Molecular Aspects of Medicine最新文献

{"title":"Corrigendum to: “Unveiling the P2X7 receptor: Exploring its mechanisms, pathogenic role in ocular diseases, and emerging therapeutic potential” [Mol. Aspect. Med. 105 (2025) 101389 https://doi.org/10.1016/j.mam.2025.101389]","authors":"Kai-Yang Chen , Hoi-Chun Chan , Chi-Ming Chan","doi":"10.1016/j.mam.2025.101425","DOIUrl":"10.1016/j.mam.2025.101425","url":null,"abstract":"","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101425"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515011","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":"Precision gene therapy: Tailoring rAAV-mediated gene therapies for inherited retinal dystrophies (IRDs)","authors":"Fábio Duarte ,&nbsp;Yvan Arsenijevic","doi":"10.1016/j.mam.2025.101424","DOIUrl":"10.1016/j.mam.2025.101424","url":null,"abstract":"<div><div>Inherited retinal dystrophies (IRDs) are a heterogeneous group of rare genetic disorders that affect multiple retinal cell types, including photoreceptors, Müller glia, bipolar cells, retinal ganglion cells (RGCs), and the retinal pigment epithelium (RPE). Recombinant adeno-associated viruses (rAAVs) have emerged as the leading vectors for gene delivery in the retina due to their safety profile and ability to drive long-term expression. However, achieving precise cell targeting and appropriate transgene regulation remains a key challenge. Recent advances in capsid engineering and the discovery of cell-type-specific regulatory elements have opened new avenues for improving the precision of rAAV-mediated therapies. These refined tools can be integrated with various therapeutic strategies, such as gene augmentation, genome editing, RNA modulation, and optogenetics, to expand the range and effectiveness of treatments for IRDs. This review focuses on recent developments in the customization of rAAV vectors to achieve cell-specific gene therapy for IRDs.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101424"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558483","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":"The crosstalk of neutrophil extracellular trap-inflammasome and their roles in disease progression","authors":"Jieqing Xiong ,&nbsp;Jiaojiao Xue ,&nbsp;Heqi Zhou ,&nbsp;Wenxiu Qi ,&nbsp;Haoyu Zhu","doi":"10.1016/j.mam.2025.101419","DOIUrl":"10.1016/j.mam.2025.101419","url":null,"abstract":"<div><div>Neutrophil extracellular traps (NETs) are a network of fibrous structures composed of DNA, histones, and antimicrobial proteins released by neutrophils, which play a crucial role in the innate immune system's defense against infection. When neutrophils encounter pathogens, they can release NETs to capture and neutralize these invaders, preventing their spread and prompting other immune cells to destroy them. The classical inflammasome is a cytoplasmic polyprotein complex activated by infectious and/or non-infectious stimuli that activates the protease caspase-1 to induce pyroptosis and promotes the maturation and release of interleukin (IL)-1β and IL-18, while the non-classical inflammasome activates cysteinyl aspartate specific proteinase (caspase)-4/11 to induce pyroptosis. Inflammasome activation is also an important component of the innate immune response. This review elaborates on the constituent proteins and molecular regulation of NETs and inflammasomes, summarizes the crosstalk between NETs and inflammasomes and its negative effects in the disease process, and also discusses the therapeutic effects of drugs targeting NETs and/or inflammasomes on related diseases.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101419"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145394878","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":"Pharmacological reprogramming of plitidepsin as a SARS-CoV-2 inhibitor","authors":"Jose Jimeno ,&nbsp;Jose Felipe Varona ,&nbsp;Jose A. Lopez-Martin ,&nbsp;Nuria Izquierdo-Useros ,&nbsp;Elisa Molina Molina ,&nbsp;Pablo Guisado-Vasco ,&nbsp;Martin Sachse ,&nbsp;Cristina Risco ,&nbsp;Alejandro Losada ,&nbsp;Salvador Fudio ,&nbsp;Erik Luepke ,&nbsp;Antonio Nieto ,&nbsp;Javier Gomez ,&nbsp;Pablo Aviles ,&nbsp;Carmen Cuevas ,&nbsp;Mehdi Bouhaddou ,&nbsp;Isabel Sola ,&nbsp;Nevan J. Krogan ,&nbsp;Luis Enjuanes ,&nbsp;Jose M. Fernandez-Sousa ,&nbsp;Kris White","doi":"10.1016/j.mam.2025.101412","DOIUrl":"10.1016/j.mam.2025.101412","url":null,"abstract":"<div><div>Selective pressures in the ocean promote the evolution of potent molecules that may be useful in therapeutic settings. Tunicates provide a rich source of bioactive molecules that have been shown to have anti-neoplastic and anti-microbial activities. Plitidepsin, a natural marine cyclic depsipeptide originally isolated from the tunicate <em>Aplidium albicans</em>, was originally developed as an anti-tumor drug, and has been approved for use in Australia in patients with advanced pretreated myeloma. Early in the SARS-CoV-2 pandemic, plitidepsin