Molecular Aspects of Medicine最新文献

{"title":"Elimination of cervical cancer: the impact of HPV vaccination, primary HPV screening, and expanded access to cancer treatment services","authors":"Michaela T. Hall ,&nbsp;Amelia Hyatt ,&nbsp;Megan A. Smith ,&nbsp;Julie Torode ,&nbsp;Telma Costa ,&nbsp;Diep Thi Ngoc Nguyen ,&nbsp;Timothy Balshaw ,&nbsp;Paul Grogan ,&nbsp;Kim Sweeny ,&nbsp;Carmen Auste ,&nbsp;Claire Nightingale ,&nbsp;Mei Ling Yap ,&nbsp;David Hawkes ,&nbsp;Andrew Vallely ,&nbsp;Monica Molano ,&nbsp;Sanchia Aranda ,&nbsp;Edward Trimble ,&nbsp;Lisa J. Whop ,&nbsp;Marion Saville ,&nbsp;Deborah Bateson ,&nbsp;Karen Canfell","doi":"10.1016/j.mam.2025.101423","DOIUrl":"10.1016/j.mam.2025.101423","url":null,"abstract":"<div><div>In 2022, over 662,000 cases of cervical cancer were diagnosed globally and over 348,000 deaths occurred from the disease, with almost 94 % of these deaths occurring in low- and lower-middle income countries (LMIC). Effective intervention strategies, including prophylactic Human Papillomavirus (HPV) vaccination for adolescents and primary HPV screening for adult women, are highly effective and cost-effective methods of prevention; however, delivering population-wide access to these prevention methods has been challenging, particularly in LMIC. The World Health Organization (WHO) has launched a global strategy for the elimination of cervical cancer as a public health problem through the scale-up of HPV vaccination, cervical screening and precancer and cancer treatment services. In this review article, we present the rationale, history and strategy behind the global cervical cancer elimination efforts, including the evidence underpinning the WHO's three pillars of cervical cancer control, and essential considerations for implementation, sustainable financing, and health systems implications. Many countries and regions are currently formulating frameworks to achieve cervical cancer elimination within their setting. Here, we consider implementation challenges for both LMIC, and high-income countries (HIC), calling upon the experiences of implementation guided by the WHO Western Pacific Region and Australian frameworks as exemplar settings.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"107 ","pages":"Article 101423"},"PeriodicalIF":10.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791243","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 viroporins, RBP dynamics, and skeletal remodeling: Targeting liquid-liquid phase separation for dual antiviral and bone-protective therapies","authors":"Ying Huai ,&nbsp;Xue Wang ,&nbsp;Jingchuan Yan,&nbsp;Shuang Li,&nbsp;Haien Zhao,&nbsp;Bo Liao","doi":"10.1016/j.mam.2026.101445","DOIUrl":"10.1016/j.mam.2026.101445","url":null,"abstract":"<div><div>Emerging and re-emerging viral pathogens, particularly Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Zika virus (ZIKV), and Chikungunya virus (CHIKV), are currently recognized as a significant global public health issue, commonly leading to devastating persistent complications including inflammatory bone disorders and long-lasting arthralgia. Although systemic cytokine storm has been reported as a significant factor, the particular intracellular processes through which these viruses affect bone homeostasis are still poorly understood. Recent studies underscore Liquid-Liquid Phase Separation (LLPS) and RNA-Binding Proteins (RBPs) as significant regulatory mechanisms manipulated by these viruses. Particularly, the SARS-CoV-2 Nucleocapsid protein exploits its intrinsically disordered regions to promote LLPS, facilitating viral assembly by the active inhibition of a key host anti-viral mechanism, known as host Stress Granules. Studies suggest that this biophysical interaction can affect the stability of the HuR RBD, impairing the nuclear <em>β</em>-catenin localization and then Wnt-mediated osteogenesis. Despite increasing recognition of post-viral musculoskeletal complications, the mechanistic links between viral persistence, host RBP dysfunction, and impaired bone remodeling remain poorly defined. This review incorporates viral LLPS, stress granule impairment, and osteogenic signaling into a unified ‘Two-Hit’ pathogenic framework. It also addresses key knowledge gaps, including the lack of longitudinal clinical validation and in vivo evidence associating LLPS impairment to skeletal disorders. Interestingly, this framework represents translational opportunities for dual-action therapeutic strategies that simultaneously impair viral condensates and recover host RBP-associated osteogenic signaling. Targeting the virus–host phase interface can introduce a potential approach not only for antiviral therapies but also for inhibiting post-viral musculoskeletal complications.