Pub Date : 2025-03-25DOI: 10.1016/j.molmed.2025.03.001
Yu Liu, Lifang Wang, Alexander Lai, Mei Kang, Yangrui Qi, Andres Merits, Xinyi Jiao, Xinyu Wang, Xiangrong Yu, Shuo Su, Zhiwen Jiang
Frequent spillovers and recent geospatial expansion of avian influenza virus (AIV) pose significant economic and public health threats. Recent advances in vaccine technologies, bioinformatics, and artificial intelligence will provide newer approaches to target genetically diverse and rapidly evolving AIVs. Here, we review recent advances in, and perspectives on, developing universal vaccines needed for the effective control of AIVs.
{"title":"Novel universal vaccines to mitigate emerging avian influenza viruses.","authors":"Yu Liu, Lifang Wang, Alexander Lai, Mei Kang, Yangrui Qi, Andres Merits, Xinyi Jiao, Xinyu Wang, Xiangrong Yu, Shuo Su, Zhiwen Jiang","doi":"10.1016/j.molmed.2025.03.001","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.03.001","url":null,"abstract":"<p><p>Frequent spillovers and recent geospatial expansion of avian influenza virus (AIV) pose significant economic and public health threats. Recent advances in vaccine technologies, bioinformatics, and artificial intelligence will provide newer approaches to target genetically diverse and rapidly evolving AIVs. Here, we review recent advances in, and perspectives on, developing universal vaccines needed for the effective control of AIVs.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721575","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 : 2025-03-24DOI: 10.1016/j.molmed.2025.03.004
Kelsey R Babcock, Doudou Yu, Ashley E Webb
Aging and Alzheimer's disease (AD) exhibit sex differences in several biological processes, including demyelination. In a recent study, Lopez-Lee et al. uncover the contributions of sex chromosomes and gonadal hormones to sex differences in demyelination and identify Toll-like receptor 7 (TLR7) as a potential target to ameliorate tauopathy-induced demyelination in men.
{"title":"A sex-biased target against demyelination in Alzheimer's disease.","authors":"Kelsey R Babcock, Doudou Yu, Ashley E Webb","doi":"10.1016/j.molmed.2025.03.004","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.03.004","url":null,"abstract":"<p><p>Aging and Alzheimer's disease (AD) exhibit sex differences in several biological processes, including demyelination. In a recent study, Lopez-Lee et al. uncover the contributions of sex chromosomes and gonadal hormones to sex differences in demyelination and identify Toll-like receptor 7 (TLR7) as a potential target to ameliorate tauopathy-induced demyelination in men.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711381","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 : 2025-03-21DOI: 10.1016/j.molmed.2025.02.001
Kasper Gryspeert, Laudonia L Dipalo, Ana L Da Silva Cunha, Mattijs Bulcaen, Marjolein M Ensinck, Marianne S Carlon
{"title":"Cystic fibrosis at a glance: from disease mechanism to therapy.","authors":"Kasper Gryspeert, Laudonia L Dipalo, Ana L Da Silva Cunha, Mattijs Bulcaen, Marjolein M Ensinck, Marianne S Carlon","doi":"10.1016/j.molmed.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.02.001","url":null,"abstract":"","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693370","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 : 2025-03-21DOI: 10.1016/j.molmed.2025.03.003
Spencer D Shelton, Vijay G Sankaran
Recent reports of gene therapy using autologous hematopoietic stem cell transplantation (HSCT) have addressed protein deficiencies of extra-hematopoietic origin. In a recent study, Srivastava et al. report that patients with hemophilia A receiving F8 lentiviral HSCT gene therapy achieved lasting factor VIII restoration and clinical improvement, marking an advance that could enable broader applications of HSCT.
{"title":"The bleeding edge: broadening horizons for hematopoietic stem cell therapies.","authors":"Spencer D Shelton, Vijay G Sankaran","doi":"10.1016/j.molmed.2025.03.003","DOIUrl":"10.1016/j.molmed.2025.03.003","url":null,"abstract":"<p><p>Recent reports of gene therapy using autologous hematopoietic stem cell transplantation (HSCT) have addressed protein deficiencies of extra-hematopoietic origin. In a recent study, Srivastava et al. report that patients with hemophilia A receiving F8 lentiviral HSCT gene therapy achieved lasting factor VIII restoration and clinical improvement, marking an advance that could enable broader applications of HSCT.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693371","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 : 2025-03-14DOI: 10.1016/j.molmed.2025.02.002
Ruth J F Loos
Over the past 30 years, significant progress has been made in understanding the genetic causes of obesity. In the coming years, catalogs that map each genetic variant to its genomic function are expected to accelerate variant-to-function (V2F) translation. Given that obesity is a heterogeneous disease, research will have to move beyond body mass index (BMI). Gene discovery efforts for more refined adiposity traits are poised to reveal additional genetic loci, pointing to new biological mechanisms. Obesity genetics research is reaching unprecedented heights and, along with a renewed interest in the development of weight-loss medication, it holds the potential to identify new drug targets. Polygenic scores (PGSs) that predict obesity risk are expected to further improve and will be particularly valuable early in life for timely prevention.
