting strategies.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"452-465"},"PeriodicalIF":12.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563777","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
Functional precision medicine: the future of cancer care. 功能性精准医疗：癌症治疗的未来。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-05-01 Epub Date: 2024-11-19 DOI: 10.1016/j.molmed.2024.10.015
Arlet M Acanda de la Rocha, Noah E Berlow, Diana J Azzam
{"title":"Functional precision medicine: the future of cancer care.","authors":"Arlet M Acanda de la Rocha, Noah E Berlow, Diana J Azzam","doi":"10.1016/j.molmed.2024.10.015","DOIUrl":"10.1016/j.molmed.2024.10.015","url":null,"abstract":"<p><p>Functional precision medicine (FPM), combining ex vivo drug sensitivity testing with genomic profiling to identify treatment options for recurrent/refractory cancer, is feasible and poised to accelerate. This forum explores the history of FPM, recent clinical advancements, and barriers to expanding the clinical utility and accessibility for pediatric/adolescent and adult cancers.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"404-408"},"PeriodicalIF":12.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682588","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
Assessment of the therapeutic potential of salubrinal for ME/CFS and long-COVID. 评估柳氮磺吡啶对 ME/CFS 和长期 COVID 的治疗潜力。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-05-01 Epub Date: 2024-10-21 DOI: 10.1016/j.molmed.2024.10.001
Aseel Warrayat, Ayah Ali, Joulin Waked, Darcy Tocci, Robert C Speth
{"title":"Assessment of the therapeutic potential of salubrinal for ME/CFS and long-COVID.","authors":"Aseel Warrayat, Ayah Ali, Joulin Waked, Darcy Tocci, Robert C Speth","doi":"10.1016/j.molmed.2024.10.001","DOIUrl":"10.1016/j.molmed.2024.10.001","url":null,"abstract":"<p><p>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating condition with no cure that shares commonality with long-COVID. This review examines current understanding of long-COVID symptoms, characteristics of the affected population, the connection with ME/CFS, and the potential for salubrinal, an agent known for its influence on cellular stress pathways, to mitigate these disorders It also describes the historical development and mechanism of action of salubrinal, to mitigate endoplasmic reticulum (ER)/cellular stress responses, that could potentially contribute to symptom improvement in both ME/CFS and long-COVID patients. Further research and clinical trials are warranted to advance our understanding of the potential role of salubrinal in improving the quality of life for individuals with long-COVID-related ME/CFS symptoms as well as ME/CFS patients.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"466-478"},"PeriodicalIF":12.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508722","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
Challenges and opportunities for conceiving genetically diverse sickle cell mice. 培育基因多样化的镰状细胞小鼠的挑战和机遇。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-05-01 Epub Date: 2024-12-05 DOI: 10.1016/j.molmed.2024.11.004
Rafiou Agoro, Gary A Churchill
{"title":"Challenges and opportunities for conceiving genetically diverse sickle cell mice.","authors":"Rafiou Agoro, Gary A Churchill","doi":"10.1016/j.molmed.2024.11.004","DOIUrl":"10.1016/j.molmed.2024.11.004","url":null,"abstract":"<p><p>A milestone in sickle cell disease (SCD) therapeutics was achieved in December 2023 with the FDA-approved gene therapy for patients aged 12 years and older. However, these therapies may only suit a fraction of patients because of cost or health risks. A better understanding of SCD outcome heterogeneity is needed to propose patient-specific pharmacological interventions. To achieve this, humanized and genetically diverse mouse models are essential for associating candidate genotypes with specific hematological traits, organ function, and disease resilience. Here, we discuss the challenges and opportunities in developing genetically diverse sickle cell mice (GDS mice). These models are expected to complement current approaches in SCD research and enhance our understanding of SCD heterogeneity and anemia.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"413-423"},"PeriodicalIF":12.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792449","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
Galectin-3 in metabolic disorders: mechanisms and therapeutic potential. 半乳糖凝集素-3在代谢紊乱中的作用：机制和治疗潜力。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-05-01 Epub Date: 2024-12-16 DOI: 10.1016/j.molmed.2024.11.006
Qian Jiang, Qijin Zhao, Pingping Li
{"title":"Galectin-3 in metabolic disorders: mechanisms and therapeutic potential.","authors":"Qian Jiang, Qijin Zhao, Pingping Li","doi":"10.1016/j.molmed.2024.11.006","DOIUrl":"10.1016/j.molmed.2024.11.006","url":null,"abstract":"<p><p>Galectin-3 (Gal3), a β-galactoside-binding lectin, is expressed predominantly in immunological and inflammatory cells. Gal3 expression is elevated in metabolic diseases, including obesity, diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD), and plays an important role in the progression of these diseases. In this review, we summarize the structure and post-translational modifications of Gal3 and the cellular functions of Gal3 according to its subcellular localization. We focused on the pathological functions and molecular mechanisms of Gal3 in various cell types. In particular, extracellular Gal3 and intracellular Gal3 may have different physiological and pathological functions. We also discuss promising Gal3 inhibitors or antibodies that are currently in clinical trials and outstanding questions and challenges for future pursuit.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"424-437"},"PeriodicalIF":12.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847655","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
