Frontiers of Medicine最新文献_第5页

Allogeneic hematopoietic stem cell transplantation could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in acute myeloid leukemia: real-world multicenter analysis in China. 异基因造血干细胞移植可克服急性髓系白血病患者DNMT3AmutNPM1mutFLT3-ITDmut的不良预后：中国现实世界多中心分析

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2025-02-01 Epub Date: 2024-12-07 DOI: 10.1007/s11684-024-1091-5

Wenxuan Huo, Yifan Shen, Jiayu Huang, Yang Yang, Shuang Fan, Xiaosu Zhao, Qi Wen, Luxiang Wang, Chuanhe Jiang, Yang Cao, Xiaodong Mo, Yang Xu, Xiaoxia Hu

{"title":"Allogeneic hematopoietic stem cell transplantation could overcome the poor prognosis of DNMT3AmutNPM1mutFLT3-ITDmut in acute myeloid leukemia: real-world multicenter analysis in China.","authors":"Wenxuan Huo, Yifan Shen, Jiayu Huang, Yang Yang, Shuang Fan, Xiaosu Zhao, Qi Wen, Luxiang Wang, Chuanhe Jiang, Yang Cao, Xiaodong Mo, Yang Xu, Xiaoxia Hu","doi":"10.1007/s11684-024-1091-5","DOIUrl":"10.1007/s11684-024-1091-5","url":null,"abstract":"The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3AmutNPM1mutFLT3-ITDmut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3AmutNPM1mutFLT3-ITDmut in AML.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"90-100"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791654","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

Prevalence and associated risk factors of carotid plaque and artery stenosis in China: a population-based study. 中国颈动脉斑块和动脉狭窄的患病率及相关风险因素：一项基于人群的研究。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2025-02-01 Epub Date: 2024-11-27 DOI: 10.1007/s11684-024-1088-0

Qingjia Zeng, Chongyang Zhang, Xinyao Liu, Shengmin Yang, Muyuan Ma, Jia Tang, Tianlu Yin, Shanshan Zhao, Wenjun Tu, Hongpu Hu

{"title":"Prevalence and associated risk factors of carotid plaque and artery stenosis in China: a population-based study.","authors":"Qingjia Zeng, Chongyang Zhang, Xinyao Liu, Shengmin Yang, Muyuan Ma, Jia Tang, Tianlu Yin, Shanshan Zhao, Wenjun Tu, Hongpu Hu","doi":"10.1007/s11684-024-1088-0","DOIUrl":"10.1007/s11684-024-1088-0","url":null,"abstract":"Stroke is a critical health issue in China, and carotid artery stenosis and plaque play key roles in its prevalence. Despite the acknowledged significance of this condition, detailed information regarding the prevalence of carotid artery stenosis and plaque across the Chinese population has been scarce. This study analyzed data from the China Stroke High-risk Population Screening and Intervention Program for 2020-2021, focusing on 194 878 Chinese adults aged 40 years and above. It assessed the prevalence of carotid artery stenosis and plaque and identified their associated risk factors. Results revealed a standardized prevalence of 0.40% for carotid artery stenosis and 36.27% for carotid plaque. Notably, the highest rates of stenosis were observed in north and south China at 0.61%, while southwestern China exhibited the highest plaque prevalence at 43.17%. Key risk factors included older age, male gender, hypertension, diabetes, stroke, smoking, and atrial fibrillation. This study highlights significant geographical and demographic disparities in the prevalence of these conditions, underlining the urgent need for targeted interventions and policy reforms. These measures are essential for reducing the incidence of stroke and improving patient outcomes, addressing this significant health challenge in China.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"64-78"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726831","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

Recurrent eosinophilia with a novel homozygous ARPC1B mutation. 复发性嗜酸性粒细胞增多伴新的纯合子ARPC1B突变。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2025-02-01 Epub Date: 2024-11-29 DOI: 10.1007/s11684-024-1106-2

Gamze Sonmez, Baris Ulum, Ates Kutay Tenekeci, Canan Caka, Ali Şahin, Alp Kazancıoğlu, Begum Ozbek, İsmail Yaz, Saliha Esenboğa, Deniz Çağdaş

