Frontiers of Medicine最新文献_第8页

Update of cellular senescence in kidney fibrosis: from mechanism to potential interventions. 肾纤维化细胞衰老的最新进展：从机制到潜在的干预措施。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-04-01 Epub Date: 2025-02-27 DOI: 10.1007/s11684-024-1117-z

Lina Yang, Liang Ma, Ping Fu, Jing Nie

引用次数: 0

Cardiomyocyte-specific long noncoding RNA Trdn-as induces mitochondrial calcium overload by promoting the m⁶A modification of calsequestrin 2 in diabetic cardiomyopathy. 心肌细胞特异性长链非编码RNA Trdn-as在糖尿病心肌病中通过促进钙sequestrin 2的m6A修饰诱导线粒体钙超载

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-04-01 Epub Date: 2025-01-17 DOI: 10.1007/s11684-024-1102-6

Xiaohan Li, Ling Liu, Han Lou, Xinxin Dong, Shengxin Hao, Zeqi Sun, Zijia Dou, Huimin Li, Wenjie Zhao, Xiuxiu Sun, Xin Liu, Yong Zhang, Baofeng Yang

{"title":"Cardiomyocyte-specific long noncoding RNA Trdn-as induces mitochondrial calcium overload by promoting the m6A modification of calsequestrin 2 in diabetic cardiomyopathy.","authors":"Xiaohan Li, Ling Liu, Han Lou, Xinxin Dong, Shengxin Hao, Zeqi Sun, Zijia Dou, Huimin Li, Wenjie Zhao, Xiuxiu Sun, Xin Liu, Yong Zhang, Baofeng Yang","doi":"10.1007/s11684-024-1102-6","DOIUrl":"10.1007/s11684-024-1102-6","url":null,"abstract":"Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca2+ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca2+ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m6A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca2+ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"329-346"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003686","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

Factors involved in human healthy aging: insights from longevity individuals. 人类健康衰老的相关因素：来自长寿个体的见解。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-04-01 Epub Date: 2025-03-22 DOI: 10.1007/s11684-024-1120-4

Fan-Qian Yin, Fu-Hui Xiao, Qing-Peng Kong

引用次数: 0

Myeloid cells: key players in tumor microenvironments. 髓系细胞：肿瘤微环境的关键参与者。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-04-01 Epub Date: 2025-03-06 DOI: 10.1007/s11684-025-1124-8

Qiaomin Hua, Zhixiong Li, Yulan Weng, Yan Wu, Limin Zheng

{"title":"Myeloid cells: key players in tumor microenvironments.","authors":"Qiaomin Hua, Zhixiong Li, Yulan Weng, Yan Wu, Limin Zheng","doi":"10.1007/s11684-025-1124-8","DOIUrl":"10.1007/s11684-025-1124-8","url":null,"abstract":"Cancer is the result of evolving crosstalk between neoplastic cell and its immune microenvironment. In recent years, immune therapeutics targeting T lymphocytes, such as immune checkpoint blockade (ICB) and CAR-T, have made significant progress in cancer treatment and validated targeting immune cells as a promising approach to fight human cancers. However, responsiveness to the current immune therapeutic agents is limited to only a small proportion of solid cancer patients. As major components of most solid tumors, myeloid cells played critical roles in regulating the initiation and sustentation of adaptive immunity, thus determining tumor progression as well as therapeutic responses. In this review, we discuss emerging data on the diverse functions of myeloid cells in tumor progression through their direct effects or interactions with other immune cells. We explain how different metabolic reprogramming impacts the characteristics and functions of tumor myeloid cells, and discuss recent progress in revealing different mechanisms-chemotaxis, proliferation, survival, and alternative sources-involved in the infiltration and accumulation of myeloid cells within tumors. Further understanding of the function and regulation of myeloid cells is important for the development of novel strategies for therapeutic exploitation in cancer.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"265-296"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566796","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

Intracellular concentration of ADA2 is a marker for monocyte differentiation and activation. 细胞内ADA2浓度是单核细胞分化和活化的标志。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-04-01 Epub Date: 2025-01-20 DOI: 10.1007/s11684-024-1110-6

Liang Dong, Bingtai Lu, Wenwen Luo, Xiaoqiong Gu, Chengxiang Wu, Luca Trotta, Mikko Seppanen, Yuxia Zhang, Andrey V Zavialov