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"107 ","pages":"Article 101445"},"PeriodicalIF":10.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926348","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":"cGAS-STING signaling in Alzheimer's disease: Microglial mechanisms and therapeutic opportunities","authors":"Faaizah Fazal ,&nbsp;Nawab John Dar ,&nbsp;Shakir Ahamad ,&nbsp;Sameera Khan ,&nbsp;Nargis Bano ,&nbsp;Supriyo Saha ,&nbsp;Aamir Nazir ,&nbsp;Shahnawaz Ali Bhat","doi":"10.1016/j.mam.2025.101444","DOIUrl":"10.1016/j.mam.2025.101444","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is increasingly recognized as a neuroinflammatory disorder driven by microglial dysfunction. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway plays a critical role in neuroinflammation and has been strongly implicated in the pathology of AD. Chronic activation of cGAS-STING contributes to neurodegeneration by driving persistent type I interferon release and excessive pro-inflammatory cytokine production. However, the pathway exhibits context-dependent effects. Transient activation promotes antiviral defense, autophagy, and cellular quality control in the central nervous system. Sustained engagement exacerbates neuroinflammation and synaptic loss. Preclinical studies demonstrate that pharmacological inhibitors (such as NR, TSG, H-151, TDI-6750, TDI-8246) mitigate amyloid beta and tau pathology, attenuate microglial reactivity, and enhance cognitive outcomes. Yet, its essential physiological roles, including antimicrobial immunity and autophagy regulation, pose challenges for therapeutic targeting. This potentially disrupts neuroimmune homeostasis. In this review, we highlight the role of cGAS-STING in AD and explore its potential as a therapeutic target using small-molecule drug candidates. Despite these promising findings, challenges remain, including optimizing blood-brain barrier (BBB) penetration, ensuring immune specificity, and addressing long-term safety concerns. Due to these challenges, no cGAS-STING inhibitors have entered clinical trials for AD. However, the future of AD treatment may involve modulation of neuroinflammatory pathways, with cGAS-STING inhibitors playing a central role in reshaping neuroimmune homeostasis.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"107 ","pages":"Article 101444"},"PeriodicalIF":10.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884627","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 potential use of anti-codon engineered tRNAs (ACE-tRNAs) to treat nonsense variants causing inherited retinal diseases","authors":"Asodu Sandeep Sarma,&nbsp;Dror Sharon","doi":"10.1016/j.mam.2025.101443","DOIUrl":"10.1016/j.mam.2025.101443","url":null,"abstract":"<div><div>Inherited retinal diseases (IRDs) are clinically and genetically complex disorders that cause blindness in about one in 3450 individuals worldwide. More than 350 genes have been implicated in IRDs showing all possible inheritance patterns. Despite the advancement of several genetic therapies, there is currently no cure for the vast majority of IRDs. By converting a sense codon into a nonsense codon, premature termination codon (PTC) variants cause abrupt termination of protein synthesis, leading to loss of protein function in most cases. Nonsense variants account for approximately 18 % of all disease-causing variants in IRDs, and there is currently no effective treatment available to correct them. In recent years, anticodon engineered tRNAs (ACE-tRNAs) or suppressor tRNAs have emerged as potential therapeutic option for treating rare diseases caused by nonsense variants. This review critically summarizes the spectrum of nonsense variants in the genetics of IRDs and examines the promise of ACE-tRNA therapy as a treatment. We focus on the therapy's mechanism of action, current advancements, and its specific advantages and limitations for addressing nonsense variant-induced IRDs.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"107 ","pages":"Article 101443"},"PeriodicalIF":10.