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Promoting proteostasis by cAMP/PKA and cGMP/PKG. 通过 cAMP/PKA 和 cGMP/PKG 促进蛋白稳态。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-29 DOI: 10.1016/j.molmed.2024.10.006
Md Salim Ahammed, Xuejun Wang
{"title":"Promoting proteostasis by cAMP/PKA and cGMP/PKG.","authors":"Md Salim Ahammed, Xuejun Wang","doi":"10.1016/j.molmed.2024.10.006","DOIUrl":"10.1016/j.molmed.2024.10.006","url":null,"abstract":"<p><p>Proteasome functional insufficiency (PFI) is implicated in neurodegeneration and heart failure, where aberrant protein aggregation is common and impairs the ubiquitin (Ub)-proteasome system (UPS), exacerbating increased proteotoxic stress (IPTS) and creating a vicious circle. Breaking this circle represents a key to treating these diseases. Protein kinase (PK)-A and PKG can activate the proteasome and promote proteasomal degradation of misfolded proteins. PKA does so by phosphorylating Ser14-RPN6/PSMD11, but how PKG activates the proteasome remains unknown. Emerging evidence supports a strategy to treat diseases with IPTS by augmenting cAMP/PKA and cGMP/PKG. Conceivably, targeted activation of PKA and PKG at proteasome nanodomains would minimize the undesired effects from their actions on other targets. In this review, we discuss PKA and PKG regulation of proteostasis via the UPS.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547656","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
Science around the world. 世界各地的科学
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-29 DOI: 10.1016/j.molmed.2024.09.007
Abel Plaza-Florido, Olga Gursky, Macarena Lorena Herrera, Charalampos D Moschopoulos, Yahya Sohrabi
{"title":"Science around the world.","authors":"Abel Plaza-Florido, Olga Gursky, Macarena Lorena Herrera, Charalampos D Moschopoulos, Yahya Sohrabi","doi":"10.1016/j.molmed.2024.09.007","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.09.007","url":null,"abstract":"","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547657","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
Immune-mediated colitis after immune checkpoint inhibitor therapy. 免疫检查点抑制剂治疗后的免疫介导结肠炎。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-29 DOI: 10.1016/j.molmed.2024.09.009
Sophie Giesler, Roxane Riemer, Theresa Lowinus, Robert Zeiser
{"title":"Immune-mediated colitis after immune checkpoint inhibitor therapy.","authors":"Sophie Giesler, Roxane Riemer, Theresa Lowinus, Robert Zeiser","doi":"10.1016/j.molmed.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.09.009","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have led to improved outcome in patients with various types of cancer. Due to inhibition of physiological anti-inflammatory mechanisms, patients treated with ICIs may develop autoimmune inflammation of the colon, associated with morbidity, decreased quality of life (QoL), and mortality. In this review, we summarize clinical and pathophysiological aspects of immune-mediated colitis (ImC), highlighting novel treatment options. In the colon, ICIs trigger resident and circulating T cell activation and infiltration of myeloid cells. In addition, the gut microbiota critically contribute to intestinal immune dysregulation and loss of barrier function, thereby propagating local and systemic inflammation. Currently available therapies for ImC include corticosteroids, antitumor necrosis factor-α (TNF-α)- and anti-integrin α<sub>4</sub>β<sub>7</sub> antibodies. Given that systemic immunosuppression might impair antitumor immune responses, novel therapeutic approaches are urgently needed.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547655","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
Clonal hematopoiesis of indeterminate potential: the root cause of, and fertile ground for, hematological malignancies. 具有不确定潜能的克隆造血：血液恶性肿瘤的根源和沃土。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-25 DOI: 10.1016/j.molmed.2024.10.005
Qiqi Zhuang, Shengjie Jin, Wei Wang, Yan Wang, Hongyan Tong, Zuyun Liu, Jie Sun
{"title":"Clonal hematopoiesis of indeterminate potential: the root cause of, and fertile ground for, hematological malignancies.","authors":"Qiqi Zhuang, Shengjie Jin, Wei Wang, Yan Wang, Hongyan Tong, Zuyun Liu, Jie Sun","doi":"10.1016/j.molmed.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.10.005","url":null,"abstract":"<p><p>Clonal hematopoiesis (CH) of indeterminate potential (CHIP), characterized by propagation of blood cell clones carrying somatic mutations in specific driver genes, is increasingly recognized as a critical factor in the development of hematological malignancies. This phenomenon, which often emerges with age, underscores the complex interplay between genetic predisposition and environmental influences in cancer initiation and progression. Recent years have witnessed significant advances in our understanding of the link between CHIP and hematological diseases. In this review, we provide a comprehensive overview of the features of CHIP and explore its role in promoting tumorigenesis and influencing treatment outcomes for blood cancers. Finally, we summarize current available tools for risk stratification and discuss management strategies for patients with CHIP.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569163","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
Human organoids and organ-on-chips in coeliac disease research. 乳糜泻研究中的人体器官组织和器官芯片。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-23 DOI: 10.1016/j.molmed.2024.10.003
Hanna L Simpson, Eline Smits, Renée Moerkens, Cisca Wijmenga, Joram Mooiweer, Iris H Jonkers, Sebo Withoff
{"title":"Human organoids and organ-on-chips in coeliac disease research.","authors":"Hanna L Simpson, Eline Smits, Renée Moerkens, Cisca Wijmenga, Joram Mooiweer, Iris H Jonkers, Sebo Withoff","doi":"10.1016/j.molmed.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.10.003","url":null,"abstract":"<p><p>Coeliac disease (CeD) is an immune-mediated disorder characterised by gluten-triggered inflammation and damage in the small intestine, with lifelong gluten-free diet (GFD) as the only treatment. It is a multifactorial disease, involving genetic and environmental susceptibility factors, and its complexity and lack of comprehensive human model systems have hindered understanding of its pathogenesis and development of new treatments. Therefore, it is crucial to establish systems that recapitulate patient genetic background and the interactions between the small intestinal epithelial barrier, immune cells, and environment that contribute to CeD. In this review, we discuss disease complexity, recent advances in stem cell biology, organoids, tissue co-cultures, and organ-on-chip (OoC) systems that facilitate the development of comprehensive human model systems, and model applications in preclinical studies of potential treatments.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508725","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