{"title":"Intracellular concentration of ADA2 is a marker for monocyte differentiation and activation.","authors":"Liang Dong, Bingtai Lu, Wenwen Luo, Xiaoqiong Gu, Chengxiang Wu, Luca Trotta, Mikko Seppanen, Yuxia Zhang, Andrey V Zavialov","doi":"10.1007/s11684-024-1110-6","DOIUrl":"10.1007/s11684-024-1110-6","url":null,"abstract":"Adenosine, a critical molecule regulating cellular function both inside and outside cells, is controlled by two human adenosine deaminases: ADA1 and ADA2. While ADA1 primarily resides in the cytoplasm, ADA2 can be transported to lysosomes within cells or secreted outside the cell. Patients with ADA2 deficiency (DADA2) often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood. Monocytes from DADA2 patients exhibit excessive TNF-α secretion and differentiate into pro-inflammatory M1-type macrophages. Our findings demonstrate that ADA2 localizes to endolysosomes within macrophages, and its intracellular concentration decreases in cells secreting TNF-α. This suggests that ADA2 may function as a lysosomal adenosine deaminase, regulating TNF-α expression by the cells. Interestingly, pneumonia patients exhibit higher ADA2 concentrations in their bronchoalveolar lavage (BAL), correlating with elevated pro-inflammatory cytokine levels. Conversely, cord blood has low ADA2 levels, creating a more immunosuppressive environment. Additionally, secreted ADA2 can bind to apoptotic cells, activating immune cells by reducing extracellular adenosine levels. These findings imply that ADA2 release from monocytes during inflammation, triggered by growth factors, may be crucial for cell activation. Targeting intracellular and extracellular ADA2 activities could pave the way for novel therapies in inflammatory and autoimmune disorders.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"359-375"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003834","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

Inhibition of cap-dependent endonuclease in influenza virus with ADC189: a pre-clinical analysis and phase I trial. ADC189抑制流感病毒帽盖依赖性核酸内切酶：临床前分析和I期试验

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-04-01 Epub Date: 2025-01-20 DOI: 10.1007/s11684-024-1115-1

Jing Wei, Yaping Deng, Xiaoyun Zhu, Xin Xiao, Yang Yang, Chunlei Tang, Jian Chen

{"title":"Inhibition of cap-dependent endonuclease in influenza virus with ADC189: a pre-clinical analysis and phase I trial.","authors":"Jing Wei, Yaping Deng, Xiaoyun Zhu, Xin Xiao, Yang Yang, Chunlei Tang, Jian Chen","doi":"10.1007/s11684-024-1115-1","DOIUrl":"10.1007/s11684-024-1115-1","url":null,"abstract":"ADC189 is a novel drug of cap-dependent endonuclease inhibitor. In our study, its antiviral efficacy was evaluated in vitro and in vivo, and compared with baloxavir marboxil and oseltamivir. A first-in-human phase I study in healthy volunteers included single ascending dose (SAD) and food effect (FE) parts. In the preclinical study, ADC189 showed potent antiviral activity against various types of influenza viruses, including H1N1, H3N2, influenza B virus, and highly pathogenic avian influenza, comparable to baloxavir marboxil. Additionally, ADC189 exhibited much better antiviral efficacy than oseltamivir in H1N1 infected mice. In the phase I study, ADC189 was rapidly metabolized to ADC189-I07, and its exposure increased proportionally with the dose. The terminal elimination half-life (T1/2) ranged from 76.69 to 98.28 hours. Of note, food had no effect on the concentration, clearance, and exposure of ADC189. It was well tolerated, with few treatment-emergent adverse events (TEAEs) reported and no serious adverse events (SAEs). ADC189 demonstrated excellent antiviral efficacy both in vitro and in vivo. It was safe, well-tolerated, and had favorable pharmacokinetic characteristics in healthy volunteers, supporting its potential for single oral dosing in clinical practice.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"347-358"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003832","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

Multifaceted function of B cells in tumorigenesis. B细胞在肿瘤发生中的多方面功能。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-04-01 Epub Date: 2025-03-22 DOI: 10.1007/s11684-025-1127-5

Na Kang, Qinghui Duan, Xin Min, Tong Li, Yuxin Li, Ji Gao, Wanli Liu

引用次数: 0

Low dose of hydroxychloroquine is associated with reduced COVID-19 mortality: a multicenter study in China. 低剂量羟氯喹与降低COVID-19死亡率相关：中国的一项多中心研究

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-04-01 Epub Date: 2025-03-04 DOI: 10.1007/s11684-025-1123-9

