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Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair. 深入了解优化急性皮肤伤口愈合和其他组织修复的外泌体疗法。
IF 3.9 3区 医学
Frontiers of Medicine Pub Date : 2024-04-01 Epub Date: 2024-01-13 DOI: 10.1007/s11684-023-1031-9
Tianjing Sun, Mo Li, Qi Liu, Anyong Yu, Kun Cheng, Jianxing Ma, Sean Murphy, Patrick Michael McNutt, Yuanyuan Zhang
{"title":"Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair.","authors":"Tianjing Sun, Mo Li, Qi Liu, Anyong Yu, Kun Cheng, Jianxing Ma, Sean Murphy, Patrick Michael McNutt, Yuanyuan Zhang","doi":"10.1007/s11684-023-1031-9","DOIUrl":"10.1007/s11684-023-1031-9","url":null,"abstract":"<p><p>Exosome therapy holds great promise as a novel approach to improve acute skin wound healing. This review provides a comprehensive overview of the current understanding of exosome biology and its potential applications in acute skin wound healing and beyond. Exosomes, small extracellular vesicles secreted by various stem cells, have emerged as potent mediators of intercellular communication and tissue repair. One advantage of exosome therapy is its ability to avoid potential risks associated with stem cell therapy, such as immune rejection or stem cells differentiating into unwanted cell types. However, further research is necessary to optimize exosome therapy, not only in the areas of exosome isolation, characterization, and engineering, but also in determining the optimal dose, timing, administration, and frequency of exosome therapy. Thus, optimization of exosome therapy is critical for the development of more effective and safer exosome-based therapies for acute skin wound healing and other diseases induced by cancer, ischemia, or inflammation. This review provides valuable insights into the potential of exosome therapy and highlights the need for further research to optimize exosome therapy for clinical use.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"258-284"},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11283324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association between ICU quality and in-hospital mortality of V-V ECMO-supported patients-the ECMO quality improvement action (EQIA) study: a national cohort study in China from 2017 to 2019. ICU质量与V-V ECMO支持患者住院死亡率的关系——ECMO质量改善行动(EQIA)研究:2017 - 2019年中国国家队列研究
IF 3.9 3区 医学
Frontiers of Medicine Pub Date : 2024-04-01 Epub Date: 2023-11-22 DOI: 10.1007/s11684-023-1014-x
Wei Cheng, Jieqing Chen, Xudong Ma, Jialu Sun, Sifa Gao, Ye Wang, Longxiang Su, Lu Wang, Wei Du, Huaiwu He, Yujie Chen, Zunzhu Li, Qi Li, Jianhua Sun, Hongbo Luo, Jinbang Liu, Guangliang Shan, Bing Du, Yanhong Guo, Dawei Liu, Chang Yin, Xiang Zhou
{"title":"Association between ICU quality and in-hospital mortality of V-V ECMO-supported patients-the ECMO quality improvement action (EQIA) study: a national cohort study in China from 2017 to 2019.","authors":"Wei Cheng, Jieqing Chen, Xudong Ma, Jialu Sun, Sifa Gao, Ye Wang, Longxiang Su, Lu Wang, Wei Du, Huaiwu He, Yujie Chen, Zunzhu Li, Qi Li, Jianhua Sun, Hongbo Luo, Jinbang Liu, Guangliang Shan, Bing Du, Yanhong Guo, Dawei Liu, Chang Yin, Xiang Zhou","doi":"10.1007/s11684-023-1014-x","DOIUrl":"10.1007/s11684-023-1014-x","url":null,"abstract":"<p><p>This cohort study was performed to explore the influence of intensive care unit (ICU) quality on in-hospital mortality of veno-venous (V-V) extracorporeal membrane oxygenation (ECMO)-supported patients in China. The study involved all V-V ECMO-supported patients in 318 of 1700 tertiary hospitals from 2017 to 2019, using data from the National Clinical Improvement System and China National Critical Care Quality Control Center. ICU quality was assessed by quality control indicators and capacity parameters. Among the 2563 V-V ECMO-supported patients in 318 hospitals, a significant correlation was found between ECMO-related complications and prognosis. The reintubation rate within 48 hours after extubation and the total ICU mortality rate were independent risk factors for higher in-hospital mortality of V-V ECMO-supported patients (cutoff: 1.5% and 7.0%; 95% confidence interval: 1.05-1.48 and 1.04-1.45; odds ratios: 1.25 and 1.23; P = 0.012 and P = 0.015, respectively). Meanwhile, the V-V ECMO center volume was a protective factor (cutoff of ≥ 50 cases within the 3-year study period; 95% confidence interval: 0.57-0.83, odds ratio: 0.69, P = 0.0001). The subgroup analysis of 864 patients in 11 high-volume centers further strengthened these findings. Thus, ICU quality may play an important role in improving the prognosis of V-V ECMO-supported patients.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"315-326"},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
