Life medicinePub Date : 2024-09-13eCollection Date: 2024-08-01DOI: 10.1093/lifemedi/lnae034
Jing Guo, Lie Wang
{"title":"The complex landscape of immune dysregulation in multisystem inflammatory syndrome in children with COVID-19.","authors":"Jing Guo, Lie Wang","doi":"10.1093/lifemedi/lnae034","DOIUrl":"10.1093/lifemedi/lnae034","url":null,"abstract":"<p><p>The immune responses following SARS-CoV-2 infection in children are still under investigation. While coronavirus disease 2019 (COVID-19) is usually mild in the paediatric population, some children develop severe clinical manifestations or multisystem inflammatory syndrome in children (MIS-C) after infection. MIS-C, typically emerging 2-6 weeks after SARS-CoV-2 exposure, is characterized by a hyperinflammatory response affecting multiple organs. This review aims to explore the complex landscape of immune dysregulation in MIS-C, focusing on innate, T cell-, and B cell-mediated immunity, and discusses the role of SARS-CoV-2 spike protein as a superantigen in MIS-C pathophysiology. Understanding these mechanisms is crucial for improving the management and outcomes for affected children.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 4","pages":"lnae034"},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054639","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}
Life medicinePub Date : 2024-09-06eCollection Date: 2024-08-01DOI: 10.1093/lifemedi/lnae032
Li Zhang, Taylor M Weiskittel, Yuqing Zhu, Dixuan Xue, Hailing Zhang, Yuxuan Shen, Hua Yu, Jingyu Li, Linxiao Hou, Hongshan Guo, Zhijun Dai, Hu Li, Jin Zhang
{"title":"Comparative dissection of transcriptional landscapes of human iPSC-NK differentiation and NK cell development.","authors":"Li Zhang, Taylor M Weiskittel, Yuqing Zhu, Dixuan Xue, Hailing Zhang, Yuxuan Shen, Hua Yu, Jingyu Li, Linxiao Hou, Hongshan Guo, Zhijun Dai, Hu Li, Jin Zhang","doi":"10.1093/lifemedi/lnae032","DOIUrl":"10.1093/lifemedi/lnae032","url":null,"abstract":"<p><p>Clinical and preclinical research has demonstrated that iPSC-derived NK (iNK) cells have a high therapeutic potential, yet poor understanding of the detailed process of their differentiation <i>in vitro</i> and their counterpart cell development <i>in vivo</i> has hindered therapeutic iNK cell production and engineering. Here we dissect the crucial differentiation of both fetal liver NK cells and iNK cells to enable the rational design of advanced iNK production protocols. We use a comparative analysis of single-cell RNA-seq (scRNA-seq) to pinpoint key factors lacking in the induced setting which we hypothesized would hinder iNK differentiation and/ or functionality. By analyzing key transcription factor regulatory networks, we discovered the importance of <i>TBX21</i>, <i>EOMES</i>, and <i>STAT5A</i> in the differentiation timeline. This analysis provides a blueprint for further engineering new iPSC lines to obtain iNK cells with enhanced functions. We validated this approach by creating a new line of STAT5A-iPSCs which can be differentiated to STAT5A-expressing macrophages with both NK cell and macrophage features such as perforin production, phagocytosis, and anti-tumor functions.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 4","pages":"lnae032"},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054628","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}
Life medicinePub Date : 2024-09-05eCollection Date: 2024-10-01DOI: 10.1093/lifemedi/lnae033
Canwei Zhang, Zesong Lin, Yankun Yu, Siqi Wu, Huaxing Huang, Ying Huang, Jiafeng Liu, Kunlun Mo, Jieying Tan, Zhuo Han, Mingsen Li, Wei Zhao, Hong Ouyang, Xiangjun Chen, Li Wang
{"title":"Deciphering the dynamic single-cell transcriptional landscape in the ocular surface ectoderm differentiation system.","authors":"Canwei Zhang, Zesong Lin, Yankun Yu, Siqi Wu, Huaxing Huang, Ying Huang, Jiafeng Liu, Kunlun Mo, Jieying Tan, Zhuo Han, Mingsen Li, Wei Zhao, Hong Ouyang, Xiangjun Chen, Li Wang","doi":"10.1093/lifemedi/lnae033","DOIUrl":"10.1093/lifemedi/lnae033","url":null,"abstract":"<p><p>The ocular surface ectoderm (OSE) is essential for the development of the ocular surface, yet the molecular mechanisms driving its differentiation are not fully understood. In this study, we used single-cell transcriptomic analysis to explore