Frontiers of Medicine最新文献_第8页

Adenosine deaminase 2 regulates the activation of the toll-like receptor 9 in response to nucleic acids. 腺苷脱氨酶 2 可调节 toll 样受体 9 对核酸的活化反应。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-10-01 Epub Date: 2024-07-30 DOI: 10.1007/s11684-024-1067-5

Liang Dong, Wenwen Luo, Skaldin Maksym, Simon C Robson, Andrey V Zavialov

{"title":"Adenosine deaminase 2 regulates the activation of the toll-like receptor 9 in response to nucleic acids.","authors":"Liang Dong, Wenwen Luo, Skaldin Maksym, Simon C Robson, Andrey V Zavialov","doi":"10.1007/s11684-024-1067-5","DOIUrl":"10.1007/s11684-024-1067-5","url":null,"abstract":"Human cells contain two types of adenosine deaminases (ADA) each with unique properties: ADA1, which is present in all cells where it modulates intracellular functions and extracellular signaling, and ADA2, which is secreted by immune cells. The exact intracellular functions of ADA2 remain undetermined and less defined than those of ADA1. ADA2 has distinct characteristics, such as low adenosine affinity, heparin-binding ability, and putative lysosomal entry. Here, we confirm that ADA2 is a lysosomal protein that binds toll-like receptor 9 (TLR9) agonists, specifically CpG oligodeoxynucleotides (CpG ODNs). We show that interferon-alpha (IFN-α) is secreted in response to TLR9 activation by CpG ODNs and natural DNA and markedly increases when ADA2 expression is downregulated in plasmacytoid dendritic cells (pDCs). Additionally, the pretreatment of pDCs with RNA further stimulates IFN-α secretion by pDCs after activation with CpG ODNs. Our findings indicate that ADA2 regulates TLR9 responses to DNA in activated pDCs. In conclusion, decreasing ADA2 expression or blocking it with specific oligonucleotides can enhance IFN-α secretion from pDCs, improving immune responses against intracellular infections and cancer.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"814-830"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792372","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

Epigenetic modifiers: catalytic or noncatalytic, that is the question. 表观遗传修饰剂：催化还是非催化，这是一个问题。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-10-01 Epub Date: 2024-09-28 DOI: 10.1007/s11684-024-1104-4

Yimin Liu, Haitao Li

引用次数: 0

Intracellular checkpoints for NK cell cancer immunotherapy. 用于 NK 细胞癌症免疫疗法的细胞内检查点。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-10-01 Epub Date: 2024-09-28 DOI: 10.1007/s11684-024-1090-6

Yingying Huang, Zhigang Tian, Jiacheng Bi

引用次数: 0

ING5 inhibits aerobic glycolysis of lung cancer cells by promoting TIE1-mediated phosphorylation of pyruvate dehydrogenase kinase 1 at Y163 ING5 通过促进 TIE1 介导的丙酮酸脱氢酶激酶 1 在 Y163 处的磷酸化来抑制肺癌细胞的有氧糖酵解

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2024-09-13 DOI: 10.1007/s11684-024-1057-7

Haihua Zhang, Xinli Liu, Junqiang Li, Jin Meng, Wan Huang, Xuan Su, Xutao Zhang, Guizhou Gao, Xiaodong Wang, Haichuan Su, Feng Zhang, Tao Zhang

