Frontiers of Medicine最新文献

CHAF1B promotes the progression of lung squamous-cell carcinoma by inhibiting SETD7 expression.

IF 3.9 3区医学

Frontiers of Medicine Pub 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":"https://doi.org/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":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-25","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

Unlocking therapeutic potential: antibacterial therapy for CRB1-associated retinal degeneration in Rd8 mice. 解锁治疗潜力：抗菌疗法治疗Rd8小鼠crb1相关视网膜变性

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2025-01-20 DOI: 10.1007/s11684-024-1112-4

Zhen He, Yufei Wang, Siyu Zhang, Zhenwang Zhao, Xiaobo Hu

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 3.9 3区医学

Frontiers of Medicine Pub 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":"https://doi.org/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":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-20","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 3.9 3区医学

Frontiers of Medicine Pub 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":"https://doi.org/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":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-20","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

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 3.9 3区医学

Frontiers of Medicine Pub 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":"https://doi.org/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":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-17","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

Metabolism and metabolomics in senescence, aging, and age-related diseases: a multiscale perspective. 衰老、衰老和年龄相关疾病的代谢和代谢组学：多尺度视角。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2025-01-17 DOI: 10.1007/s11684-024-1116-0

Ziyi Wang, Hongying Zhu, Wei Xiong

引用次数: 0

Non small cell lung cancer with SMARCA4 deficiency harboring rare EGFR mutations exhibited significant tumor response when treated with afatinib: a case report. 携带罕见EGFR突变的SMARCA4缺乏症的非小细胞肺癌在使用阿法替尼治疗时表现出显著的肿瘤反应：一份病例报告。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2025-01-14 DOI: 10.1007/s11684-024-1118-y

Xiaotong Qiu, Liangkun You, Chongwei Wang, Jin Sheng

引用次数: 0

Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control. 典型和非典型NOTCH信号在癌症的非遗传抗性：不同的和协调的控制。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2025-01-02 DOI: 10.1007/s11684-024-1107-1

Xianzhe Huang, Wenwei Chen, Yanyan Wang, Dmytro Shytikov, Yanwen Wang, Wangyi Zhu, Ruyi Chen, Yuwei He, Yanjia Yang, Wei Guo

{"title":"Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.","authors":"Xianzhe Huang, Wenwei Chen, Yanyan Wang, Dmytro Shytikov, Yanwen Wang, Wangyi Zhu, Ruyi Chen, Yuwei He, Yanjia Yang, Wei Guo","doi":"10.1007/s11684-024-1107-1","DOIUrl":"https://doi.org/10.1007/s11684-024-1107-1","url":null,"abstract":"Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy. These subpopulations, e.g., cancer stem-like cells, cancer cells with epithelial-to-mesenchymal transition, and drug-tolerant persisters, are protected by their resistance traits at cellular and molecular levels. This review summarizes recent advances in the research on resistant populations and their resistance traits. NOTCH signaling, as a central regulator of nongenetic resistance, is discussed with a special focus on its canonical maintenance of resistant cancer cells and noncanonical regulation of their resistance traits. This novel view of canonical and noncanonical NOTCH signaling pathways is translated into our proposal of reshaping therapeutic strategies targeting NOTCH signaling in resistant cancer cells. We hope that this review will lead researchers to study the canonical and noncanonical arms of NOTCH signaling as an integrated resistant mechanism, thus promoting the development of innovative therapeutic strategies.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914246","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

Gallstones, cholecystectomy, and cancer risk: an observational and Mendelian randomization study. 胆结石、胆囊切除术和癌症风险：一项观察性孟德尔随机研究。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-12-26 DOI: 10.1007/s11684-024-1111-5

Yuanyue Zhu, Linhui Shen, Yanan Huo, Qin Wan, Yingfen Qin, Ruying Hu, Lixin Shi, Qing Su, Xuefeng Yu, Li Yan, Guijun Qin, Xulei Tang, Gang Chen, Yu Xu, Tiange Wang, Zhiyun Zhao, Zhengnan Gao, Guixia Wang, Feixia Shen, Xuejiang Gu, Zuojie Luo, Li Chen, Qiang Li, Zhen Ye, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Lulu Chen, Tianshu Zeng, Jiajun Zhao, Yiming Mu, Weiqing Wang, Guang Ning, Jieli Lu, Min Xu, Yufang Bi, Weiguo Hu

{"title":"Gallstones, cholecystectomy, and cancer risk: an observational and Mendelian randomization study.","authors":"Yuanyue Zhu, Linhui Shen, Yanan Huo, Qin Wan, Yingfen Qin, Ruying Hu, Lixin Shi, Qing Su, Xuefeng Yu, Li Yan, Guijun Qin, Xulei Tang, Gang Chen, Yu Xu, Tiange Wang, Zhiyun Zhao, Zhengnan Gao, Guixia Wang, Feixia Shen, Xuejiang Gu, Zuojie Luo, Li Chen, Qiang Li, Zhen Ye, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Lulu Chen, Tianshu Zeng, Jiajun Zhao, Yiming Mu, Weiqing Wang, Guang Ning, Jieli Lu, Min Xu, Yufang Bi, Weiguo Hu","doi":"10.1007/s11684-024-1111-5","DOIUrl":"https://doi.org/10.1007/s11684-024-1111-5","url":null,"abstract":"This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893763","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

Does the outcome of acupuncture differ according to the location of sham needling points in acupuncture trials for migraine? A systematic review and network meta-analysis. 在治疗偏头痛的针灸试验中，假穴位的位置不同，针灸的效果是否不同？系统回顾和网络荟萃分析。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-12-20 DOI: 10.1007/s11684-024-1109-z

Boram Lee, Chan-Young Kwon, Hye Won Lee, Arya Nielsen, L Susan Wieland, Tae-Hun Kim, Stephen Birch, Terje Alraek, Myeong Soo Lee

{"title":"Does the outcome of acupuncture differ according to the location of sham needling points in acupuncture trials for migraine? A systematic review and network meta-analysis.","authors":"Boram Lee, Chan-Young Kwon, Hye Won Lee, Arya Nielsen, L Susan Wieland, Tae-Hun Kim, Stephen Birch, Terje Alraek, Myeong Soo Lee","doi":"10.1007/s11684-024-1109-z","DOIUrl":"https://doi.org/10.1007/s11684-024-1109-z","url":null,"abstract":"Various acupuncture clinical trials have been conducted on migraine; however, the conclusions remain controversial especially when acupuncture was compared with sham acupuncture. Sham acupuncture is sometimes performed at the same acupuncture points used for verum acupuncture despite the evidence on acupuncture point specificity. Four databases were searched for sham acupuncture or waiting list-controlled acupuncture trials for migraine on December 25, 2023. Sham acupuncture was classified according to the needling points: sham acupuncture therapy at verum points (SATV) or at sham points (SATS). Network meta-analysis was performed based on the frequentist framework for headache pain intensity and response rate. A total of 18 studies involving 1936 participants were analyzed. Headache pain intensity and response rate were significantly improved in verum acupuncture compared with SATS. However, there was no significant difference between SATV and verum acupuncture. When comparing SATS and SATV, there was no significant difference in headache pain intensity and response rate; however, the results were in favor of SATV. The effect of the risk of bias on the certainty of evidence between verum and sham acupunctures was judged to be generally low. SATV should not be misused as a placebo control to evaluate the efficacy of acupuncture.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863925","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