was shown to have potent preclinical efficacy against the virus, suggesting that it could be repurposed for the treatment of COVID-19. This review summarizes the clinical development of plitidepsin first as an anti-tumor drug, before providing a recapitulation of current efforts to repurpose the molecule as an antiviral therapy. The pharmacokinetic and pharmacodynamic data on plitidepsin will be analyzed, and the various experimental lines of evidence in support of the molecule's multifactorial mechanism of action will be explored. Finally, the available data on the use of plitidepsin in patients with COVID-19 will be presented, including results from a Phase I proof-of-concept study, real-world data from immunocompromised patients, and a look of results from a Phase III clinical trial that confirms the working hypothesis.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101412"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145497262","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":"Multidimensional review of viral infectious ocular diseases: Post-Pandemic epidemiology and future directions for control","authors":"Chang Liu ,&nbsp;Qianhao Yang ,&nbsp;Yang Shen ,&nbsp;Mengqiao Xu","doi":"10.1016/j.mam.2025.101428","DOIUrl":"10.1016/j.mam.2025.101428","url":null,"abstract":"<div><div>Viral Infectious Ocular Diseases (VIODs) remain a major global cause of vision loss, ranging from highly transmissible conjunctivitis to blinding keratitis and complex neuro-ophthalmic syndromes. Furthermore, the Coronavirus Disease 2019 (COVID-19) pandemic and subsequent reported ocular diseases have fundamentally changed the landscape of VIOD epidemiology and management. Epidemiological data indicate heterogeneous effects on common infections such as Adenoviral conjunctivitis due to varying compliance with hygiene measures. Concurrently, systemic immunological events, notably those induced by COVID-19 infection or certain vaccinations, have been linked to the reactivation of latent <em>Alphaherpesviruses,</em> including <em>Herpes Simplex Virus</em> (HSV) and <em>Varicella Zoster Virus</em> (VZV).</div><div>The metagenomic next-generation sequencing (mNGS) offers a significantly improved diagnostic yield (up to 92.7 % in some cohorts) for complex infectious keratitis compared to conventional methods, providing an unbiased tool crucial for timely, targeted treatment. Therapeutic challenges are defined by the persistent threat of antiviral resistance, primarily driven by mutations in the viral Thymidine Kinase (TK) gene. To overcome poor ocular bioavailability, novel drug delivery systems (NDDS), such as Acyclovir-loaded Niosomes and Cubosomes, show promise by enabling sustained drug release and enhanced corneal permeation. Effective future VIOD control requires a multi-pronged strategy integrating robust global surveillance, rapid deployment of advanced molecular diagnostics, and the clinical implementation of resistance-beating therapies delivered via optimized nanocarrier platforms.</div><div>This review provides the current understanding of VIODs, focusing on the epidemiological shifts observed post-2020, advancements in molecular diagnostics, challenges posed by antiviral resistance, and the emergence of next-generation therapeutic strategies.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101428"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145606357","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":"The double-edged sword: How SARS-CoV-2 might fuel lung cancer: Investigating the potential oncogenic mechanisms of the novel coronavirus in lung carcinogenesis","authors":"Wang Shen ,&nbsp;Yaohua Guo ,&nbsp;Cheng Ai ,&nbsp;Xuehai Wang ,&nbsp;Gang Li","doi":"10.1016/j.mam.2025.101413","DOIUrl":"10.1016/j.mam.2025.101413","url":null,"abstract":"<div><div>The COVID-19 pandemic, caused by SARS-CoV-2, has had far-reaching consequences beyond acute respiratory illness, with growing evidence suggesting potential long-term oncogenic effects. Lung cancer, a leading cause of cancer-related mortality, may intersect with COVID-19 through shared molecular pathways and altered disease dynamics. SARS-CoV-2 can exacerbate outcomes in existing cancer patients and potentially contribute to de novo lung carcinogenesis or accelerate progression via chronic inflammation, oxidative stress, immune dysregulation, cellular senescence, cell cycle disruption, metabolic reprogramming, and autophagy impairment. It has been proven that although the SARS virus is not capable of integrating into the host genome, it uses the mechanisms of other human oncoviruses to cause lung cancer. Post-COVID-19 pulmonary fibrosis, observed in up to one-third of severe cases, may act as a tumor precursor bridge through sustained tissue remodeling, extracellular matrix stiffness, and hypoxia-induced epithelial-mesenchymal transition. Epidemiological studies indicate increased cancer-related mortality, metastatic reactivation of dormant cancer cells, and diagnostic delays, shifting presentations toward advanced stages during the pandemic. Synergistic risk factors, including smoking, air pollution, occupational exposures, and genetic predispositions, may further amplify oncogenic potential. The convergence of viral, environmental, and host factors creates a critical need for vigilant surveillance, biomarker development, and preventive strategies. This study aims to synthesize current epidemiological evidence, elucidate the molecular and cellular mechanisms by which SARS-CoV-2 may influence lung carcinogenesis, and highlight clinical implications to guide future research, screening, and therapeutic interventions.