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Novel universal vaccines to mitigate emerging avian influenza viruses.
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-25 DOI: 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.

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引用次数: 0
A sex-biased target against demyelination in Alzheimer's disease.
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-24 DOI: 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.

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引用次数: 0
Cystic fibrosis at a glance: from disease mechanism to therapy.
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-21 DOI: 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}
引用次数: 0
The bleeding edge: broadening horizons for hematopoietic stem cell therapies.
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-21 DOI: 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.

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引用次数: 0
Genetic causes of obesity: mapping a path forward.
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-14 DOI: 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.

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引用次数: 0
Molecular evolution of central nervous system metastasis and therapeutic implications. 中枢神经系统转移的分子演化及治疗意义。
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-01 Epub Date: 2024-10-17 DOI: 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.

中枢神经系统(CNS)转移瘤的发病率越来越高,预后越来越差,这给肿瘤学带来了巨大挑战,需要改进治疗策略。最近的研究揭示了脑转移瘤复杂的基因组结构,确定了独特的、潜在的、可操作的基因改变。这些发现为靶向治疗提供了新途径,凸显了精准医学方法在治疗中枢神经系统转移瘤方面的潜力。然而,要将这些发现转化为临床实践,需要克服各种挑战,如用于表征的组织的可用性、分子检测的可及性、通过血脑屏障(BBB)的药物递送以及解决瘤内和瘤间遗传异质性等。这篇综述探讨了中枢神经系统转移瘤演变的新见解、其发展的分子机制以及对治疗干预的影响。
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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 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-01 Epub Date: 2024-11-08 DOI: 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.

转化医学对于解决健康问题和转化研究成果以改善人口健康至关重要。这篇《科学与社会》的文章强调了转化医学在墨西哥的潜力。文章讨论了转化过程中遇到的障碍和挑战,为墨西哥未来的医疗保健事业注入了乐观主义精神。
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引用次数: 0
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 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-01 Epub Date: 2024-10-29 DOI: 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.

蛋白酶体功能不全(PFI)与神经退行性变和心力衰竭有关,在这两种疾病中,蛋白质异常聚集很常见,并且会损害泛素(Ub)-蛋白酶体系统(UPS),加剧蛋白毒性应激(IPTS)的增加,形成恶性循环。打破这种恶性循环是治疗这些疾病的关键。蛋白激酶(PK)-A 和 PKG 可以激活蛋白酶体,促进错误折叠蛋白的蛋白酶体降解。PKA 通过磷酸化 Ser14-RPN6/PSMD11 来实现这一目的,但 PKG 如何激活蛋白酶体仍是未知数。新的证据支持通过增强 cAMP/PKA 和 cGMP/PKG 来治疗 IPTS 疾病的策略。可以想象,在蛋白酶体纳米域有针对性地激活 PKA 和 PKG 将最大限度地减少它们对其他靶点的不良影响。在本综述中,我们将讨论 PKA 和 PKG 通过 UPS 对蛋白稳态的调控。
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引用次数: 0
Bridging translational gaps in Mexico's new science era.
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-01 Epub Date: 2025-01-21 DOI: 10.1016/j.molmed.2025.01.003
Eduardo Perez-Campos, Victor Del Rio, Hector A Cabrera-Fuentes
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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 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-01 Epub Date: 2024-10-21 DOI: 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。
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引用次数: 0
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