Life medicine最新文献_第7页

Advancements in robotic arm-based 3D bioprinting for biomedical applications 基于机械臂的三维生物打印技术在生物医学应用方面的进展

Life medicine Pub Date : 2023-11-21 DOI: 10.1093/lifemedi/lnad046

Kai Li, Wen Hui Huang, Hai Tao Guo, Yan Yan Liu, Shuxian Chen, Heng Liu, Qi Gu

引用次数: 0

Tmem88 plays an essential role in pharyngeal pouch progenitor specification by inhibiting Wnt/β-catenin signaling Tmem88通过抑制Wnt/β-catenin信号在咽袋祖细胞规格化过程中发挥重要作用

Life medicine Pub Date : 2023-11-17 DOI: 10.1093/lifemedi/lnad044

Jingwen Liu, Liping Yang, Zidong Lu, Qiang Wan

{"title":"Tmem88 plays an essential role in pharyngeal pouch progenitor specification by inhibiting Wnt/β-catenin signaling","authors":"Jingwen Liu, Liping Yang, Zidong Lu, Qiang Wan","doi":"10.1093/lifemedi/lnad044","DOIUrl":"https://doi.org/10.1093/lifemedi/lnad044","url":null,"abstract":"Pharyngeal pouches, which are endodermal outpockets that segment the pharyngeal arches, play a crucial role in the development of craniofacial skeletons in vertebrate embryos. Our previous study successfully identified pharyngeal pouch progenitors (PPPs) in zebrafish embryos and emphasized the significance of BMP2b signaling in their specification. However, the specific mechanism by which these progenitors originate from endodermal cells remains largely unknown. Here we found that the pharmacological activation of Wnt signaling pathway disrupts the emergence of PPPs and subsequently hinders the formation of pharyngeal pouches. Moreover, we have identified the expression of tmem88a and tmem88b (collectively known as tmem88a/b) in PPPs during the early-somite stages. Furthermore, the deficiency of tmem88a/b leads to an excessive accumulation of β-catenin in both the cytoplasm and nucleus of endodermal cells that are intended to differentiate into PPPs. Importantly, suppressing the hyperactivation of Wnt/β-catenin signaling through pharmacological treatment, the defects in PPP specification in tmem88a/b−/− mutants are successfully rescued. In summary, our findings establish a clear connection between the specification of PPPs and the regulation of Wnt signaling mediated by Tmem88. These results underscore the pivotal role of Tmem88 in the development of pharyngeal pouches.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"24 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139264028","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

Secretagogin regulates asynchronous and spontaneous glutamate release in hippocampal neurons through interaction with Doc2α 分泌素通过与Doc2α的相互作用调节海马神经元的异步和自发谷氨酸释放

Life medicine Pub Date : 2023-11-14 DOI: 10.1093/lifemedi/lnad041

Yingfeng Tu, Jiao Qin, Qiao-Ming Zhang, Tie-Shan Tang, Lifang Wang, Jun Yao

引用次数: 0

Vitamin C derivative/AA2P promotes erythroid differentiation by upregulating CA1 维生素C衍生物/AA2P通过上调CA1促进红细胞分化

Life medicine Pub Date : 2023-11-13 DOI: 10.1093/lifemedi/lnad043

Xiaoyu Tan, Meng Li, Yue Liang, Xiuyan Ruan, Zhaojun Zhang, Xiangdong Fang

{"title":"Vitamin C derivative/AA2P promotes erythroid differentiation by upregulating <i>CA1</i>","authors":"Xiaoyu Tan, Meng Li, Yue Liang, Xiuyan Ruan, Zhaojun Zhang, Xiangdong Fang","doi":"10.1093/lifemedi/lnad043","DOIUrl":"https://doi.org/10.1093/lifemedi/lnad043","url":null,"abstract":"Abstract Vitamin C is used to treat anaemia; however, the mechanism through which vitamin C promotes erythroid differentiation is not comprehensively understood. The in vitro erythroid differentiation induction system can reveal the differentiation mechanism and provide materials for the clinical transfusion of erythrocytes and treatment of anaemia. This process can be promoted by adding small-molecule compounds. In this study, we added L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AA2P), a derivative of vitamin C, to an erythroid differentiation system induced by umbilical cord blood haematopoietic stem and progenitor cells in vitro and detected its effect on erythroid differentiation using single-cell transcription sequencing technology combined with non-targeted metabolism detection. AA2P increased the proportion of late basophilic erythroblasts, upregulating the expression of erythroid-related regulatory molecules GATA1, KLF1, ALAS2, and the globins HBG and HBB. CA1 is a target gene of AA2P, and CA1 knockdown affected the expression of globin-related genes. AA2P also increased glycolysis and decreased oxidative phosphorylation to facilitate terminal erythroid differentiation and enhanced the proliferation of early erythroid progenitors by altering the cell cycle. These results provide a reliable basis for using vitamin C to improve the efficiency of erythropoiesis in vitro and for the clinical treatment of anaemia.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"51 24","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136281770","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