{"title":"Recurrent eosinophilia with a novel homozygous ARPC1B mutation.","authors":"Gamze Sonmez, Baris Ulum, Ates Kutay Tenekeci, Canan Caka, Ali Şahin, Alp Kazancıoğlu, Begum Ozbek, İsmail Yaz, Saliha Esenboğa, Deniz Çağdaş","doi":"10.1007/s11684-024-1106-2","DOIUrl":"10.1007/s11684-024-1106-2","url":null,"abstract":"Cytoskeletal network dysregulation is a pivotal determinant in various immunodeficiencies and autoinflammatory conditions. This report reviews the significance of actin remodeling in disease pathogenesis, focusing on the Arp2/3 complex and its regulatory subunit actin related protein 2/3 complex subunit 1B (ARPC1B). A spectrum of cellular dysfunctions associated with ARPC1B deficiency, impacting diverse immune cell types, is elucidated. The study presents a patient featuring recurrent and persistent eosinophilia attributed to homozygous ARPC1B mutation alongside concomitant compound heterozygous cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. We used ARPC1B antibody to stain the patient's peripheral blood lymphocytes and those of the control. The defect in the ARPC1B gene in the present patient caused absent/low expression by immunofluorescence microscopy. The intricate interplay between cytoskeletal defects and immunological manifestations underscores the complexity of disease phenotypes, warranting further exploration for targeted therapeutic strategies.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"174-180"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750669","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

Ferroptosis contributes to immunosuppression. 铁蛋白沉积症会导致免疫抑制。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2025-02-01 Epub Date: 2024-11-19 DOI: 10.1007/s11684-024-1080-8

Nina He, Dun Yuan, Minjie Luo, Qing Xu, Zhongchi Wen, Ziqin Wang, Jie Zhao, Ying Liu

{"title":"Ferroptosis contributes to immunosuppression.","authors":"Nina He, Dun Yuan, Minjie Luo, Qing Xu, Zhongchi Wen, Ziqin Wang, Jie Zhao, Ying Liu","doi":"10.1007/s11684-024-1080-8","DOIUrl":"10.1007/s11684-024-1080-8","url":null,"abstract":"As a novel form of cell death, ferroptosis is mainly regulated by the accumulation of soluble iron ions in the cytoplasm and the production of lipid peroxides and is closely associated with several diseases, including acute kidney injury, ischemic reperfusion injury, neurodegenerative diseases, and cancer. The term \"immunosuppression\" refers to various factors that can directly harm immune cells' structure and function and affect the synthesis, release, and biological activity of immune molecules, leading to the insufficient response of the immune system to antigen production, failure to successfully resist the invasion of foreign pathogens, and even organ damage and metabolic disorders. An immunosuppressive phase commonly occurs in the progression of many ferroptosis-related diseases, and ferroptosis can directly inhibit immune cell function. However, the relationship between ferroptosis and immunosuppression has not yet been published due to their complicated interactions in various diseases. Therefore, this review deeply discusses the contribution of ferroptosis to immunosuppression in specific cases. In addition to offering new therapeutic targets for ferroptosis-related diseases, the findings will help clarify the issues on how ferroptosis contributes to immunosuppression.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"1-22"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667505","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 : 2025-02-01 Epub 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":"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":"79-89"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","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

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 : 2025-02-01 Epub 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":"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":"23-52"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","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

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 : 2025-02-01 Epub Date: 2025-01-14 DOI: 10.1007/s11684-024-1118-y

Xiaotong Qiu, Liangkun You, Chongwei Wang, Jin Sheng

引用次数: 0

Mitochondrial-associated programmed-cell-death patterns for predicting the prognosis of non-small-cell lung cancer. 用于预测非小细胞肺癌预后的线粒体相关程序性细胞死亡模式。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2025-02-01 Epub Date: 2024-11-22 DOI: 10.1007/s11684-024-1093-3