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101413"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159378","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":"Viruses in gastrointestinal cancers: Molecular pathogenesis, oncogenic mechanisms, and translational perspectives","authors":"Bin Liu ,&nbsp;Chengjiang Liu ,&nbsp;Caroline Sunggip ,&nbsp;GuangJin Pu ,&nbsp;Dong Deng","doi":"10.1016/j.mam.2025.101415","DOIUrl":"10.1016/j.mam.2025.101415","url":null,"abstract":"<div><div>Viral pathogens are one of the most significant causes of human carcinogenesis, contributing to up to 15–20 % of worldwide cancers. The gastrointestinal (GI) tract is one of the most vulnerable human organ system to virus-mediated tumorigenesis as a result of frequent exposure to viral infections and various immunological processes. The present review aims to describe the dual roles of viral infections in the development of gastrointestinal cancers (GICs), with a focus on Human Immunodeficiency Virus (HIV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). HIV represents an oncological challenge in the era of effective antiretroviral therapy (ART), where significant immune dysfunction, persistent inflammation, and gut microbiome disruption render infected patients more susceptible to various GICs. On the other hand, SARS-CoV-2 is an emerging viral pathogen whose potential role in oncogenesis remains controversial yet biologically plausible. In this context, SARS-CoV-2 tropism to the gastrointestinal tissues and its capacity to drive cytokine storms, profound dysbiosis, and immune exhaustion raise significant questions regarding its potential to act as a pro-tumorigenic factor. Discussing mechanistic insights from well-known oncogenic viral pathogens, the present review describes the direct and indirect mechanisms by which these two major viruses may affect GI tumorigenesis. Moreover, this review translates these mechanisms into clinical perspectives, underscoring implications for diagnostics, prevention, and therapeutic strategies, while highlighting urgent research priorities for long-term surveillance and biomarker discovery. It highlights the importance of continuous scientific awareness to address the increasing cancer risks presented by emerging and re-emerging viruses through bridging virology and oncology.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101415"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515028","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":"Neuroteratogenic mechanisms of Zika virus (ZIKV) infection: Insights into fetal brain development disruption and congenital Zika syndrome: A systematic review","authors":"Samira Sanami ,&nbsp;Seyedeh Zahra Banihashemian ,&nbsp;Saghar Amirpour ,&nbsp;Farnaz Alibabaei ,&nbsp;Ali Babaeizad ,&nbsp;Mohammad Yousefi ,&nbsp;Majid Eslami","doi":"10.1016/j.mam.2025.101418","DOIUrl":"10.1016/j.mam.2025.101418","url":null,"abstract":"<div><div>The Zika virus (ZIKV), a mosquito-borne <em>Flavivirus</em>, has emerged as a global health threat due to its severe neuroteratogenic effects, particularly during pregnancy. This mechanistic-to-translational synthesis examines how ZIKV disrupts fetal brain development and links molecular events to clinical manifestations of Congenital Zika Syndrome (CZS). Our review advances prior summaries by presenting a unifying neural progenitor cell (NPC)-centric pathway framework that integrates viral entry, host signaling disruption, cell fate outcomes, and imaging correlates. Once transmitted vertically, the virus targets NPCs, impairing proliferation, triggering apoptosis, and halting the cell cycle. It modulates host pathways such as PI3K-Akt-mTOR and p53 to enhance autophagy, avoid immune detection, and sustain replication. ZIKV also interferes with RNA interference and synaptic formation, contributing to cortical thinning, ventriculomegaly, and agenesis of the corpus callosum. Inflammatory responses further exacerbate tissue damage as ZIKV activates TLRs and inflammasomes, increasing proinflammatory cytokines and pyroptosis. Brain organoid and imaging studies highlight the virus’s NPC tropism and capacity for lasting neurodevelopmental impairment—even in normocephalic infants. Importantly, ZIKV exhibits SOX2-dependent permissiveness with integrin αvβ5 functioning as a key dependency/attachment factor in neural and glioblastoma stem cells, distinguishing transcriptional state from receptor function. This intersection of neurotropism and potential oncolytic activity underscores the dual pathogenic and therapeutic implications of ZIKV. Literature was synthesized according to a predefined search strategy, with evidence appraised for quality, strengths, and limitations. This review highlights mechanistic pathways linking viral replication, immune modulation, and disrupted neurodevelopment, emphasizing implications for surveillance, therapeutic targets, and maternal-fetal health preparedness.