Efficient repair of human genetic defect by CRISPR/Cas9 mediated interlocus gene conversion CRISPR/Cas9介导的基因座间转换对人类遗传缺陷的有效修复

Life medicine Pub Date : 2023-11-13 DOI: 10.1093/lifemedi/lnad042

Fei Yang, Yiyun Wang, Qiudao Wang, Jingtao Pang, Guolong Liu, Yang Yang, Shenguang Qin, Ying Zhang, Yongrong Lai, Bin Fu, Yating Zhu, Mengyao Wang, Ryo Kurita, Yukio Nakamura, Dan Liang, Yuxuan Wu

{"title":"Efficient repair of human genetic defect by CRISPR/Cas9 mediated interlocus gene conversion","authors":"Fei Yang, Yiyun Wang, Qiudao Wang, Jingtao Pang, Guolong Liu, Yang Yang, Shenguang Qin, Ying Zhang, Yongrong Lai, Bin Fu, Yating Zhu, Mengyao Wang, Ryo Kurita, Yukio Nakamura, Dan Liang, Yuxuan Wu","doi":"10.1093/lifemedi/lnad042","DOIUrl":"https://doi.org/10.1093/lifemedi/lnad042","url":null,"abstract":"DNA double-strand breaks (DSBs) induced by gene editing tools are primarily repaired through non-homologous end joining (NHEJ) or homology-directed repair (HDR) using synthetic DNA templates. However, error-prone NHEJ may result in unexpected indels at the targeted site. For most genetic disorders, precise HDR correction using exogenous homologous sequence is ideal. But the therapeutic application of HDR might be especially challenging given the requirement for the codelivery of exogenous DNA templates with toxicity into cells, and the low efficiency of HDR could also limit its clinical application. In this study, we efficiently repair pathogenic mutations in HBB coding regions of hematopoietic stem cells (HSCs) using CRISPR/Cas9-mediated gene conversion (CRISPR/GC) using the paralog gene HBD as the internal template. After transplantation, these edited HSCs successfully repopulate the hematopoietic system and generate erythroid cells with significantly reduced thalassemia propensity. Moreover, a range of pathogenic gene mutations causing β-thalassemia in HBB coding regions were effectively converted to normal wild-type sequences without exogenous DNA templates using CRISPR/GC. This highlights the promising potential of CRISPR/GC, independent of synthetic DNA templates, for genetic disease gene therapy.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"43 21","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136281930","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

Deubiquitination of SARM1 by USP13 regulates SARM1 activation and axon degeneration USP13介导的SARM1去泛素化调控SARM1的激活和轴突退化

Life medicine Pub Date : 2023-11-04 DOI: 10.1093/lifemedi/lnad040

Wenkai Yue, Kai Zhang, Mingsheng Jiang, Wenjing Long, Jihong Cui, Yunxia Li, Yaoyang Zhang, Ang Li, Yanshan Fang