the dynamic cellular trajectories and regulatory networks during the <i>in vitro</i> differentiation of embryonic stem cells (ESCs) into the OSE lineage. We identified nine distinct cell subpopulations undergoing differentiation along three main developmental branches: neural crest, neuroectodermal, and surface ectodermal lineages. Key marker gene expression, transcription factor activity, and signaling pathway insights revealed stepwise transitions from undifferentiated ESCs to fate-specified cell types, including a PAX6 + TP63 + population indicative of OSE precursors. Comparative analysis with mouse embryonic development confirmed the model's accuracy in mimicking <i>in vivo</i> epiblast-to-surface ectoderm dynamics. By integrating temporal dynamics of transcription factor activation and cell-cell communication, we constructed a comprehensive molecular atlas of the differentiation pathway from ESCs to distinct ectodermal lineages. This study provides new insights into the cellular heterogeneity and regulatory mechanisms of OSE development, aiding the understanding of ocular surface biology and the design of cell-based therapies for ocular surface disorders.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 5","pages":"lnae033"},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054647","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}
Life medicinePub Date : 2024-08-31eCollection Date: 2024-08-01DOI: 10.1093/lifemedi/lnae030
Lin Sun, Zhensheng Yue, Lin Wang
{"title":"Research on the function of epigenetic regulation in the inflammation of non-alcoholic fatty liver disease.","authors":"Lin Sun, Zhensheng Yue, Lin Wang","doi":"10.1093/lifemedi/lnae030","DOIUrl":"10.1093/lifemedi/lnae030","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition, characterized by a spectrum that progresses from simple hepatic steatosis to nonalcoholic steatohepatitis, which may eventually lead to cirrhosis and hepatocellular carcinoma. The precise pathogenic mechanisms underlying NAFLD and its related metabolic disturbances remain elusive. Epigenetic modifications, which entail stable transcriptional changes without altering the DNA sequence, are increasingly recognized as pivotal. The principal forms of epigenetic modifications include DNA methylation, histone modifications, chromatin remodeling, and noncoding RNAs. These alterations participate in the regulation of hepatic lipid metabolism, insulin resistance, mitochondrial injury, oxidative stress response, and release of inflammatory cytokines, all of which are associated with the onset and progression of NAFLD. This review discussed recent advances in understanding the potential epigenetic regulation of inflammation in NAFLD. Unraveling these epigenetic mechanisms may facilitate the identification of early diagnostic biomarkers and the development of targeted therapeutic strategies for NAFLD.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 4","pages":"lnae030"},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054636","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}
Life medicinePub Date : 2024-08-29eCollection Date: 2024-08-01DOI: 10.1093/lifemedi/lnae031
Jiaojiao Chen, Maoxin Fang, Yuwei Li, Haodong Ding, Xinyu Zhang, Xiaoyi Jiang, Jinlan Zhang, Chengcheng Zhang, Zhigang Lu, Min Luo
{"title":"Cell surface protein-protein interaction profiling for biological network analysis and novel target discovery.","authors":"Jiaojiao Chen, Maoxin Fang, Yuwei Li, Haodong Ding, Xinyu Zhang, Xiaoyi Jiang, Jinlan Zhang, Chengcheng Zhang, Zhigang Lu, Min Luo","doi":"10.1093/lifemedi/lnae031","DOIUrl":"10.1093/lifemedi/lnae031","url":null,"abstract":"<p><p>The secretome is composed of cell surface membrane proteins and extracellular secreted proteins that are synthesized via secretory machinery, accounting for approximately one-third of human protein-encoding genes and playing central roles in cellular communication with the external environment. Secretome protein-protein interactions (SPPIs) mediate cell proliferation, apoptosis, and differentiation, as well as stimulus- or cell-specific responses that regulate a diverse range of biological processes. Aberrant SPPIs are associated with diseases including cancer, immune disorders, and illness caused by infectious pathogens. Identifying