Pub Date : 2025-12-06DOI: 10.1016/j.mam.2025.101429
Chenmoji Wang , Mengjuan Wei , Yu Wang , Huimin He , Chengcheng Huang , Deshan Liu , Yun Qiao
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.
{"title":"Vav3, a potential diagnostic and prognostic marker of diabetes, regulates glycolipid metabolism","authors":"Chenmoji Wang , Mengjuan Wei , Yu Wang , Huimin He , Chengcheng Huang , Deshan Liu , 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":"2025-12-06","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}
Pub Date : 2025-12-05DOI: 10.1016/j.mam.2025.101430
Yinrui Feng , Qingshan Yang , Dan Wang , Qing Chu , Zhenfang Zhou , Yundi Liu , Kefei Chen , Volker M. Lauschke
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.
{"title":"Zinc bioavailability in alcohol-associated liver disease: Mechanisms and therapeutic implications","authors":"Yinrui Feng , Qingshan Yang , Dan Wang , Qing Chu , Zhenfang Zhou , Yundi Liu , Kefei Chen , 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":"2025-12-05","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}
Pub Date : 2025-12-01DOI: 10.1016/j.mam.2025.101426
Gonzalo Ferreira , Luisina Chavarría , Agustín DeMarco , Franco Bernech , Romina Cardozo , Axel Santander , Lucía Domínguez , Nicolás Mujica , Luis Sobrevia , Garth L. Nicolson
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 UPR 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.
{"title":"Membrane remodeling, ion channels, Ca2+ signaling, and stress pathways as molecular links between type 2 diabetes and cancer","authors":"Gonzalo Ferreira , Luisina Chavarría , Agustín DeMarco , Franco Bernech , Romina Cardozo , Axel Santander , Lucía Domínguez , Nicolás Mujica , Luis Sobrevia , 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 (Ca<sup>2+</sup>) 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. Ca<sup>2+</sup> influx, K<sup>+</sup>, and Na<sup>+</sup> are particularly affected, contributing to dysregulated excitability, proliferation, and immune modulation. Disturbed ion transport leads to intracellular Ca<sup>2+</sup> overload or oscillatory defects, impairing insulin secretion in diabetes and activating pro-oncogenic pathways in cancer. A sustained Ca<sup>2+</sup> 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 Ca<sup>2+</sup> 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}
Pub Date : 2025-12-01DOI: 10.1016/j.mam.2025.101428
Chang Liu , Qianhao Yang , Yang Shen , Mengqiao Xu
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 Alphaherpesviruses, including Herpes Simplex Virus (HSV) and Varicella Zoster Virus (VZV).
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.
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.
{"title":"Multidimensional review of viral infectious ocular diseases: Post-Pandemic epidemiology and future directions for control","authors":"Chang Liu , Qianhao Yang , Yang Shen , 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}
Pub Date : 2025-12-01DOI: 10.1016/j.mam.2025.101427
Pei Liu , Weiwei Wang , Kun Zhao , Hong Zhang , Mingqiang Liu , Jianlei Li , Yadong Guo , Anquan Shang , Yongqiang Sun
Bone
and bone-marrow associated cancers, including osteosarcoma, Ewing sarcoma, multiple myeloma, and various leukemias, are highly aggressive tumors with limited therapeutic options and poor outcomes. Viruses play a paradoxical role in these diseases, acting both as pathogenic drivers and as potential therapeutic agents. On one hand, oncogenic viruses such as Epstein–Barr virus (EBV), human T-cell leukemia virus type 1 (HTLV-1), and hepatitis viruses have been implicated in the initiation and progression of certain hematologic and skeletal malignancies. On the other hand, oncolytic viruses have emerged as promising ‘friends,’ engineered to selectively infect, lyse, and stimulate immune responses against malignant cells within the unique microenvironment of bone and bone marrow. This duality raises critical questions about how viral biology intersects with cancer pathogenesis and therapy. In this review, we explore the evidence for viral pathogens as both foes that contribute to tumorigenesis and friends that can be harnessed as novel therapeutic platforms. We further highlight delivery challenges, safety considerations, and translational opportunities that may shape the future of virotherapy for bone and marrow cancers.