{"title":"Genetic causes of obesity: mapping a path forward.","authors":"Ruth J F Loos","doi":"10.1016/j.molmed.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.02.002","url":null,"abstract":"<p><p>Over the past 30 years, significant progress has been made in understanding the genetic causes of obesity. In the coming years, catalogs that map each genetic variant to its genomic function are expected to accelerate variant-to-function (V2F) translation. Given that obesity is a heterogeneous disease, research will have to move beyond body mass index (BMI). Gene discovery efforts for more refined adiposity traits are poised to reveal additional genetic loci, pointing to new biological mechanisms. Obesity genetics research is reaching unprecedented heights and, along with a renewed interest in the development of weight-loss medication, it holds the potential to identify new drug targets. Polygenic scores (PGSs) that predict obesity risk are expected to further improve and will be particularly valuable early in life for timely prevention.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634703","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 : 2025-03-01Epub Date: 2024-10-17DOI: 10.1016/j.molmed.2024.09.008
David Gritsch, Priscilla K Brastianos
The increasing prevalence and poor prognosis of central nervous system (CNS) metastases pose a significant challenge in oncology, necessitating improved therapeutic strategies. Recent research has shed light on the complex genomic landscape of brain metastases, identifying unique and potentially actionable genetic alterations. These insights offer new avenues for targeted therapy, highlighting the potential of precision medicine approaches in treating CNS metastases. However, translating these discoveries into clinical practice requires overcoming challenges such as availability of tissue for characterization, access to molecular testing, drug delivery across the blood-brain barrier (BBB) and addressing intra- and intertumoral genetic heterogeneity. This review explores novel insights into the evolution of CNS metastases, the molecular mechanisms underlying their development, and implications for therapeutic interventions.
{"title":"Molecular evolution of central nervous system metastasis and therapeutic implications.","authors":"David Gritsch, Priscilla K Brastianos","doi":"10.1016/j.molmed.2024.09.008","DOIUrl":"10.1016/j.molmed.2024.09.008","url":null,"abstract":"<p><p>The increasing prevalence and poor prognosis of central nervous system (CNS) metastases pose a significant challenge in oncology, necessitating improved therapeutic strategies. Recent research has shed light on the complex genomic landscape of brain metastases, identifying unique and potentially actionable genetic alterations. These insights offer new avenues for targeted therapy, highlighting the potential of precision medicine approaches in treating CNS metastases. However, translating these discoveries into clinical practice requires overcoming challenges such as availability of tissue for characterization, access to molecular testing, drug delivery across the blood-brain barrier (BBB) and addressing intra- and intertumoral genetic heterogeneity. This review explores novel insights into the evolution of CNS metastases, the molecular mechanisms underlying their development, and implications for therapeutic interventions.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"240-251"},"PeriodicalIF":12.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475606","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}
Pub Date : 2025-03-01Epub Date: 2024-11-08DOI: 10.1016/j.molmed.2024.10.011
Carlos Federico Cota-Romero, Guillermo Aquino-Jarquin
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.
{"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":"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":"197-201"},"PeriodicalIF":12.8,"publicationDate":"2025-03-01","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}
Pub Date : 2025-03-01Epub Date: 2024-10-29DOI: 10.1016/j.molmed.2024.10.006
Md Salim Ahammed, Xuejun Wang
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.
{"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":"224-239"},"PeriodicalIF":12.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908951/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-01-21DOI: 10.1016/j.molmed.2025.01.003
Eduardo Perez-Campos, Victor Del Rio, Hector A Cabrera-Fuentes
{"title":"Bridging translational gaps in Mexico's new science era.","authors":"Eduardo Perez-Campos, Victor Del Rio, Hector A Cabrera-Fuentes","doi":"10.1016/j.molmed.2025.01.003","DOIUrl":"10.1016/j.molmed.2025.01.003","url":null,"abstract":"","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"202-203"},"PeriodicalIF":12.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024871","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 : 2025-03-01Epub Date: 2024-10-21DOI: 10.1016/j.molmed.2024.09.006
Yilan Tang, Zhiyan Wang, Jin Cao, Yiheng Tu
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.
骨关节炎(OA)是一种以关节退化和持续疼痛为特征的常见关节疾病,给个人和社会都带来了沉重的负担。虽然 OA 传统上被视为一种局部外周疾病,但最近的临床前和临床研究揭示了骨骼和大脑之间的重要联系,凸显了 OA 的系统性。骨-脑轴中的神经元通路、分子信号传导、昼夜节律和遗传基础在导致 OA 发生和发展的复杂相互作用中起着至关重要的作用。本综述探讨了骨与脑在 OA 进展过程中相互影响的新证据,并讨论了骨-脑轴对开发有效干预措施以控制 OA 的潜在贡献。
{"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":"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":"281-295"},"PeriodicalIF":12.8,"publicationDate":"2025-03-01","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}