cGAS-STING DNA-sensing in inflammatory bowel diseases. 炎症性肠病中的 cGAS-STING DNA 传感。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-23 DOI: 10.1016/j.molmed.2024.10.002
Georges Dimitrov, Bernhard Ryffel, Dieudonnée Togbe, Valérie Quesniaux
{"title":"cGAS-STING DNA-sensing in inflammatory bowel diseases.","authors":"Georges Dimitrov, Bernhard Ryffel, Dieudonnée Togbe, Valérie Quesniaux","doi":"10.1016/j.molmed.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.10.002","url":null,"abstract":"<p><p>Inflammatory bowel diseases (IBD) are chronic, incurable pathologies with unknown causes, affecting millions of people. Pediatric-onset IBD, starting before the age of 18 years, are increasing, with more aggressive and extensive features than adult-onset IBD. These differences remain largely unexplained. Intestinal mucosal damage, cell death, DNA release from nuclear, mitochondrial, or microbiota sources, and DNA-sensing activating the cGAS-STING pathway may contribute to disease evolution. Increased colonic cGAS and STING are increasingly reported in experimental and human IBD. However, limited knowledge of the mechanisms involved hinders the development of new therapeutic options. Here, we discuss recent advances and unresolved questions regarding DNA release, DNA sensor activation, and the role and therapeutic potential of the cGAS-STING pathway in inflammatory colitis.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508724","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 Hodgkin lymphoma research. 霍奇金淋巴瘤研究进展。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-22 DOI: 10.1016/j.molmed.2024.10.004
Ralf Küppers
{"title":"Advances in Hodgkin lymphoma research.","authors":"Ralf Küppers","doi":"10.1016/j.molmed.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.10.004","url":null,"abstract":"<p><p>Hodgkin lymphoma (HL) has been and still is the most enigmatic lymphoid malignancy in humans. Since the first molecular analysis of isolated Hodgkin and Reed-Sternberg (HRS) tumor cells of classic HL 30 years ago, substantial advances in our understanding of HL have been made. This review describes the cellular origin of HL, summarizes the current knowledge about the genetic lesions in HRS cells, and highlights the role of Epstein-Barr virus (EBV) in HL pathogenesis. Moreover, the pathobiological roles of altered gene expression and deregulated signaling pathways are discussed and key aspects of the HL microenvironment are presented.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508721","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 monoamine oxidases in cancer: advances and opportunities. 以癌症中的单胺氧化酶为靶点：进展与机遇。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-21 DOI: 10.1016/j.molmed.2024.09.010
Jing Wei, Boyang Jason Wu
{"title":"Targeting monoamine oxidases in cancer: advances and opportunities.","authors":"Jing Wei, Boyang Jason Wu","doi":"10.1016/j.molmed.2024.09.010","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.09.010","url":null,"abstract":"<p><p>Monoamine oxidases (MAOs) are a crucial pair of isoenzymes responsible for degrading monoamine neurotransmitters and dietary amines. In addition to extensive studies of their roles in the context of brain functions and disorders over decades, emerging evidence indicates that MAOs are also often dysregulated and associated with clinical outcomes in diverse cancers, with the ability to differentially regulate cancer growth, invasion, metastasis, progression, and therapy response depending on the cancer type. In this review, we summarize recent advances in understanding the clinical relevance, functional importance, and mechanisms of MAOs in a broad range of cancers, and discuss the application and therapeutic benefit of MAO inhibitors (MAOIs) for cancer treatment, highlighting the roles of MAOs as novel regulators, prognostic biomarkers, and therapeutic targets in cancer.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508726","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
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 : 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":"https://doi.org/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":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-21","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
Bone-brain crosstalk in osteoarthritis: pathophysiology and interventions. 骨关节炎中的骨脑串扰：病理生理学和干预措施。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-10-21 DOI: 10.1016/j.molmed.2024.09.006
Yilan Tang, Zhiyan Wang, Jin Cao, Yiheng Tu
{"title":"Bone-brain crosstalk in osteoarthritis: pathophysiology and interventions.","authors":"Yilan Tang, Zhiyan Wang, Jin Cao, Yiheng Tu","doi":"10.1016/j.molmed.2024.09.006","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.09.006","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a prevalent articular disorder characterized by joint degeneration and persistent pain; it imposes a significant burden on both individuals and society. While OA has traditionally been viewed as a localized peripheral disorder, recent preclinical and clinical studies have revealed the crucial interconnections between the bone and the brain, highlighting the systemic nature of OA. The neuronal pathway, molecular signaling, circadian rhythms, and genetic underpinnings within the bone-brain axis play vital roles in the complex interplay that contributes to OA initiation and progression. This review explores emerging evidence of the crosstalk between the bone and brain in OA progression, and discusses the potential contributions of the bone-brain axis to the development of effective interventions for managing OA.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508723","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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