WIREs Mechanisms of Disease最新文献

Galectin-9 Modulates Autoimmunity: Roles in Tissue Inflammation and Organ Involvement. 半凝集素-9调节自身免疫：在组织炎症和器官受累中的作用。

IF 5.4 3区医学

WIREs Mechanisms of Disease Pub Date : 2026-07-01 DOI: 10.1002/wsbm.70010

Fangyu Liu, Xuanyi Zhou, Jing Luo, Zihan Wang, Qingwen Tao

引用次数: 0

Protein Homeostasis and Mitochondrial Quality Control in Neurodegeneration. 神经退行性疾病中的蛋白质稳态和线粒体质量控制。

IF 5.4 3区医学

WIREs Mechanisms of Disease Pub Date : 2026-07-01 DOI: 10.1002/wsbm.70014

Rosa Di Lorenzo, Rola S Zeidan, Riccardo Calvani, Vito Pesce, Emanuele Marzetti, Anna Picca

引用次数: 0

Friend or Foe? The Dual Role of Ferroptosis in Tumor Immunity and Immunotherapy. 朋友还是敌人？铁下垂在肿瘤免疫和免疫治疗中的双重作用。

IF 5.4 3区医学

WIREs Mechanisms of Disease Pub Date : 2026-03-01 DOI: 10.1002/wsbm.70009

Fangyu Liu, Mairepaiti Halimulati, Jing Luo, Liqun Jia, Qingwen Tao

{"title":"Friend or Foe? The Dual Role of Ferroptosis in Tumor Immunity and Immunotherapy.","authors":"Fangyu Liu, Mairepaiti Halimulati, Jing Luo, Liqun Jia, Qingwen Tao","doi":"10.1002/wsbm.70009","DOIUrl":"https://doi.org/10.1002/wsbm.70009","url":null,"abstract":"Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, plays a context-dependent dual role in tumor immunity and immunotherapy. On one hand, it can act as an immunogenic cell death mechanism, releasing damage-associated molecular patterns that activate dendritic cells and promote T cell priming. On the other hand, ferroptosis may suppress antitumor immunity by triggering death or dysfunction in key immune cells, including T lymphocytes, dendritic cells, and macrophages. This review synthesizes current insights into the molecular determinants of ferroptosis sensitivity within the tumor microenvironment. It examines how immune cells can induce ferroptosis in cancer cells, and how tumors evolve resistance through upregulation of proteins like GPX4 and FSP1 or metabolic rewiring. The interplay between ferroptosis and immunity offers promising therapeutic avenues, such as combining ferroptosis inducers with immune checkpoint inhibitors or employing nanotechnology for targeted delivery. However, the net immunogenic outcome depends on temporal, cellular, and microenvironmental factors. Future strategies must aim to selectively induce immunogenic ferroptosis in tumors while preserving immune cell function, leveraging biomarkers and microenvironment modulation to optimize combination therapies in cancer immunotherapy.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"18 2-3","pages":"e70009"},"PeriodicalIF":5.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Nager Syndrome Revisited: Integrating In Vivo and In Vitro Models to Decipher SF3B4-Dependent Tissue Coordination. 重新审视Nager综合征：整合体内和体外模型来破译sf3b4依赖的组织协调。

IF 5.4 3区医学

WIREs Mechanisms of Disease Pub Date : 2026-01-01 DOI: 10.1002/wsbm.70007

Jingru Qin, Zulvikar Syambani Ulhaq, William Ka Fai Tse

{"title":"Nager Syndrome Revisited: Integrating In Vivo and In Vitro Models to Decipher SF3B4-Dependent Tissue Coordination.","authors":"Jingru Qin, Zulvikar Syambani Ulhaq, William Ka Fai Tse","doi":"10.1002/wsbm.70007","DOIUrl":"10.1002/wsbm.70007","url":null,"abstract":"Nager syndrome (NS) is a rare congenital disorder primarily characterized by mandibulofacial dysostosis and upper limb anomalies. Pathogenic variants in SF3B4, which encodes a core spliceosomal component, represent the primary known genetic cause of NS. This review synthesizes recent findings from cellular, zebrafish, Xenopus, and mouse models to elucidate how SF3B4 deficiency perturbs neural crest cell (NCC) biology and multi-tissue development. Loss of SF3B4 induces widespread splicing abnormalities, with preferential exon skipping affecting AT-rich and GC-poor exons, thereby altering the expression of genes critical for NCC survival, proliferation, migration, and lineage specification. These cellular defects are further exacerbated by oxidative stress and activation of the p53 pathway, resulting in a broad spectrum of developmental abnormalities involving craniofacial, cardiac, skeletal, and sensory (auditory and ocular) systems. Together, these findings highlight the essential role of SF3B4 in coordinating early morphogenesis. Cross-species comparisons reveal conserved NCC vulnerabilities alongside model-specific phenotypes, highlighting the challenge of linking individual splicing alterations to distinct structural outcomes in NS. Future research directions include defining tissue-specific SF3B4-dependent splicing targets, developing human induced pluripotent stem cell-derived models, and exploring therapeutic strategies aimed at restoring splicing homeostasis or compensating for disrupted developmental signaling pathways. This article is categorized under: Congenital Diseases > Molecular and Cellular Physiology Congenital Diseases > Genetics/Genomics/Epigenetics Congenital Diseases > Stem Cells and Development.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"18 1","pages":"e70007"},"PeriodicalIF":5.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