{"title":"ING5 inhibits aerobic glycolysis of lung cancer cells by promoting TIE1-mediated phosphorylation of pyruvate dehydrogenase kinase 1 at Y163","authors":"Haihua Zhang, Xinli Liu, Junqiang Li, Jin Meng, Wan Huang, Xuan Su, Xutao Zhang, Guizhou Gao, Xiaodong Wang, Haichuan Su, Feng Zhang, Tao Zhang","doi":"10.1007/s11684-024-1057-7","DOIUrl":"https://doi.org/10.1007/s11684-024-1057-7","url":null,"abstract":"Aerobic glycolysis is critical for tumor growth and metastasis. Previously, we have found that the overexpression of the inhibitor of growth 5 (ING5) inhibits lung cancer aggressiveness and epithelial–mesenchymal transition (EMT). However, whether ING5 regulates lung cancer metabolism reprogramming remains unknown. Here, by quantitative proteomics, we showed that ING5 differentially regulates protein phosphorylation and identified a new site (Y163) of the key glycolytic enzyme PDK1 whose phosphorylation was upregulated 13.847-fold. By clinical study, decreased p-PDK1Y163 was observed in lung cancer tissues and correlated with poor survival. p-PDK1Y163 represents the negative regulatory mechanism of PDK1 by causing PDHA1 dephosphorylation and activation, leading to switching from glycolysis to oxidative phosphorylation, with increasing oxygen consumption and decreasing lactate production. These effects could be impaired by PDK1Y163F mutation, which also impaired the inhibitory effects of ING5 on cancer cell EMT and invasiveness. Mouse xenograft models confirmed the indispensable role of p-PDK1Y163 in ING5-inhibited tumor growth and metastasis. By siRNA screening, ING5-upregulated TIE1 was identified as the upstream tyrosine protein kinase targeting PDK1Y163. TIE1 knockdown induced the dephosphorylation of PDK1Y163 and increased the migration and invasion of lung cancer cells. Collectively, ING5 overexpression—upregulated TIE1 phosphorylates PDK1Y163, which is critical for the inhibition of aerobic glycolysis and invasiveness of lung cancer cells.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":"10 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178393","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

Dronedarone inhibits the proliferation of esophageal squamous cell carcinoma through the CDK4/CDK6-RB1 axis in vitro and in vivo 决奈达隆通过 CDK4/CDK6-RB1 轴在体外和体内抑制食管鳞状细胞癌的增殖

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2024-09-13 DOI: 10.1007/s11684-024-1062-x

Bo Li, Jing Zhang, Yin Yu, Yinhua Li, Yingying Chen, Xiaokun Zhao, Ang Li, Lili Zhao, Mingzhu Li, Zitong Wang, Xuebo Lu, Wenjie Wu, Yueteng Zhang, Zigang Dong, Kangdong Liu, Yanan Jiang

{"title":"Dronedarone inhibits the proliferation of esophageal squamous cell carcinoma through the CDK4/CDK6-RB1 axis in vitro and in vivo","authors":"Bo Li, Jing Zhang, Yin Yu, Yinhua Li, Yingying Chen, Xiaokun Zhao, Ang Li, Lili Zhao, Mingzhu Li, Zitong Wang, Xuebo Lu, Wenjie Wu, Yueteng Zhang, Zigang Dong, Kangdong Liu, Yanan Jiang","doi":"10.1007/s11684-024-1062-x","DOIUrl":"https://doi.org/10.1007/s11684-024-1062-x","url":null,"abstract":"Treatment options for patients with esophageal squamous cell carcinoma (ESCC) often result in poor prognosis and declining health-related quality of life. Screening FDA-approved drugs for cancer chemoprevention is a promising and cost-efficient strategy. Here, we found that dronedarone, an antiarrhythmic drug, could inhibit the proliferation of ESCC cells. Moreover, we conducted phosphorylomics analysis to investigate the mechanism of dronedarone-treated ESCC cells. Through computational docking models and pull-down assays, we demonstrated that dronedarone could directly bind to CDK4 and CDK6 kinases. We also proved that dronedarone effectively inhibited ESCC proliferation by targeting CDK4/CDK6 and blocking the G0/G1 phase through RB1 phosphorylation inhibition by in vitro kinase assays and cell cycle assays. Subsequently, we found that knocking out CDK4 and CDK6 decreased the susceptibility of ESCC cells to dronedarone. Furthermore, dronedarone suppressed the growth of ESCC in patient-derived tumor xenograft models in vivo. Thus, our study demonstrated that dronedarone could be repurposed as a CDK4/6 inhibitor for ESCC chemoprevention.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":"109 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178394","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

