{"title":"A comprehensive Bayesian analysis assessing the effectiveness of lymphocyte immunotherapy for recurrent spontaneous abortion","authors":"Rongzhou Chen, Haohan Xu, Yujia Hou, Hanghang Liu, Zheng Zheng, Shaohua Ma","doi":"10.1093/lifemedi/lnad049","DOIUrl":"https://doi.org/10.1093/lifemedi/lnad049","url":null,"abstract":"\u0000 Recurrent spontaneous abortion (RSA) affects 2%–5% of couples worldwide and remains a subject of debate regarding the effectiveness of lymphocyte immunotherapy (LIT) due to limited retrospective studies. We conducted a comprehensive Bayesian analysis to assess the impact of LIT on RSA. Using data from the Shenzhen Maternity and Child Healthcare Hospital (2001–2020, n = 2,316), a Bayesian generalized linear model with predictive projection feature selection was employed. Our analysis revealed a significant improvement in live birth rates for RSA patients undergoing LIT. Notably, LIT had a greater impact compared to the other 85 factors considered. To mitigate research bias, we conducted a Bayesian meta-analysis combining our dataset with 19 previously reported studies (1985–2021, n = 4,246). Additionally, we developed an empirical model highlighting the four key factors, they are LIT result, age, paternal blood type and anticardiolipin antibody. Younger age (19–27), paternal blood type B, and a positive anticardiolipin antibody (IgM) were associated with better therapeutic outcomes in LIT for RSA. These findings aid clinicians in identifying suitable candidates for LIT and improving treatment outcomes.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"44 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138588407","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}
Life medicinePub Date : 2023-11-23DOI: 10.1093/lifemedi/lnad048
Xuan-Cheng He, Jian Wang, Min-Yang Shi, Chang-Mei Li, Zhao-Qian Teng
{"title":"Hypoxia-induced one-carbon metabolic reprogramming in glioma stem-like cells","authors":"Xuan-Cheng He, Jian Wang, Min-Yang Shi, Chang-Mei Li, Zhao-Qian Teng","doi":"10.1093/lifemedi/lnad048","DOIUrl":"https://doi.org/10.1093/lifemedi/lnad048","url":null,"abstract":"Glioma stem cells (GSCs) in the hypoxic niches contribute to tumor initiation, progression, and recurrence in glioblastoma (GBM). Metabolic pathways are altered in GSCs under hypoxia, but the mechanism underlying the altered one-carbon metabolism in GSCs by hypoxia is largely unknown. Here, we report that hypoxia induces down-regulation of DHFR as well as up-regulation of MAT2A in GBM tumorsphere cells, and confers them the ability of cell proliferation that is independent of exogenous folate. Importantly, short-term inhibition of the methionine cycle or exposure to the MAT2A inhibitor is sufficient to cripple the tumor-initiating capability of GBM tumorsphere cells. Therefore, we present a novel perspective on how hypoxia alters the pattern of one-carbon metabolism in GBM tumorsphere cells and provide evidence that restriction of methionine intake or targeting MAT2A inhibits the tumorigenicity of GBM tumorsphere cells.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139245649","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}
Life medicinePub Date : 2023-11-23DOI: 10.1093/lifemedi/lnad047
Dewei Zhou, Dandan Li, Hao Nie, Jun Duan, Sarah Liu, Yujia Wang, Wei Zuo
{"title":"Generation of renal tubular organoids from adult SOX9+ kidney progenitor cells","authors":"Dewei Zhou, Dandan Li, Hao Nie, Jun Duan, Sarah Liu, Yujia Wang, Wei Zuo","doi":"10.1093/lifemedi/lnad047","DOIUrl":"https://doi.org/10.1093/lifemedi/lnad047","url":null,"abstract":"The pathogenesis of several kidney diseases results in the eventual destruction of the renal tubular system, which can progress to end-stage renal disease. Previous studies have demonstrated the involvement of a population of SOX9-positive cells in kidney regeneration and repair process following kidney injury. However, the ability of these cells to autonomously generate kidney organoids has never been investigated. Here, we isolated SOX9+ kidney progenitor cells (KPCs) from both mice and humans, and tested their differentiation potential in vitro. The data showed that the human SOX9+ KPC could self-assembly into organoids with kidney-like morphology. We also used single-cell RNA sequencing to characterize the organoid cell populations, and identified four distinct types of renal tubular cells. Comparing to the induced pluripotent stem cell (iPSC)-derived kidney organoids, KPC demonstrated more tubular differentiation potential but failed to differentiate into glomerular cells. KPC-derived organoid formation involved expression of genes related to metanephric development and followed a similar mechanism to renal injury repair in acute kidney injury (AKI) patients. Altogether, our study provided a potentially useful approach to generate kidney tubular organoids for future application.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"45 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139245369","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}