SARS-CoV-2: A Liver Brief. SARS-CoV-2：肝脏简介

IF 4.9 3区医学

WIREs Mechanisms of Disease Pub Date : 2025-11-01 DOI: 10.1002/wsbm.70005

Youness Limami, Hicham Wahnou, Martin Ndayambaje, Soufyane Hba, Oumaima Chgari, Mounia Ammara, Riad El Kebbaj, Abdallah Naya, Mounia Oudghiri, Raphaël Emmanuel Duval

{"title":"SARS-CoV-2: A Liver Brief.","authors":"Youness Limami, Hicham Wahnou, Martin Ndayambaje, Soufyane Hba, Oumaima Chgari, Mounia Ammara, Riad El Kebbaj, Abdallah Naya, Mounia Oudghiri, Raphaël Emmanuel Duval","doi":"10.1002/wsbm.70005","DOIUrl":"https://doi.org/10.1002/wsbm.70005","url":null,"abstract":"The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has revealed the virus's ability to induce multi-organ damage, including significant liver injury. The molecular mechanisms of liver dysfunction in COVID-19 patients are explored, focusing on direct viral infection, immune-mediated damage, and the gut-liver axis. SARS-CoV-2 enters liver cells through the Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) receptors, but alternative pathways, such as CD209/Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN) and AXL receptors, can also contribute to viral entry. Additionally, immune responses, particularly the cytokine storm, exacerbate liver inflammation, leading to hepatocyte damage. Pre-existing liver conditions, such as metabolic-associated fatty liver disease (MAFLD), alcohol-related liver disease (ALD), and liver fibrosis, heighten the risk of severe outcomes in COVID-19 patients. Post-COVID-19 liver complications, including fibrosis progression and persistent liver damage, have been reported, with emerging evidence suggesting chronic inflammation, viral persistence, and autoimmune reactions as potential contributors. Furthermore, Drug-Induced Liver Injury (DILI) from COVID-19 treatments remains a concern, highlighting the need for careful management. Consequently, understanding the interplay between SARS-CoV-2 and the liver is critical for improving patient outcomes and developing targeted therapies to mitigate liver-related complications in both acute and Long COVID-19 phases. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"17 6","pages":"e70005"},"PeriodicalIF":4.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145432310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Anna Karenina Principle, Immune-Oncology-Microbiome Trio and Cancer Microbiome Therapy. 安娜卡列尼娜原则，免疫-肿瘤-微生物组三重奏和癌症微生物组治疗。