{"title":"Deubiquitination of SARM1 by USP13 regulates SARM1 activation and axon degeneration","authors":"Wenkai Yue, Kai Zhang, Mingsheng Jiang, Wenjing Long, Jihong Cui, Yunxia Li, Yaoyang Zhang, Ang Li, Yanshan Fang","doi":"10.1093/lifemedi/lnad040","DOIUrl":"https://doi.org/10.1093/lifemedi/lnad040","url":null,"abstract":"Abstract Sterile alpha and Toll/interleukin 1 receptor motif-containing protein 1 (SARM1) is regarded as a key protein and a central executor of the self-destruction of injured axons. To identify novel molecular players and understand the mechanisms regulating SARM1 function, we investigated the interactome of SARM1 by proximity-labeling and proteomic profiling. Among the SARM1-assoicated proteins, we uncovered that overexpression (OE) of ubiquitin-specific peptidase 13 (USP13) delayed injury-induced axon degeneration. OE of an enzyme-dead USP13 failed to protect injured axons, indicating that the deubiquitinase activity of USP13 was required for its axonal protective effect. Further investigation revealed that USP13 deubiquitinated SARM1, which increased the inhibitory interaction between the N-terminal armadillo repeat motif (ARM) and C-terminal Toll/interleukin-1 receptor (TIR) domains of the SARM1 protein, thereby suppressing SARM1 activation in axon injury. Collectively, these findings suggest that increase of USP13 activity enhances the self-inhibition of SARM1, which may provide a strategy to mitigate axon degeneration in injury and disease.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"54 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135775854","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

Sugt1 loss in skeletal muscle stem cells impairs muscle regeneration and causes premature muscle aging 骨骼肌干细胞中的Sugt1缺失会损害肌肉再生并导致肌肉过早老化

Life medicine Pub Date : 2023-11-02 DOI: 10.1093/lifemedi/lnad039

Zhiming He, Xiaona Chen, Gexin Liu, Yuying Li, Feng Yang, Hao Sun, Huating Wang

{"title":"Sugt1 loss in skeletal muscle stem cells impairs muscle regeneration and causes premature muscle aging","authors":"Zhiming He, Xiaona Chen, Gexin Liu, Yuying Li, Feng Yang, Hao Sun, Huating Wang","doi":"10.1093/lifemedi/lnad039","DOIUrl":"https://doi.org/10.1093/lifemedi/lnad039","url":null,"abstract":"Abstract Adult skeletal muscle stem cells (MuSCs) are essential for muscle homeostasis and regeneration. During aging, the number of MuSC and their regenerative capacity gradually decline but the underlying mechanisms remain elusive. Here we identify Sugt1 (suppressor of G2 allele of SKP1 homolog), which is a chaperone for kinetochore function during mitosis and is essential for muscle regeneration by regulating MuSCs proliferation. Sugt1 expression level is low in quiescent MuSCs but highly induced when the cells become activated and expand as proliferating myoblasts. Inducible inactivation of Sugt1 in MuSCs causes impaired muscle regeneration upon acute injury by impairing MuSC proliferation. Furthermore, loss of Sugt1 leads to cell cycle arrest in the G2/M phase and cellular senescence. Moreover, long-term loss of Sugt1 in MuSCs results in precocious muscle aging by inhibiting MuSC cell proliferation and promoting cellular senescence. Mechanistically, we identify a cytosolic E3 ubiquitin-ligase, Trim21 as a protein interacting partner for Sugt1 in myoblast cells. We further demonstrate that Sugt1 promotes the ubiquitination of p21 via Trim21; and Sugt1 loss causes p21 accumulation to inhibit cell cycle progression and stimulates cellular senescence. Collectively, our findings uncover that Sugt1 is an essential regulator for MuSC regenerative function during muscle regeneration and aging.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"57 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135975152","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

From Clone to Synthetic Embryos 从克隆到合成胚胎

Life medicine Pub Date : 2023-10-24 DOI: 10.1093/lifemedi/lnad038

Carlos A Pinzón-Arteaga, Leqian Yu

引用次数: 0

A CRISPR/Cas9-based kinome screen identifies ErbB signaling as a new regulator of human naïve pluripotency and totipotency 基于CRISPR/ cas9的kinome筛选鉴定出ErbB信号作为人类naïve多能性和全能性的新调节剂

Life medicine Pub Date : 2023-10-20 DOI: 10.1093/lifemedi/lnad037

Jiayu Li, Xiwen Lin, Liangfu Xie, Jingru Zhao, Chunsheng Han, Hongkui Deng, Jun Xu

引用次数: 0

In situ neuronal regeneration: the potential of astrocytes 原位神经元再生:星形胶质细胞的潜能

Life medicine Pub Date : 2023-10-03 DOI: 10.1093/lifemedi/lnad036

Rongbang Tan, Reiner F Haseloff, Yuqian Mo, Jingjing Zhang

引用次数: 0