Expert Reviews in Molecular Medicine最新文献

{"title":"Synergizing Radiotherapy and Immune Checkpoint Inhibitors in Malignant Solid Tumours: Mechanistic Insights and Translational Frontiers.","authors":"Jiahui Dai, Lingwei Ma, Xinyi Han, Xiong Li, Lingfei Han, Wei Wang","doi":"10.1017/erm.2026.10041","DOIUrl":"10.1017/erm.2026.10041","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy (RT) and immune checkpoint inhibitors (ICIs) have each transformed the treatment of malignant solid tumors (STs). Beyond direct tumor killing, RT remodels the tumor microenvironment (TME), promotes antigen release, and enhances immune activation. ICIs targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1) restore antitumor immunity by reversing T cell exhaustion. Increasing evidence indicates that RT can synergize with ICIs through mechanisms such as the abscopal effect, immunogenic cell death (ICD), and activation of the cyclic guanosine monophosphate-adenosine monophosphate (cGMP-AMP) synthase-stimulator of interferon genes (cGAS-STING) pathway.</p><p><strong>Methods: </strong>This review summarizes current radiobiological, immunological, and clinical evidence regarding the synergistic effects of RT and ICIs in malignant STs, with a focus on underlying mechanisms, recent clinical advances, and translational challenges.</p><p><strong>Results: </strong>RT can enhance tumor immunogenicity, promote immune priming, and reshape the TME to improve the efficacy of ICIs. Synergy between RT and ICIs is associated with ICD induction, cGAS‒STING activation, enhanced systemic antitumor immunity, and modulation of immune cell infiltration and checkpoint signaling. Clinical studies across multiple STs have shown encouraging efficacy and manageable safety, although outcomes vary according to tumor type, disease stage, radiation schedule, and patient selection.</p><p><strong>Conclusions: </strong>RT combined with ICIs is a promising therapeutic strategy for malignant STs. Further optimization of treatment regimens and biomarker-guided patient selection will be essential to maximize clinical benefit and enable more precise combination therapies.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e17"},"PeriodicalIF":5.5,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147391430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Lipidomic Responses to Inflammation and Physical Insult: A Comparative Review Across Blunt Force Trauma, Thermal Burn Injury, and Viral Infection.","authors":"Harrison Szemray, Nathan Geoffrey Lawler, Samantha Lodge, Julien Wist, Luke Whiley","doi":"10.1017/erm.2026.10038","DOIUrl":"10.1017/erm.2026.10038","url":null,"abstract":"<p><p>Acute insults ranging from blunt force trauma and thermal injury to pathogenic infection elicit systemic inflammatory cascades intended to limit further tissue damage. These responses are accompanied by metabolic disturbances that generate distinct biochemical signatures measurable through advanced analytical platforms, such as mass spectrometry and nuclear magnetic resonance spectroscopy (NMR). Although numerous studies have examined these metabolic alterations, findings remain fragmented across clinical and analytical disciplines, leaving it unclear whether the systemic metabolic response to acute insult is fundamentally conserved or insult-specific. In this comparative review, we consolidate evidence across diverse injury and infection contexts to identify shared metabolic patterns, context-dependent differences, and critical gaps in current understanding. Here, we focus on lipid and lipoprotein profiling of blood plasma and serum. We present exemplar case studies spanning traumatic brain injury, burn injury, and SARS-CoV-2 infection to illustrate how lipid and lipoprotein perturbations differ or converge across insult types. Notable observations include consistently elevated palmitic acid (16:0) and reduced phosphatidylcholine species across all three conditions, suggesting these features may represent cross-condition biomarkers and highlighting the value of comparative metabolic profiling. By integrating evidence across diverse contexts, we propose a framework describing the interplay between lipid metabolism, lipoprotein dynamics, and inflammatory activation. Finally, we discuss the translational potential of metabolic phenotyping in enhancing patient stratification, refining prognostic modelling, and improving patient outcomes.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e11"},"PeriodicalIF":5.5,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Tumor Cells: Emerging Frontiers in Cancer Technology.","authors":"Parth Agarwal, Rachana Raman, Manasa Bhagwat, Prasoon Agarwal, Praveen Kumar","doi":"10.1017/erm.2026.10039","DOIUrl":"10.1017/erm.2026.10039","url":null,"abstract":"<p><strong>Background: </strong>Circulating tumour cells (CTCs) are unique cells that originate from the main tumor site. They circulate in the bloodstream, and are implicated in metastasis, immune evasion and recurrence in various cancers. Associated biomarkers of importance for CTC detection include epithelial cell adhesion molecule (EpCAM), human epidermal growth factor receptor 2 (HER2), programmed death ligand-1 (PD-L1), cluster of differentiation 45 (CD45) and other cancer-specific biomolecules. Their roles as standalone biomarkers, have been thoroughly examined in CTC detection, isolation and targeting.