IF 4.9 3区医学

WIREs Mechanisms of Disease Pub Date : 2025-11-01 DOI: 10.1002/wsbm.70004

Zhanshan Sam Ma

{"title":"Anna Karenina Principle, Immune-Oncology-Microbiome Trio and Cancer Microbiome Therapy.","authors":"Zhanshan Sam Ma","doi":"10.1002/wsbm.70004","DOIUrl":"https://doi.org/10.1002/wsbm.70004","url":null,"abstract":"The immune-oncology-microbiome (IOM) trio highlights the significant role of microbiomes in cancer progression by modulating immune evasion, genomic instability, and inflammation-key hallmarks of cancer. While microbiomes can exert both protective and detrimental effects on tumor development and treatment response, the mechanistic underpinnings-particularly those involving intratumoral microbiomes-remain poorly understood. To elucidate these dynamics, we frame the interplay between cancer, immune cells, and microbiomes through the lens of the Anna Karenina Principle (AKP)-using Leo Tolstoy's aphorism: \"All happy families are alike; each unhappy family is unhappy in its own way.\" In biomedical terms, this translates to: all healthy systems including intratumoral microbiomes are alike, but each dysfunctional system fails in its own way. We hypothesize that either AKP or its inverse (anti-AKP) may govern microbial interactions that influence cancer progression. Analyzing four published cancer tissue microbiome datasets (Nejman 2020, Science), we identified two distinct patterns: AKP-driven increased microbial heterogeneity in lung and ovarian cancers, and anti-AKP-driven decreased heterogeneity in breast and colon cancers. We further propose cancer microbiome therapy (CMT) as an emerging frontier in microbiome-based therapeutics. The CMT may include the following strategies: (i) Restoring a healthy microbiome (including barrier tissue, tumor, blood microbiomes) to enhance immune function through ecosystem engineering; (ii) Developing specific microbial agents (species or their metabolites) to modulate crossroads of cancer immunotherapy; (iii) Engineering microbial agents to suppress cancer-causing microbes (oncomicrobes and complicit) and halt cancer progression; (iv) Reviving historical approaches like Coley's toxin and oncolytic viruses for direct cancer cell targeting. This article is categorized under: Cancer > Genetics/Genomics/Epigenetics Cancer > Computational Models.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"17 6","pages":"e70004"},"PeriodicalIF":4.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

The Nucleolus and Its Associated Pathologies. 核仁及其相关病理。

IF 4.9 3区医学

WIREs Mechanisms of Disease Pub Date : 2025-09-01 DOI: 10.1002/wsbm.70003

Marvin J Menjivar-Vallecillo, Nadia V Padilla-Claros, Pilar Gavarrete-Garrido, Sherlyn A León-Castañeda, Héctor M Ramos-Zaldívar

{"title":"The Nucleolus and Its Associated Pathologies.","authors":"Marvin J Menjivar-Vallecillo, Nadia V Padilla-Claros, Pilar Gavarrete-Garrido, Sherlyn A León-Castañeda, Héctor M Ramos-Zaldívar","doi":"10.1002/wsbm.70003","DOIUrl":"https://doi.org/10.1002/wsbm.70003","url":null,"abstract":"The nucleolus, traditionally known for its role in ribosome biogenesis, is now recognized for its broader functions, including cellular stress adaptation and its involvement in various pathological processes, such as ribosomal alterations, viral infections, autoimmune disorders, and age-related diseases. Disruptions in nucleolar function can impair protein synthesis, cellular homeostasis, and immune responses, leading to multisystem disorders and increased susceptibility to neoplasms. This review classifies nucleolus-associated diseases into seven categories: deficiencies in protein synthesis, ribosomal and non-ribosomal alterations, cancer and nucleolar alterations, diseases related to aging and cellular stress, autoimmune diseases, and viral diseases. Understanding the complexity of the nucleolus and its dysfunctions represents a fundamental step toward advancing knowledge of the molecular basis of these pathologies, laying the groundwork for future research addressing its implications in cell biology and the development of human diseases. This article is categorized under: Immune System Diseases > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"17 5","pages":"e70003"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Biomedical Models: Use of Zebrafish as a Multi-Utility In Vivo Tool Box. 生物医学模型：使用斑马鱼作为一个多用途的体内工具箱。

IF 4.6 3区医学

WIREs Mechanisms of Disease Pub Date : 2025-07-01 DOI: 10.1002/wsbm.70002

Barsha Mohanty, Masmarika Mohan, Dechamma Pandyanda Nanjappa, Rathika D Shenoy, Giridhar B Hosmane, Gunimala Chakraborty, Anirban Chakraborty

{"title":"Biomedical Models: Use of Zebrafish as a Multi-Utility In Vivo Tool Box.","authors":"Barsha Mohanty, Masmarika Mohan, Dechamma Pandyanda Nanjappa, Rathika D Shenoy, Giridhar B Hosmane, Gunimala Chakraborty, Anirban Chakraborty","doi":"10.1002/wsbm.70002","DOIUrl":"https://doi.org/10.1002/wsbm.70002","url":null,"abstract":"Molecular research has gradually revealed the biological significance of genetically encoded information and how this information is transmitted and utilized in a cell. The scientific advances of the last few decades have brought about paradigm shifts in the strategies traditionally used to decipher biological information. From unidirectional approaches, we now have multidirectional model-system-based integrated OMICs that aim to describe the pathophysiology of diseases through a combination of genetic, transcriptomic, proteomic, and metabolomic data. Compared to other vertebrate models, zebrafish have a wealth of advantages that make them a powerful tool with a wide range of applications in biomedical research. The high degree of genetic conservation with humans, coupled with the availability of various gene manipulation techniques, has made zebrafish an immensely popular multi-utility genetic toolbox. This review describes the advances in the field of zebrafish-based biomedical research with a focus on its applications in disease modeling, functional omics, toxicology, and pharmacology. This article is categorized under: Cancer > Genetics/Genomics/Epigenetics Infectious Diseases > Molecular and Cellular Physiology Congenital Diseases > Molecular and Cellular Physiology.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"17 4","pages":"e70002"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Harnessing Noncanonical Proteins for Next-Generation Drug Discovery and Diagnosis. 利用非规范蛋白进行新一代药物发现和诊断。

