Cell Research最新文献_第9页

Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans 以促炎性 T 细胞为靶点，将其作为一种新的治疗方法，有望解决人类动脉粥样硬化问题

IF 44.1 1区生物学

Cell Research Pub Date : 2024-03-15 DOI: 10.1038/s41422-024-00945-0

Lin Fan, Junwei Liu, Wei Hu, Zexin Chen, Jie Lan, Tongtong Zhang, Yang Zhang, Xianpeng Wu, Zhiwei Zhong, Danyang Zhang, Jinlong Zhang, Rui Qin, Hui Chen, Yunfeng Zong, Jianmin Zhang, Bing Chen, Jun Jiang, Jifang Cheng, Jingyi Zhou, Zhiwei Gao, Zhenjie Liu, Ying Chai, Junqiang Fan, Pin Wu, Yinxuan Chen, Yuefeng Zhu, Kai Wang, Ying Yuan, Pintong Huang, Ying Zhang, Huiqin Feng, Kaichen Song, Xun Zeng, Wei Zhu, Xinyang Hu, Weiwei Yin, Wei Chen, Jian’an Wang

{"title":"Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans","authors":"Lin Fan, Junwei Liu, Wei Hu, Zexin Chen, Jie Lan, Tongtong Zhang, Yang Zhang, Xianpeng Wu, Zhiwei Zhong, Danyang Zhang, Jinlong Zhang, Rui Qin, Hui Chen, Yunfeng Zong, Jianmin Zhang, Bing Chen, Jun Jiang, Jifang Cheng, Jingyi Zhou, Zhiwei Gao, Zhenjie Liu, Ying Chai, Junqiang Fan, Pin Wu, Yinxuan Chen, Yuefeng Zhu, Kai Wang, Ying Yuan, Pintong Huang, Ying Zhang, Huiqin Feng, Kaichen Song, Xun Zeng, Wei Zhu, Xinyang Hu, Weiwei Yin, Wei Chen, Jian’an Wang","doi":"10.1038/s41422-024-00945-0","DOIUrl":"10.1038/s41422-024-00945-0","url":null,"abstract":"Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 6","pages":"407-427"},"PeriodicalIF":44.1,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00945-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic engineering of the paclitaxel anticancer drug 紫杉醇抗癌药物的代谢工程。

IF 28.1 1区生物学

Cell Research Pub Date : 2024-03-14 DOI: 10.1038/s41422-024-00950-3

Audrey Oudin, Nicolas Papon, Vincent Courdavault

引用次数: 0

Multiple cancer cell types release LIF and Gal3 to hijack neural signals 多种癌细胞类型释放 LIF 和 Gal3，劫持神经信号。

IF 44.1 1区生物学

Cell Research Pub Date : 2024-03-11 DOI: 10.1038/s41422-024-00946-z

Qun Xu, Ying Cao, Fanni Kong, Jiaqi Liu, Xin Chen, Yifei Zhao, Chin-Hui Lai, Xin Zhou, Hao Hu, Wei Fu, Jian Chen, Jing Yang

{"title":"Multiple cancer cell types release LIF and Gal3 to hijack neural signals","authors":"Qun Xu, Ying Cao, Fanni Kong, Jiaqi Liu, Xin Chen, Yifei Zhao, Chin-Hui Lai, Xin Zhou, Hao Hu, Wei Fu, Jian Chen, Jing Yang","doi":"10.1038/s41422-024-00946-z","DOIUrl":"10.1038/s41422-024-00946-z","url":null,"abstract":"Neural signals can significantly influence cancer prognosis. However, how cancer cells may proactively modulate the nervous system to benefit their own survival is incompletely understood. In this study, we report an overlapping pattern of brain responses, including that in the paraventricular nucleus of the hypothalamus, in multiple mouse models of peripheral cancers. A multi-omic screening then identifies leukemia inhibitory factor (LIF) and galectin-3 (Gal3) as the key cytokines released by these cancer cell types to trigger brain activation. Importantly, increased plasma levels of these two cytokines are observed in patients with different cancers. We further demonstrate that pharmacologic or genetic blockage of cancer cell-derived LIF or Gal3 signaling abolishes the brain responses and strongly inhibits tumor growth. In addition, ablation of peripheral sympathetic actions can similarly restore antitumor immunity. These results have elucidated a novel, shared mechanism of multiple cancer cell types hijacking the nervous system to promote tumor progression.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 5","pages":"345-354"},"PeriodicalIF":44.1,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00946-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Treating insomnia with 40 Hz light flicker 用 40 赫兹闪烁光治疗失眠症

