Pub Date : 2025-09-13DOI: 10.1016/j.mam.2025.101410
Nataliya V. Zharova , Filipp D. Mikhailidi , Darya A. Kabanova , Alena Y. Tatarintseva , Olga L. Polyakova , Yury O. Zharikov , Nikolai A. Zharov , Sergey N. Ryagin , André Pontes-Silva , Tatiana S. Zharikova
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.
{"title":"Influence of microbiota composition on the pathogenesis of type 2 diabetes: Physiological aspects","authors":"Nataliya V. Zharova , Filipp D. Mikhailidi , Darya A. Kabanova , Alena Y. Tatarintseva , Olga L. Polyakova , Yury O. Zharikov , Nikolai A. Zharov , Sergey N. Ryagin , André Pontes-Silva , 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":"2025-09-13","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}
Pub Date : 2025-09-12DOI: 10.1016/j.mam.2025.101399
Yubin Li , Guanghan Fan , Huadong He
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.
{"title":"Urogenital manifestations of SARS-CoV-2, MPXV and Zika virus: A comprehensive review","authors":"Yubin Li , Guanghan Fan , 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":"2025-09-12","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}
Pub Date : 2025-09-12DOI: 10.1016/j.mam.2025.101401
Xiang Li , Rui Ding , Hui Wang , Sijing Chen , Xirui Fan , Yiyao Duan , Jun Hu , Hao Hu , Rui Wu , Rong Qin
SUMOylation is a critical post-translational modification that modulates protein activity, stability, and subcellular distribution through the covalent attachment of SUMO proteins (SUMO1-5) to specific targets. This process is mediated by a cascade of enzymes, including E1, E2, E3 ligases, and deSUMOylation enzymes, enabling precise control over diverse biological functions such as gene expression, cell cycle regulation, DNA damage repair, signaling cascades, and metabolic pathways.
Dysregulation of SUMOylation enzymes has been contributes to cancer initiation, and treatment resistance, by enhancing tumor cell motility, aggressiveness, and epithelial-mesenchymal transition (EMT). In gastrointestinal malignancies—including gastric, hepatic, colorectal, esophageal, gallbladder, and pancreatic cancers—SUMOylation drives tumor growth, metastasis, and invasiveness by reprogramming metabolic processes, signaling networks, and the surrounding tumor niche. Additionally, it contributes to resistance against chemotherapy and radiotherapy.
Understanding the molecular basis of SUMOylation not only underscores its significance in oncogenesis but also provides a foundation for developing novel anticancer therapies.
{"title":"Research advancements on sumoylation in gastrointestinal cancers","authors":"Xiang Li , Rui Ding , Hui Wang , Sijing Chen , Xirui Fan , Yiyao Duan , Jun Hu , Hao Hu , Rui Wu , Rong Qin","doi":"10.1016/j.mam.2025.101401","DOIUrl":"10.1016/j.mam.2025.101401","url":null,"abstract":"<div><div>SUMOylation is a critical post-translational modification that modulates protein activity, stability, and subcellular distribution through the covalent attachment of SUMO proteins (SUMO1-5) to specific targets. This process is mediated by a cascade of enzymes, including E1, E2, E3 ligases, and deSUMOylation enzymes, enabling precise control over diverse biological functions such as gene expression, cell cycle regulation, DNA damage repair, signaling cascades, and metabolic pathways.</div><div>Dysregulation of SUMOylation enzymes has been contributes to cancer initiation, and treatment resistance, by enhancing tumor cell motility, aggressiveness, and epithelial-mesenchymal transition (EMT). In gastrointestinal malignancies—including gastric, hepatic, colorectal, esophageal, gallbladder, and pancreatic cancers—SUMOylation drives tumor growth, metastasis, and invasiveness by reprogramming metabolic processes, signaling networks, and the surrounding tumor niche. Additionally, it contributes to resistance against chemotherapy and radiotherapy.</div><div>Understanding the molecular basis of SUMOylation not only underscores its significance in oncogenesis but also provides a foundation for developing novel anticancer therapies.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"106 ","pages":"Article 101401"},"PeriodicalIF":10.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050660","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 : 2025-08-30DOI: 10.1016/j.mam.2025.101397
Ling Zhong , Liu Wang , Jibran Nehal Syed , Jielin Yang , Yuwei Zhang
The accelerating pace of global aging underscores the urgent need to address age-related physiological decline and its associated pathologies. The liver, a central organ for metabolic and immune regulation, undergoes structural and functional deterioration with advanced age, positioning liver aging as a critical concern in geriatric medicine. Due to the liver's cellular heterogeneity and complex physiology, our understanding of its aging mechanisms remains fragmented, lacking an integrated framework to consolidate factors such as oxidative stress, inflammaging, metabolic reprogramming, genomic instability, and epigenetic dysregulation. This review systematically summarizes the physiological processes and molecular mechanisms of liver aging, explores its contributions to disease progression, and discusses current intervention strategies, including dietary and exercise regimens, pharmacological therapies, and gene-editing technologies. By synthesizing existing evidence, this review provides a theoretical framework to advance the understanding of the pathophysiological mechanisms underlying liver aging and inform the development of innovative anti-aging interventions.