{"title":"A framework of biomarkers for skeletal aging: a consensus statement by the Aging Biomarker Consortium","authors":"Jinlong Suo, Yibo Gan, Yangli Xie, Shuqin Xu, Jianfang Wang, Di Chen, Lin Chen, Lianfu Deng, Shiqing Feng, Jingdong Jackie Han, Qing Jiang, Guanghua Lei, Peng Liu, Xianghang Luo, Xin Ma, Jing Qu, Chunli Song, P. Tang, Tingting Tang, Sijia Wang, Xiaochun Wei, Chengtie Wu, Guozhi Xiao, Liu Yang, Licheng Zhang, Weiqi Zhang, Zhenlin Zhang, Guanghui Liu, Changqing Zhang, Gang Pei, Jian Luo, Rui Yue, Weiguo Zou","doi":"10.1093/lifemedi/lnad045","DOIUrl":"https://doi.org/10.1093/lifemedi/lnad045","url":null,"abstract":"The skeleton is an important structural and metabolic organ in human body, while aging is the physiological basis for degenerative skeletal diseases. China has the largest aging population in the world and faces great challenges in preventing and managing diseases related to skeletal aging. To address these challenges, the Aging China Biomarkers Consortium (ABC) has reached an expert consensus on biomarkers of skeletal aging by synthesizing the literature and insights from scientists and clinicians. The consensus provides a comprehensive assessment of biomarkers associated with skeletal aging and proposes a systematic framework that categorizes biomarkers into three dimensions, namely, functional, structural, and humoral dimensions. Within each dimension, the ABC recommended clinical and evidential research-based biomarkers for physiological aging and degenerative pathologies of the skeleton. This expert consensus aims to lay the foundation for future studies to assess the prediction, diagnosis, early warning and treatment of diseases associated with skeletal aging, with the ultimate goal of improving the skeletal health of elderly populations in China and around the world.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139247679","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}
Life medicinePub Date : 2023-11-21DOI: 10.1093/lifemedi/lnad046
Kai Li, Wen Hui Huang, Hai Tao Guo, Yan Yan Liu, Shuxian Chen, Heng Liu, Qi Gu
{"title":"Advancements in robotic arm-based 3D bioprinting for biomedical applications","authors":"Kai Li, Wen Hui Huang, Hai Tao Guo, Yan Yan Liu, Shuxian Chen, Heng Liu, Qi Gu","doi":"10.1093/lifemedi/lnad046","DOIUrl":"https://doi.org/10.1093/lifemedi/lnad046","url":null,"abstract":"3D bioprinting emerges as a critical tool in biofabricating functional 3D tissue or organ equivalents for regenerative medicine. Bioprinting techniques have been making strides in integrating automation, customization, and digitalization in coping with diverse tissue engineering scenarios. The convergence of robotic arm-based 3D bioprinting techniques, especially in situ 3D bioprinting, is a versatile toolbox in the industrial field, promising for biomedical application and clinical research. In this review, we first introduce conceptualized modalities of robotic arm-based bioprinting from a mechanical perspective, which involves configurative categories of current robot arms regarding conventional bioprinting strategies. Recent advances in robotic arm-based bioprinting in tissue engineering have been summarized in distinct tissues and organs. Ultimately, we systematically discuss relative advantages, disadvantages, challenges, and future perspectives from bench to bedside for biomedical application.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"14 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139253244","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}
Life medicinePub Date : 2023-11-17DOI: 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}
Life medicinePub Date : 2023-11-14DOI: 10.1093/lifemedi/lnad041
Yingfeng Tu, Jiao Qin, Qiao-Ming Zhang, Tie-Shan Tang, Lifang Wang, Jun Yao
{"title":"Secretagogin regulates asynchronous and spontaneous glutamate release in hippocampal neurons through interaction with Doc2α","authors":"Yingfeng Tu, Jiao Qin, Qiao-Ming Zhang, Tie-Shan Tang, Lifang Wang, Jun Yao","doi":"10.1093/lifemedi/lnad041","DOIUrl":"https://doi.org/10.1093/lifemedi/lnad041","url":null,"abstract":"Abstract Synaptic vesicle (SV) exocytosis is orchestrated by protein machineries consisting of the SNARE complex, Ca2+ sensors and their partners. Secretagogin (SCGN) is a Ca2+ binding protein involved in multiple forms of vesicle secretion. Although SCGN is implicated in multiple neurological disorders, its role in SV exocytosis in neurons remains unknown. Here, using knockout (KO) and knockdown (KD) techniques, we report that SCGN could regulate the asynchronous and spontaneous forms of excitatory but not inhibitory SV exocytosis in mouse hippocampal neurons. Furthermore, SCGN functioned in glutamate release via directly interacting with Doc2α, a high-affinity Ca2+ sensor specific for asynchronous and spontaneous SV exocytosis. Conversely, the interaction with SCGN is also required for Doc2α to execute its Ca2+ sensor function in SV release. Together, our study revealed that SCGN plays an important role in asynchronous and spontaneous glutamate release through its interaction with Doc2α.","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"101 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134957621","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}
{"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}
{"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}
Life medicinePub Date : 2023-11-04DOI: 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}