International review of cell and molecular biology最新文献

{"title":"Engineering interleukin-10 for therapeutic applications.","authors":"Yufei Zheng, Román García-Fuentes, Aline Risson, Fernando Aranda, Pedro Berraondo","doi":"10.1016/bs.ircmb.2026.02.006","DOIUrl":"10.1016/bs.ircmb.2026.02.006","url":null,"abstract":"<p><p>Interleukin-10 (IL-10) is a key immunoregulatory cytokine with potent anti-inflammatory and immunomodulatory functions. Its pleiotropic effects and short half-life, however, have posed challenges for direct therapeutic use. To overcome these hurdles, diverse engineering strategies have been developed to enhance IL-10 stability, tailor its activity, and target its delivery. This review describes the major approaches to IL-10 modification, including fusion proteins (e.g. cytokine/cytokine fusion, IL-10-Fc fusions for half-life extension, and bispecific constructs), encapsulation systems (nanoparticles and hydrogels for sustained or localized release), protein engineering of IL-10 monomers/dimers to modulate receptor engagement (decoupling pro- vs anti-inflammatory signaling), targeted delivery methods (antibody-mediated tissue targeting and intestinal-specific release), and receptor-based fusion proteins (immunoadhesins) to modulate IL-10 signaling. For each strategy, we highlight representative preclinical studies and clinical programs, examining pharmacodynamics, pharmacokinetics, efficacy in disease models (cancer, autoimmunity, colitis, fibrosis, transplantation), and translational potential. Advantages and limitations such as immunogenicity, delivery efficiency, and scalability are critically discussed. These advances collectively illustrate how bioengineering is unlocking IL-10 therapeutic potential while mitigating its prior limitations, paving the way for next-generation cytokine immunotherapies.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"401 ","pages":"201-223"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in biomaterials.","authors":"Feiming Li, Zhenzhen Wu, Siyuan Chen, Ziqi Huang, Chao Liang, Sang Jin Lee","doi":"10.1016/bs.ircmb.2025.11.005","DOIUrl":"10.1016/bs.ircmb.2025.11.005","url":null,"abstract":"<p><p>Biomaterials have emerged as a cornerstone of modern medicine, significantly advancing patient care across various clinical applications. This chapter delves into the evolution and classification of biomaterials, highlighting both synthetic and natural types, and elucidating their critical roles in prosthetics, drug delivery systems, and regenerative medicine. The historical context of biomaterials reveals their initial use in ancient practices, evolving into sophisticated materials engineered for enhanced biocompatibility and functionality. With technological advancements, materials such as metals, polymers, and composites have been developed to facilitate seamless integration with biological systems, minimizing complications and improving device durability. Innovative fabrication techniques, including 3D bioprinting, electrospinning, and microfluidic systems, have expanded the potential for creating complex structures that closely mimic natural tissues, revolutionizing tissue engineering and organ replacement strategies. The chapter emphasizes the transformative impact of nanoscale materials in drug delivery and diagnostics, offering targeted therapies, improved imaging methods, and enhanced therapeutic efficacy. Despite considerable progress, challenges remain, including long-term performance, regulatory compliance, and biocompatibility. As the field evolves, interdisciplinary collaboration and ongoing research are vital to overcoming these challenges. This overview aims to inform readers about the latest advancements in biomaterials and their myriad applications, fostering continued innovation in biomedical engineering for improved health outcomes.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"402 ","pages":"1-59"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex matters in macroautophagy: Sex-driven differences in autophagic function in aging and aging related-diseases.","authors":"José Ignacio García-Muñoz, Alicia Domenech-Bendaña, Lucia Gimeno-Mallench, Alejandro Ponce-Mora, Álvaro F Fernández, Daniel López-López, Jose Luis Nieto-Torres, Eloy Bejarano","doi":"10.1016/bs.ircmb.2026.07.006","DOIUrl":"https://doi.org/10.1016/bs.ircmb.2026.07.006","url":null,"abstract":"<p><p>Autophagy is a fundamental cellular process essential for maintaining homeostasis, particularly in the context of aging and age-related diseases. Increasing evidence highlights biological sex as a critical modulator of autophagy, influencing its basal activity, regulatory pathways, and responsiveness to stress. Distinct autophagic profiles in males and females (across tissues, species and developmental stages) may underlie sex-specific vulnerabilities and divergent disease trajectories. These