{"title":"Liver aging: underlying mechanisms and therapeutic strategies","authors":"Ling Zhong , Liu Wang , Jibran Nehal Syed , Jielin Yang , Yuwei Zhang","doi":"10.1016/j.mam.2025.101397","DOIUrl":"10.1016/j.mam.2025.101397","url":null,"abstract":"<div><div>The accelerating pace of global aging underscores the urgent need to address age-related physiological decline and its associated pathologies. The liver, a central organ for metabolic and immune regulation, undergoes structural and functional deterioration with advanced age, positioning liver aging as a critical concern in geriatric medicine. Due to the liver's cellular heterogeneity and complex physiology, our understanding of its aging mechanisms remains fragmented, lacking an integrated framework to consolidate factors such as oxidative stress, inflammaging, metabolic reprogramming, genomic instability, and epigenetic dysregulation. This review systematically summarizes the physiological processes and molecular mechanisms of liver aging, explores its contributions to disease progression, and discusses current intervention strategies, including dietary and exercise regimens, pharmacological therapies, and gene-editing technologies. By synthesizing existing evidence, this review provides a theoretical framework to advance the understanding of the pathophysiological mechanisms underlying liver aging and inform the development of innovative anti-aging interventions.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"105 ","pages":"Article 101397"},"PeriodicalIF":10.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916860","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 : 2025-08-29DOI: 10.1016/j.mam.2025.101400
Heng'an Ge , Zhoutong Shi , Centao Liu , Jingwei Lu , Ying Yao , Biao Cheng
Gene therapy offers a transformative approach for treating debilitating bone disorders by delivering therapeutic genetic material to target sites. The efficacy and safety of this approach are heavily reliant on the chosen delivery vehicle, either viral or non-viral vectors. Viral vectors are characterized by high transduction efficiency and the potential for long-term expression, as exemplified by Adeno-Associated Viruses (AAVs) and lentiviruses. However, their use is tempered by concerns over immunogenicity, manufacturing complexity, and safety. In contrast, non-viral vectors, which employ synthetic or physical methods, offer compelling advantages in safety, reduced immunogenicity, and manufacturing scalability but traditionally suffer from lower delivery efficiency. Ongoing research focuses on enhancing their cellular uptake and stability through advanced strategies such as lipid and polymer complexation and physical methods, aiming for targeted delivery to bone tissue. This includes the development of various nanocarriers and hydrogels designed to overcome physiological barriers. This study aims to comprehensively review and compare the current landscape of viral and non-viral gene therapy vectors, highlighting their mechanisms, advantages, disadvantages, and clinical applicability in the context of bone tissue regeneration and the treatment of bone disorders, with a focus on recent advancements and future directions to enhance therapeutic efficacy and safety.