</p><p><strong>Methods: </strong>This review collates key findings on CTC characteristics and biomarker identification. The most recent CTC isolation and detection technologies are discussed, along with individual approaches based on inclusion and exclusion of cell-specific biomarkers. Emerging treatments integrating CTCs, including nanocarrier-mediated drug delivery, have been analyzed. We have discussed both the physical and research barriers in the current landscape.</p><p><strong>Results: </strong>Recent advances have determined that such biomarkers are more reliable when associated with secondary biomarkers, due to concerns regarding immune evasion and low sensitivity. The identification of these molecules has fast-tracked the development of several groundbreaking technologies.</p><p><strong>Conclusion: </strong>The prognostic and predictive role of CTCs in various cancers revealed promising results. The development of integrative therapeutics can enhance patient survival and quality of life. These advancements depend on addressing key issues, such as molecular characterization and low abundance of CTCs.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e10"},"PeriodicalIF":5.5,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Synuclein in Lewy Body Diseases: Progress, Remaining Challenges and Future Perspectives.","authors":"Imogen J H Grimwade, Grey Enticknap, Eduardo De Pablo Fernandez, Cara Louise Croft","doi":"10.1017/erm.2026.10037","DOIUrl":"10.1017/erm.2026.10037","url":null,"abstract":"<p><p>Lewy bodies (LBs) are the main pathological feature of the neurodegenerative diseases Parkinson's disease and Dementia with LBs. Since their discovery over 100 years ago, it is only in the last three decades, that, a wealth of genetic, pathological and pre-clinical evidence puts the spotlight on accumulated α-Synuclein (α-Syn) as the main component of LBs and implicated as a driver of these diseases. This has catapulted clinical trials for these diseases focussing on strategies to remove, reduce, disaggregate and prevent propagation of α-Syn. Advances in technical approaches have started to build a bigger picture of the complexity of LBs extending beyond α-Syn. There is still much to be learned about the processes underlying the formation and structure of LBs and their relationship to neurodegeneration. This will likely impact upon how we target these diseases therapeutically, diagnose them and build clinical trials. Here, we will discuss LBs in the context of α-Syn and other features, modelling strategies and how to direct research moving forwards in order to get clinical results. A more complete understanding of LBs and potential novel targets that drive their formation will likely lead to better outcomes in LB diseases.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e7"},"PeriodicalIF":5.5,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146214824","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":"Mediating Cross-Talk: How Uterus-Derived Extracellular Vesicles Influence Early Embryo Development and Implantation.","authors":"Qiuyu Yu, Lei Jin, Bo Zhang","doi":"10.1017/erm.2026.10034","DOIUrl":"10.1017/erm.2026.10034","url":null,"abstract":"<p><strong>Background: </strong>Blastocyst formation represents an essential requirement for subsequent implantation. Successful embryo implantation depends on adequate endometrial receptivity and appropriate embryo-maternal communication. Uterus-derived extracellular vesicles (EVs), as biological nanoscale particles carrying non-coding RNAs (nc-RNAs), DNAs, proteins and lipids, play a crucial role in promoting cellular interaction<u>s</u> and regulating maternal-foetal dialogue.</p><p><strong>Method: </strong>This article systematically searched the PubMed database and used the following keyword combinations for literature screening : (exosome * OR 'extracellular vesicle') AND (uter OR blastocysti) AND (blastocyst OR embryo*).</p><p><strong>Result: </strong>The composition of uterus-derived EVs exhibits variation across different physiological periods and plays different roles. Compared with the proliferative phase, EVs during the peri-implantation period contain more molecules related to cell differentiation, cell cycle, cell migration and invasion, apoptosis and antioxidant activity. The EVs discovered from uterine fluid, primary human endometrial epithelial cells (EECs), endometrial stromal cell and so forth have been shown to be internalised by embryos and trophoblast cell. The cargoes carried by EVs, mainly miRNA and proteins, regulate embryonic development and invasion-related pathways or molecules, supporting blastocyst formation and implantation. Similarly, EVs collected from dysfunctional uterus have been proved to disrupt critical reproductive processes, impairing both embryo development and implantation potential.