Cell insight最新文献

{"title":"Gene therapy strategies for aging intervention","authors":"Yaobin Jing ,&nbsp;Jie Ren ,&nbsp;Jing Qu ,&nbsp;Guang-Hui Liu","doi":"10.1016/j.cellin.2025.100254","DOIUrl":"10.1016/j.cellin.2025.100254","url":null,"abstract":"<div><div>Aging is characterized by a progressive decline in organ and tissue structure and function, significantly increasing the risk of many chronic diseases. Developing interventions to delay aging holds the potential to reduce the burden of age-associated diseases and promote healthy longevity. Gene therapy has emerged as a clinically transformable approach, leveraging advanced gene editing and delivery systems to target the molecular underpinnings of aging. This review systematically explores the potential of gene therapy strategies in aging intervention, focusing on approaches that enhance genomic and epigenetic stability, restore metabolic homeostasis, modulate immune responses, and rejuvenate senescent cells. By providing a comprehensive overview and forward-looking insights, this article aims to inform future research directions and translational applications of gene therapy in mitigating aging-related decline.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 4","pages":"Article 100254"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IRF1 amplifies HSV-1-triggered antiviral innate immunity in a feed-forward manner","authors":"Ming Gao ,&nbsp;Yining Qi ,&nbsp;Junjie Zhang","doi":"10.1016/j.cellin.2025.100255","DOIUrl":"10.1016/j.cellin.2025.100255","url":null,"abstract":"<div><div>Herpes simplex virus 1 (HSV-1) is a prevalent human pathogen that establishes lifelong infection and causes a wide range of diseases. Antiviral innate immunity is critical for controlling HSV-1 replication; however, how host cells elicit a full spectrum of antiviral innate immune responses against HSV-1 remains poorly understood. Here, our studies indicate that Interferon regulatory factor 1 (IRF1) amplifies HSV-1-induced antiviral innate immunity in a feed-forward manner. Our data reveal that HSV-1 infection induces IRF1 expression, and MITA/STING contributes to the induction of IRF1 during HSV-1 infection. Moreover, IRF1 restricts HSV-1 replication dependent on its DNA-binding activity. Knockout of IRF1 significantly diminishes the induction of a large subset of interferon-stimulated genes (ISGs) critical for antiviral defense during HSV-1 infection. Notably, IRF1 interacts with IRF3, promoting its recruitment to the promoters of ISGs as well as type I and III interferons, thereby facilitating the activation of antiviral signaling. These findings uncover a novel amplifying role of IRF1 in HSV-1-induced antiviral immunity, which deepens our understanding of innate immune responses against viral infections.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 4","pages":"Article 100255"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The roles of macrophages and monocytes in COVID-19 Severe Respiratory Syndrome","authors":"Jun Li ,&nbsp;Rui Shan ,&nbsp;Heather Miller ,&nbsp;Alexander Filatov ,&nbsp;Maria G. Byazrova ,&nbsp;Lu Yang ,&nbsp;Chaohong Liu","doi":"10.1016/j.cellin.2025.100250","DOIUrl":"10.1016/j.cellin.2025.100250","url":null,"abstract":"<div><div>The global COVID-19 pandemic has highlighted the pivotal role of the immune system in the development of severe respiratory symptoms, termed COVID-19 Severe Respiratory Syndrome (COVID-19-SR). This review aims to dissect the involvement of lung macrophages and monocytes in orchestrating immune responses to SARS-CoV-2, influencing disease severity and outcomes. Initially, we provide an overview of SARS-CoV-2's invasion process and the body's primary immune defense mechanisms, including the antibody complement system and cytokine production. We then delve into the roles of the monocyte-macrophage system in mediating hyperinflammation and cytokine storms, discussing how abnormal cytokine and chemokine levels contribute to disease progression. Subsequent sections examine the perturbations and overactivation of the