EBV-associated lymphoproliferative disease post-CAR-T cell therapy. CAR-T 细胞疗法后的 EBV 相关淋巴组织增生性疾病。
IF 3.9 3区 医学
Frontiers of Medicine Pub Date : 2024-04-01 Epub Date: 2024-02-08 DOI: 10.1007/s11684-023-1032-8
Shiyuan Zhang, Xiaoxi Zhou, Shangkun Zhang, Na Wang, Tongcun Zhang, Donghua Zhang, Qilin Ao, Yang Cao, Liang Huang
{"title":"EBV-associated lymphoproliferative disease post-CAR-T cell therapy.","authors":"Shiyuan Zhang, Xiaoxi Zhou, Shangkun Zhang, Na Wang, Tongcun Zhang, Donghua Zhang, Qilin Ao, Yang Cao, Liang Huang","doi":"10.1007/s11684-023-1032-8","DOIUrl":"10.1007/s11684-023-1032-8","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV)-associated lymphoproliferative diseases (EBV-LPDs) are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation (HSCT). However, their occurrence and treatment post-chimeric antigen receptor-modified T (CAR-T) cell therapy has not been reported. Two patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment. After receiving CAR-T cell therapy in tandem with autologous HSCT, the patients achieved complete remission. However, with a median time of 38.5 months after CAR-T cell therapy, B-cell-derived EBV-LPDs were diagnosed, and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting agents. Collectively, our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy, especially in patients who previously had EBV-positive disorders, and they can be resolved by immune normalization strategy or B-cell depleting therapy.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"394-398"},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma: a multi-center integrated analysis of microbiome, metabolome, and transcriptome data. 微生物组亚群决定透明细胞肾细胞癌的肿瘤预后和分子特征:对微生物组、代谢组和转录组数据的多中心综合分析。
IF 3.9 3区 医学
Frontiers of Medicine Pub Date : 2024-04-01 Epub Date: 2023-12-15 DOI: 10.1007/s11684-023-1029-3
Wenjin Chen, Xiuwu Pan, Wang Zhou, Da Xu, Jiaxin Chen, Keqin Dong, Weijie Chen, Brian Rini, Xingang Cui
{"title":"Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma: a multi-center integrated analysis of microbiome, metabolome, and transcriptome data.","authors":"Wenjin Chen, Xiuwu Pan, Wang Zhou, Da Xu, Jiaxin Chen, Keqin Dong, Weijie Chen, Brian Rini, Xingang Cui","doi":"10.1007/s11684-023-1029-3","DOIUrl":"10.1007/s11684-023-1029-3","url":null,"abstract":"","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"399-402"},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138798813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis. 外周免疫细胞中的 N6-甲基腺苷修饰失调是肌萎缩性脊髓侧索硬化症的发病机制之一。
IF 8.1 3区 医学
Frontiers of Medicine Pub Date : 2024-04-01 Epub Date: 2024-03-16 DOI: 10.1007/s11684-023-1035-5
Di He, Xunzhe Yang, Liyang Liu, Dongchao Shen, Qing Liu, Mingsheng Liu, Xue Zhang, Liying Cui
{"title":"Dysregulated N<sup>6</sup>-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis.","authors":"Di He, Xunzhe Yang, Liyang Liu, Dongchao Shen, Qing Liu, Mingsheng Liu, Xue Zhang, Liying Cui","doi":"10.1007/s11684-023-1035-5","DOIUrl":"10.1007/s11684-023-1035-5","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a progressive neurogenerative disorder with uncertain origins. Emerging evidence implicates N6-methyladenosine (m<sup>6</sup>A) modification in ALS pathogenesis. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and liquid chromatography-mass spectrometry were utilized for m<sup>6</sup>A profiling in peripheral immune cells and serum proteome analysis, respectively, in patients with ALS (n = 16) and controls (n = 6). The single-cell transcriptomic dataset (GSE174332) of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes. Analysis of peripheral immune cells revealed extensive RNA hypermethylation, highlighting candidate genes with differential m<sup>6</sup>A modification and expression, including C-X3-C motif chemokine receptor 1 (CX3CR1). In RAW264.7 macrophages, disrupted CX3CR1 signaling affected chemotaxis, potentially influencing immune cell migration in ALS. Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS. Cell type-specific expression variations of these genes in the central nervous system (CNS), particularly microglia, were observed. Intercellular communication between neurons and glial cells was selectively altered in ALS CNS. This integrated approach underscores m<sup>6</sup>A dysregulation in immune cells as a potential ALS contributor.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"285-302"},"PeriodicalIF":8.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Associations of sleeping patterns and isotemporal substitution of other behavior with the prevalence of CKD in Chinese adults. 睡眠模式和其他行为的同时间替代与中国成人慢性肾病患病率的关系
