Cell Stress最新文献_第2页

A versatile method for the identification of senolytic compounds 鉴定衰老化合物的多功能方法

IF 6.4

Cell Stress Pub Date : 2023-12-01 DOI: 10.15698/cst2023.12.292

Chiara Annunziata, Francesca Castoldi, Jan Schlegel, Hazel X. Ang, Mina Ristovska, Stefania Melini, Robert Welch, Christian G. Riedel, Federico Pietrocola

{"title":"A versatile method for the identification of senolytic compounds","authors":"Chiara Annunziata, Francesca Castoldi, Jan Schlegel, Hazel X. Ang, Mina Ristovska, Stefania Melini, Robert Welch, Christian G. Riedel, Federico Pietrocola","doi":"10.15698/cst2023.12.292","DOIUrl":"https://doi.org/10.15698/cst2023.12.292","url":null,"abstract":"The increased burden of senescent cells is as a well-established hallmark of aging and age-related diseases. This finding sparked significant interest in the identification of molecules capable of selectively eliminating senescent cells, so-called senolytics. Here, we fine-tuned a method for the identification of senolytics that is compatible with high-content fluorescence microscopy. We used spectral detector imaging to measure the emission spectrum of unlabeled control or senescent cells. We observed that senescent cells exhibited higher levels of autofluorescence than their non-senescent counterparts, particularly in the cytoplasmic region. Building on this result, we devised a senolytic assay based on co-culturing quiescent and senescent cells, fluorescently tagged in the nuclear region through the overexpression of H2B-GFP and H2B-RFP, respectively. We validated this approach by showing that first generation senolytics were effective in reducing the number of RFP+ nuclei leaving the count of GFP+ nuclei unaffected. The result was confirmed by flow cytometry analysis of nuclei isolated from these quiescent-senescent cell co-cultures. We found that this system enables to capture cell type-specific effects of senolytics as in the case of fisetin, which kills senescent Mouse Embryonic Fibroblasts but not senescent human melanoma SK-MEL-103 cells. This approach is amenable to genetic and chemical screening for the discovery of senolytic compounds in that it overcomes the limitations of current methods, which rely upon costly chemical reagents or fluorescence microscopy using cells labeled with fluorescent cytoplasmic probes that overlap with the autofluorescence signal emitted by senescent cells.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"270 1","pages":"105 - 111"},"PeriodicalIF":6.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138991430","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

STING-driven activation of T cells: relevance for the adoptive cell therapy of cancer. sting驱动的T细胞活化:与癌症过继细胞治疗的相关性

IF 6.4

Cell Stress Pub Date : 2023-11-14 eCollection Date: 2023-11-01 DOI: 10.15698/cst2023.11.291

Fabian Richter, Christophe Paget, Lionel Apetoh

{"title":"STING-driven activation of T cells: relevance for the adoptive cell therapy of cancer.","authors":"Fabian Richter, Christophe Paget, Lionel Apetoh","doi":"10.15698/cst2023.11.291","DOIUrl":"https://doi.org/10.15698/cst2023.11.291","url":null,"abstract":"Adoptive cell therapy (ACT) can successfully treat hematopoietic cancers but lacks efficacy against solid tumors. This is due to insufficient T cell infiltration, high tumor heterogeneity, frequent antigen loss with subsequent tumor escape, and the immunosuppressive tumor microenvironment (TME). Alternative methods to boost the anticancer efficacy of adoptively transferred cells are actively pursued. Among adjuvants that are utilized to stimulate anticancer immune responses, ligands of the stimulator of interferon genes (STING) pathway have received increasing attention. STING activation can trigger dendritic cell (DC) activation and endogenous immune responses, thereby preventing tumor escape. Activation of the STING pathway in the context of ACT was accordingly associated with improved T cell trafficking and persistence in the TME combined with the reduced presence of immunosuppressive cells. Recent findings also suggest cell-intrinsic effects of STING ligands on T cells. Activation of the STING signaling pathway was in this regard shown to enhance effector functions of CD4+ and CD8+ T cells, suggesting that the STING signaling could be exploited to harness T cell anticancer functions. In this review, we will discuss how the STING signaling can be used to enhance the anticancer efficacy of ACT.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"7 11","pages":"95-104"},"PeriodicalIF":6.4,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10642958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134650058","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