monocyte-macrophage compartment during infection, linking these changes to the observed immune dysregulation in COVID-19 patients. In light of these insights, we explore therapeutic strategies targeting macrophages, such as dexamethasone, antisense lipid nanoparticles(ALN), and inhaled recombinant human granulocyte-macrophage colony-stimulating factor (rh-GM-CSF), which aim to modulate inflammation, suppress viral replication, and enhance viral clearance. Additional potential treatments include GSDMD inhibitors and GPR183 antagonists, which warrant further investigation. This review synthesizes current understanding of the immunopathology underlying COVID-19-SR, proposing macrophage- and monocyte-centered therapeutic avenues and outlining future research priorities essential for advancing clinical management and improving patient outcomes.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 4","pages":"Article 100250"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144570714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"cGAS, an innate dsDNA sensor with multifaceted functions","authors":"Yutong Liu ,&nbsp;Pinglong Xu","doi":"10.1016/j.cellin.2025.100249","DOIUrl":"10.1016/j.cellin.2025.100249","url":null,"abstract":"<div><div>Cyclic GMP-AMP synthase (cGAS) functions as a pivotal intracellular sensor for the innate immune sensing of double-stranded DNA (dsDNA), monitoring those nucleic acids from foreign and endogenous sources. Upon assembling into cellular condensates with dsDNA and regulators, cGAS synthesizes 2′3′-cGAMP that activates the downstream STING signaling. This activation triggers a variety of intracellular responses, including autophagy, mRNA translation, interferon signaling, and inflammatory responses. Context-dependently, cGAS resides in diverse cellular compartments, including the nucleus, micronuclei, plasma membrane, and organelle surfaces. Beyond its DNA-sensing role, cGAS can play complex roles in these locations, such as DNA damage repairing, membrane restoration, chromatin condensation, angiogenesis, and aging regulation. This comprehensive review summarizes recent advances in the activation, regulation, and pharmacological management of cGAS, focusing on its molecular mechanisms, post-translational modifications (PTMs), and therapeutic interventions. The functional implications of cGAS in various disease contexts, including infectious diseases, autoinflammatory diseases, autoimmune diseases, aging, and cancers, are also covered.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 3","pages":"Article 100249"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intratumor HIF-1α modulates production of a cachectic ligand to cause host wasting","authors":"Gen Xiao ,&nbsp;Yingge Li ,&nbsp;Yanhui Hu ,&nbsp;Kai Tan ,&nbsp;Mengyang Wang ,&nbsp;Kerui Zhu ,&nbsp;Mingkui San ,&nbsp;Qian Cheng ,&nbsp;Dilinigeer Tayier ,&nbsp;Tingting Hu ,&nbsp;Peixuan Dang ,&nbsp;Jiaying Li ,&nbsp;Chen Cheng ,&nbsp;Norbert Perrimon ,&nbsp;Zhiyong Yang ,&nbsp;Wei Song","doi":"10.1016/j.cellin.2025.100247","DOIUrl":"10.1016/j.cellin.2025.100247","url":null,"abstract":"<div><div>Tumor-host interactions play critical roles in cancer-associated cachexia. Previous studies have identified several cachectic proteins secreted by tumors that impair metabolic homeostasis in multiple organs, leading to host wasting. The molecular mechanisms by which malignant tumors regulate the production or secretion of these cachectic proteins, however, still remain largely unknown. In this study, we used different <em>Drosophila</em> cachexia models to investigate how malignant tumors regulate biosynthesis of ImpL2, a conserved cachectic protein that inhibits systemic insulin/IGF signaling and suppresses anabolism of host organs. Through bioinformatic and biochemical analysis, we found that hypoxia-inducible factor HIF-1α/Sima directly binds to the promoter region of <em>ImpL2</em> gene for the first time, promoting its transcription in both tumors and non-tumor cells. Interestingly, expressing HphA to moderately suppress