the receptor/ligand for a secretome protein or pathogen can be a challenging task, and many SPPIs remain obscure, with a large number of orphan receptors and ligands, as well as viruses with unknown host receptors, populating the SPPI network. In addition, proteins with known receptors/ligands may also interact with alternative uncharacterized partners and exert context-dependent effects. In the past few decades, multiple varied approaches have been developed to identify SPPIs, and these methods have broad applications in both basic and translational research. Here, we review and discuss the technologies for SPPI profiling and the application of these technologies in identifying novel targets for immunotherapy and anti-infectious agents.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 4","pages":"lnae031"},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054626","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}
Life medicinePub Date : 2024-08-20eCollection Date: 2024-06-01DOI: 10.1093/lifemedi/lnae029
Si-Yi Su, Chuting He, Jie Ren, Moshi Song
{"title":"Global insights into aging: a multidisciplinary approach to understanding and addressing age-related challenges.","authors":"Si-Yi Su, Chuting He, Jie Ren, Moshi Song","doi":"10.1093/lifemedi/lnae029","DOIUrl":"10.1093/lifemedi/lnae029","url":null,"abstract":"<p><p>Aging has ascended to the forefront of scientific exploration, demanding a concerted global focus. The 2024 China Aging Science Conference and International Conference on Aging Biology hosted a panel discussion that brought international experts to delve into the complexities of aging research. The discussion underscores the imperative need for a multidisciplinary approach, integrating reductionist and holistic perspectives to unravel the molecular and epigenetic underpinnings of the aging process. Experts advocate for elucidating aging mechanisms and biomarkers, with a focus on translating scientific discoveries into tangible societal benefits. The discussion also emphasizes the importance of international and interdisciplinary collaborations, calling for more support to innovate for healthy aging and tackle age-related challenges.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 3","pages":"lnae029"},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054537","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}
Life medicinePub Date : 2024-07-31eCollection Date: 2024-10-01DOI: 10.1093/lifemedi/lnae028
Qiancheng Zhang, Fengyuan Sun, Ruifeng Zhang, Donghong Zhao, Ran Zhu, Xin Cheng, Xin Long, Xinling Hou, Rui Yan, Yu Cao, Fan Guo, Long Yan, Yuqiong Hu
{"title":"The evolution of ovarian somatic cells characterized by transcriptome and chromatin accessibility across rodents, monkeys, and humans.","authors":"Qiancheng Zhang, Fengyuan Sun, Ruifeng Zhang, Donghong Zhao, Ran Zhu, Xin Cheng, Xin Long, Xinling Hou, Rui Yan, Yu Cao, Fan Guo, Long Yan, Yuqiong Hu","doi":"10.1093/lifemedi/lnae028","DOIUrl":"10.1093/lifemedi/lnae028","url":null,"abstract":"<p><p>The ovary plays a crucial role in the reproductive system of female mammals by producing mature oocytes through folliculogenesis. Non-human model organisms are extensively utilized in research on human ovarian biology, thus necessitating the investigation of conservation and divergence in molecular mechanisms across species. In this study, we employed integrative single-cell analysis of transcriptome and chromatin accessibility to identify the evolutionary conservation and divergence patterns of ovaries among humans, monkeys, mice, rats, and rabbits. Our analyses revealed that theca cells exhibited the most significant changes during evolution based on scRNA-seq and scATAC-seq datasets. Furthermore, we discovered common <i>cis</i>-regulatory architectures in theca cells across species by conducting joint analyses of scRNA-seq and scATAC-seq datasets. These findings have potential applications in non-human biomedical and genetic research to validate molecular mechanisms found in human organisms. Additionally, our investigation into non-coding genomic regions identified intergenic highly transcribed regions (igHTRs) that may contribute to the evolution of species-specific phenotypic traits. Overall, our study provides valuable insights into understanding the molecular characteristics of adult ovaries while offering new perspectives for studying human ovarian physiology and diseases.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 5","pages":"lnae028"},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054586","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}
