Molecular Aspects of Medicine最新文献_第2页

Liver aging: underlying mechanisms and therapeutic strategies 肝衰老：潜在机制和治疗策略

IF 10.3 2区医学

Molecular Aspects of Medicine Pub Date : 2025-08-30 DOI: 10.1016/j.mam.2025.101397

Ling Zhong , Liu Wang , Jibran Nehal Syed , Jielin Yang , Yuwei Zhang

{"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}

引用次数: 0

Viral and non-viral vectors for gene therapy in the treatment of bone-related disorders: molecular insights and clinical perspectives 用于骨相关疾病的基因治疗的病毒和非病毒载体：分子见解和临床观点

IF 10.3 2区医学

Molecular Aspects of Medicine Pub Date : 2025-08-29 DOI: 10.1016/j.mam.2025.101400

Heng'an Ge , Zhoutong Shi , Centao Liu , Jingwei Lu , Ying Yao , Biao Cheng

{"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}

引用次数: 0

Optogenetic tools and their applications for therapeutic intervention in end-stage inherited retinal diseases 光遗传学工具及其在终末期遗传性视网膜疾病治疗干预中的应用

IF 10.3 2区医学

Molecular Aspects of Medicine Pub Date : 2025-08-28 DOI: 10.1016/j.mam.2025.101388

Elizaveta Podoliak , Gabriela Guzman , Volker Busskamp

{"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}

引用次数: 0

Evolution of the incidence of male fertility disorders over the last decades 近几十年来男性生育障碍发病率的演变

IF 10.3 2区医学

Molecular Aspects of Medicine Pub Date : 2025-08-28 DOI: 10.1016/j.mam.2025.101398

Francesco Pallotti , Alessandra Buonacquisto , Gaia Cicolani , Anna Chiara Conflitti , Francesco Lombardo , Donatella Paoli

引用次数: 0

Molecular mechanism involved in sarcopenia and frailty, diagnosis and therapy 肌少症和虚弱的分子机制、诊断和治疗。

IF 10.3 2区医学

Molecular Aspects of Medicine Pub Date : 2025-08-07 DOI: 10.1016/j.mam.2025.101387

Jose Viña, Maria Carmen Gomez-Cabrera

引用次数: 0

Unveiling the P2X7 receptor: Exploring its mechanisms, pathogenic role in ocular diseases, and emerging therapeutic potential 揭示P2X7受体：探索其在眼部疾病中的机制、致病作用和新的治疗潜力

IF 10.3 2区医学

Molecular Aspects of Medicine Pub Date : 2025-07-28 DOI: 10.1016/j.mam.2025.101389

Kai-Yang Chen , Hoi-Chun Chan , Chi-Ming Chan

{"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}

引用次数: 0

Mitophagy: A key regulator of radiotherapy resistance in the tumor immune microenvironment 线粒体自噬：肿瘤免疫微环境中放疗抵抗的关键调节因子

IF 8.7 2区医学

Molecular Aspects of Medicine Pub Date : 2025-07-20 DOI: 10.1016/j.mam.2025.101385

Jing Xia , Jing Jin , Shuang Dai , HaoHan Fan , KeLiang Chen , JianMei Li , Feng Luo , Xingchen Peng

{"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}

引用次数: 0

Respiratory emerging viruses and drug resistance in lung cancer: challenges and new perspectives in treatment 呼吸道新发病毒和肺癌的耐药：治疗的挑战和新观点

IF 8.7 2区医学

Molecular Aspects of Medicine Pub Date : 2025-07-15 DOI: 10.1016/j.mam.2025.101383

Qiang Wu , Wen Li , Hongli Liu , Yinyin Xue , Kaili Huang , Hossein Pourghadamyari , Zhenkun Liu

