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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 : 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":"https://doi.org/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":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-21","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
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 : 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":"https://doi.org/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":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-21","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
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 : 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":"https://doi.org/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":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chronobiological and neuroendocrine insights into dry eye. 从时间生物学和神经内分泌学角度看干眼症。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-11-16 DOI: 10.1016/j.molmed.2024.10.012
Licheng Li, Haoyu Li, Baihua Chen
{"title":"Chronobiological and neuroendocrine insights into dry eye.","authors":"Licheng Li, Haoyu Li, Baihua Chen","doi":"10.1016/j.molmed.2024.10.012","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.10.012","url":null,"abstract":"<p><p>Dry eye, a prevalent ocular surface disease, is significantly influenced by modern lifestyle factors such as night-shift work and extended screen time. Emerging evidence suggests a strong correlation between disturbances in circadian rhythm, sleep disorders, and dry eye. However, the precise underlying mechanisms remain unclear. Recent studies have underscored the crucial role of circadian rhythms and neuroendocrine regulation in maintaining ocular surface health. Advances in treatment strategies targeting neuroendocrine pathways have shown promising developments. This review explores the interplay between circadian rhythms, neuroendocrine regulation, and the ocular surface, examines the impact of circadian disruption on the pathophysiology of dry eye, and proposes intervention strategies to alleviate dry eye associated with disturbances in circadian rhythms.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648977","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
Advancements and challenges in mouse models of Alzheimer's disease. 阿尔茨海默病小鼠模型的进展与挑战。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-11-14 DOI: 10.1016/j.molmed.2024.10.010
Zhengjiang Qian, Yanjiao Li, Keqiang Ye
{"title":"Advancements and challenges in mouse models of Alzheimer's disease.","authors":"Zhengjiang Qian, Yanjiao Li, Keqiang Ye","doi":"10.1016/j.molmed.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.10.010","url":null,"abstract":"<p><p>Alzheimer's disease (AD) poses a significant health challenge worldwide, and the development of effective treatments necessitates a comprehensive understanding of its pathophysiology. Mouse models have been instrumental in offering insights into the crucial pathogenesis of AD. However, current models rarely recapitulate all aspects of AD pathology in patients; thus, translating the findings from mouse to human clinical trials has proved to be complex. In this review, we outline the development of some prevalently used AD mice, with a particular emphasis on the latest advances in newly generated models. In addition, we discuss the advantages and limitations in mouse models of AD and their applications in blood-based biomarkers. Finally, we speculate on potential future research directions.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639993","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
Significant challenges to translating breakthrough science in Mexico. 墨西哥在转化突破性科学方面面临重大挑战。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-11-08 DOI: 10.1016/j.molmed.2024.10.011
Carlos Federico Cota-Romero, Guillermo Aquino-Jarquin
{"title":"Significant challenges to translating breakthrough science in Mexico.","authors":"Carlos Federico Cota-Romero, Guillermo Aquino-Jarquin","doi":"10.1016/j.molmed.2024.10.011","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.10.011","url":null,"abstract":"<p><p>Translational medicine is crucial for addressing health issues and translating research findings to improve population health. This Science and Society article highlights the potential of translational medicine in Mexico. It discusses the obstacles and challenges encountered in the translation process, instilling a sense of optimism for the future of healthcare in Mexico.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628998","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 : 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":"https://doi.org/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":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-07","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
Striking senescence with sodium transporter inhibition. 通过抑制钠转运体来阻止衰老
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-11-01 Epub Date: 2024-07-14 DOI: 10.1016/j.molmed.2024.07.002
Bettina Schock, Steven O'Reilly
{"title":"Striking senescence with sodium transporter inhibition.","authors":"Bettina Schock, Steven O'Reilly","doi":"10.1016/j.molmed.2024.07.002","DOIUrl":"10.1016/j.molmed.2024.07.002","url":null,"abstract":"<p><p>Senescence is associated with multiple morbidities and therapeutic targeting of these cells is a key aim. In a recent study, Katsuumi et al. found that targeting sodium-glucose co-transporter 2 (SGLT2) promoted immune clearance of senescent cells via programmed cell death-1 ligand (PD-L1) suppression, thus promoting immunosurveillance. This could have profound implications for many age-related diseases, including cancer and frailty.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"1004-1006"},"PeriodicalIF":12.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617167","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
Lost in translation: challenges of current pharmacotherapy for sarcopenia. 翻译中的迷失：当前肌肉疏松症药物疗法面临的挑战。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-11-01 Epub Date: 2024-06-15 DOI: 10.1016/j.molmed.2024.05.016
Shih-Yin Tsai
{"title":"Lost in translation: challenges of current pharmacotherapy for sarcopenia.","authors":"Shih-Yin Tsai","doi":"10.1016/j.molmed.2024.05.016","DOIUrl":"10.1016/j.molmed.2024.05.016","url":null,"abstract":"<p><p>A healthy lifespan relies on independent living, in which active skeletal muscle is a critical element. The cost of not recognizing and acting earlier on unhealthy or aging muscle could be detrimental, since muscular weakness is inversely associated with all-cause mortality. Sarcopenia is characterized by a decline in skeletal muscle mass and strength and is associated with aging. Exercise is the only effective therapy to delay sarcopenia development and improve muscle health in older adults. Although numerous interventions have been proposed to reduce sarcopenia, none has yet succeeded in clinical trials. This review evaluates the biological gap between recent clinical trials targeting sarcopenia and the preclinical studies on which they are based, and suggests an alternative approach to bridge the discrepancy.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"1047-1060"},"PeriodicalIF":12.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331846","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
Ubiquitin-like modification dependent proteasomal degradation and disease therapy. 依赖蛋白酶体降解的泛素样修饰与疾病治疗。
IF 12.8 1区 医学
Trends in molecular medicine Pub Date : 2024-11-01 Epub Date: 2024-06-08 DOI: 10.1016/j.molmed.2024.05.005
Tiantian Wang, Jie Jiang, Xue Zhang, Xisong Ke, Yi Qu
{"title":"Ubiquitin-like modification dependent proteasomal degradation and disease therapy.","authors":"Tiantian Wang, Jie Jiang, Xue Zhang, Xisong Ke, Yi Qu","doi":"10.1016/j.molmed.2024.05.005","DOIUrl":"10.1016/j.molmed.2024.05.005","url":null,"abstract":"<p><p>Although it is believed that ubiquitin (Ub) modification is required for protein degradation in the proteasome system (UPS), several proteins are subject to Ub-independent proteasome degradation, and in many cases ubiquitin-like (UBL) modifications, including neddylation, FAT10ylation, SUMOylation, ISGylation, and urmylation, are essential instead. In this Review, we focus on UBL-dependent proteasome degradation (UBLPD), on proteasome regulators especially shuttle factors and receptors, as well as potential competition and coordination with UPS. We propose that there is a distinct UBL-proteasome system (UBLPS) that might be underestimated in protein degradation. Finally, we investigate the association of UBLPD with muscle wasting and neurodegenerative diseases in which the proteasome is abnormally activated and impaired, respectively, and suggest strategies to modulate UBLPD for disease therapy.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"1061-1075"},"PeriodicalIF":12.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293763","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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