Wu He, Ke Xu, Yongcui Yan, Gen Li, Bo Yu, Junfang Wu, Kaineng Zhong, Da Zhou, Dao Wen Wang

引用次数: 0

CHAF1B promotes the progression of lung squamous-cell carcinoma by inhibiting SETD7 expression. CHAF1B通过抑制SETD7的表达促进肺鳞状细胞癌的进展。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-04-01 Epub Date: 2025-01-25 DOI: 10.1007/s11684-024-1122-2

Zhuo Zheng, Yongfang Lin, Hua Guo, Zheng Liu, Xiaoliang Jie, Guizhen Wang, Guangbiao Zhou

{"title":"CHAF1B promotes the progression of lung squamous-cell carcinoma by inhibiting SETD7 expression.","authors":"Zhuo Zheng, Yongfang Lin, Hua Guo, Zheng Liu, Xiaoliang Jie, Guizhen Wang, Guangbiao Zhou","doi":"10.1007/s11684-024-1122-2","DOIUrl":"10.1007/s11684-024-1122-2","url":null,"abstract":"The p60 subunit of the chromatin assembly factor-1 complex, that is, chromatin assembly factor-1 subunit B (CHAF1B), is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal. CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy. However, its expression and clinical significance in lung squamous-cell carcinoma (LUSC) remain unclear. In this study, we performed weighted gene correlation network analysis to analyze the Gene Expression Omnibus GSE68793 LUSC dataset and identified CHAF1B as one of the most important driver gene candidates. Immunohistochemical analysis of 126 LUSC tumor samples and 80 adjacent normal lung tissues showed the marked upregulation of CHAF1B in tumor tissues and the negative association of its expression level with patient survival outcomes. Silencing of CHAF1B suppressed LUSC proliferation in vitro and LUSC tumor growth in vivo. Furthermore, bulk RNA sequencing of CHAF1B knockdown cells indicated SET domain containing 7 (SETD7) as a significant CHAF1B target gene. In addition, CHAF1B competitively binds to the SETD7 promoter region and represses its transcription. Altogether, these results imply that CHAF1B plays a vital role in LUSC tumorigenesis and may represent a potential molecular target for this deadly disease.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"318-328"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037894","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

Single-cell transcriptome analyses of PBMCs reveal the immunological characteristics of individuals with phlegm-dampness constitution. pbmc的单细胞转录组分析揭示了痰湿体质个体的免疫学特征。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-04-01 Epub Date: 2025-03-24 DOI: 10.1007/s11684-024-1113-3

Weibo Zhao, Liqiang Zhou, Yixing Wang, Ji Wang, Yi Eve Sun, Qi Wang

{"title":"Single-cell transcriptome analyses of PBMCs reveal the immunological characteristics of individuals with phlegm-dampness constitution.","authors":"Weibo Zhao, Liqiang Zhou, Yixing Wang, Ji Wang, Yi Eve Sun, Qi Wang","doi":"10.1007/s11684-024-1113-3","DOIUrl":"10.1007/s11684-024-1113-3","url":null,"abstract":"Ancient traditional Chinese medicine (TCM) doctrine says \"The superior doctor prevents illnesses,\" pointing out preventative medicine as the ultimate goal for medical care. TCM recognizes that genetic predisposition and environmental and lifestyle influences contribute to diseases. It divides people into eight constitutions in addition to one normal/healthy kind. People with one of the eight subhealth constitutions are prone to develop different kinds of corresponding illnesses. The goal for this type of categorization is to help people take preemptive measures to prevent or delay disease onset. As the peripheral immune system through surveying the body, it can capture information from essentially all organs and reflect anomalies occurring in each organ. Thus, the detailed profiling of the peripheral immune-system function can generally reflect a person's overall heath state. In this study, we performed the single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from individuals with Tanshi (phlegm dampness) constitution. They were prone to develop metabolic disorders including diabetes. scRNA-seq revealed greatly reduced mucosal-associated invariable T cell content and heightened TNFα-NFκB, JAK-STAT, and interferon signaling. These findings indicated heightened chronic inflammation, as well as increased hypoxia/apoptosis responses, likely resulting from frequent sleep apnea that Tanshi individuals experienced. Altogether, this pilot study demonstrated effectiveness in using scRNA-seq to reveal molecular-immunological bases for constitution categorization, thereby substantiating that preventative medicine originated from TCM.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"376-385"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700199","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