differences are evident in conditions such as neurodegeneration, cardiovascular disease, cancer, sarcopenia or chronic inflammation, all of which are commonly associated with aging. Indeed, aging is a major risk factor for the onset and progression of these pathologies. Importantly, sex-dependent variations in autophagy might also impact the efficacy and safety of therapeutic interventions, challenging the validity of uniform treatment strategies. Despite growing recognition of these disparities, significant knowledge gaps remain. This review summarizes current understanding of sex-related differences in autophagy, focusing on genetic and hormonal influences across the lifespan. The evidence supports the need for future research to systematically incorporate sex as a biological variable in experimental design and data analysis, utilize dynamic assessments of autophagy flux and investigate the interplay among genetic, hormonal, epigenetic, and post-translational regulatory mechanisms. Developing preclinical models that reflect human diversity-including genetic heterogeneity and relevant hormonal states-is imperative. Embracing the complexity of sex-dependent autophagy regulation is essential for translating mechanistic insights into effective, personalized interventions that improve health outcomes for both women and men.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"406 ","pages":"213-273"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysosomal function and homeostasis: From cellular adaptation to disease pathogenesis.","authors":"Satoshi Minami, Maho Hamasaki","doi":"10.1016/bs.ircmb.2026.04.002","DOIUrl":"https://doi.org/10.1016/bs.ircmb.2026.04.002","url":null,"abstract":"<p><p>Lysosomes were once considered terminal degradative organelles responsible for disposing of cellular waste. However, recent studies have revealed that lysosomes serve as dynamic signalling and metabolic hubs at the center of diverse biological processes, including nutrient sensing, metabolic regulation, membrane trafficking, autophagy, inflammation, and cell death. To support this broad functional repertoire, lysosomes must possess robust mechanisms to maintain their integrity in the face of damage or stress. In response to lysosomal membrane damage, cells engage multilayered adaptive mechanisms that act in coordination-membrane repair (Repair), selective removal of damaged organelles (Removal), and de novo biogenesis of lysosomes (Regeneration). These processes are mediated by a range of molecular pathways, including the ESCRT complex, the PITT pathway, lysophagy, and TFEB-dependent lysosomal regeneration. Notably, recent findings highlight the noncanonical autophagy-like pathway known as ATG8ylation (conjugation of ATG8s on single membranes), which is activated via the STING-V-ATPase-ATG16L1 axis and functions as a critical hub connecting multiple arms of the lysosomal damage response. In this review, we systematically outline the molecular basis of lysosomal damage responses, including ATG8ylation, and explore how these networks are implicated in a broad spectrum of pathological conditions such as aging, neurodegeneration, cancer, obesity-related disorders, and immune dysfunction. Understanding these lysosomal quality control mechanisms not only sheds light on the fundamental principles of organelle homeostasis but also opens new avenues for therapeutic innovation.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"406 ","pages":"1-42"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers for cancer therapy-related cardiovascular toxicity.","authors":"Jiaxin Song, Shuqin Liu, Xiaohui Shi, Junli Gao, Michail Spanos, Qiulian Zhou, Junjie Xiao","doi":"10.1016/bs.ircmb.2024.12.003","DOIUrl":"10.1016/bs.ircmb.2024.12.003","url":null,"abstract":"<p><p>Cancer treatment-induced cardiovascular toxicity (CTR-CVT) represents a significant challenge, with molecular mechanisms involving oxidative stress, inflammation, and direct cardiomyocyte damage. Common treatments such as anthracyclines and targeted therapies like trastuzumab are known to disrupt cardiac function through mechanisms including mitochondrial dysfunction, dysregulation of ion channels, and induction of apoptosis. Traditional biomarkers for CTR-CVT have included cardiac troponins and natriuretic peptides, which reflect acute myocardial injury and heart failure. Recent advances have introduced novel biomarkers such as microRNAs (miRNAs), including miR-29 and miR-223-3p, and proteomic markers like immunoglobulins and cytokines, which offer insights into subclinical cardiac damage and inflammatory responses. High-throughput technologies, including aptamers and proximity extension assays, have further enhanced the ability to screen for biomarkers with increased specificity and sensitivity. Integrating these traditional and emerging biomarkers provides a comprehensive approach for early detection of CTR-CVT, ultimately helping improve patient outcomes in cancer therapy.