Cell insight最新文献

cGAS, an innate dsDNA sensor with multifaceted functions cGAS，一种具有多方面功能的先天dsDNA传感器

Cell insight Pub Date : 2025-04-17 DOI: 10.1016/j.cellin.2025.100249

Yutong Liu , Pinglong Xu

{"title":"cGAS, an innate dsDNA sensor with multifaceted functions","authors":"Yutong Liu , 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":"2025-04-17","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}

引用次数: 0

Corrigendum to “STING guides the STX17-SNAP29-VAMP8 complex assembly to control autophagy” [Cell Insight 3 (2024) 100147] “STING引导STX17-SNAP29-VAMP8复合物组装控制自噬”的勘误表[Cell Insight 3 (2024) 100147]

Cell insight Pub Date : 2025-04-11 DOI: 10.1016/j.cellin.2025.100239

Xiaoyu Song , Yufeng Xi , Ming Dai , Tao Li , Shihao Du , Yuxin Zhu , Mengjie Li , Yunze Li , Siqi Liu , Xia Ding , Xuebiao Yao , Ying Lai , Xing Liu

引用次数: 0

Targeting PD-1 post-translational modifications for improving cancer immunotherapy 靶向PD-1翻译后修饰改善癌症免疫治疗

Cell insight Pub Date : 2025-04-10 DOI: 10.1016/j.cellin.2025.100248

Jie Shi , Chuan He , Li Chen , Xixin Xing , Wenyi Wei , Jinfang Zhang

{"title":"Targeting PD-1 post-translational modifications for improving cancer immunotherapy","authors":"Jie Shi , Chuan He , Li Chen , Xixin Xing , Wenyi Wei , 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":"2025-04-10","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}

引用次数: 0

Intratumor HIF-1α modulates production of a cachectic ligand to cause host wasting 肿瘤内HIF-1α调节一种病毒质配体的产生，导致宿主消瘦

Cell insight Pub Date : 2025-04-08 DOI: 10.1016/j.cellin.2025.100247

Gen Xiao , Yingge Li , Yanhui Hu , Kai Tan , Mengyang Wang , Kerui Zhu , Mingkui San , Qian Cheng , Dilinigeer Tayier , Tingting Hu , Peixuan Dang , Jiaying Li , Chen Cheng , Norbert Perrimon , Zhiyong Yang , Wei Song

{"title":"Intratumor HIF-1α modulates production of a cachectic ligand to cause host wasting","authors":"Gen Xiao , Yingge Li , Yanhui Hu , Kai Tan , Mengyang Wang , Kerui Zhu , Mingkui San , Qian Cheng , Dilinigeer Tayier , Tingting Hu , Peixuan Dang , Jiaying Li , Chen Cheng , Norbert Perrimon , Zhiyong Yang , 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><sup><em>3SA</em></sup> gut tumors or larval <em>scrib</em><sup><em>1</em></sup> <em>Ras</em><sup><em>V12</em></sup> 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":"2025-04-08","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}

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Cell insight Pub Date : 2025-04-01 DOI: 10.1016/S2772-8927(25)00015-X

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The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruption TRPV4在急性睡眠剥夺引起的记忆障碍中的作用：钙调节失调和突触可塑性破坏的机制

Cell insight Pub Date : 2025-03-31 DOI: 10.1016/j.cellin.2025.100240

Meimei Guo , Feiyang Zhang , Sha Liu , Yi Zhang , Lesheng Wang , Jian Song , Wei Wei , Xiang Li

{"title":"The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruption","authors":"Meimei Guo , Feiyang Zhang , Sha Liu , Yi Zhang , Lesheng Wang , Jian Song , Wei Wei , Xiang Li","doi":"10.1016/j.cellin.2025.100240","DOIUrl":"10.1016/j.cellin.2025.100240","url":null,"abstract":"<div><div>Acute sleep deprivation (ASD) impairs memory formation, but the underlying mechanisms remain unclear. In this study, we employed an ASD model combined with fear conditioning to investigate these mechanisms. mRNA sequencing revealed upregulated expression of Transient Receptor Potential Vanilloid 4 (TRPV4), a nonselective Ca<sup>2+</sup>-permeable cation channel critical for calcium signaling, in mice with ASD-induced memory impairments. Notably, TRPV4 knockdown reversed ASD-induced memory deficits. ASD was associated with increased intracellular Ca<sup>2+</sup> concentrations, reduced spine density, and decreased expression of postsynaptic density protein 95 (PSD95), a key regulator of synaptic plasticity. These findings suggest that ASD may cause Ca<sup>2+</sup> overload, leading to disrupted synaptic plasticity and impaired learning and memory. Importantly, TRPV4 knockdown significantly reduced Ca<sup>2+</sup> concentrations, mitigated synaptic plasticity impairments, and contributed to memory restoration. Together, these findings demonstrate a protective role of TRPV4 knockdown against ASD-induced memory deficits and highlight TRPV4 as a potential therapeutic target for memory impairment associated with ASD.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 3","pages":"Article 100240"},"PeriodicalIF":0.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815800","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}

