Frontiers of Medicine最新文献_第10页

Innovation-driven trend shaping COVID-19 vaccine development in China 中国 COVID-19 疫苗研发的创新驱动趋势

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-12-16 DOI: 10.1007/s11684-023-1034-6

Yuntao Zhang, Yuxiu Zhao, Hongyang Liang, Ying Xu, Chuge Zhou, Yuzhu Yao, Hui Wang, Xiaoming Yang

引用次数: 0

GID complex regulates the differentiation of neural stem cells by destabilizing TET2. GID 复合物通过破坏 TET2 的稳定性来调节神经干细胞的分化。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2023-12-01 Epub Date: 2023-09-14 DOI: 10.1007/s11684-023-1007-9

Meiling Xia, Rui Yan, Wenjuan Wang, Meng Zhang, Zhigang Miao, Bo Wan, Xingshun Xu

{"title":"GID complex regulates the differentiation of neural stem cells by destabilizing TET2.","authors":"Meiling Xia, Rui Yan, Wenjuan Wang, Meng Zhang, Zhigang Miao, Bo Wan, Xingshun Xu","doi":"10.1007/s11684-023-1007-9","DOIUrl":"10.1007/s11684-023-1007-9","url":null,"abstract":"Brain development requires a delicate balance between self-renewal and differentiation in neural stem cells (NSC), which rely on the precise regulation of gene expression. Ten-eleven translocation 2 (TET2) modulates gene expression by the hydroxymethylation of 5-methylcytosine in DNA as an important epigenetic factor and participates in the neuronal differentiation. Yet, the regulation of TET2 in the process of neuronal differentiation remains unknown. Here, the protein level of TET2 was reduced by the ubiquitin-proteasome pathway during NSC differentiation, in contrast to mRNA level. We identified that TET2 physically interacts with the core subunits of the glucose-induced degradation-deficient (GID) ubiquitin ligase complex, an evolutionarily conserved ubiquitin ligase complex and is ubiquitinated by itself. The protein levels of GID complex subunits increased reciprocally with TET2 level upon NSC differentiation. The silencing of the core subunits of the GID complex, including WDR26 and ARMC8, attenuated the ubiquitination and degradation of TET2, increased the global 5-hydroxymethylcytosine levels, and promoted the differentiation of the NSC. TET2 level increased in the brain of the Wdr26+/- mice. Our results illustrated that the GID complex negatively regulates TET2 protein stability, further modulates NSC differentiation, and represents a novel regulatory mechanism involved in brain development.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"1204-1218"},"PeriodicalIF":3.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10234969","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

Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission and Ca²⁺ homeostasis in a murine model of HFpEF. 小檗碱通过调节 Drp1 介导的线粒体分裂和 Ca2+ 平衡，缓解小鼠高频心衰模型的心肌舒张功能障碍。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-12-01 Epub Date: 2023-09-01 DOI: 10.1007/s11684-023-0983-0

Miyesaier Abudureyimu, Mingjie Yang, Xiang Wang, Xuanming Luo, Junbo Ge, Hu Peng, Yingmei Zhang, Jun Ren

{"title":"Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission and Ca2+ homeostasis in a murine model of HFpEF.","authors":"Miyesaier Abudureyimu, Mingjie Yang, Xiang Wang, Xuanming Luo, Junbo Ge, Hu Peng, Yingmei Zhang, Jun Ren","doi":"10.1007/s11684-023-0983-0","DOIUrl":"10.1007/s11684-023-0983-0","url":null,"abstract":"Heart failure with preserved ejection fraction (HFpEF) displays normal or near-normal left ventricular ejection fraction, diastolic dysfunction, cardiac hypertrophy, and poor exercise capacity. Berberine, an isoquinoline alkaloid, possesses cardiovascular benefits. Adult male mice were assigned to chow or high-fat diet with L-NAME (\"two-hit\" model) for 15 weeks. Diastolic function was assessed using echocardiography and noninvasive Doppler technique. Myocardial morphology, mitochondrial ultrastructure, and cardiomyocyte mechanical properties were evaluated. Proteomics analysis, autophagic flux, and intracellular Ca2+ were also assessed in chow and HFpEF mice. The results show exercise intolerance and cardiac diastolic dysfunction in \"two-hit\"-induced HFpEF model, in which unfavorable geometric changes such as increased cell size, interstitial fibrosis, and mitochondrial swelling occurred in the myocardium. Diastolic dysfunction was indicated by the elevated E value, mitral E/A ratio, and E/e' ratio, decreased e' value and maximal velocity of re-lengthening (-dL/dt), and prolonged re-lengthening in HFpEF mice. The effects of these processes were alleviated by berberine. Moreover, berberine ameliorated autophagic flux, alleviated Drp1 mitochondrial localization, mitochondrial Ca2+ overload and fragmentation, and promoted intracellular Ca2+ reuptake into sarcoplasmic reticulum by regulating phospholamban and SERCA2a. Finally, berberine alleviated diastolic dysfunction in \"two-hit\" diet-induced HFpEF model possibly because of the promotion of autophagic flux, inhibition of mitochondrial fragmentation, and cytosolic Ca2+ overload.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"1219-1235"},"PeriodicalIF":8.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10127594","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