{"title":"Viral pathogens in bone- and bone-marrow derived malignancies: Friends or foes?","authors":"Pei Liu , Weiwei Wang , Kun Zhao , Hong Zhang , Mingqiang Liu , Jianlei Li , Yadong Guo , Anquan Shang , Yongqiang Sun","doi":"10.1016/j.mam.2025.101427","DOIUrl":"10.1016/j.mam.2025.101427","url":null,"abstract":"<div><h3>Bone</h3><div>and bone-marrow associated cancers, including osteosarcoma, Ewing sarcoma, multiple myeloma, and various leukemias, are highly aggressive tumors with limited therapeutic options and poor outcomes. Viruses play a paradoxical role in these diseases, acting both as pathogenic drivers and as potential therapeutic agents. On one hand, oncogenic viruses such as Epstein–Barr virus (EBV), human T-cell leukemia virus type 1 (HTLV-1), and hepatitis viruses have been implicated in the initiation and progression of certain hematologic and skeletal malignancies. On the other hand, oncolytic viruses have emerged as promising ‘friends,’ engineered to selectively infect, lyse, and stimulate immune responses against malignant cells within the unique microenvironment of bone and bone marrow. This duality raises critical questions about how viral biology intersects with cancer pathogenesis and therapy. In this review, we explore the evidence for viral pathogens as both foes that contribute to tumorigenesis and friends that can be harnessed as novel therapeutic platforms. We further highlight delivery challenges, safety considerations, and translational opportunities that may shape the future of virotherapy for bone and marrow cancers.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101427"},"PeriodicalIF":10.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145606774","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}
Pub Date : 2025-11-18DOI: 10.1016/j.mam.2025.101424
Fábio Duarte , Yvan Arsenijevic
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.
{"title":"Precision gene therapy: Tailoring rAAV-mediated gene therapies for inherited retinal dystrophies (IRDs)","authors":"Fábio Duarte , 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":"2025-11-18","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}
Pub Date : 2025-11-12DOI: 10.1016/j.mam.2025.101425
Kai-Yang Chen, Hoi-Chun Chan, Chi-Ming Chan
{"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":"https://doi.org/10.1016/j.mam.2025.101425","url":null,"abstract":"","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":" ","pages":"101425"},"PeriodicalIF":10.3,"publicationDate":"2025-11-12","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}
Pub Date : 2025-11-12DOI: 10.1016/j.mam.2025.101415
Bin Liu , Chengjiang Liu , Caroline Sunggip , GuangJin Pu , Dong Deng
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.
{"title":"Viruses in gastrointestinal cancers: Molecular pathogenesis, oncogenic mechanisms, and translational perspectives","authors":"Bin Liu , Chengjiang Liu , Caroline Sunggip , GuangJin Pu , 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":"2025-11-12","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}
Pub Date : 2025-11-10DOI: 10.1016/j.mam.2025.101421
Subo Cai , Xiao Liang , Hongshuai Wu , Xinyu Li , Qi Pu
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.
{"title":"Navigating the ocular barrier: Viral- and nanotechnology-based delivery systems as promising therapeutic agents for ocular diseases","authors":"Subo Cai , Xiao Liang , Hongshuai Wu , Xinyu Li , 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":"2025-11-10","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}
Pub Date : 2025-11-10DOI: 10.1016/j.mam.2025.101412
Jose Jimeno , Jose Felipe Varona , Jose A. Lopez-Martin , Nuria Izquierdo-Useros , Elisa Molina Molina , Pablo Guisado-Vasco , Martin Sachse , Cristina Risco , Alejandro Losada , Salvador Fudio , Erik Luepke , Antonio Nieto , Javier Gomez , Pablo Aviles , Carmen Cuevas , Mehdi Bouhaddou , Isabel Sola , Nevan J. Krogan , Luis Enjuanes , Jose M. Fernandez-Sousa , Kris White
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 Aplidium albicans, 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.
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