{"title":"Viral and non-viral vectors for gene therapy in the treatment of bone-related disorders: molecular insights and clinical perspectives","authors":"Heng'an Ge , Zhoutong Shi , Centao Liu , Jingwei Lu , Ying Yao , Biao Cheng","doi":"10.1016/j.mam.2025.101400","DOIUrl":"10.1016/j.mam.2025.101400","url":null,"abstract":"<div><div>Gene therapy offers a transformative approach for treating debilitating bone disorders by delivering therapeutic genetic material to target sites. The efficacy and safety of this approach are heavily reliant on the chosen delivery vehicle, either viral or non-viral vectors. Viral vectors are characterized by high transduction efficiency and the potential for long-term expression, as exemplified by Adeno-Associated Viruses (AAVs) and lentiviruses. However, their use is tempered by concerns over immunogenicity, manufacturing complexity, and safety. In contrast, non-viral vectors, which employ synthetic or physical methods, offer compelling advantages in safety, reduced immunogenicity, and manufacturing scalability but traditionally suffer from lower delivery efficiency. Ongoing research focuses on enhancing their cellular uptake and stability through advanced strategies such as lipid and polymer complexation and physical methods, aiming for targeted delivery to bone tissue. This includes the development of various nanocarriers and hydrogels designed to overcome physiological barriers. This study aims to comprehensively review and compare the current landscape of viral and non-viral gene therapy vectors, highlighting their mechanisms, advantages, disadvantages, and clinical applicability in the context of bone tissue regeneration and the treatment of bone disorders, with a focus on recent advancements and future directions to enhance therapeutic efficacy and safety.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"105 ","pages":"Article 101400"},"PeriodicalIF":10.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916859","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}
Retinal degenerative diseases pose significant therapeutic challenges; however, optogenetic vision restoration offers a promising strategy that is independent of mutations and disease progression. Optogenetic tools consisting of photosensitive membrane proteins can be ectopically expressed in retinal cells, effectively converting them into artificial photoreceptors. This review outlines the development and application of optogenetic tools to restore light sensitivity in degenerated retinas. A thorough understanding of retinal cell morphology, pathological remodeling, and functional loss is critical to identifying optimal cellular targets to maximize retinal signal restoration and achieve challenging visual outcomes. Precise delivery and expression of tailored optogenetic tools in specific retinal cell types is critical for clinical success. While recent efforts have focused on achieving vision restoration at ambient light levels, other considerations such as dynamic light adaptation, inner retinal signal processing, and improved visual resolution have emerged as critical factors. Technologies such as optogenetic stimulation goggles integrated with artificial intelligence have the potential to improve visual quality in treated patients. This review also summarizes the preclinical fundamentals and highlights the first clinical successes, underscoring that optogenetic vision restoration is on its way to becoming an effective therapy for restoring meaningful vision to people affected by blindness.
{"title":"Optogenetic tools and their applications for therapeutic intervention in end-stage inherited retinal diseases","authors":"Elizaveta Podoliak , Gabriela Guzman , Volker Busskamp","doi":"10.1016/j.mam.2025.101388","DOIUrl":"10.1016/j.mam.2025.101388","url":null,"abstract":"<div><div>Retinal degenerative diseases pose significant therapeutic challenges; however, optogenetic vision restoration offers a promising strategy that is independent of mutations and disease progression. Optogenetic tools consisting of photosensitive membrane proteins can be ectopically expressed in retinal cells, effectively converting them into artificial photoreceptors. This review outlines the development and application of optogenetic tools to restore light sensitivity in degenerated retinas. A thorough understanding of retinal cell morphology, pathological remodeling, and functional loss is critical to identifying optimal cellular targets to maximize retinal signal restoration and achieve challenging visual outcomes. Precise delivery and expression of tailored optogenetic tools in specific retinal cell types is critical for clinical success. While recent efforts have focused on achieving vision restoration at ambient light levels, other considerations such as dynamic light adaptation, inner retinal signal processing, and improved visual resolution have emerged as critical factors. Technologies such as optogenetic stimulation goggles integrated with artificial intelligence have the potential to improve visual quality in treated patients. This review also summarizes the preclinical fundamentals and highlights the first clinical successes, underscoring that optogenetic vision restoration is on its way to becoming an effective therapy for restoring meaningful vision to people affected by blindness.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"105 ","pages":"Article 101388"},"PeriodicalIF":10.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907976","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 : 2025-08-28DOI: 10.1016/j.mam.2025.101398
Francesco Pallotti , Alessandra Buonacquisto , Gaia Cicolani , Anna Chiara Conflitti , Francesco Lombardo , Donatella Paoli
Male reproductive health evaluation involves andrological and sexological clinical problems but, on a wider scale, it also involves other public health issues, including lifestyle and metabolic factors. These factors, especially if combined with pre-existing andrological diseases, have been found to be significantly associated with semen parameters impairment and, thus, male infertility. A hypothesized trend of decline of male fertility has been debated in the last years and this aspect is strictly intertwined with the evolution of the incidence of male fertility disorders over the last decades. It should be stressed that all these factors harbour relevant repercussions for both individual reproductive health as well as broader socio-economic and demographic issues. Thus, the aim of this review is to perform a short and critical overview of the andrological issues affecting the reproductive outcomes of the infertile male as well as provide a comprehensive and critical overview of the male fertility decline issue.