Adolescent polycystic ovary syndrome: an endocrine-metabolic mode in response to ectopic fat. 青春期多囊卵巢综合征：异位脂肪反应的内分泌代谢模式。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-05-01 Epub Date: 2025-04-22 DOI: 10.1016/j.molmed.2025.03.011
Cristina Garcia-Beltran, Francis de Zegher, Lourdes Ibáñez
{"title":"Adolescent polycystic ovary syndrome: an endocrine-metabolic mode in response to ectopic fat.","authors":"Cristina Garcia-Beltran, Francis de Zegher, Lourdes Ibáñez","doi":"10.1016/j.molmed.2025.03.011","DOIUrl":"10.1016/j.molmed.2025.03.011","url":null,"abstract":"","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"492-493"},"PeriodicalIF":12.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014994","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
Follow the CSF flow: probing multiciliated ependymal cells in brain pathology. 追踪 CSF 流：探测脑病理学中的多纤毛上皮细胞。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-05-01 Epub Date: 2024-11-07 DOI: 10.1016/j.molmed.2024.10.007
Adam M R Groh, Liam Hodgson, Danilo Bzdok, Jo Anne Stratton
{"title":"Follow the CSF flow: probing multiciliated ependymal cells in brain pathology.","authors":"Adam M R Groh, Liam Hodgson, Danilo Bzdok, Jo Anne Stratton","doi":"10.1016/j.molmed.2024.10.007","DOIUrl":"10.1016/j.molmed.2024.10.007","url":null,"abstract":"<p><p>Multiciliated ependymal cells regulate cerebrospinal fluid (CSF) microcirculation and form a dynamic CSF-brain interface. Emerging evidence suggests that ependymal cells enter reactive states in response to pathology that are associated with ciliary and junctional protein alterations. The drivers of these alterations, likely from both acquired and inherited mechanisms, remain elusive.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"409-412"},"PeriodicalIF":12.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628997","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
Gasdermins in pyroptosis, inflammation, and cancer. 焦亡、炎症和癌症中的气胚乳。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-04-29 DOI: 10.1016/j.molmed.2025.04.003
Rui Min, Yang Bai, Ning-Rui Wang, Xing Liu
{"title":"Gasdermins in pyroptosis, inflammation, and cancer.","authors":"Rui Min, Yang Bai, Ning-Rui Wang, Xing Liu","doi":"10.1016/j.molmed.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.04.003","url":null,"abstract":"<p><p>Pyroptosis is a type of programmed inflammatory cell death characterized by balloon-like swelling, membrane rupture, and the release of inflammatory cytokines and danger signals. Pyroptosis is directly triggered by activated gasdermins (GSDMs) which bind to membrane phospholipids, oligomerize, and form pores in cell membranes. GSDM activation is mediated by various effector proteases via cleavage of the linker region or post-translational modification to release the active N-terminal fragment in response to a variety of pathogenic or intrinsic danger signals. GSDM-mediated pyroptosis is involved in the pathogenesis of an array of infectious and inflammatory diseases and cancers. This review discusses recent advances related to the physiological and pathological functions of GSDM-mediated pyroptosis, as well as therapeutic strategies targeting pyroptosis.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033847","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
Mesothelial and immune cells interplay in the tumor microenvironment. 间皮细胞和免疫细胞在肿瘤微环境中相互作用。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2025-04-29 DOI: 10.1016/j.molmed.2025.03.014
Rong Sheng, Yujia Yin, Xipeng Wang
{"title":"Mesothelial and immune cells interplay in the tumor microenvironment.","authors":"Rong Sheng, Yujia Yin, Xipeng Wang","doi":"10.1016/j.molmed.2025.03.014","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.03.014","url":null,"abstract":"<p><p>Mesothelial cells (MCs) constitute a dynamic mesothelium in which their numerous crucial functions synergistically interact with other cells to maintain serosal integrity and homeostasis. Previous studies have confirmed the crucial role of interactions between MCs and tumor cells in tumorigenesis and progression in the tumor microenvironment (TME). However, recent research has found that MCs can induce an immunosuppressive microenvironment by secreting various cytokines, chemokines, and exosomes which recruit immunosuppressive cells or interact with immune cells, thus contributing to tumor progression. This review primarily examines the immunoregulatory role of MCs in the TME of mesothelioma and metastatic pleural and peritoneal carcinomas. It also explores the potential mechanisms by which these interactions induce immunosuppression and their impact on tumor growth and therapy.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999237","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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