Protein & Cell最新文献_第9页

Drug repurposing screening and mechanism analysis based on human colorectal cancer organoids. 基于人类结直肠癌器官组织的药物再利用筛选和机制分析。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-04-01 DOI: 10.1093/procel/pwad038

Yunuo Mao, Wei Wang, Jingwei Yang, Xin Zhou, Yongqu Lu, Junpeng Gao, Xiao Wang, Lu Wen, Wei Fu, Fuchou Tang

{"title":"Drug repurposing screening and mechanism analysis based on human colorectal cancer organoids.","authors":"Yunuo Mao, Wei Wang, Jingwei Yang, Xin Zhou, Yongqu Lu, Junpeng Gao, Xiao Wang, Lu Wen, Wei Fu, Fuchou Tang","doi":"10.1093/procel/pwad038","DOIUrl":"10.1093/procel/pwad038","url":null,"abstract":"Colorectal cancer (CRC) is a highly heterogeneous cancer and exploring novel therapeutic options is a pressing issue that needs to be addressed. Here, we established human CRC tumor-derived organoids that well represent both morphological and molecular heterogeneities of original tumors. To efficiently identify repurposed drugs for CRC, we developed a robust organoid-based drug screening system. By combining the repurposed drug library and computation-based drug prediction, 335 drugs were tested and 34 drugs with anti-CRC effects were identified. More importantly, we conducted a detailed transcriptome analysis of drug responses and divided the drug response signatures into five representative patterns: differentiation induction, growth inhibition, metabolism inhibition, immune response promotion, and cell cycle inhibition. The anticancer activities of drug candidates were further validated in the established patient-derived organoids-based xenograft (PDOX) system in vivo. We found that fedratinib, trametinib, and bortezomib exhibited effective anticancer effects. Furthermore, the concordance and discordance of drug response signatures between organoids in vitro and pairwise PDOX in vivo were evaluated. Our study offers an innovative approach for drug discovery, and the representative transcriptome features of drug responses provide valuable resources for developing novel clinical treatments for CRC.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"285-304"},"PeriodicalIF":21.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9665176","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

Emerging clinical relevance of microbiome in cancer: promising biomarkers and therapeutic targets. 癌症微生物组的新临床相关性：有前景的生物标志物和治疗靶点。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-04-01 DOI: 10.1093/procel/pwad052

Jia-Hao Dai, Xi-Rong Tan, Han Qiao, Na Liu

引用次数: 0

Ca2+ binding to the C2E domain of otoferlin is required for hair cell exocytosis and hearing. Ca2+与奥托费林C2E结构域的结合是毛细胞外泌和听觉所必需的。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-04-01 DOI: 10.1093/procel/pwad058

Han Chen, Mehar Monga, Qinghua Fang, Loujin Slitin, Jakob Neef, Shashank S Chepurwar, Regina Célia Mingroni Netto, Karina Lezirovitz, Alfredo Tabith, Fritz Benseler, Nils Brose, Kathrin Kusch, Carolin Wichmann, Nicola Strenzke, Barbara Vona, Julia Preobraschenski, Tobias Moser

引用次数: 0

Correction to: Low-dose chloroquine treatment extends the lifespan of aged rats. 更正:低剂量氯喹治疗可延长老年大鼠的寿命。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-04-01 DOI: 10.1093/procel/pwad053

引用次数: 0

METTL9-catalyzed histidine methylation of S100A9 suppresses the anti-Staphylococcus aureus activity of neutrophils. METTL9 催化的 S100A9 组氨酸甲基化抑制了中性粒细胞抗金黄色葡萄球菌的活性。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2024-02-29 DOI: 10.1093/procel/pwad047

Dan Cao, Mengyue Lv, Chi Hu, Shukai Li, Siwen Wang, Chao Xu, Wen Pan

引用次数: 0

The ubiquitin codes in cellular stress responses. 细胞应激反应中的泛素密码。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-02-29 DOI: 10.1093/procel/pwad045