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101418"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145379545","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":"Antisense oligonucleotides for inherited retinal diseases: a comprehensive review","authors":"Hossein D. Banadaki ,&nbsp;Alejandro Garanto ,&nbsp;Rob W.J. Collin","doi":"10.1016/j.mam.2025.101416","DOIUrl":"10.1016/j.mam.2025.101416","url":null,"abstract":"<div><div>Inherited retinal diseases (IRDs) are a genetically and clinically heterogeneous group of disorders that cause progressive vision loss and often lead to blindness. The complexity of these conditions arises from pathogenic variants in over 330 different genes, making the development of effective treatments highly challenging. Antisense oligonucleotides (ASOs) have emerged as a promising therapeutic approach for IRDs, offering precise regulation of transcript expression and composition. Unlike traditional gene augmentation therapies, ASOs provide a flexible and sequence-specific strategy by modulating splicing patterns, blocking translation, or promoting RNA degradation. Advancements in ASO chemistry, including backbone and sugar modifications, have significantly improved their uptake, stability, specificity, and therapeutic efficacy, facilitating their application in a variety of diseases. This review provides a comprehensive analysis of ASO-based strategies for IRDs, touching upon their mechanisms of action, chemical modifications, delivery strategies, and current clinical advancements. Additionally, we discuss the challenges that remain, such as off-target effects, delivery barriers, and long-term safety concerns, while highlighting future innovations that may enhance the efficacy and safety of ASOs and broaden their clinical applicability. As ASO-based therapies continue to progress through preclinical and clinical development, they hold significant potential to reshape the therapeutic landscape for IRDs, offering personalized and targeted treatments for patients with these devastating conditions.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101416"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214227","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":"Emerging and Re-emerging viral infections and their ocular manifestations: A focus on ocular neovascularization","authors":"Dan Li ,&nbsp;Qing Ye ,&nbsp;Jianhao Bai ,&nbsp;Wencui Wan","doi":"10.1016/j.mam.2025.101396","DOIUrl":"10.1016/j.mam.2025.101396","url":null,"abstract":"<div><div>Emerging and re-emerging viral infections represent a significant and escalating global health concern, frequently associated with a spectrum of systemic complications. Among these, ocular manifestations are increasingly recognized, contributing substantially to visual morbidity. The present review aims to provide an overview of the ocular sequelae of major emerging and re-emerging viral pathogens, highlighting their suggested and established roles in ocular neovascularization (ONV). It discusses the virological and immunological mechanisms, including direct viral cytopathic effects, virally-induced inflammation, dysregulation of angiogenic and anti-angiogenic factors (e.g., Vascular Endothelial Growth Factor), and activation of hypoxia-inducible pathways, which can contribute to neovascular processes in various ocular compartments such as the cornea, iris, retina, and choroid. The major viral agents addressed in this review are Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Human Immunodeficiency Virus (HIV), West Nile virus (WNV), Dengue Virus (DENV), and other viruses with known or suspected ONV association. This study reviewed and summarized the literature regarding case reports and experimental models describing the association of these viral agents with ONV. Furthermore, it addresses diagnostic considerations and therapeutic strategies. Understanding the intricate interplay between these viral infections and ocular neovascular pathways is crucial for developing targeted therapeutic strategies to prevent vision loss in affected populations.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101396"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202159","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}