Molecular Aspects of Medicine最新文献

{"title":"Nobel 2026: Optogenetics - how we can control the nerve cells of others!","authors":"Mihnea P Dragomir, George A Calin","doi":"10.1016/j.mam.2026.101523","DOIUrl":"https://doi.org/10.1016/j.mam.2026.101523","url":null,"abstract":"","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":" ","pages":"101523"},"PeriodicalIF":13.8,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149301907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Withdrawal notice to \"Gene-environment interactions that influence CVD, lipid traits, obesity, diabetes, and hypertension appear to be able to influence gene therapy\" [Mol. Aspect. Med. 94, (2023), 101213].","authors":"Moataz Dowaidar","doi":"10.1016/j.mam.2026.101520","DOIUrl":"10.1016/j.mam.2026.101520","url":null,"abstract":"","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":" ","pages":"101520"},"PeriodicalIF":13.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149117442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence and the future of molecular aspects of medicine.","authors":"George A Calin, Valerie Teng-Broug","doi":"10.1016/j.mam.2026.101515","DOIUrl":"https://doi.org/10.1016/j.mam.2026.101515","url":null,"abstract":"","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":" ","pages":"101515"},"PeriodicalIF":13.8,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein kinase D: Integrating cancer and metabolic disorders","authors":"A. Shemy ,&nbsp;B. Sanchez ,&nbsp;H. Mizuno ,&nbsp;J. Van Lint ,&nbsp;A. Voet","doi":"10.1016/j.mam.2026.101446","DOIUrl":"10.1016/j.mam.2026.101446","url":null,"abstract":"<div><div>Obesity and type II diabetes mellitus (T2DM) are intricately linked to elevated cancer risk. Protein Kinase D (PKD) isoforms (PKD1, PKD2, and PKD3) have emerged as pivotal mediators at the centre of metabolic and oncogenic signalling. This review discusses isoform-specific roles of PKDs in the pathophysiology of both metabolic disorders and tumour progression. PKD1 exhibits a context-dependent dual role in cancer, acting as a tumour suppressor by reinforcing epithelial adhesion and restricting invasion in several carcinomas, yet exerting pro-tumorigenic effects in specific tissues such as the pancreas and skin. Metabolically, PKD1 supports insulin secretion in pancreatic β cells while promoting adipocyte lipogenesis and suppressing thermogenesis, mechanisms that contribute to systemic insulin resistance and may prime the tumour microenvironment. PKD2 promotes tumour progression through sustained hypoxia signalling, matrix remodelling, and immune evasion, driven by its regulation of HIF-1α, Snail, β-catenin, and PD-L1. PKD3 facilitates oncogenic proliferation and metabolic rewiring, particularly enhancing glycolysis via the p65/PFKFB3 axis and modulating insulin/glucagon signalling in hepatocytes. Obesity- or diabetes-related factors, such as diacylglycerol, leptin, and pro-inflammatory cytokines, enhance PKD signalling across tissues, reinforcing its role in connecting metabolic disorders to cancer. These findings highlight PKD isoforms as potential therapeutic targets, particularly in cancer settings where metabolic dysfunction plays a contributing role. While current PKD inhibitors lack isoform specificity, future therapeutic strategies focused on PKD2 and PKD3 modulation may offer selective control over invasion, immune evasion, and metabolic reprogramming in metabolically comorbid cancer patients.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"108 ","pages":"Article 101446"},"PeriodicalIF":10.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational readthrough using TRIDs - Achievements and challenges for the treatment of inherited retinal disorders","authors":"Kerstin Nagel-Wolfrum ,&nbsp;Nicole Wenck ,&nbsp;Mark Zorin","doi":"10.1016/j.mam.2026.101455","DOIUrl":"10.1016/j.mam.2026.101455","url":null,"abstract":"<div><div>Pathogenic nonsense variants introduce premature termination codons (PTCs) into gene coding sequences, resulting in truncated, typically nonfunctional proteins. Translational readthrough has emerged as a promising therapeutic strategy for genetic diseases caused by nonsense variants. Small molecules, known as translational readthrough-inducing drugs (TRIDs), act as therapeutic agents, by allowing the translation machinery to suppress nonsense variants. TRIDs induce ribosomes to bypass aberrant stop codons favoring the incorporation of near-cognate amino acids at PTC sites. This restores the synthesis of full-length, potentially functional proteins. As TRIDs function on the mRNA level, they enable the expression of various heterogeneous isoforms of the target gene, and moreover the size of the gene is not relevant. This paves the way for the treatment of patients carrying PTCs in genes with many splice variants and in large genes. Although the efficacy of TRIDs varies across genes and PTCs, one TRID could potentially be applied for different disease-causing genes, making the strategy particularly attractive from an economic perspective for rare and ultra-rare disorders. Here we describe basic aspects of translational readthrough, TRIDs currently under investigation for the treatment of Inherited Retinal Disorders and discuss the current needs to improve translational readthrough therapy. Finally, we describe a “pipeline” to identify the best TRIDs for a specific gene/PTC, which could provide a customized readthrough approach for each patient with a PTC-caused disease.