{"title":"Evolution of the incidence of male fertility disorders over the last decades","authors":"Francesco Pallotti , Alessandra Buonacquisto , Gaia Cicolani , Anna Chiara Conflitti , Francesco Lombardo , Donatella Paoli","doi":"10.1016/j.mam.2025.101398","DOIUrl":"10.1016/j.mam.2025.101398","url":null,"abstract":"<div><div>Male reproductive health evaluation involves andrological and sexological clinical problems but, on a wider scale, it also involves other public health issues, including lifestyle and metabolic factors. These factors, especially if combined with pre-existing andrological diseases, have been found to be significantly associated with semen parameters impairment and, thus, male infertility. A hypothesized trend of decline of male fertility has been debated in the last years and this aspect is strictly intertwined with the evolution of the incidence of male fertility disorders over the last decades. It should be stressed that all these factors harbour relevant repercussions for both individual reproductive health as well as broader socio-economic and demographic issues. Thus, the aim of this review is to perform a short and critical overview of the andrological issues affecting the reproductive outcomes of the infertile male as well as provide a comprehensive and critical overview of the male fertility decline issue.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"105 ","pages":"Article 101398"},"PeriodicalIF":10.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908091","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 : 2025-08-07DOI: 10.1016/j.mam.2025.101387
Jose Viña, Maria Carmen Gomez-Cabrera
{"title":"Molecular mechanism involved in sarcopenia and frailty, diagnosis and therapy","authors":"Jose Viña, Maria Carmen Gomez-Cabrera","doi":"10.1016/j.mam.2025.101387","DOIUrl":"10.1016/j.mam.2025.101387","url":null,"abstract":"","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"105 ","pages":"Article 101387"},"PeriodicalIF":10.3,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805126","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 : 2025-07-28DOI: 10.1016/j.mam.2025.101389
Kai-Yang Chen , Hoi-Chun Chan , Chi-Ming Chan
Purinergic signaling, mediated by extracellular ATP (eATP) and P2 receptors, plays a vital role in physiological and pathological processes. The P2X7 receptor (P2X7R), a ligand-gated cation channel, is crucial in inflammation, cell death, and immune responses. Widely expressed in retinal cells, P2X7R contributes to visual function regulation and retinal degeneration. This review explores P2X7R involvement in retinal diseases, including age-related macular degeneration (AMD), Behçet's disease (BD), diabetic retinopathy (DR), glaucoma, retinitis pigmentosa (RP), uveitis, Stargardt's disease (STGD), and toxoplasmosis.
P2X7R activation drives inflammation, oxidative stress, apoptosis, and immune dysregulation. For instance, it contributes to RPE degeneration in AMD, vascular proliferation in DR, neuroinflammation in glaucoma, and photoreceptor loss in RP. In uveitis, P2X7R enhances Th1 and Th17 responses. Targeting P2X7R with antagonists or modulators holds therapeutic potential, offering strategies to preserve retinal function and prevent vision loss in these debilitating diseases.