Life medicinePub Date : 2024-06-28eCollection Date: 2024-06-01DOI: 10.1093/lifemedi/lnae025
Jinbao Ye, La Yan, Yu Yuan, Fang Fu, Lu Yuan, Xinxin Fan, Juanyu Zhou, Yuedan Zhu, Xingzhu Liu, Gang Ren, Haiyang Chen
{"title":"Natural flavonoid glycosides Chrysosplenosides I & A rejuvenate intestinal stem cell aging via activation of PPARγ signaling.","authors":"Jinbao Ye, La Yan, Yu Yuan, Fang Fu, Lu Yuan, Xinxin Fan, Juanyu Zhou, Yuedan Zhu, Xingzhu Liu, Gang Ren, Haiyang Chen","doi":"10.1093/lifemedi/lnae025","DOIUrl":"10.1093/lifemedi/lnae025","url":null,"abstract":"<p><p>The decline in intestinal stem cell (ISC) function is a hallmark of aging, contributing to compromised intestinal regeneration and increased incidence of age-associated diseases. Novel therapeutic agents that can rejuvenate aged ISCs are of paramount importance for extending healthspan. Here, we report on the discovery of Chrysosplenosides I and A (CAs 1 & 2), flavonol glycosides from the Xizang medicinal plant <i>Chrysosplenium axillare</i> Maxim., which exhibit potent anti-aging effects on ISCs. Our research, using <i>Drosophila</i> models, reveals that CAs 1 & 2 treatments not only restrain excessive ISC proliferation, thereby preserving intestinal homeostasis, but also extend the lifespan of aging <i>Drosophila</i>. In aged mouse intestinal organoids, CAs 1 & 2 enhance the growth and budding of intestinal organoids, indicating improved regenerative capacity. Mechanistic investigations show that CAs 1 & 2 exert their effects by activating the peroxisome proliferator-activated receptor-gamma (PPARγ) and concurrently inhibiting the epidermal growth factor receptor (EGFR) signaling pathways. Our findings position CAs 1 & 2 as promising candidates for ameliorating ISC aging and suggest that targeting PPARγ, in particular, may offer a therapeutic strategy to counteract age-related intestinal dysfunction.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 3","pages":"lnae025"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054598","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}
Life medicinePub Date : 2024-06-28eCollection Date: 2024-06-01DOI: 10.1093/lifemedi/lnae024
Ya Ren, Mingxu Chen, Ziyang Wang, Jing-Dong J Han
{"title":"Oral microbiota in aging and diseases.","authors":"Ya Ren, Mingxu Chen, Ziyang Wang, Jing-Dong J Han","doi":"10.1093/lifemedi/lnae024","DOIUrl":"10.1093/lifemedi/lnae024","url":null,"abstract":"<p><p>Human microbiomes are microbial populations that form a symbiotic relationship with humans. There are up to 1000 species on the surface of human skin and mucosal system, among which gut microbiota attracts the most interest. As the beginning of the digestive tract, oral cavity is also an important microbial habitat in the human body which is the first line of defense against pathogens entering the body. Many studies have revealed that oral microbial dysbiosis could not only contribute to oral diseases but also whole-body systemic diseases and health status. Oral microorganisms can enter the gastrointestinal tract with saliva and food, or enter the blood circulation through mouth breakage, thus causing systemic inflammation and aging-related diseases including some causal links to Alzheimer's disease. A series of changes take place in oral microbial composition during development, with different age stages marked by different dominant microbial species. Despite a lack of comprehensive studies on aging oral microbiota, through systemic inflammation, oral pathogenic microbes are likely to contribute inflammatory aging. As inflammaging is a key signature and one of the causes for accelerated aging, improving the structure of oral microbiome may be not only a new strategy for disease prevention and treatment, but also for aging intervention.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 3","pages":"lnae024"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054604","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}