Pub Date : 2024-06-25DOI: 10.1016/j.molmed.2024.06.003
Runzhi Chen, Xinhua Chen, Jiangtao Gao
Unveiling a metabolic mystery, this article explores how 3-O-acylated bile acids, specifically 3-O-succinylated cholic acid (3-sucCA) and 3-acetylated cholic acid (3-acetyCA), modified by gut microbes Bacteroides uniformis and Christensenella minuta, respectively, may either disrupt or harmonize our metabolic processes, offering novel therapeutic avenues for conditions such as metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes mellitus (T2D).
{"title":"3-O-acylated bile acids: disrupters or harmonizers of metabolism?","authors":"Runzhi Chen, Xinhua Chen, Jiangtao Gao","doi":"10.1016/j.molmed.2024.06.003","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.06.003","url":null,"abstract":"<p><p>Unveiling a metabolic mystery, this article explores how 3-O-acylated bile acids, specifically 3-O-succinylated cholic acid (3-sucCA) and 3-acetylated cholic acid (3-acetyCA), modified by gut microbes Bacteroides uniformis and Christensenella minuta, respectively, may either disrupt or harmonize our metabolic processes, offering novel therapeutic avenues for conditions such as metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes mellitus (T2D).</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141459475","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}
Pub Date : 2024-06-24DOI: 10.1016/j.molmed.2024.06.006
Abel Plaza-Florido, Inmaculada Pérez-Prieto, Alejandro Lucia
The molecular mechanisms behind the potential 'anti-aging' effects of exercise remain to be elucidated. Janssens et al. studied the lipidome of different mouse tissues and human skeletal muscle. They identified an evolutionary conserved 'lipid aging' signature, characterized by bis(monoacylglycero)phosphate accumulation, which, at the muscle level, can be attenuated by exercise.
{"title":"The aging lipidome: exercise is medicine.","authors":"Abel Plaza-Florido, Inmaculada Pérez-Prieto, Alejandro Lucia","doi":"10.1016/j.molmed.2024.06.006","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.06.006","url":null,"abstract":"<p><p>The molecular mechanisms behind the potential 'anti-aging' effects of exercise remain to be elucidated. Janssens et al. studied the lipidome of different mouse tissues and human skeletal muscle. They identified an evolutionary conserved 'lipid aging' signature, characterized by bis(monoacylglycero)phosphate accumulation, which, at the muscle level, can be attenuated by exercise.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451599","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}
Pub Date : 2024-06-18DOI: 10.1016/j.molmed.2024.05.017
Shamim Ahmed, Alon Herschhorn
An effective HIV-1 vaccine is still not available, and most vaccine efficacy trials conducted over the years resulted in no significant overall protection. Here we highlight several insights gained from these trials as well as emerging questions that may be important for further guidance to advance current research directions.
{"title":"Insights from HIV-1 vaccine and passive immunization efficacy trials.","authors":"Shamim Ahmed, Alon Herschhorn","doi":"10.1016/j.molmed.2024.05.017","DOIUrl":"10.1016/j.molmed.2024.05.017","url":null,"abstract":"<p><p>An effective HIV-1 vaccine is still not available, and most vaccine efficacy trials conducted over the years resulted in no significant overall protection. Here we highlight several insights gained from these trials as well as emerging questions that may be important for further guidance to advance current research directions.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421051","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}
Pub Date : 2024-06-17DOI: 10.1016/j.molmed.2024.05.012
Steven O'Reilly, Pei-Suen Tsou, John Varga
Cellular senescence is a key hallmark of aging. It has now emerged as a key mediator in normal tissue turnover and is associated with a variety of age-related diseases, including organ-specific fibrosis and systemic sclerosis (SSc). This review discusses the recent evidence of the role of senescence in tissue fibrosis, with an emphasis on SSc, a systemic autoimmune rheumatic disease. We discuss the physiological role of these cells, their role in fibrosis, and that targeting these cells specifically could be a new therapeutic avenue in fibrotic disease. We argue that targeting senescent cells, with senolytics or senomorphs, is a viable therapeutic target in fibrotic diseases which remain largely intractable.