Xueyan Shi, Sichong Han, Guizhen Wang, Guangbiao Zhou

{"title":"Mitochondrial-associated programmed-cell-death patterns for predicting the prognosis of non-small-cell lung cancer.","authors":"Xueyan Shi, Sichong Han, Guizhen Wang, Guangbiao Zhou","doi":"10.1007/s11684-024-1093-3","DOIUrl":"10.1007/s11684-024-1093-3","url":null,"abstract":"Mitochondria are the convergence point of multiple pathways that trigger programmed cell death (PCD). Mitochondrial-associated PCD (mtPCD) is involved in the pathogenesis of several diseases. However, the role of mtPCD in the prognostic prediction of cancers including non-small-cell lung cancer (NSCLC) remains to be investigated. Here, 12 mtPCD patterns were analyzed in transcriptomics, genomics, and clinical data collected from 4 datasets containing 977 patients. A risk-score assessment system containing 18 genes was established. We found that NSCLC patients with a high-risk score had a poorer prognosis. A nomogram was constructed by incorporating the risk score with clinical features. The risk score was further associated with clinicopathological information, tumor-mutation frequency, and immunotherapy responses. NSCLC patients with a high risk score had more Treg cells infiltration. However, these patients had higher tumor-mutation burden scores and may be more sensitive to immunotherapy. Moreover, receptor-interacting serine/threonine protein kinase 2 (RIPK2) was selected from mtPCD gene model for validation. We found that RIPK2 exhibited oncogenic function, and its expression level was inversely associated with the overall survival of NSCLC. Taken together, our results indicated the accuracy and practicability of the mtPCD gene model and RIPK2 in predicting the prognosis of NSCLC.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"101-120"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686518","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

TRIM4 modulates the ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitor in ovarian cancer. TRIM4在卵巢癌中调节泛素介导的hnRNPDL降解并减弱对CDK4/6抑制剂的敏感性。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2025-02-01 Epub Date: 2024-12-07 DOI: 10.1007/s11684-024-1103-5

Xiaoxia Che, Xin Guan, Yiyin Ruan, Lifei Shen, Yuhong Shen, Hua Liu, Chongying Zhu, Tianyu Zhou, Yiwei Wang, Weiwei Feng

{"title":"TRIM4 modulates the ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitor in ovarian cancer.","authors":"Xiaoxia Che, Xin Guan, Yiyin Ruan, Lifei Shen, Yuhong Shen, Hua Liu, Chongying Zhu, Tianyu Zhou, Yiwei Wang, Weiwei Feng","doi":"10.1007/s11684-024-1103-5","DOIUrl":"10.1007/s11684-024-1103-5","url":null,"abstract":"Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"121-133"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791662","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

The novel anthraquinone compound Kanglexin prevents endothelial-to-mesenchymal transition in atherosclerosis by activating FGFR1 and suppressing integrin β1/TGFβ signaling. 新型蒽醌化合物Kanglexin通过激活FGFR1和抑制整合素β1/TGFβ信号传导，防止动脉粥样硬化中的内皮细胞向间质转化。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-12-01 Epub Date: 2024-10-21 DOI: 10.1007/s11684-024-1077-3

Yixiu Zhao, Zhiqi Wang, Jing Ren, Huan Chen, Jia Zhu, Yue Zhang, Jiangfei Zheng, Shifeng Cao, Yanxi Li, Xue Liu, Na An, Tao Ban, Baofeng Yang, Yan Zhang

{"title":"The novel anthraquinone compound Kanglexin prevents endothelial-to-mesenchymal transition in atherosclerosis by activating FGFR1 and suppressing integrin β1/TGFβ signaling.","authors":"Yixiu Zhao, Zhiqi Wang, Jing Ren, Huan Chen, Jia Zhu, Yue Zhang, Jiangfei Zheng, Shifeng Cao, Yanxi Li, Xue Liu, Na An, Tao Ban, Baofeng Yang, Yan Zhang","doi":"10.1007/s11684-024-1077-3","DOIUrl":"10.1007/s11684-024-1077-3","url":null,"abstract":"Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"1068-1086"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462768","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