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"399 ","pages":"1-42"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine network in immunosuppression and tumor development in glioblastoma.","authors":"Rocío Granda-Díaz, Alejandra Martínez-Pérez, Candelaria Aguilar-García, Christian Sordo-Bahamonde","doi":"10.1016/bs.ircmb.2026.02.004","DOIUrl":"10.1016/bs.ircmb.2026.02.004","url":null,"abstract":"<p><p>Glioblastoma (GBM) remains one of the most aggressive primary brain tumors, with a profoundly immunosuppressive microenvironment. Cytokines, chemokines, and growth factors are central to this immunosuppression, impairing the function of T cells, NK cells, dendritic cells, and promoting the recruitment of regulatory immune populations. Importantly, these soluble mediators also act directly on glioma cells, enhancing their proliferation, survival, invasion, and resistance to therapy. This chapter outlines the intricate network of cytokine-driven pathways in GBM, emphasizing their immunosuppressive functions and tumor-intrinsic effects, and discusses their implications for therapeutic intervention. Key factors such as TGF-β and IL-10 are highlighted for their dual roles in modulating immune responses and promoting tumor growth, while other cytokines, including IL-6, IL-1β, and CXCL12, contribute to a highly dynamic and redundant signaling environment. Type I and II interferons, traditionally seen as antitumoral, are shown to have paradoxical effects under chronic exposure, promoting immune exhaustion and inhibitory immune checkpoint upregulation. Given the complexity and adaptability of cytokine networks in GBM, single-target strategies have had limited success. Future therapies will need to adopt a systems-level approach, simultaneously disrupting multiple pathways and considering the spatial and temporal heterogeneity of the tumor microenvironment to achieve durable clinical responses.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"401 ","pages":"139-171"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunocytokines based on IL-12 for cancer therapy: Enhancing efficacy and reducing toxicity.","authors":"Uxue Beloki, Laura Salaberry, Ángela Covo-Vergara, Carla Ortuño-Moya, Noelia Silva-Pilipich, Cristian Smerdou","doi":"10.1016/bs.ircmb.2025.03.003","DOIUrl":"10.1016/bs.ircmb.2025.03.003","url":null,"abstract":"<p><p>Interleukin-12 (IL-12) is one of the most potent antitumor agents, but its clinical use is restricted by its high systemic toxicity. Many recent studies have shown that IL-12 toxicity can be reduced by fusing it to antibodies that target the tumor. These types of fusion molecules, also called immunocytokines (ICKs), allow to concentrate the activity of IL-12 in the tumor microenvironment (TME) while decreasing its systemic levels. The antibodies that have been used to engineer IL-12-based ICKs include those targeting tumor antigens, such as CEA and mesothelin, molecules overexpressed in the TME, such as extra domains of fibronectin and DNA/histone complexes exposed in necrotic areas, and immune checkpoints, such as PD-1 and PD-L1. In general, IL-12-based ICKs have shown an improved efficacy and safety profile compared to IL-12 in many preclinical tumor models, as well as synergistic effects when combined with other immunostimulatory molecules like immune checkpoint inhibitors. This has led to clinical trials in which two ICKs, namely huBC1-IL12 and NHS-IL-12 targeting fibronectin extra domain B and DNA/histone complexes, respectively, have been evaluated. These initial trials have shown a high degree of safety, as well as activation of antitumor immune responses in treated patients.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"401 ","pages":"113-138"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The double-edged role of interferon gamma in cancer immunity.","authors":"Candelaria Aguilar-García, Alejandra Martínez-Pérez, Rocío Granda-Díaz, Segundo Gonzalez","doi":"10.1016/bs.ircmb.2026.02.003","DOIUrl":"10.1016/bs.ircmb.2026.02.003","url":null,"abstract":"<p><p>Interferon-gamma (IFN-γ) is a pivotal cytokine that coordinates the immune response to infections caused by viruses and intracellular pathogens. Knockout (KO) mice lacking IFN-γ exhibited a significant reduction in the capacity of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells to eliminate tumor cells, resulting in accelerated tumor growth and metastasis. These findings underscore the key role of IFN-γ in regulating the antitumor immune response. However, many advanced tumors exhibit dysregulated IFN-γ signaling, which exerts direct protumoral and immunosuppressive effects, thereby allowing cancer cells to evade immune surveillance and promoting cancer progression. This dual role of IFN-γ in regulating cancer immunity has limited its therapeutic use in cancer. Understanding the specific conditions under which IFN-γ has an antitumoral or a protumoral role is a challenge for optimizing its use in cancer therapy.