{"title":"Senescence and tissue fibrosis: opportunities for therapeutic targeting.","authors":"Steven O'Reilly, Pei-Suen Tsou, John Varga","doi":"10.1016/j.molmed.2024.05.012","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.05.012","url":null,"abstract":"<p><p>Cellular senescence is a key hallmark of aging. It has now emerged as a key mediator in normal tissue turnover and is associated with a variety of age-related diseases, including organ-specific fibrosis and systemic sclerosis (SSc). This review discusses the recent evidence of the role of senescence in tissue fibrosis, with an emphasis on SSc, a systemic autoimmune rheumatic disease. We discuss the physiological role of these cells, their role in fibrosis, and that targeting these cells specifically could be a new therapeutic avenue in fibrotic disease. We argue that targeting senescent cells, with senolytics or senomorphs, is a viable therapeutic target in fibrotic diseases which remain largely intractable.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421053","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}
Pub Date : 2024-06-17DOI: 10.1016/j.molmed.2024.05.013
Alessandro Cherubini, Sara Della Torre, Serena Pelusi, Luca Valenti
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition. MASLD is a sexually dimorphic condition, with its development and progression influenced by sex chromosomes and hormones. Estrogens typically protect against, whereas androgens promote, MASLD. Therapeutic approaches for a sex-specific personalized medicine include estrogen replacement, androgen blockers, and novel drugs targeting hormonal pathways. However, the interactions between hormonal factors and inherited genetic variation impacts MASLD risk, necessitating more tailored therapies. Understanding sex disparities and the role of estrogens could improve MASLD interventions and management, whereas clinical trials addressing sex differences are crucial for advancing personalized treatment. This review explores the underappreciated impact of sexual dimorphism in MASLD and discusses the potential therapeutic application of sex-related hormones.
{"title":"Sexual dimorphism of metabolic dysfunction-associated steatotic liver disease.","authors":"Alessandro Cherubini, Sara Della Torre, Serena Pelusi, Luca Valenti","doi":"10.1016/j.molmed.2024.05.013","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.05.013","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition. MASLD is a sexually dimorphic condition, with its development and progression influenced by sex chromosomes and hormones. Estrogens typically protect against, whereas androgens promote, MASLD. Therapeutic approaches for a sex-specific personalized medicine include estrogen replacement, androgen blockers, and novel drugs targeting hormonal pathways. However, the interactions between hormonal factors and inherited genetic variation impacts MASLD risk, necessitating more tailored therapies. Understanding sex disparities and the role of estrogens could improve MASLD interventions and management, whereas clinical trials addressing sex differences are crucial for advancing personalized treatment. This review explores the underappreciated impact of sexual dimorphism in MASLD and discusses the potential therapeutic application of sex-related hormones.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421054","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}
Pub Date : 2024-06-15DOI: 10.1016/j.molmed.2024.05.016
Shih-Yin Tsai
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.
{"title":"Lost in translation: challenges of current pharmacotherapy for sarcopenia.","authors":"Shih-Yin Tsai","doi":"10.1016/j.molmed.2024.05.016","DOIUrl":"https://doi.org/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":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-06-15","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}
Pub Date : 2024-06-12DOI: 10.1016/s1471-4914(24)00145-x
No Abstract
无摘要
{"title":"Subscription and Copyright Information","authors":"","doi":"10.1016/s1471-4914(24)00145-x","DOIUrl":"https://doi.org/10.1016/s1471-4914(24)00145-x","url":null,"abstract":"No Abstract","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141521536","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}
Pub Date : 2024-06-12DOI: 10.1016/s1471-4914(24)00142-4
No Abstract
无摘要
{"title":"Advisory Board and Contents","authors":"","doi":"10.1016/s1471-4914(24)00142-4","DOIUrl":"https://doi.org/10.1016/s1471-4914(24)00142-4","url":null,"abstract":"No Abstract","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141529003","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}
Pub Date : 2024-06-07DOI: 10.1016/j.molmed.2024.05.005
Tiantian Wang, Jie Jiang, Xue Zhang, Xisong Ke, Yi Qu
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.
{"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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-06-07","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}
Pub Date : 2024-06-01Epub Date: 2024-05-10DOI: 10.1016/j.molmed.2024.04.007
Elizabeth M Viglianti, Andrea L Oliverio, Lisa M Meeks, Amy Bohnert, Sue Anne Bell
Sexual harassment in academia is endemic driven by gender-based inequalities and sustained through organizational tolerance, and its impact extends beyond the primary victim(s). Applying principles of emergency management provides a framework for institutions to balance their obligations to the primary victim(s) while also acknowledging the need to restore the well-being and culture of secondary victims.
{"title":"Responding to the ripple effects of sexual harassment: an emergency management framework.","authors":"Elizabeth M Viglianti, Andrea L Oliverio, Lisa M Meeks, Amy Bohnert, Sue Anne Bell","doi":"10.1016/j.molmed.2024.04.007","DOIUrl":"10.1016/j.molmed.2024.04.007","url":null,"abstract":"<p><p>Sexual harassment in academia is endemic driven by gender-based inequalities and sustained through organizational tolerance, and its impact extends beyond the primary victim(s). Applying principles of emergency management provides a framework for institutions to balance their obligations to the primary victim(s) while also acknowledging the need to restore the well-being and culture of secondary victims.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909129","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}