Chromatin assembly factor-1 preserves genome stability in ctf4Δ cells by promoting sister chromatid cohesion. 染色质组装因子-1通过促进姐妹染色单体内聚来保持ctf4Δ细胞基因组的稳定性。

IF 6.4

Cell Stress Pub Date : 2023-09-11 DOI: 10.15698/cst2023.09.289

Nagham Ghaddar, Pierre Luciano, Vincent Géli, Yves Corda

{"title":"Chromatin assembly factor-1 preserves genome stability in ctf4Δ cells by promoting sister chromatid cohesion.","authors":"Nagham Ghaddar, Pierre Luciano, Vincent Géli, Yves Corda","doi":"10.15698/cst2023.09.289","DOIUrl":"https://doi.org/10.15698/cst2023.09.289","url":null,"abstract":"Chromatin assembly and the establishment of sister chromatid cohesion are intimately connected to the progression of DNA replication forks. Here we examined the genetic interaction between the heterotrimeric chromatin assembly factor-1 (CAF-1), a central component of chromatin assembly during replication, and the core replisome component Ctf4. We find that CAF-1 deficient cells as well as cells affected in newly-synthesized H3-H4 histones deposition during DNA replication exhibit a severe negative growth with ctf4Δ mutant. We dissected the role of CAF-1 in the maintenance of genome stability in ctf4Δ yeast cells. In the absence of CTF4, CAF-1 is essential for viability in cells experiencing replication problems, in cells lacking functional S-phase checkpoint or functional spindle checkpoint, and in cells lacking DNA repair pathways involving homologous recombination. We present evidence that CAF-1 affects cohesin association to chromatin in a DNA-damage-dependent manner and is essential to maintain cohesion in the absence of CTF4. We also show that Eco1-catalyzed Smc3 acetylation is reduced in absence of CAF-1. Furthermore, we describe genetic interactions between CAF-1 and essential genes involved in cohesin loading, cohesin stabilization, and cohesin component indicating that CAF-1 is crucial for viability when sister chromatid cohesion is affected. Finally, our data indicate that the CAF-1-dependent pathway required for cohesion is functionally distinct from the Rtt101-Mms1-Mms22 pathway which functions in replicated chromatin assembly. Collectively, our results suggest that the deposition by CAF-1 of newly-synthesized H3-H4 histones during DNA replication creates a chromatin environment that favors sister chromatid cohesion and maintains genome integrity.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"7 9","pages":"69-89"},"PeriodicalIF":6.4,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10505505","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

Sensitive, non-immunogenic in vivo imaging of cancer metastases and immunotherapy response. 对癌症转移和免疫疗法反应进行灵敏、非免疫原性的体内成像。

IF 6.4

Cell Stress Pub Date : 2023-08-14 DOI: 10.15698/cst2023.08.288

Joseph R Merrill, Alessandra Inguscio, Taemoon Chung, Breanna Demestichas, Libia A Garcia, Jill Habel, David Y Lewis, Tobias Janowitz, Scott K Lyons

{"title":"Sensitive, non-immunogenic in vivo imaging of cancer metastases and immunotherapy response.","authors":"Joseph R Merrill, Alessandra Inguscio, Taemoon Chung, Breanna Demestichas, Libia A Garcia, Jill Habel, David Y Lewis, Tobias Janowitz, Scott K Lyons","doi":"10.15698/cst2023.08.288","DOIUrl":"10.15698/cst2023.08.288","url":null,"abstract":"Non-invasive imaging of tumors expressing reporter transgenes is a popular preclinical method for studying tumor development and response to therapy in vivo due to its ability to distinguish signal from tumors over background noise. However, the utilized transgenes, such as firefly luciferase, are immunogenic and, therefore, impact results when expressed in immune-competent hosts. This represents an important limitation, given that cancer immunology and immunotherapy are currently among the most impactful areas of research and therapeutic development. Here we present a non-immunogenic preclinical tumor imaging approach. Based on the expression of murine sodium iodide symporter (mNIS), it facilitates sensitive, non-invasive detection of syngeneic tumor cells in immune-competent tumor models without additional immunogenicity arising from exogenous transgenic protein or selection marker expression. NIS-expressing tumor cells internalize the gamma-emitting [99mTc]pertechnetate ion and so can be detected by SPECT (single photon emission computed tomography). Using a mouse model of pancreatic ductal adenocarcinoma hepatic metastases in immune-competent C57BL/6 mice, we demonstrate that the technique enables the detection of very early metastatic lesions and longitudinal assessment of immunotherapy responses using precise and quantifiable whole-body SPECT/CT imaging.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"7 8","pages":"59-68"},"PeriodicalIF":6.4,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10152930","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