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145866322","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":"Membrane remodeling, ion channels, Ca2+ signaling, and stress pathways as molecular links between type 2 diabetes and cancer","authors":"Gonzalo Ferreira ,&nbsp;Luisina Chavarría ,&nbsp;Agustín DeMarco ,&nbsp;Franco Bernech ,&nbsp;Romina Cardozo ,&nbsp;Axel Santander ,&nbsp;Lucía Domínguez ,&nbsp;Nicolás Mujica ,&nbsp;Luis Sobrevia ,&nbsp;Garth L. Nicolson","doi":"10.1016/j.mam.2025.101426","DOIUrl":"10.1016/j.mam.2025.101426","url":null,"abstract":"<div><div>The interrelationship between type 2 diabetes mellitus (T2DM) and cancer reflects a convergence of molecular disturbances involving metabolism, inflammation, and cellular stress, often underpinned by genetic alterations. This review examines some key shared mechanisms of progression, with a focus on changes in plasma membrane dynamics, ion channel remodeling, Calcium (Ca²⁺) signaling, mitochondrial dysfunction, unfolded protein response, and oxidative stress. Changes in membrane composition, fluidity, lipid raft organization, and glycosylation affect receptor function and intracellular signaling in both diseases. These structural changes often occur in conjunction with the remodeling of ion channels. Ca²⁺ influx, K⁺, and Na⁺ are particularly affected, contributing to dysregulated excitability, proliferation, and immune modulation. Disturbed ion transport leads to intracellular Ca²⁺ overload or oscillatory defects, impairing insulin secretion in diabetes and activating pro-oncogenic pathways in cancer. A sustained Ca²⁺ imbalance further triggers the maladaptive activation of the UPR, while also affecting mitochondrial function. In T2DM, this response promotes β-cell dysfunction and insulin resistance, whereas in cancer, selective <span>UPR</span> engagement supports cell survival, angiogenesis, and immune evasion. Oxidative stress acts as both a trigger and amplifier in this cascade. Lipid peroxidation and mitochondrial dysfunction reinforce membrane instability and propagate damage, accelerating both metabolic decline and tumor progression. Therapeutically, interventions such as membrane lipid replacement and Ca²⁺ channel blockers are being explored for their dual potential in addressing some of these molecular dysfunctions. By integrating molecular and epidemiological perspectives, this review highlights the potential of using precision therapies that target some of the overlapping properties of T2DM and cancer, offering a more unified strategy to confront these global health challenges.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101426"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617748","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":"Influence of microbiota composition on the pathogenesis of type 2 diabetes: Physiological aspects","authors":"Nataliya V. Zharova ,&nbsp;Filipp D. Mikhailidi ,&nbsp;Darya A. Kabanova ,&nbsp;Alena Y. Tatarintseva ,&nbsp;Olga L. Polyakova ,&nbsp;Yury O. Zharikov ,&nbsp;Nikolai A. Zharov ,&nbsp;Sergey N. Ryagin ,&nbsp;André Pontes-Silva ,&nbsp;Tatiana S. Zharikova","doi":"10.1016/j.mam.2025.101410","DOIUrl":"10.1016/j.mam.2025.101410","url":null,"abstract":"<div><div>The development of type 2 diabetes may be influenced by enterotypes and bacterial metabolites. The most important of these are short-chain fatty acids (SCFAs), which play a role in forming the gut-brain axis and in the process of lipogenesis. An increase in lipogenesis can lead to obesity. High levels of adipose tissue in the body trigger chronic inflammation and insulin resistance. This review examines how microbiota composition influences the pathogenesis of type 2 diabetes and the possibility of regulating microbiota through proper nutrition, fecal microbiota transplantation, and prebiotics and probiotics. Additionally, the review notes that an imbalance in the gut microbiota can contribute to diabetes progression and increase cancer risk through inflammatory and immune mechanisms.