IF 44.1 1区生物学

Cell Research Pub Date : 2024-03-08 DOI: 10.1038/s41422-024-00948-x

P. Lorenzo Bozzelli, Li-Huei Tsai

引用次数: 0

The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb 快速接近标记系统 PhastID 将 ATP6AP1 鉴定为 Rheb 的非传统 GEF。

IF 44.1 1区生物学

Cell Research Pub Date : 2024-03-06 DOI: 10.1038/s41422-024-00938-z

Ran Feng, Feng Liu, Ruofei Li, Zhifen Zhou, Zhuoheng Lin, Song Lin, Shengcheng Deng, Yingying Li, Baoting Nong, Ying Xia, Zhiyi Li, Xiaoqin Zhong, Shuhan Yang, Gang Wan, Wenbin Ma, Su Wu, Zhou Songyang

{"title":"The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb","authors":"Ran Feng, Feng Liu, Ruofei Li, Zhifen Zhou, Zhuoheng Lin, Song Lin, Shengcheng Deng, Yingying Li, Baoting Nong, Ying Xia, Zhiyi Li, Xiaoqin Zhong, Shuhan Yang, Gang Wan, Wenbin Ma, Su Wu, Zhou Songyang","doi":"10.1038/s41422-024-00938-z","DOIUrl":"10.1038/s41422-024-00938-z","url":null,"abstract":"Rheb is a small G protein that functions as the direct activator of the mechanistic target of rapamycin complex 1 (mTORC1) to coordinate signaling cascades in response to nutrients and growth factors. Despite extensive studies, the guanine nucleotide exchange factor (GEF) that directly activates Rheb remains unclear, at least in part due to the dynamic and transient nature of protein–protein interactions (PPIs) that are the hallmarks of signal transduction. Here, we report the development of a rapid and robust proximity labeling system named Pyrococcus horikoshii biotin protein ligase (PhBPL)-assisted biotin identification (PhastID) and detail the insulin-stimulated changes in Rheb-proximity protein networks that were identified using PhastID. In particular, we found that the lysosomal V-ATPase subunit ATP6AP1 could dynamically interact with Rheb. ATP6AP1 could directly bind to Rheb through its last 12 amino acids and utilizes a tri-aspartate motif in its highly conserved C-tail to enhance Rheb GTP loading. In fact, targeting the ATP6AP1 C-tail could block Rheb activation and inhibit cancer cell proliferation and migration. Our findings highlight the versatility of PhastID in mapping transient PPIs in live cells, reveal ATP6AP1’s role as an unconventional GEF for Rheb, and underscore the importance of ATP6AP1 in integrating mTORC1 activation signals through Rheb, filling in the missing link in Rheb/mTORC1 activation.","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":"34 5","pages":"355-369"},"PeriodicalIF":44.1,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41422-024-00938-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An all-in-one targeted protein degradation platform guided by degradation condensates-bridging bi-specific nanobodies 降解凝聚物桥接双特异性纳米抗体引导的一体化靶向蛋白质降解平台

IF 44.1 1区生物学

Cell Research Pub Date : 2024-03-05 DOI: 10.1038/s41422-024-00942-3

Wen Jia, Weijie Li, Zengpeng Li, Pilong Li