IF 3.9 3区 医学
Frontiers of Medicine Pub Date : 2024-04-01 Epub Date: 2023-12-05 DOI: 10.1007/s11684-023-1019-5
Yi Ding, Xiaoli Xu, Zhuojun Xin, Qiuyu Cao, Jiaojiao Huang, Xianglin Wu, Yanan Huo, Qin Wan, Yingfen Qin, Ruying Hu, Lixin Shi, Qing Su, Xuefeng Yu, Li Yan, Guijun Qin, Xulei Tang, Gang Chen, Min Xu, Tiange Wang, Zhiyun Zhao, Zhengnan Gao, Guixia Wang, Feixia Shen, Zuojie Luo, Li Chen, Qiang Li, Zhen Ye, Yinfei Zhang, Chao Liu, Youmin Wang, Tao Yang, Huacong Deng, Lulu Chen, Tianshu Zeng, Jiajun Zhao, Yiming Mu, Shengli Wu, Yuhong Chen, Jieli Lu, Weiqing Wang, Guang Ning, Yu Xu, Yufang Bi, Mian Li
{"title":"Associations of sleeping patterns and isotemporal substitution of other behavior with the prevalence of CKD in Chinese adults.","authors":"Yi Ding, Xiaoli Xu, Zhuojun Xin, Qiuyu Cao, Jiaojiao Huang, Xianglin Wu, Yanan Huo, Qin Wan, Yingfen Qin, Ruying Hu, Lixin Shi, Qing Su, Xuefeng Yu, Li Yan, Guijun Qin, Xulei Tang, Gang Chen, Min Xu, Tiange Wang, Zhiyun Zhao, Zhengnan Gao, Guixia Wang, Feixia Shen, Zuojie Luo, Li Chen, Qiang Li, Zhen Ye, Yinfei Zhang, Chao Liu, Youmin Wang, Tao Yang, Huacong Deng, Lulu Chen, Tianshu Zeng, Jiajun Zhao, Yiming Mu, Shengli Wu, Yuhong Chen, Jieli Lu, Weiqing Wang, Guang Ning, Yu Xu, Yufang Bi, Mian Li","doi":"10.1007/s11684-023-1019-5","DOIUrl":"10.1007/s11684-023-1019-5","url":null,"abstract":"<p><p>Studies have found a U-shaped relationship between sleep duration and chronic kidney disease (CKD) risk, but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD. We included 104 538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study, with self-reported time of daily-life behavior. Using isotemporal substitution models, we found that substituting 1 h of sleeping with sitting, walking, or moderate-to-vigorous physical activity was associated with a lower CKD prevalence. Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population. In stratified analysis, a lower CKD prevalence related to substitution toward physical activity was found in long sleepers. More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes, and they benefited from other behavior substitutions toward a more active way. The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys, in which the pernicious link with oversleep could be reversed by time reallocation to physical activity. The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"303-314"},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138482278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Human pangenome: far-reaching implications in precision medicine. 人类泛基因组:对精准医疗的深远影响。
IF 3.9 3区 医学
Frontiers of Medicine Pub Date : 2024-04-01 Epub Date: 2023-12-29 DOI: 10.1007/s11684-023-1039-1
Yingyan Yu, Hongzhuan Chen
{"title":"Human pangenome: far-reaching implications in precision medicine.","authors":"Yingyan Yu, Hongzhuan Chen","doi":"10.1007/s11684-023-1039-1","DOIUrl":"10.1007/s11684-023-1039-1","url":null,"abstract":"","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"403-409"},"PeriodicalIF":3.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unraveling the complex roles of macrophages in obese adipose tissue: an overview. 解读巨噬细胞在肥胖脂肪组织中的复杂作用:综述。
IF 8.1 3区 医学
Frontiers of Medicine Pub Date : 2024-04-01 Epub Date: 2024-01-02 DOI: 10.1007/s11684-023-1033-7
Chang Peng, Jun Chen, Rui Wu, Haowen Jiang, Jia Li
{"title":"Unraveling the complex roles of macrophages in obese adipose tissue: an overview.","authors":"Chang Peng, Jun Chen, Rui Wu, Haowen Jiang, Jia Li","doi":"10.1007/s11684-023-1033-7","DOIUrl":"10.1007/s11684-023-1033-7","url":null,"abstract":"<p><p>Macrophages, a heterogeneous population of innate immune cells, exhibit remarkable plasticity and play pivotal roles in coordinating immune responses and maintaining tissue homeostasis within the context of metabolic diseases. The activation of inflammatory macrophages in obese adipose tissue leads to detrimental effects, inducing insulin resistance through increased inflammation, impaired thermogenesis, and adipose tissue fibrosis. Meanwhile, adipose tissue macrophages also play a beneficial role in maintaining adipose tissue homeostasis by regulating angiogenesis, facilitating the clearance