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101410"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050661","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":"Navigating the ocular barrier: Viral- and nanotechnology-based delivery systems as promising therapeutic agents for ocular diseases","authors":"Subo Cai ,&nbsp;Xiao Liang ,&nbsp;Hongshuai Wu ,&nbsp;Xinyu Li ,&nbsp;Qi Pu","doi":"10.1016/j.mam.2025.101421","DOIUrl":"10.1016/j.mam.2025.101421","url":null,"abstract":"<div><div>While the intricate and precisely specialized structure of the human eye is critical for its appropriate function, it also presents a number of anatomical and physiological barriers, such as tight junctions, enzymatic degradation, and dynamic fluid turnover, which highly restrict the intraocular bioavailability of various therapeutic compounds. This is more significant for those therapeutic compounds that are used for complications affecting the posterior segment. Accordingly, conventional therapeutic strategies for common ocular complications such as diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, and infectious keratitis significantly demand invasive administration approaches and multiple injections, frequently resulting in various side effects and suboptimal therapeutic consequences. To address these major challenges, novel technologies, such as viral- and nanotechnology-based delivery systems, have provided emerging opportunities to bypass ocular barriers and facilitate targeted, maintained, and efficient drug and gene delivery. The present review aims to comprehensively describe the current advancements in both viral- and nanotechnology-based strategies for ocular diseases. It discusses the complex molecular structure and physiological functions of the ocular barriers, focusing on the exact mechanisms that restrict drug permeation. Moreover, this review describes the design principles, physicochemical properties, and therapeutic potential of diverse viral- and nanotechnology-based delivery systems. Their efficacy and safety profiles are thoroughly discussed across various pre-clinical and clinical studies. Furthermore, the review discusses the emergence of hybrid viral-nanotechnology delivery systems that combine the strengths of both approaches, offering enhanced targeting precision and biocompatibility. The major challenges linked to the clinical translation of these novel technologies, such as aspects of biocompatibility and immunogenicity are also addressed. This review highlights the significant transformative potential of viral vectors and nanotechnology in reforming ocular disease management and increasing patient quality of life.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101421"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145497249","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":"Cross-talk between cancer and diabetes: Exploring shared molecular pathways in cellular metabolism and signaling","authors":"Zhangzhi Tang ,&nbsp;Nuo Xu ,&nbsp;Pin Lyu ,&nbsp;Hui Zhao ,&nbsp;Wenjie Zheng","doi":"10.1016/j.mam.2025.101420","DOIUrl":"10.1016/j.mam.2025.101420","url":null,"abstract":"<div><div>Diabetes and cancer are among the most prevalent chronic diseases globally, drawing increasing attention due to their shared features of metabolic and signaling dysregulation. Epidemiological evidence indicates that type 2 diabetes significantly elevates the risk of developing multiple types of tumors. This review highlights the key molecular intersections between diabetic pathophysiology and oncogenic processes, with a focus on how hyperinsulinemia and hyperglycemia contribute to tumor initiation and progression. These effects are primarily mediated through profound metabolic reprogramming, including hyperactivation of the hexosamine biosynthetic pathway (HBP) and the accumulation of advanced glycation end-products (AGEs), which promote sustained oxidative stress and chronic inflammation. Consequently, the tumor microenvironment (TME) undergoes substantial remodeling. The metabolism and function of immune cells are disrupted, promoting immune evasion. Meanwhile, cancer cells adapt by engaging mechanisms such as diabetes-induced epigenetic reprogramming, activation of the unfolded protein response (UPR), and alterations in the gut microbiota, thereby enhancing their survival advantage. Emerging evidence suggests that anti-diabetic agents targeting these metabolic intersections exhibit dual roles in cancer therapy, offering both therapeutic potential and potential risks. To address these complexities, future efforts should conduct multi-omics technologies to dissect the metabolic heterogeneity of diabetes-associated tumors, paving the way for precise and personalized therapeutic strategies for patients with this comorbidity.