Epidemiology, pathogenesis, and management of Coronavirus disease 2019-associated stroke. 2019年冠状病毒病相关中风的流行病学、发病机制和管理。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-12-01 Epub Date: 2024-01-02 DOI: 10.1007/s11684-023-1041-7

Lu Liu, Chenxia Zhou, Huimin Jiang, Huimin Wei, Yifan Zhou, Chen Zhou, Xunming Ji

引用次数: 0

Lack of CFAP54 causes primary ciliary dyskinesia in a mouse model and human patients. 在小鼠模型和人类患者中，缺乏CFAP54会导致原发性纤毛运动障碍。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-12-01 Epub Date: 2023-09-19 DOI: 10.1007/s11684-023-0997-7

Xinyue Zhao, Haijun Ge, Wenshuai Xu, Chongsheng Cheng, Wangji Zhou, Yan Xu, Junping Fan, Yaping Liu, Xinlun Tian, Kai-Feng Xu, Xue Zhang

{"title":"Lack of CFAP54 causes primary ciliary dyskinesia in a mouse model and human patients.","authors":"Xinyue Zhao, Haijun Ge, Wenshuai Xu, Chongsheng Cheng, Wangji Zhou, Yan Xu, Junping Fan, Yaping Liu, Xinlun Tian, Kai-Feng Xu, Xue Zhang","doi":"10.1007/s11684-023-0997-7","DOIUrl":"10.1007/s11684-023-0997-7","url":null,"abstract":"Primary ciliary dyskinesia (PCD) is a highly heterogeneous recessive inherited disorder. FAP54, the homolog of CFAP54 in Chlamydomonas reinhardtii, was previously demonstrated as the C1d projection of the central microtubule apparatus of flagella. A Cfap54 knockout mouse model was then reported to have PCD-relevant phenotypes. Through whole-exome sequencing, compound heterozygous variants c.2649_2657delinC (p. E883Dfs*47) and c.7312_7313insCGCAGGCTGAATTCTTGG (p. T2438delinsTQAEFLA) in a new suspected PCD-relevant gene, CFAP54, were identified in an individual with PCD. Two missense variants, c.4112A>C (p. E1371A) and c.6559C>T (p. P2187S), in CFAP54 were detected in another unrelated patient. In this study, a minigene assay was conducted on the frameshift mutation showing a reduction in mRNA expression. In addition, a CFAP54 in-frame variant knock-in mouse model was established, which recapitulated the typical symptoms of PCD, including hydrocephalus, infertility, and mucus accumulation in nasal sinuses. Correspondingly, two missense variants were deleterious, with a dramatic reduction in mRNA abundance from bronchial tissue and sperm. The identification of PCD-causing variants of CFAP54 in two unrelated patients with PCD for the first time provides strong supportive evidence that CFAP54 is a new PCD-causing gene. This study further helps expand the disease-associated gene spectrum and improve genetic testing for PCD diagnosis in the future.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"1236-1249"},"PeriodicalIF":8.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41172966","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

Passive antibody therapy in emerging infectious diseases. 新发传染病的被动抗体治疗。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-12-01 Epub Date: 2023-12-02 DOI: 10.1007/s11684-023-1021-y