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"401 ","pages":"173-199"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in bioinformatics: Integration of biomolecular simulations and virtual reality for revolutionizing disease mechanism elucidation and therapeutic development.","authors":"Arli Aditya Parikesit, Arif Nur Muhammad Ansori, Viol Dhea Kharisma, Hery Purnobasuki, Yudhi Nugraha","doi":"10.1016/bs.ircmb.2025.11.004","DOIUrl":"10.1016/bs.ircmb.2025.11.004","url":null,"abstract":"<p><p>Virtual reality and biomolecular simulations currently lie at the leading edge in dissecting the molecular pathways underlying the disease. This chapter will discuss how the integrations of various technologies will extend knowledge about complex biological processes and their contribution to disease pathophysiology. Advances in molecular dynamics (MD) simulations currently make it possible to record the behavior of proteins and other biomolecules with accurate temporal resolution and full atom detail. Such simulations include information on critical structural changes related to diseases, interactions with possible medication, and functionality of proteins. With recently improved speed, accuracy, and accessibility, MD. has become a basic research and drug development tool. From the researcher's point of view, virtual reality has revolutionized how one can conceptualize and interact with molecular structures. Virtual reality (VR) is a method that uses the three-dimensional presentation of biomolecules as manipulable virtual objects for intuitive insight into molecular interactions and structural connections. In this way, virtual technology can be very helpful in investigating complex chemical systems and creating new theories. It facilitates the Cloud-based co-creation of environments in cloud systems for molecular modeling. The same technologies allow real-time research collaboration by sharing and changing virtual molecules. These cooperative situations reward the generation of new ideas and information, which might provide novel discoveries that more direct approaches could not realize. This chapter will discuss the range of computational methods applied to elucidate molecular recognition mechanisms and will cover improved sampling methods and in silico screening. It will also describe how such techniques may be applied to investigate viral proteins and help develop vaccines and drugs during the COVID-19 pandemic. The combination of the predictive power of MD. Simulations with intuitive visualization capabilities from VR would allow researchers to achieve an unprecedented understanding of the molecular origin of many diseases. This should inspire innovation in therapeutic intervention and accelerate discovery in molecular biology.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"402 ","pages":"211-236"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DOGMA-seq and multimodal, single-cell analysis in acute myeloid leukemia.","authors":"JangKeun Kim, Nathan Schanzer, Ruth Subhash Singh, Mohammed I Zaman, J Sebastian Garcia-Medina, Jacqueline Proszynski, Saravanan Ganesan, Dan Landau, Christopher Y Park, Ari M Melnick, Christopher E Mason","doi":"10.1016/bs.ircmb.2024.08.001","DOIUrl":"10.1016/bs.ircmb.2024.08.001","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a complex cancer, yet advances in recent years from integrated genomics methods have helped improve diagnosis, treatment, and means of patient stratification. A recent example of a powerful, multimodal method is DOGMA-seq, which can measure chromatin accessibility, gene expression, and cell-surface protein levels from the same individual cell simultaneously. Previous bimodal single-cell techniques, such as CITE-seq (Cellular indexing of transcriptomes and epitopes), have only permitted the transcriptome and cell-surface protein expression measurement. DOGMA-seq, however, builds on this foundation and has implications for examining epigenomic, transcriptomic, and proteomic interactions between various cell types. This technique has the potential to be particularly useful in the study of cancers such as AML. This is because the cellular mechanisms that drive AML are rather heterogeneous and require a more complete understanding of the interplay between the genetic mutations, disruptions in RNA transcription and translation, and surface protein expression that cause these cancers to develop and evolve. This technique will hopefully contribute to a more clear and complete understanding of the growth and progression of complex cancers.</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"390 ","pages":"67-108"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}