Xiangpeng Sheng, Zhixiong Xia, Hanting Yang, Ronggui Hu

{"title":"The ubiquitin codes in cellular stress responses.","authors":"Xiangpeng Sheng, Zhixiong Xia, Hanting Yang, Ronggui Hu","doi":"10.1093/procel/pwad045","DOIUrl":"10.1093/procel/pwad045","url":null,"abstract":"Ubiquitination/ubiquitylation, one of the most fundamental post-translational modifications, regulates almost every critical cellular process in eukaryotes. Emerging evidence has shown that essential components of numerous biological processes undergo ubiquitination in mammalian cells upon exposure to diverse stresses, from exogenous factors to cellular reactions, causing a dazzling variety of functional consequences. Various forms of ubiquitin signals generated by ubiquitylation events in specific milieus, known as ubiquitin codes, constitute an intrinsic part of myriad cellular stress responses. These ubiquitination events, leading to proteolytic turnover of the substrates or just switch in functionality, initiate, regulate, or supervise multiple cellular stress-associated responses, supporting adaptation, homeostasis recovery, and survival of the stressed cells. In this review, we attempted to summarize the crucial roles of ubiquitination in response to different environmental and intracellular stresses, while discussing how stresses modulate the ubiquitin system. This review also updates the most recent advances in understanding ubiquitination machinery as well as different stress responses and discusses some important questions that may warrant future investigation.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"157-190"},"PeriodicalIF":21.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9837931","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

Long-term in vivo chimeric cells tracking in non-human primate. 非人灵长类动物体内长期嵌合细胞追踪。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-02-29 DOI: 10.1093/procel/pwad049

Junmo Wu, Yu Kang, Xiang Luo, Shaoxing Dai, Yuxi Shi, Zhuoyao Li, Zengli Tang, Zhenzhen Chen, Ran Zhu, Pengpeng Yang, Zifan Li, Hong Wang, Xinglong Chen, Ziyi Zhao, Weizhi Ji, Yuyu Niu

{"title":"Long-term in vivo chimeric cells tracking in non-human primate.","authors":"Junmo Wu, Yu Kang, Xiang Luo, Shaoxing Dai, Yuxi Shi, Zhuoyao Li, Zengli Tang, Zhenzhen Chen, Ran Zhu, Pengpeng Yang, Zifan Li, Hong Wang, Xinglong Chen, Ziyi Zhao, Weizhi Ji, Yuyu Niu","doi":"10.1093/procel/pwad049","DOIUrl":"10.1093/procel/pwad049","url":null,"abstract":"Non-human primates (NHPs) are increasingly used in preclinical trials to test the safety and efficacy of biotechnology therapies. Nonetheless, given the ethical issues and costs associated with this model, it would be highly advantageous to use NHP cellular models in clinical studies. However, developing and maintaining the naïve state of primate pluripotent stem cells (PSCs) remains difficult as does in vivo detection of PSCs, thus limiting biotechnology application in the cynomolgus monkey. Here, we report a chemically defined, xeno-free culture system for culturing and deriving monkey PSCs in vitro. The cells display global gene expression and genome-wide hypomethylation patterns distinct from monkey-primed cells. We also found expression of signaling pathways components that may increase the potential for chimera formation. Crucially for biomedical applications, we were also able to integrate bioluminescent reporter genes into monkey PSCs and track them in chimeric embryos in vivo and in vitro. The engineered cells retained embryonic and extra-embryonic developmental potential. Meanwhile, we generated a chimeric monkey carrying bioluminescent cells, which were able to track chimeric cells for more than 2 years in living animals. Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models for clinical studies.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"207-222"},"PeriodicalIF":21.1,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41163976","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

Cryo-EM structure of cannabinoid receptor CB1-β-arrestin complex. 大麻素受体 CB1-β-restin 复合物的冷冻电镜结构。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-02-29 DOI: 10.1093/procel/pwad055

Yuxia Wang, Lijie Wu, Tian Wang, Junlin Liu, Fei Li, Longquan Jiang, Zhongbo Fan, Yanan Yu, Na Chen, Qianqian Sun, Qiwen Tan, Tian Hua, Zhi-Jie Liu

引用次数: 0

Ergothioneine and its congeners: anti-ageing mechanisms and pharmacophore biosynthesis. 麦角硫因及其同系物：抗衰老机制和药源生物合成。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-02-29 DOI: 10.1093/procel/pwad048

Li Chen, Liping Zhang, Xujun Ye, Zixin Deng, Changming Zhao

引用次数: 0

Correction to: EGFR signaling augments TLR4 cell surface expression and function in macrophages via regulation of Rab5a activation. 更正为表皮生长因子受体信号通过调节 Rab5a 的活化增强巨噬细胞中 TLR4 细胞表面的表达和功能。