{"title":"Unveiling the P2X7 receptor: Exploring its mechanisms, pathogenic role in ocular diseases, and emerging therapeutic potential","authors":"Kai-Yang Chen , Hoi-Chun Chan , Chi-Ming Chan","doi":"10.1016/j.mam.2025.101389","DOIUrl":"10.1016/j.mam.2025.101389","url":null,"abstract":"<div><div>Purinergic signaling, mediated by extracellular ATP (eATP) and P2 receptors, plays a vital role in physiological and pathological processes. The P2X7 receptor (P2X7R), a ligand-gated cation channel, is crucial in inflammation, cell death, and immune responses. Widely expressed in retinal cells, P2X7R contributes to visual function regulation and retinal degeneration. This review explores P2X7R involvement in retinal diseases, including age-related macular degeneration (AMD), Behçet's disease (BD), diabetic retinopathy (DR), glaucoma, retinitis pigmentosa (RP), uveitis, Stargardt's disease (STGD), and toxoplasmosis.</div><div>P2X7R activation drives inflammation, oxidative stress, apoptosis, and immune dysregulation. For instance, it contributes to RPE degeneration in AMD, vascular proliferation in DR, neuroinflammation in glaucoma, and photoreceptor loss in RP. In uveitis, P2X7R enhances Th1 and Th17 responses. Targeting P2X7R with antagonists or modulators holds therapeutic potential, offering strategies to preserve retinal function and prevent vision loss in these debilitating diseases.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"105 ","pages":"Article 101389"},"PeriodicalIF":10.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144720951","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 : 2025-07-20DOI: 10.1016/j.mam.2025.101385
Jing Xia , Jing Jin , Shuang Dai , HaoHan Fan , KeLiang Chen , JianMei Li , Feng Luo , Xingchen Peng
Cancer remains a leading global cause of mortality, with radiation therapy (RT) as a cornerstone of treatment despite frequent radioresistance. Emerging evidence indicates that mitophagy activation contributes to adaptive radioresistance of cancer cells within the tumor microenvironment (TME). In this review, we highlight the dual role of mitophagy in modulating RT resistance and shaping the immune landscape of the TME. Mitophagy enhances cancer cell resilience by clearing radiation-damaged mitochondria, preserving metabolic homeostasis and reducing oxidative stress, while simultaneously altering the balance between immune activation and suppression within the TME. To provide mechanistic insight, we summarize key mitophagy-regulating pathways—including the PINK1/Parkin axis, BNIP3/NIX, and FUNDC1-mediated mechanisms—that respond to RT-induced mitochondrial stress and represent potential therapeutic targets. Furthermore, we explore how the interplay between mitophagy, metabolic reprogramming, and immune modulation shapes resistance not only to RT but also to immunotherapies such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T (CAR-T) cell therapy. Additionally, we examine how Type 2 diabetes(T2DM) mellitus impacts this process, as its associated metabolic disturbances exacerbate mitochondrial vulnerability to radiation and create an immunosuppressive milieu that compromises the tumor immune landscape. Understanding these interactions may support development of personalized therapeutic strategies for diabetic cancer patients.
{"title":"Mitophagy: A key regulator of radiotherapy resistance in the tumor immune microenvironment","authors":"Jing Xia , Jing Jin , Shuang Dai , HaoHan Fan , KeLiang Chen , JianMei Li , Feng Luo , Xingchen Peng","doi":"10.1016/j.mam.2025.101385","DOIUrl":"10.1016/j.mam.2025.101385","url":null,"abstract":"<div><div>Cancer remains a leading global cause of mortality, with radiation therapy (RT) as a cornerstone of treatment despite frequent radioresistance. Emerging evidence indicates that mitophagy activation contributes to adaptive radioresistance of cancer cells within the tumor microenvironment (TME). In this review, we highlight the dual role of mitophagy in modulating RT resistance and shaping the immune landscape of the TME. Mitophagy enhances cancer cell resilience by clearing radiation-damaged mitochondria, preserving metabolic homeostasis and reducing oxidative stress, while simultaneously altering the balance between immune activation and suppression within the TME. To provide mechanistic insight, we summarize key mitophagy-regulating pathways—including the PINK1/Parkin axis, BNIP3/NIX, and FUNDC1-mediated mechanisms—that respond to RT-induced mitochondrial stress and represent potential therapeutic targets. Furthermore, we explore how the interplay between mitophagy, metabolic reprogramming, and immune modulation shapes resistance not only to RT but also to immunotherapies such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T (CAR-T) cell therapy. Additionally, we examine how Type 2 diabetes(T2DM) mellitus impacts this process, as its associated metabolic disturbances exacerbate mitochondrial vulnerability to radiation and create an immunosuppressive milieu that compromises the tumor immune landscape. Understanding these interactions may support development of personalized therapeutic strategies for diabetic cancer patients.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"105 ","pages":"Article 101385"},"PeriodicalIF":8.7,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665892","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}
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