HIF-1α/Sima activity in adult <em>yki</em>^<em>3SA</em> gut tumors or larval <em>scrib</em>^<em>1</em> <em>Ras</em>^<em>V12</em> disc tumors sufficiently decreased <em>ImpL2</em> expression and improved organ wasting, without affecting tumor growth. We further revealed conserved regulatory mechanisms conserved across species, as intratumor HIF-1α enhances the production of IGFBP-5, a mammalian homolog of fly ImpL2, contributing to organ wasting in both tumor-bearing mice and patients. Therefore, our study provides novel insights into the mechanisms by which tumors regulate production of cachectic ligands and the pathogenesis of cancer-induced cachexia.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 3","pages":"Article 100247"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid and direct discovery of functional tumor specific neoantigens by high resolution mass spectrometry and novel algorithm prediction","authors":"Huajian Tian ,&nbsp;Guifei Li ,&nbsp;Cookson K.C. Chiu ,&nbsp;E. Li ,&nbsp;Yuzong Chen ,&nbsp;Ting Zhu ,&nbsp;Min Hu ,&nbsp;Yanjie Wang ,&nbsp;Suping Wen ,&nbsp;Jiajia Li ,&nbsp;Shuangxue Luo ,&nbsp;Zhicheng Chen ,&nbsp;Huimei Zeng ,&nbsp;Nan Zheng ,&nbsp;Jinyong Wang ,&nbsp;Weijun Shen ,&nbsp;Xi Kang","doi":"10.1016/j.cellin.2025.100251","DOIUrl":"10.1016/j.cellin.2025.100251","url":null,"abstract":"<div><div>While immune cell therapies have transformed cancer treatment, achieving comparable success in solid tumors remains a significant challenge compared to hematologic malignancies like non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). Over the past four decades, various immunotherapeutic strategies, including tumor vaccines, tumor-infiltrating lymphocyte (TIL) therapies, and T cell receptor (TCR) therapies, have demonstrated clinical efficacy in select solid tumors, suggesting potential advantages over CAR-T and CAR-NK cell therapies in specific contexts. The dynamic nature of the cancer-immunity cycle, characterized by the continuous evolution of tumor-specific neoantigens, enables tumors to evade immune surveillance. This highlights the urgent need for rapid and accurate identification of functional tumor neoantigens to inform the design of personalized tumor vaccines. These vaccines can be based on mRNA, dendritic cells (DCs), or synthetic peptides. In this study, we established a novel platform integrating immunoprecipitation-mass spectrometry (IP-MS) for efficient and direct identification of tumor-specific neoantigen peptides. By combining this approach with our proprietary AI-based prediction algorithm and high-throughput <em>in vitro</em> functional validation, we can generate patient-specific neoantigen candidates within six weeks, accelerating personalized tumor vaccine development.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 3","pages":"Article 100251"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “STING guides the STX17-SNAP29-VAMP8 complex assembly to control autophagy” [Cell Insight 3 (2024) 100147]","authors":"Xiaoyu Song ,&nbsp;Yufeng Xi ,&nbsp;Ming Dai ,&nbsp;Tao Li ,&nbsp;Shihao Du ,&nbsp;Yuxin Zhu ,&nbsp;Mengjie Li ,&nbsp;Yunze Li ,&nbsp;Siqi Liu ,&nbsp;Xia Ding ,&nbsp;Xuebiao Yao ,&nbsp;Ying Lai ,&nbsp;Xing Liu","doi":"10.1016/j.cellin.2025.100239","DOIUrl":"10.1016/j.cellin.2025.100239","url":null,"abstract":"","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 3","pages":"Article 100239"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single cell sequencing and spatial multiomics of diabetic kidney segmentation insights zonation-specific therapeutic metabolic pathways","authors":"Shi Qiu ,&nbsp;Zhibo Wang ,&nbsp;Sifan Guo ,&nbsp;Dandan Xie ,&nbsp;Ying Cai ,&nbsp;Xian Wang ,&nbsp;Chunsheng Lin ,&nbsp;Songqi Tang ,&nbsp;Yiqiang Xie ,&nbsp;Aihua Zhang","doi":"10.1016/j.cellin.2025.100252","DOIUrl":"10.1016/j.cellin.2025.100252","url":null,"abstract":"<div><div>Diabetic nephropathy (DN) exhibits profound spatial metabolic heterogeneity across kidney regions, yet how compartmentalized pathways drive disease progression remains poorly defined. A