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"108 ","pages":"Article 101455"},"PeriodicalIF":10.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding emerging viral sepsis: Molecular crosstalk, dysregulation, and precision strategies","authors":"Bin Wang ,&nbsp;Yujian Fu ,&nbsp;Fang Duan ,&nbsp;Sijun Pan ,&nbsp;Yang Zheng","doi":"10.1016/j.mam.2025.101442","DOIUrl":"10.1016/j.mam.2025.101442","url":null,"abstract":"<div><div>Emerging and re-emerging viral pathogens pose a major challenge to global public health systems. One of the most significant complications associated with these viruses is viral sepsis, a severe condition characterized by organ dysfunction resulting from an unregulated host response to a viral infection. The present review comprehensively describes the molecular mechanisms underlying viral sepsis induced by emerging and re-emerging viral pathogens, such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), influenza virus, dengue virus (DENV), Ebola virus (EBOV), and human immunodeficiency virus (HIV). It discusses the complex molecular interactions between particular viral factors and host cellular pathways, highlighting significant dysregulations in various immune responses, metabolic reprogramming, and endothelial integrity that induce sepsis development. Furthermore, this review thoroughly addresses nascent precision strategies, including advanced diagnostics, targeted therapeutics, and immunomodulatory interventions, carefully tailored to distinct viral etiologies and host endotypes. By shedding light on the intricate molecular landscape of viral sepsis, this review aims to provide a robust framework for future mechanistic research and accelerate the development of effective, personalized interventions to combat this challenging complication.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"107 ","pages":"Article 101442"},"PeriodicalIF":10.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vav3, a potential diagnostic and prognostic marker of diabetes, regulates glycolipid metabolism","authors":"Chenmoji Wang ,&nbsp;Mengjuan Wei ,&nbsp;Yu Wang ,&nbsp;Huimin He ,&nbsp;Chengcheng Huang ,&nbsp;Deshan Liu ,&nbsp;Yun Qiao","doi":"10.1016/j.mam.2025.101429","DOIUrl":"10.1016/j.mam.2025.101429","url":null,"abstract":"<div><div>Vav3 can significantly affect the energy metabolism of cancer cells by changing the cytoskeletal structure, involving the mechanism of disulfidptosis, while affecting the function of glucose transporters, regulating cellular glucose and lipid metabolism. This provides an interesting research idea for the exploration of the pathogenesis of diabetes and the targeted regulation of glucose and lipid metabolism. Vav3 protein not only participates in β-cell damage in type 1 diabetes but also extensively regulates insulin release and glucose metabolism in type 2 diabetes. Vav3 proteins directly or indirectly regulate energy metabolism in multiple organs such as the pancreas, skeletal muscle, and liver and are involved in some pathological processes such as oxidative stress, inflammation, and autophagy. These pathological processes are not only regulated by the Vav3 protein, but also in turn affect the expression level of the Vav3 gene, exacerbating the progression of diabetic complications such as diabetic osteoporosis and even diabetes-related cancers. Therefore, the regulated molecular patterns of Vav3 in the microenvironment of diabetic glucose and lipid metabolism disorder provide a new direction for further exploration of diabetic energy metabolism mechanism. Vav3 may be a potential diagnostic and prognostic marker of diabetes. Meanwhile, as an oncogene, it also builds a bridge and increases the depth of the connection between diabetes and cancer.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"107 ","pages":"Article 101429"},"PeriodicalIF":10.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145685645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting emerging viruses with phage display-driven engineered antibodies: Bridging molecular design and clinical application","authors":"Ah Hyun Cho ,&nbsp;Su Yeon Cho ,&nbsp;Soohyun Kim ,&nbsp;Sukmook Lee","doi":"10.1016/j.mam.2025.101441","DOIUrl":"10.1016/j.mam.2025.101441","url":null,"abstract":"<div><div>Phage display (PD) is a powerful platform that accelerates the discovery and engineering of therapeutic antibodies across diverse diseases, including emerging and re-emerging viral infections. The COVID-19 pandemic highlighted the urgency for rapid and adaptable antibody development against highly mutable pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PD technology enables the rapid and high-throughput identification, optimization, and efficient reformatting of virus-neutralizing antibodies, yielding fully PD-derived antibodies and reformatted derivatives from PD fragments without requiring convalescent