IF 4.6 3区医学

WIREs Mechanisms of Disease Pub Date : 2025-05-01 DOI: 10.1002/wsbm.70001

Nachiket Rajinikanth, Ruchi Chauhan, Sudhakaran Prabakaran

{"title":"Harnessing Noncanonical Proteins for Next-Generation Drug Discovery and Diagnosis.","authors":"Nachiket Rajinikanth, Ruchi Chauhan, Sudhakaran Prabakaran","doi":"10.1002/wsbm.70001","DOIUrl":"10.1002/wsbm.70001","url":null,"abstract":"Noncanonical proteins, encoded by previously overlooked genomic regions (part of the \"dark genome\"), are emerging as crucial players in human health and disease, expanding our understanding of the \"dark proteome.\" This review explores their landscape, including proteins derived from long non-coding RNAs, circular RNAs, and alternative open reading frames. Recent advances in ribosome profiling, mass spectrometry, and proteogenomics have unveiled their involvement in critical cellular processes. We examine their roles in cancer, neurological disorders, cardiovascular diseases, and infectious diseases, highlighting their potential as novel biomarkers and therapeutic targets. The review addresses challenges in identifying and characterizing these proteins, particularly recently evolved ones, and discusses implications for drug discovery, including cancer immunotherapy and neoantigen sources. By synthesizing recent findings, we underscore the significance of noncanonical proteins in expanding our understanding of the human genome and proteome, and their promise in developing innovative diagnostic tools and targeted therapies. This overview aims to stimulate further research into this unexplored biological space, potentially revolutionizing approaches to disease treatment and personalized medicine.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"17 3","pages":"e70001"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanical Forces in Tumor Growth and Treatment: Perspectives From Biology, Physics, Engineering, and Mathematical Modeling. 肿瘤生长和治疗中的机械力：来自生物学、物理学、工程学和数学建模的观点。

IF 4.6 3区医学

WIREs Mechanisms of Disease Pub Date : 2025-03-01 DOI: 10.1002/wsbm.70000

Farshad Moradi Kashkooli, Fatemeh Mirala, Masoud H H Tehrani, Mahvash Alirahimi, Mohammad Souri, Aryan Golzaryan, Saptarshi Kar, Madjid Soltani

{"title":"Mechanical Forces in Tumor Growth and Treatment: Perspectives From Biology, Physics, Engineering, and Mathematical Modeling.","authors":"Farshad Moradi Kashkooli, Fatemeh Mirala, Masoud H H Tehrani, Mahvash Alirahimi, Mohammad Souri, Aryan Golzaryan, Saptarshi Kar, Madjid Soltani","doi":"10.1002/wsbm.70000","DOIUrl":"10.1002/wsbm.70000","url":null,"abstract":"The progression of tumors is influenced by mechanical forces and biological elements, such as hypoxia and angiogenesis. Mechanical factors, including stress, pressure, interstitial fluid pressure, and cellular traction forces, compromise normal tissue architecture, augmenting stiffness and thus promoting tumor growth and invasion. The selective elimination of specific tumor components can reduce growth-induced mechanical stress, thereby improving therapeutic efficacy. Furthermore, stress-relief drugs have the potential in enhancing chemotherapy outcomes. In this setting, computational modeling functions as an essential tool for quantitatively elucidating the mechanical principles underlying tumor formation. These models can precisely replicate the impact of mechanical pressures on solid tumors, offering insight into the regulation of tumor behavior by these forces. Tumor growth produces mechanical forces, including compression, displacement, and deformation, leading to irregular stress patterns, expedited tumor advancement, and reduced treatment efficacy. This review analyzes the impact of mechanical forces on carcinogenesis and solid tumor proliferation, emphasizing the significance of stress alleviation in regulating tumor growth. Furthermore, we investigate the influence of mechanical forces on tumor dissemination and emphasize the promise of integrating computational modeling with force-targeted cancer therapies to improve treatment efficacy by tackling the fundamental mechanics of tumor proliferation.","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"17 2","pages":"e70000"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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