Evaluation of molecular residual disease in operable non-small cell lung cancer with gene fusions, MET exon skipping or de novo MET amplification. 对基因融合、MET 外显子跳越或新的 MET 扩增的可手术非小细胞肺癌分子残留病进行评估。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-08-01 Epub Date: 2024-05-28 DOI: 10.1007/s11684-024-1060-z

Rui Fu, Yuanyuan Xiong, Miao Cai, Fang Li, Rongrong Chen, Yilong Wu, Wenzhao Zhong

{"title":"Evaluation of molecular residual disease in operable non-small cell lung cancer with gene fusions, MET exon skipping or de novo MET amplification.","authors":"Rui Fu, Yuanyuan Xiong, Miao Cai, Fang Li, Rongrong Chen, Yilong Wu, Wenzhao Zhong","doi":"10.1007/s11684-024-1060-z","DOIUrl":"10.1007/s11684-024-1060-z","url":null,"abstract":"Gene fusions and MET alterations are rare and difficult to detect in plasma samples. The clinical detection efficacy of molecular residual disease (MRD) based on circulating tumor DNA (ctDNA) in patients with non-small cell lung cancer (NSCLC) with these mutations remains unknown. This prospective, non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions (ALK, ROS1, RET, and FGFR1), MET exon 14 skipping or de novo MET amplification. We analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021- and 338-gene panels, respectively. Detectable MRD correlated with a significantly higher recurrence rate (P < 0.001), yielding positive predictive values of 100% and 90.9%, and negative predictive values of 82.4% and 86.4% at landmark and longitudinal time points, respectively. Patients with detectable MRD showed reduced disease-free survival (DFS) compared to those with undetectable MRD (P < 0.001). Patients who harbored tissue-derived fusion/MET alterations in their MRD had reduced DFS compared to those who did not (P = 0.05). To our knowledge, this is the first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET alterations. Patients with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"735-743"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157319","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

Real-world effectiveness and safety of Janus kinase 1 inhibitors for the treatment of moderate-to-severe atopic dermatitis: a single-center, prospective study in China. Janus 激酶 1 抑制剂治疗中重度特应性皮炎的实际有效性和安全性：一项在中国进行的单中心前瞻性研究。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-08-01 Epub Date: 2024-07-16 DOI: 10.1007/s11684-024-1063-9

Yihui Chen, Qiaozhi Cao, Cong Peng, Bingjing Zhou, Yu Jiang, Xiang Chen, Jie Li

引用次数: 0

Moderate expression of CD39 in GPC3-CAR-T cells shows high efficacy against hepatocellular carcinoma. CD39 在 GPC3-CAR-T 细胞中的适度表达显示出对肝细胞癌的高疗效。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-08-01 Epub Date: 2024-06-04 DOI: 10.1007/s11684-024-1071-9

Fan Zou, Jialiang Wei, Jialang Zhuang, Yafang Liu, Jizhou Tan, Xianzhang Huang, Ting Liu

{"title":"Moderate expression of CD39 in GPC3-CAR-T cells shows high efficacy against hepatocellular carcinoma.","authors":"Fan Zou, Jialiang Wei, Jialang Zhuang, Yafang Liu, Jizhou Tan, Xianzhang Huang, Ting Liu","doi":"10.1007/s11684-024-1071-9","DOIUrl":"10.1007/s11684-024-1071-9","url":null,"abstract":"CD39 serves as a crucial biomarker for neoantigen-specific CD8+ T cells and is associated with antitumor activity and exhaustion. However, the relationship between CD39 expression levels and the function of chimeric antigen receptor T (CAR-T) cells remains controversial. This study aimed to investigate the role of CD39 in the functional performance of CAR-T cells against hepatocellular carcinoma (HCC) and explore the therapeutic potential of CD39 modulators, such as mitochondrial division inhibitor-1 (mdivi-1), or knockdown CD39 through short hairpin RNA. Our findings demonstrated that glypican-3-CAR-T cells with moderate CD39 expression exhibited a strong antitumor activity, while high and low levels of CD39 led to an impaired cellular function. Methods modulating the proportion of CD39 intermediate (CD39int)-phenotype CAR-T cells such as mdivi-1 and CD39 knockdown enhanced and impaired T cell function, respectively. The combination of mdivi-1 and CD39 knockdown in CAR-T cells yielded the highest proportion of infiltrated CD39int CAR-T cells and demonstrated a robust antitumor activity in vivo. In conclusion, this study revealed the crucial role of CD39 in CAR-T cell function, demonstrated the potential therapeutic efficacy of combining mdivi-1 with CD39 knockdown in HCC, and provided a novel treatment strategy for HCC patients in the field of cellular immunotherapy.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"708-720"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237292","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