{"title":"Respiratory emerging viruses and drug resistance in lung cancer: challenges and new perspectives in treatment","authors":"Qiang Wu , Wen Li , Hongli Liu , Yinyin Xue , Kaili Huang , Hossein Pourghadamyari , Zhenkun Liu","doi":"10.1016/j.mam.2025.101383","DOIUrl":"10.1016/j.mam.2025.101383","url":null,"abstract":"<div><div>Emerging viral pathogens, particularly those targeting the respiratory system such as SARS-CoV-2 and influenza virus, pose significant challenges for patients with lung cancer. These patients show increased susceptibility to serious infections caused by these viruses as a result of immunosuppression from various therapies such as immunotherapy, chemotherapy, and targeted agents. Respiratory viral infections can induce tumor progression and drug resistance through affecting the tumor microenvironment (TME), modulating immune checkpoints, or interfering with therapeutic efficacy. The present review discusses the reciprocal interactions between these viral pathogens and lung cancer, underscoring mechanisms by which SARS-CoV-2 and influenza viruses affect the lung cancer TME promoting tumor progression, immune evasion, and ultimately, resistance to anti-cancer therapies such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Sections discussed in this study include: (i) increased susceptibility to viral infections, (ii) virus-induced modulation of the tumor microenvironment, and (iii) mechanisms of therapy resistance. This review also addresses emerging strategies, such as oncolytic virotherapy, as potential candidates for lung cancer treatment. It aims to provide new perspectives on therapeutic optimization for patients with lung cancer in the context of SARS-CoV-2 and influenza viruses, by reviewing evidence from virology, oncology, and immunology.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"104 ","pages":"Article 101383"},"PeriodicalIF":8.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632758","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}

引用次数: 0

Protein and RNA chaperones 蛋白质和RNA伴侣

IF 8.7 2区医学

Molecular Aspects of Medicine Pub Date : 2025-07-14 DOI: 10.1016/j.mam.2025.101384

Bikash R. Sahoo, James CA. Bardwell

引用次数: 0

The role of free fatty acid receptors activation in pancreatic disorders 游离脂肪酸受体激活在胰腺疾病中的作用

IF 8.7 2区医学

Molecular Aspects of Medicine Pub Date : 2025-07-12 DOI: 10.1016/j.mam.2025.101386

Julia Lis, Jakub Fichna, Aleksandra Tarasiuk-Zawadzka

{"title":"The role of free fatty acid receptors activation in pancreatic disorders","authors":"Julia Lis, Jakub Fichna, Aleksandra Tarasiuk-Zawadzka","doi":"10.1016/j.mam.2025.101386","DOIUrl":"10.1016/j.mam.2025.101386","url":null,"abstract":"<div><div>Free fatty acid receptors (FFARs), a subset of G protein-coupled receptors, play a pivotal role in metabolic and immune homeostasis by modulating signaling pathways in response to free fatty acids. The four main FFARs (FFAR1, FFAR2, FFAR3, and FFAR4) are especially significant in pancreatic function, regulating insulin secretion, inflammation, and glucose metabolism. These receptors are involved in key pancreatic disorders, including acute pancreatitis (AP), pancreatic cancer (PC), type 1 diabetes (T1D), and type 2 diabetes (T2D).</div><div>FFAR1, FFAR3, and FFAR4 exhibit protective effects against AP due to their anti-inflammatory properties. In PC, FFAR1 inhibits tumor cell motility, while FFAR2 downregulation may contribute to tumor progression. FFAR3 plays a role in limiting tumor proliferation, whereas FFAR4 has a dual effect, promoting metastasis while also triggering tumor cell apoptosis. In T1D, FFAR2 and FFAR4 help regulate glycemia without directly stimulating insulin secretion. In T2D, all four FFARs contribute to glycemic control and may protect pancreatic β-cells.</div><div>Despite their therapeutic potential, the precise mechanisms underlying FFAR function in pancreatic disorders remain incompletely understood. Ongoing research aims to clarify these pathways, identify optimal ligands, and assess the safety and efficacy of FFAR-targeted therapies. This growing body of evidence underscores the importance of FFARs as potential targets for innovative treatments in pancreatic diseases.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"104 ","pages":"Article 101386"},"PeriodicalIF":8.7,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605148","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}

引用次数: 0