</p><p><strong>Conclusion: </strong>This review summarises the multiple effects of uterus-derived EVs on successful embryo implantation, including the effects on pre-implantation embryo development and embryo implantation ability.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e13"},"PeriodicalIF":5.5,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Lactylation in Liver Disease: A Comprehensive Review.","authors":"Sipu Wang, Jie Zhang, Chao Sun","doi":"10.1017/erm.2026.10036","DOIUrl":"10.1017/erm.2026.10036","url":null,"abstract":"<p><strong>Background: </strong>Lactate, generated through glycolysis, plays a dual role as both a metabolic substrate and a signalling molecule, influencing cellular functions in pathophysiological scenarios. Protein lactylation, a recently identified form of post-translational modification mediated by lactate, has garnered significant and increasing attention. Globally, hepatic disorders pose a significant public health burden, frequently involving disruptions in glucose metabolism and consequent lactate buildup.</p><p><strong>Methods: </strong>This comprehensive review examines the discovery, regulatory mechanisms and pathogenic roles of lactylation in diverse liver disorders, while critically evaluating emerging lactylation-targeted therapeutics to guide future translational research.</p><p><strong>Results: </strong>Lactylation modifications play a pivotal role in various pathophysiological processes, including hepatic inflammation, liver fibrosis, ischaemic injury, tumour growth and metastasis.</p><p><strong>Conclusions: </strong>Modulation of lactylation pathways, coupled with pharmacological control of lactate synthesis and shuttling, emerges as a strategic approach to liver disease therapeutics.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e8"},"PeriodicalIF":5.5,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bile Acid Metabolism Regulates Ovarian Function: Networks and Reproductive Health Applications.","authors":"Wei Liu, Bo Zhang","doi":"10.1017/erm.2026.10035","DOIUrl":"10.1017/erm.2026.10035","url":null,"abstract":"<p><strong>Background: </strong>Bile acids (BAs) are crucial metabolic regulators and signaling molecules involved in lipid metabolism and ovarian function. They primarily affect follicular development, steroidogenesis, and oocyte maturation through systemic circulation and transporter-mediated uptake (e.g., NTCP, ASBT) rather than local ovarian synthesis. Increasing evidence indicates that BA dysregulation is associated with multiple reproductive pathologies.</p><p><strong>Methods: </strong>This review is based on the authors' own work and a comprehensive PubMed search of the literature to date on bile acids and female reproduction. PubMed was searched using the terms \"bile acid AND ovary,\" \"bile acid AND oocyte,\" and \"bile acid AND reproduction.\" Retrieved records were screened for relevance to ovarian physiology and pathology, including folliculogenesis, steroidogenesis, granulosa cell function, oocyte maturation, and reproductive disorders, and 51 articles were ultimately included in this review.</p><p><strong>Results: </strong>Studies show significant BA dysregulation in reproductive disorders. In polycystic ovary syndrome (PCOS), elevated glycochenodeoxycholic acid (GCDCA) and taurocholic acid (TCA) correlate with hyperandrogenemia. Excessive BAs can induce endoplasmic reticulum (ER) stress and granulosa cell apoptosis; for example, glycodeoxycholic acid (GDCA) promotes a BAX/BCL-2 imbalance and may accelerate follicular atresia. In contrast, protective BAs such as ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) alleviate ER stress and oxidative damage and may improve oocyte quality. Mechanistically, BAs regulate steroidogenic enzymes (e.g., StAR, CYP11A1) via the nuclear receptor FXR and modulate ovarian function through pathways including EGF-ERK1/2 and PERK-ATF4. Moreover, the gut-BA-ovary axis has emerged as a metabolic hub linking environmental factors to reproductive function, potentially contributing to PCOS pathogenesis and ovarian reserve decline through an integrated regulatory network.</p><p><strong>Conclusions: </strong>BA-mediated signaling networks play important roles in ovarian physiology and reproductive disease. BAs and BA-related pathways may serve as novel biomarkers and therapeutic targets for reproductive disorders.