引用次数: 0

Unveiling racial disparities in prostate cancer using an integrative genomic and transcriptomic analysis 利用综合基因组学和转录组学分析揭示前列腺癌的种族差异

Cell insight Pub Date : 2025-02-17 DOI: 10.1016/j.cellin.2025.100238

Abdalla Elbialy , Akshay Sood , Shang-Jui Wang , Peng Wang , Ahmed Fadiel , Anil V. Parwani , Steven Huang , Gennady Shvets , Nagireddy Putluri , Jenny Li , Xuefeng Liu

{"title":"Unveiling racial disparities in prostate cancer using an integrative genomic and transcriptomic analysis","authors":"Abdalla Elbialy , Akshay Sood , Shang-Jui Wang , Peng Wang , Ahmed Fadiel , Anil V. Parwani , Steven Huang , Gennady Shvets , Nagireddy Putluri , Jenny Li , Xuefeng Liu","doi":"10.1016/j.cellin.2025.100238","DOIUrl":"10.1016/j.cellin.2025.100238","url":null,"abstract":"<div><div>Prostate cancer exhibits significant racial disparities, with African American (AA) individuals showing ∼64% higher incidence and 2.3 times greater mortality rates compared to their Caucasian (CA) counterparts. Understanding the complex interplay of genetic, environmental, lifestyle, socioeconomic, and healthcare access factors is crucial for developing effective interventions to reduce this disproportionate burden.</div><div>This study aims to uncover the genetic and transcriptomic differences driving these disparities through a comprehensive analysis using RNA sequencing (RNA-seq) and exome sequencing of prostate cancer tissues from both Black and White patients.</div><div>Our transcriptomics analysis revealed enhanced activity in pathways linked to immune response and cellular interactions in AA prostate cancer samples, with notable regulation by histone-associated transcription factors (HIST1H1A, HIST1H1D, and HIST1H1B) suggests potential involvement of histone modification mechanisms. Additionally, pseudogenes and long non-coding RNAs (lncRNAs) among the regulated genes indicate non-coding elements' role in these disparities.</div><div>Exome sequencing identified unique variants in AA patient samples within key genes, including TP73 (tumor suppression), XYLB (metabolism), ALDH4A1 (oxidative stress), PTPRB (cellular signaling), and HLA-DRB5 (immune response). These genetic variations likely contribute to disease progression and therapy response disparities.</div><div>This study highlights the importance of considering genetic and epigenetic variations in developing tailored therapeutic approaches to improve treatment efficacy and reduce mortality rates across diverse populations.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 2","pages":"Article 100238"},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The interplay between Salmonella and host: Mechanisms and strategies for bacterial survival 沙门氏菌与宿主之间的相互作用：细菌生存的机制和策略

Cell insight Pub Date : 2025-02-13 DOI: 10.1016/j.cellin.2025.100237

Hongyu Zhao , Xinyue Zhang , Ningning Zhang , Li Zhu , Huan Lian

{"title":"The interplay between Salmonella and host: Mechanisms and strategies for bacterial survival","authors":"Hongyu Zhao , Xinyue Zhang , Ningning Zhang , Li Zhu , Huan Lian","doi":"10.1016/j.cellin.2025.100237","DOIUrl":"10.1016/j.cellin.2025.100237","url":null,"abstract":"<div><div>Salmonella, an intracellular pathogen, infects both humans and animals, causing diverse diseases such as gastroenteritis and enteric fever. The <em>Salmonella</em> type III secretion system (T3SS), encoded within its pathogenicity islands (SPIs), is critical for bacterial virulence by directly delivering multiple effectors into eukaryotic host cells. <em>Salmonella</em> utilizes these effectors to facilitate its survival and replication within the host through modulating cytoskeletal dynamics, inflammatory responses, the biogenesis of <em>Salmonella</em>-containing vacuole (SCV), and host cell survival. Moreover, these effectors also interfere with immune responses via inhibiting innate immunity or antigen presentation. In this review, we summarize the current progress in the survival strategies employed by <em>Salmonella</em> and the molecular mechanisms underlying its interactions with the host. Understanding the interplay between <em>Salmonella</em> and host can enhance our knowledge of the bacterium's pathogenic processes and provide new insights into how it manipulates host cellular physiological activities to ensure its survival.</div></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"4 2","pages":"Article 100237"},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Cell insight Pub Date : 2025-02-01 DOI: 10.1016/S2772-8927(25)00004-5

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The cell autonomous and non-autonomous roles of itaconate in immune response 衣康酸在免疫应答中的细胞自主和非自主作用。

Cell insight Pub Date : 2025-02-01 DOI: 10.1016/j.cellin.2024.100224

Chao Chen , Xinjian Li

引用次数: 0