samples or animal immunization. This approach supports a proactive and scalable strategy for pandemic preparedness. This review provides a comprehensive overview of PD-derived therapeutic antibodies targeting infectious diseases, focusing on approved agents and candidates in clinical or preclinical development for SARS-CoV-2. We highlight recent case studies, including our own, showing the successful application of PD in generating potent neutralizing and multispecific antibody formats. These offer functional advantages such as enhanced breadth and affinity while also serving as versatile molecular tools for elucidating viral pathogenesis and immune evasion mechanisms. Despite PD's technological strengths, the clinical advancement of PD-derived candidates has been influenced by external circumstances associated with the evolving pandemic landscape, highlighting the need to strategically leverage PD's strengths to accelerate translational outcomes in future outbreaks. This review offers a well-rounded viewpoint on PD, outlining its applications, addressing its challenges, and incorporating emerging innovations into PD workflows. These advances position PD-derived candidates as a strategic, versatile, and rapid-response platform that bridges molecular insights with clinical translation, offering a robust framework for addressing current and future infectious disease challenges.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"107 ","pages":"Article 101441"},"PeriodicalIF":10.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serine metabolism in the central nervous system: advances and challenges on a conditionally essential amino acid","authors":"Natasa Kustrimovic,&nbsp;Valentina Rabattoni,&nbsp;Daniele Riva,&nbsp;Zoraide Motta,&nbsp;Silvia Sacchi,&nbsp;Loredano Pollegioni","doi":"10.1016/j.mam.2025.101438","DOIUrl":"10.1016/j.mam.2025.101438","url":null,"abstract":"<div><div>Once considered a non-essential amino acid, L-serine (L-Ser) is now recognized as conditionally essential in the brain, orchestrating a complex network of metabolic and signalling pathways. L-Ser provides carbon units to the one-carbon metabolism, supporting nucleotide synthesis and methylation reactions, and serves as a precursor for phosphatidylserine and sphingolipids. L-Ser plays crucial roles in glutathione and heme metabolism and interfaces with mitochondrial one-carbon pathways, thereby linking it to energy production, redox homeostasis, and epigenetic regulation. Its conversion into glycine and D-serine further supports neurotransmission, synaptic plasticity, and cognitive functions. Throughout the lifespan, L-Ser and its derivatives contribute to maintaining neuronal and glial homeostasis. However, fundamental questions remain regarding how L-Ser biosynthesis, transport, and compartmentalization are coordinated in the intact brain and how their dysregulation contributes to disease. Current knowledge largely derives from cancer biology or <em>in vitro</em> models, and translating these insights to the central nervous system poses major challenges. The lack of specific tools to monitor L-Ser flux <em>in vivo</em>, limited understanding of post-translational regulation of key enzymes and incomplete mapping of transport mechanisms across the blood–brain barrier still hampers deeper mechanistic and translational insight. This review compiles the most recent evidence, emphasizing the translational relevance of L-Ser-based interventions and underscoring the urgent need for systematic clinical trials to fully evaluate its therapeutic potential.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"107 ","pages":"Article 101438"},"PeriodicalIF":10.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc bioavailability in alcohol-associated liver disease: Mechanisms and therapeutic implications","authors":"Yinrui Feng ,&nbsp;Qingshan Yang ,&nbsp;Dan Wang ,&nbsp;Qing Chu ,&nbsp;Zhenfang Zhou ,&nbsp;Yundi Liu ,&nbsp;Kefei Chen ,&nbsp;Volker M. Lauschke","doi":"10.1016/j.mam.2025.101430","DOIUrl":"10.1016/j.mam.2025.101430","url":null,"abstract":"<div><div>Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide. Hepatic zinc deficiency is a consistent feature of ALD, yet the therapeutic efficacy of zinc supplementation remains limited. This review examines the causal role of zinc deficiency in ALD pathogenesis and highlights low zinc bioavailability as a key determinant in disease progression. We discuss the regulatory roles of zinc transporters (ZIPs, ZnTs), metallothioneins, and redox-sensitive ligands in maintaining zinc homeostasis. Furthermore, we introduce zinc-glutathione (ZnGSH) as a novel zinc formulation that improves intestinal absorption and hepatic utilization of zinc. Unlike conventional zinc salts, ZnGSH overcomes multiple physiological barriers to zinc uptake in ALD, offering enhanced bioavailability in both gut and liver tissues. Thus, supplementation with bioavailable zinc may present a promising therapeutic strategy for ALD and, potentially, also other chronic liver diseases.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"107 ","pages":"Article 101430"},"PeriodicalIF":10.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}