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101420"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145394911","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 viruses as triggers of human endogenous retrovirus activation: Implications for aging and age-related pathologies","authors":"Yan Wu ,&nbsp;Shuai Huang ,&nbsp;Qian Sha ,&nbsp;Jing Yu","doi":"10.1016/j.mam.2025.101422","DOIUrl":"10.1016/j.mam.2025.101422","url":null,"abstract":"<div><div>The human genome contains a substantial legacy of ancient retroviral infections known as Human Endogenous Retroviruses (HERVs), composing 8 % of our DNA. In healthy young individuals, these elements are kept dormant by robust epigenetic mechanisms, primarily DNA methylation and repressive H3K9me3 histone marks. However, this epigenetic silencing deteriorates with age, leading to the reactivation of HERVs, particularly the youngest HERV-K subfamily. This report posits that this HERV awakening is not a passive byproduct of aging but an active, transmissible driver of pathology. The reactivation of HERVs leads to the production of retrovirus-like particles (RVLPs) that can induce senescence in healthy neighboring cells, propagating a contagious aging phenomenon. Furthermore, the accumulation of HERV-derived dsRNA and reverse-transcribed DNA triggers chronic innate immune responses through pathways including cGAS-STING and IFIH1-MAVS, fueling the systemic, low-grade inflammation characteristic of inflammaging, catalytically accelerated by exogenous viral infections. Pathogens such as SARS-CoV-2, Epstein-Barr Virus (EBV), and Herpes Simplex Virus (HSV-1) can directly transactivate HERVs via their own viral proteins, overwhelming the already compromised epigenetic controls in an aging host. This mechanistic link between viral triggers and endogenous retroviral activity is strongly implicated in a range of age-related diseases, including neurodegenerative disorders such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS), where the HERV-K envelope protein is directly neurotoxic. It is also linked to autoimmune diseases like Multiple Sclerosis and various cancers. This report synthesizes these findings and identifies a novel mechanistic link between viral activity, chronic inflammation, and the onset of age-related diseases.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101422"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483552","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":"Urogenital manifestations of SARS-CoV-2, MPXV and Zika virus: A comprehensive review","authors":"Yubin Li ,&nbsp;Guanghan Fan ,&nbsp;Huadong He","doi":"10.1016/j.mam.2025.101399","DOIUrl":"10.1016/j.mam.2025.101399","url":null,"abstract":"<div><div>The current century has been associated with the outbreaks of emerging and re-emerging viral infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), monkeypox virus (MPXV), and Zika virus (ZIKV). Although their common clinical manifestations are currently well-known, the urogenital system is gaining attention as a significant, though often underappreciated, anatomical site for emerging and re-emerging viral infections, disease development, and transmission. The present review aims to comprehensively discuss the urogenital complications linked to the infections caused by these viruses, with a primary focus on describing their suggested and established roles in the development of urogenital sequelae. It reviews various molecular and cellular mechanisms, such as direct viral pathogen cytopathic activity, virally-mediated inflammation, and the nephrotoxic side effects of specific medications, by which SARS-CoV-2, MPXV, and ZIKV may affect various parts of the urogenital system. In this context, SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for cell entry, which is frequently present in the urogenital tissues, resulting in urogenital injuries. Zika virus exhibits a distinct tropism for the male reproductive tract, demonstrating prolonged viral persistence in semen that facilitates sexual transmission and is linked to testicular damage and adverse congenital outcomes. The present study also addresses diagnostic considerations and therapeutic strategies in the context of urogenital sequelae associated with these viruses. Understanding the intricate molecular basis of these viral-caused sequelae is crucial for improving differential diagnosis and introducing targeted therapeutic strategies.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101399"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050659","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}