Efficacy of acupuncture in refractory irritable bowel syndrome patients: a randomized controlled trial. 针灸对难治性肠易激综合征患者的疗效：随机对照试验。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-08-01 Epub Date: 2024-07-03 DOI: 10.1007/s11684-024-1073-7

Jun Zhao, Hui Zheng, Xin Wang, Xuefei Wang, Yunzhou Shi, Chaorong Xie, Qingfeng Tao, Da Li, Jingwen Sun, Junjian Tian, Junxia Gao, Huimin Liu, Suhua Shi, Jinxia Ni, Rongdan Xue, Hui Hu, Min Chen, Shuguang Yu, Zhigang Li

{"title":"Efficacy of acupuncture in refractory irritable bowel syndrome patients: a randomized controlled trial.","authors":"Jun Zhao, Hui Zheng, Xin Wang, Xuefei Wang, Yunzhou Shi, Chaorong Xie, Qingfeng Tao, Da Li, Jingwen Sun, Junjian Tian, Junxia Gao, Huimin Liu, Suhua Shi, Jinxia Ni, Rongdan Xue, Hui Hu, Min Chen, Shuguang Yu, Zhigang Li","doi":"10.1007/s11684-024-1073-7","DOIUrl":"10.1007/s11684-024-1073-7","url":null,"abstract":"Previous studies have confirmed that acupuncture for irritable bowel syndrome (IBS) provided an additional benefit over usual care alone. Therefore, we performed a multicenter, randomized, sham-controlled trial to assess the efficacy and safety of acupuncture versus sham acupuncture for refractory IBS in patients in the context of conventional treatments. Patients in the acupuncture and sham acupuncture groups received real or sham acupuncture treatment in 3 sessions per week for a total of 12 sessions. The primary outcome was a change in the IBS-Symptom Severity Scale (IBS-SSS) score from baseline to week 4. A total of 521 participants were screened, and 170 patients (85 patients per group) were enrolled and included in the intention-to-treat analysis. Baseline characteristics were comparable across the two groups. From baseline to 4 weeks, the IBS-SSS total score decreased by 140.0 (95% CI: 126.0 to 153.9) in the acupuncture group and 64.4 (95% CI: 50.4 to 78.3) in the sham acupuncture group. The between-group difference was 75.6 (95% CI: 55.8 to 95.4). Acupuncture efficacy was maintained during the 4-week follow-up period. There were no serious adverse events. In conclusion, acupuncture provided benefits when combined with treatment as usual, providing more options for the treatment of refractory IBS.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"678-689"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491628","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

Transparency and reporting characteristics of randomized controlled trials with Chinese herbal medicine formulas interventions. 中药配方干预随机对照试验的透明度和报告特点。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-08-01 Epub Date: 2024-07-23 DOI: 10.1007/s11684-024-1092-4

Juan Wang, Dongni Shi, Yaochen Wang, Xuanqi Zhang, Han Li, Xihong Wang, Shufeng Luo, Lihan Hu, Jiashuai Deng, Lin Zhang, Chung Tai Lau, Chung Wah Cheng, Fei Han, Ji Li, Ping Wang, Aiping Lyu, Zhaoxiang Bian, Xuan Zhang

引用次数: 0