deeper understanding of the organizational spatial environment and metabolic pathways of diabetic kidney damage will provide new insights to develop new therapies. By integrating high-resolution spatial multi-omics and single-cell transcriptomics, we mapped region-specific metabolic dysregulation in diabetic kidneys, identifying glutathione metabolism, pentose phosphate, and glycolytic pathways as zonally disrupted in cortical and medullary regions. Spatial metabolomics revealed distinct anatomical clustering of ten clinically associated metabolites, while spatial proteomic profiling uncovered sixty-four region-enriched proteins linked to these pathways. Specifically, depending on anatomic location, spatial protein signatures across multiple regions of diabetic mouse kidneys were enriched in each segmentation, respectively. Cross-species integration identified GPX3 as a fibroblast-enriched biomarker strongly correlated with kidney dysfunction and closely related to clinical indicators. Notably, astragaloside IV (ASIV) treatment reversed spatial metabolic perturbations in diabetic mice, restoring glutathione and glycolytic pathway activity in a compartment-specific manner. Single-cell analyses identified five cell types—endothelial cells, fibroblasts, epithelial cells, macrophages and neutrophils—and further revealed fibroblasts as key contributors to regulatory effects via GPX3 overexpression. Importantly, the higher expression of Gpx3 in fibroblasts compared to other cell types, Gpx3 (AUC = 0.995), was further validated, demonstrating the high sensitivity and specificity for DN patients. This multimodal atlas establishes the spatially resolved metabolic blueprint of DN, bridging molecular zoning with anatomical localization of renal tissue to unveil actionable therapeutic targets for metabolic disorders in kidney disease.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 3","pages":"Article 100252"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting PD-1 post-translational modifications for improving cancer immunotherapy","authors":"Jie Shi ,&nbsp;Chuan He ,&nbsp;Li Chen ,&nbsp;Xixin Xing ,&nbsp;Wenyi Wei ,&nbsp;Jinfang Zhang","doi":"10.1016/j.cellin.2025.100248","DOIUrl":"10.1016/j.cellin.2025.100248","url":null,"abstract":"<div><div>Programmed cell death protein 1 (PD-1) is a critical immune checkpoint receptor that suppresses immune responses largely through its interaction with PD-L1. Tumors exploit this mechanism to evade immune surveillance, positioning immune checkpoint inhibitors targeting the PD-1/PD-L1 axis as groundbreaking advancements in cancer therapy. However, the overall effectiveness of these therapies is often constrained by an incomplete understanding of the underlying mechanisms. Recent research has uncovered the pivotal role of various post-translational modifications (PTMs) of PD-1, including ubiquitination, UFMylation, phosphorylation, palmitoylation, and glycosylation, in regulating its protein stability, localization, and protein-protein interactions. As much, dysregulation of these PTMs can drive PD-1-mediated immune evasion and contribute to therapeutic resistance. Notably, targeting PD-1 PTMs with small-molecule inhibitors or monoclonal antibodies (MAbs) has shown potential to bolster anti-tumor immunity in both pre-clinical mouse models and clinical trials. This review highlights recent findings on PD-1's PTMs and explores emerging therapeutic strategies aimed at modulating these modifications. By integrating these mechanistic insights, the development of combination cancer immunotherapies can be further rationally advanced, offering new avenues for more effective and durable treatments.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 3","pages":"Article 100248"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover","authors":"","doi":"10.1016/S2772-8927(25)00032-X","DOIUrl":"10.1016/S2772-8927(25)00032-X","url":null,"abstract":"","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 3","pages":"Article 100258"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}