of dead adipocytes, and promoting mitochondrial transfer. Exploring the heterogeneity of macrophages in obese adipose tissue is crucial for unraveling the pathogenesis of obesity and holds significant potential for targeted therapeutic interventions. Recently, the dual effects and some potential regulatory mechanisms of macrophages in adipose tissue have been elucidated using single-cell technology. In this review, we present a comprehensive overview of the intricate activation mechanisms and diverse functions of macrophages in adipose tissue during obesity, as well as explore the potential of drug delivery systems targeting macrophages, aiming to enhance the understanding of current regulatory mechanisms that may be potentially targeted for treating obesity or metabolic diseases.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"205-236"},"PeriodicalIF":8.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Arginine methylation of ALKBH5 by PRMT6 promotes breast tumorigenesis via LDHA-mediated glycolysis PRMT6 对 ALKBH5 的精氨酸甲基化通过 LDHA 介导的糖酵解促进乳腺肿瘤发生
IF 8.1 3区 医学
Frontiers of Medicine Pub Date : 2024-03-11 DOI: 10.1007/s11684-023-1028-4
{"title":"Arginine methylation of ALKBH5 by PRMT6 promotes breast tumorigenesis via LDHA-mediated glycolysis","authors":"","doi":"10.1007/s11684-023-1028-4","DOIUrl":"https://doi.org/10.1007/s11684-023-1028-4","url":null,"abstract":"<h3>Abstract</h3> <p>ALKBH5 is a master regulator of N6-methyladenosine (m<sup>6</sup>A) modification, which plays a crucial role in many biological processes. Here, we show that ALKBH5 is required for breast tumor growth. Interestingly, PRMT6 directly methylates ALKBH5 at R283, which subsequently promotes breast tumor growth. Furthermore, arginine methylation of ALKBH5 by PRMT6 increases LDHA RNA stability via m<sup>6</sup>A demethylation, leading to increased aerobic glycolysis. Moreover, PRMT6-mediated ALKBH5 arginine methylation is confirmed in PRMT6-knockout mice. Collectively, these findings identify a PRMT6-ALKBH5-LDHA signaling axis as a novel target for the treatment of breast cancer.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":"36 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140099820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and nucleocytoplasmic localization of Lipin1. Lipin3的单足性通过破坏Lipin1的表达和核质定位而导致高甘油三酯血症和肥胖。
IF 8.1 3区 医学
Frontiers of Medicine Pub Date : 2024-02-01 Epub Date: 2023-09-30 DOI: 10.1007/s11684-023-1003-0
Fang Wang, Yuxing Liu, Yi Dong, Meifang Zhao, Hao Huang, Jieyuan Jin, Liangliang Fan, Rong Xiang
{"title":"Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and nucleocytoplasmic localization of Lipin1.","authors":"Fang Wang, Yuxing Liu, Yi Dong, Meifang Zhao, Hao Huang, Jieyuan Jin, Liangliang Fan, Rong Xiang","doi":"10.1007/s11684-023-1003-0","DOIUrl":"10.1007/s11684-023-1003-0","url":null,"abstract":"<p><p>Lipin proteins including Lipin 1-3 act as transcriptional co-activators and phosphatidic acid phosphohydrolase enzymes, which play crucial roles in lipid metabolism. However, little is known about the function of Lipin3 in triglyceride (TG) metabolism. Here, we identified a novel mutation (NM_001301860: p.1835A>T/p.D612V) of Lipin3 in a large family with hypertriglyceridemia (HTG) and obesity through whole-exome sequencing and Sanger sequencing. Functional studies revealed that the novel variant altered the half-life and stability of the Lipin3 protein. Hence, we generated Lipin3 heterozygous knockout (Lipin3-heKO) mice and cultured primary hepatocytes to explore the pathophysiological roles of Lipin3 in TG metabolism. We found that Lipin3-heKO mice exhibited obvious obesity, HTG, and non-alcoholic fatty liver disorder. Mechanistic study demonstrated that the haploinsufficiency of Lipin3 in primary hepatocytes may induce the overexpression and abnormal distribution of Lipin1 in cytosol and nucleoplasm. The increased expression of Lipin1 in cytosol may contribute to TG anabolism, and the decreased Lipin1 in nucleoplasm can reduce PGC1α, further leading to mitochondrial dysfunction and reduced TG catabolism. Our study suggested that Lipin3 was a novel disease-causing gene inducing obesity and HTG. We also established a relationship between Lipin3 and mitochondrial dysfunction.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"180-191"},"PeriodicalIF":8.1,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41112229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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