Molecular targets of spermidine: implications for cancer suppression. 亚精胺的分子靶点:对癌症抑制的影响。

IF 6.4

Cell Stress Pub Date : 2023-07-01 DOI: 10.15698/cst2023.07.281

Andreas Zimmermann, Sebastian J Hofer, Frank Madeo

{"title":"Molecular targets of spermidine: implications for cancer suppression.","authors":"Andreas Zimmermann, Sebastian J Hofer, Frank Madeo","doi":"10.15698/cst2023.07.281","DOIUrl":"https://doi.org/10.15698/cst2023.07.281","url":null,"abstract":"Spermidine is a ubiquitous, natural polyamine with geroprotective features. Supplementation of spermidine extends the lifespan of yeast, worms, flies, and mice, and dietary spermidine intake correlates with reduced human mortality. However, the crucial role of polyamines in cell proliferation has also implicated polyamine metabolism in neoplastic diseases, such as cancer. While depleting intracellular polyamine biosynthesis halts tumor growth in mouse models, lifelong external spermidine administration in mice does not increase cancer incidence. In contrast, a series of recent findings points to anti-neoplastic properties of spermidine administration in the context of immunotherapy. Various molecular mechanisms for the anti-aging and anti-cancer properties have been proposed, including the promotion of autophagy, enhanced translational control, and augmented mitochondrial function. For instance, spermidine allosterically activates mitochondrial trifunctional protein (MTP), a bipartite protein complex that mediates three of the four steps of mitochondrial fatty acid (β-oxidation. Through this action, spermidine supplementation is able to restore MTP-mediated mitochondrial respiratory capacity in naïve CD8+ T cells to juvenile levels and thereby improves T cell activation in aged mice. Here, we put this finding into the context of the previously described molecular target space of spermidine.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"7 7","pages":"50-58"},"PeriodicalIF":6.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9816794","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

Novel insights at the crossroads of antibiotic use and cancer risk. 抗生素使用和癌症风险交叉路口的新见解。

IF 6.4

Cell Stress Pub Date : 2023-06-01 DOI: 10.15698/cst2023.06.280

Nermina Malanovic, Djenana Vejzovic

引用次数: 1

CRISPR-activation screen identified potassium channels for protection against mycotoxins through cell cycle progression and mitochondrial function. crispr激活筛选通过细胞周期进程和线粒体功能鉴定了防止霉菌毒素的钾通道。

IF 6.4

Cell Stress Pub Date : 2023-05-01 DOI: 10.15698/cst2023.05.279

Yulong Tang, Simeng Liao, Zhuyuan Nie, Guangwei Kuang, Chunxiao Ji, Dan Wan, Liuqin He, Fengna Li, Xiangfeng Kong, Kai Zhan, Bie Tan, Xin Wu, Yulong Yin