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e9"},"PeriodicalIF":5.5,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting CD39 as a Therapeutic for Cancer Immunotherapy.","authors":"Zhongliang Li, Weiguo Xu, Hang Fai Kwok","doi":"10.1017/erm.2026.10033","DOIUrl":"10.1017/erm.2026.10033","url":null,"abstract":"<p><p>CD39 plays a pivotal role in the ATP-to-adenosine signalling pathway, serving as a critical mediator of immune suppression within the tumour microenvironment. Increasing preclinical evidence indicates that its inhibition can restore antitumour immunity and improve the efficacy of established treatments. In this review, we summarise the biology of CD39, its role in shaping the immunosuppressive tumour microenvironment, and therapeutic strategies currently under development. We also discuss early clinical progress and safety considerations, along with major challenges and future perspectives. Targeting CD39 represents a promising strategy to overcome tumour-induced immunosuppression and ongoing advances in therapeutic development could usher in next-generation immunotherapies.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e5"},"PeriodicalIF":5.5,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12935479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative <i>in vitro and in silico</i> models to reduce animal use: a crucial technological advance in dermatological sciences.","authors":"Carla Zanatelli, Luiza Pretto, Thaís Casagrande Paim, Márcia Rosângela Wink","doi":"10.1017/erm.2026.10032","DOIUrl":"10.1017/erm.2026.10032","url":null,"abstract":"<p><strong>Introduction: </strong>Alternative models are tools to replace and reduce the number of animals used in biomedical sciences, for either research or tests of industrial products. Several new alternative models have been developed in the most diverse fields. Their implementation has led to significant advances in the dermatological cosmetic industry, enabling chemical and molecular screening without animal use. However, limitations remain, particularly regarding tissue microenvironment complexity and systemic metabolic responses.</p><p><strong>Objectives: </strong>The objective of this viewpoint is to present the existing alternative models available for dermatological sciences, evaluate their applications and discuss their advantages and disadvantages, as well as the future perspectives for safe clinical translation.</p><p><strong>Results: </strong>In vitro and in silico approaches provide reliable platforms for toxicity, irritation, sensitization, and topical efficacy in cosmetic and dermatological research. Advanced systems, including human skin equivalents, bioprinted skin, and skin-on-a-chip platforms, enhance physiological relevance and mechanistic insight compared with two-dimensional cultures. However, limitations related to tissue complexity, systemic metabolic integration, standardization, and scalability still restrict their ability to fully replace in vivo models.</p><p><strong>Conclusion: </strong>Therefore, it is expected that future developments in alternative technologies will further enable the reduction of animal model use, while still providing reliable and translatable knowledge applicable across scientific disciplines.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e6"},"PeriodicalIF":5.5,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031187","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":"Main events and mechanism of human erythrocyte ageing.","authors":"Yao-Xiong Huang","doi":"10.1017/erm.2025.10030","DOIUrl":"10.1017/erm.2025.10030","url":null,"abstract":"<p><p>Erythrocytes play a crucial role in human life and are a good model for single-cell ageing research. Therefore, the mechanism of erythrocyte ageing has been a serious concern for researchers. Here, we investigate the ageing mechanism of human erythrocytes in circulation with a new approach. We first try to discover all the factors that affect erythrocyte ageing from the existing findings about the interactions of erythrocytes with the environment during circulation and the resulting alterations in the cells during their ageing process. Then, we define the main events in erythrocyte ageing according to the incidence and strength of the interactions and the magnitude of the biophysical and biochemical alterations induced by these interactions. With the main events as a guide for tracking the ageing process and analysing the causes and consequences of the events taking place during erythrocyte ageing, we depict the pathways and framework of the ageing mechanism. We hope that understanding the ageing mechanism of erythrocytes will help people to have a deep insight into the biophysical and biochemical processes of cell ageing and their molecular basis. Additionally, it may offer solutions to different fundamental and practical problems related to erythrocyte ageing, storage lesions, transfusion and diseases.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e4"},"PeriodicalIF":5.5,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12935475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145960542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}