Xiaoming Yang

引用次数: 0

Revisiting China's response to coronavirus disease 2019. 重新审视 2019 年中国应对冠状病毒疾病的措施。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-12-01 Epub Date: 2024-02-01 DOI: 10.1007/s11684-024-1059-5

Guangbiao Zhou, Saijuan Chen, Zongjiu Zhang, Zhu Chen

引用次数: 0

Extracellular vesicle-carried GTF2I from mesenchymal stem cells promotes the expression of tumor-suppressive FAT1 and inhibits stemness maintenance in thyroid carcinoma. 间充质干细胞携带的细胞外囊泡GTF2I可促进抑制肿瘤的FAT1的表达，并抑制甲状腺癌的干性维持。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-12-01 Epub Date: 2023-09-14 DOI: 10.1007/s11684-023-0999-5

Jie Shao, Wenjuan Wang, Baorui Tao, Zihao Cai, Haixia Li, Jinhong Chen

{"title":"Extracellular vesicle-carried GTF2I from mesenchymal stem cells promotes the expression of tumor-suppressive FAT1 and inhibits stemness maintenance in thyroid carcinoma.","authors":"Jie Shao, Wenjuan Wang, Baorui Tao, Zihao Cai, Haixia Li, Jinhong Chen","doi":"10.1007/s11684-023-0999-5","DOIUrl":"10.1007/s11684-023-0999-5","url":null,"abstract":"Through bioinformatics predictions, we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma (TC). Further, Pearson's correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression. Therefore, we selected them for this present study, where the effects of bone marrow mesenchymal stem cell-derived EVs (BMSDs-EVs) enriched with GTF2I were evaluated on the epithelial-to-mesenchymal transition (EMT) and stemness maintenance in TC. The under-expression of GTF2I and FAT1 was validated in TC cell lines. Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells, EMT, and stemness maintenance. Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression. MSC-EVs could shuttle GTF2I into TPC-1 cells, where GTF2I inhibited TC malignant phenotypes, EMT, and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation. In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice. Taken together, our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"1186-1203"},"PeriodicalIF":8.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10236574","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

BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical models. BGB-A445是一种新型的非配体阻断激动性抗OX40抗体，在临床前模型中表现出优异的免疫激活和抗肿瘤作用。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-12-01 Epub Date: 2023-09-25 DOI: 10.1007/s11684-023-0996-8

Beibei Jiang, Tong Zhang, Minjuan Deng, Wei Jin, Yuan Hong, Xiaotong Chen, Xin Chen, Jing Wang, Hongjia Hou, Yajuan Gao, Wenfeng Gong, Xing Wang, Haiying Li, Xiaosui Zhou, Yingcai Feng, Bo Zhang, Bin Jiang, Xueping Lu, Lijie Zhang, Yang Li, Weiwei Song, Hanzi Sun, Zuobai Wang, Xiaomin Song, Zhirong Shen, Xuesong Liu, Kang Li, Lai Wang, Ye Liu

{"title":"BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical models.","authors":"Beibei Jiang, Tong Zhang, Minjuan Deng, Wei Jin, Yuan Hong, Xiaotong Chen, Xin Chen, Jing Wang, Hongjia Hou, Yajuan Gao, Wenfeng Gong, Xing Wang, Haiying Li, Xiaosui Zhou, Yingcai Feng, Bo Zhang, Bin Jiang, Xueping Lu, Lijie Zhang, Yang Li, Weiwei Song, Hanzi Sun, Zuobai Wang, Xiaomin Song, Zhirong Shen, Xuesong Liu, Kang Li, Lai Wang, Ye Liu","doi":"10.1007/s11684-023-0996-8","DOIUrl":"10.1007/s11684-023-0996-8","url":null,"abstract":"OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"1170-1185"},"PeriodicalIF":8.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138793","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

Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges. 改善胰腺癌的预后：从流行病学、基因组变化和治疗挑战中获得启示。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-12-01 Epub Date: 2023-12-27 DOI: 10.1007/s11684-023-1050-6

Zhichen Jiang, Xiaohao Zheng, Min Li, Mingyang Liu

引用次数: 0