{"title":"CRISPR-activation screen identified potassium channels for protection against mycotoxins through cell cycle progression and mitochondrial function.","authors":"Yulong Tang, Simeng Liao, Zhuyuan Nie, Guangwei Kuang, Chunxiao Ji, Dan Wan, Liuqin He, Fengna Li, Xiangfeng Kong, Kai Zhan, Bie Tan, Xin Wu, Yulong Yin","doi":"10.15698/cst2023.05.279","DOIUrl":"https://doi.org/10.15698/cst2023.05.279","url":null,"abstract":"Zearalenone (ZEA) exposure has carcinogenic effects on human and animal health by exhibiting intestinal, hepatic, and renal toxicity. At present, the underlying mechanisms on how ZEA induces apoptosis and damage to tissues still remain unclear. In this study, we aimed to identify genes that modulate the cellular response to ZEA using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screening, and further validate novel gene functions to elucidate molecular mechanisms underlying particular biological processes in vivo and in vitro. Two ZEA-resistant cell lines, designated Ov-KCNJ4 and Ov-KCNJ12, were yielded by CRISPR activation screening which had significant changes in ZEA resistance and growth rates. Results showed that ZEA could interact with the cell membrane proteins KCNJ4 and KCNJ12, inducing cell cycle arrest, disruption of DNA replication and base excision repair. Overexpression of KCNJ4 and KCNJ12 was involved in ZEA resistance by regulating cell cycle to neutralize toxicity, sustaining mitochondrial morphology and function via attenuating the damage from oxidative stress in the KCNJ4-mitoKATP pathway. In vivo experiments showed that AAV-KCNJ4 delivery significantly improved ZEA-induced renal impairment and increased antioxidative enzyme activity by improving mitochondrial function. Our findings suggest that increasing potassium channel levels may be a putative therapeutic target for mycotoxin-induced damage.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"7 5","pages":"34-45"},"PeriodicalIF":6.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9432533","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

Macrolide antibiotics activate the integrated stress response and promote tumor proliferation. 大环内酯类抗生素激活综合应激反应，促进肿瘤增殖。

IF 6.4

Cell Stress Pub Date : 2023-04-01 DOI: 10.15698/cst2023.04.278

Xin Yu, Ai-Ling Tian, Ping Wang, Juanjuan Li, Juan Wu, Bei Li, Zhou Liu, Siqing Liu, Zhijie Gao, Si Sun, Shengrong Sun, Yi Tu, Qi Wu

{"title":"Macrolide antibiotics activate the integrated stress response and promote tumor proliferation.","authors":"Xin Yu, Ai-Ling Tian, Ping Wang, Juanjuan Li, Juan Wu, Bei Li, Zhou Liu, Siqing Liu, Zhijie Gao, Si Sun, Shengrong Sun, Yi Tu, Qi Wu","doi":"10.15698/cst2023.04.278","DOIUrl":"https://doi.org/10.15698/cst2023.04.278","url":null,"abstract":"Macrolide antibiotics are widely used antibacterial agents that are associated with autophagy inhibition. This study aimed to investigate the association between macrolide antibiotics and malignant tumors, as well as the effect on autophagy, reactive oxygen species (ROS) accumulation and integrated stress response (ISR). The meta-analysis indicated a modestly higher risk of cancer in macrolide antibiotic ever-users compared to non-users. Further experiments showed that macrolides block autophagic flux by inhibiting lysosomal acidification. Additionally, azithromycin, a representative macrolide antibiotic, induced the accumulation of ROS, and stimulated the ISR and the activation of transcription factor EB (TFEB) and TFE3 in a ROS-dependent manner. Finally, animal experiments confirmed that azithromycin promoted tumor progression in vivo, which could be receded by N-acetylcysteine, an inhibitor of ROS and ISR. Overall, this study reveals the potential role of macrolide antibiotics in malignant progression and highlights the need for further investigation into their effects.","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"7 4","pages":"20-33"},"PeriodicalIF":6.4,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9930702","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: 1

Impact of microbiota on breast cancer hormone therapy. 微生物群对乳腺癌激素治疗的影响。

IF 6.4

Cell Stress Pub Date : 2023-03-01 DOI: 10.15698/cst2023.03.277

Safae Terrisse, Laurence Zitvogel, Guido Kroemer

引用次数: 1

Chronic heart failure following hemorrhagic myocardial infarction: mechanism, treatment and outlook. 出血性心肌梗死后慢性心力衰竭:机制、治疗和前景。

IF 6.4

Cell Stress Pub Date : 2023-02-01 DOI: 10.15698/cst2023.02.276

Shing Fai Chan, Keyur Vora, Rohan Dharmakumar

引用次数: 1