Frontiers of Medicine最新文献_第6页

Echocardiographic Measurements in Normal Chinese Adults (EMINCA) II focusing on left ventricular and left atrial size and function by three-dimensional echocardiography. 中国正常成人超声心动图测量（EMINCA）II》侧重于通过三维超声心动图测量左心室和左心房的大小和功能。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-08-01 Epub Date: 2024-05-18 DOI: 10.1007/s11684-023-1045-3

Yingbin Wang, Yu Zhang, Guihua Yao, Hong Tang, Lixin Chen, Lixue Yin, Tiangang Zhu, Jianjun Yuan, Wei Han, Jun Yang, Xianhong Shu, Ya Yang, Yulin Wei, Yanli Guo, Weidong Ren, Dongmei Gao, Guilin Lu, Ji Wu, Hongning Yin, Yuming Mu, Jiawei Tian, Lijun Yuan, Xiaojing Ma, Hongyan Dai, Yunchuan Ding, Mingyan Ding, Qing Zhou, Hao Wang, Di Xu, Mei Zhang, Yun Zhang

{"title":"Echocardiographic Measurements in Normal Chinese Adults (EMINCA) II focusing on left ventricular and left atrial size and function by three-dimensional echocardiography.","authors":"Yingbin Wang, Yu Zhang, Guihua Yao, Hong Tang, Lixin Chen, Lixue Yin, Tiangang Zhu, Jianjun Yuan, Wei Han, Jun Yang, Xianhong Shu, Ya Yang, Yulin Wei, Yanli Guo, Weidong Ren, Dongmei Gao, Guilin Lu, Ji Wu, Hongning Yin, Yuming Mu, Jiawei Tian, Lijun Yuan, Xiaojing Ma, Hongyan Dai, Yunchuan Ding, Mingyan Ding, Qing Zhou, Hao Wang, Di Xu, Mei Zhang, Yun Zhang","doi":"10.1007/s11684-023-1045-3","DOIUrl":"10.1007/s11684-023-1045-3","url":null,"abstract":"Current guidelines encourage large studies in a diverse population to establish normal reference ranges for three-dimensional (3D) echocardiography for different ethnic groups. This study was designed to establish the normal values of 3D-left ventricular (LV) and left atrial (LA) volume and function in a nationwide, population-based cohort of healthy Han Chinese adults. A total of 1117 healthy volunteers aged 18-89 years were enrolled from 28 collaborating laboratories in China. Two sets of 3D echocardiographic instruments were used, and full-volume echocardiographic images were recorded and transmitted to a core laboratory for image analysis with a vendor-independent off-line workstation. Finally, 866 volunteers (mean age of 48.4 years, 402 men) were qualified for final analysis. Most parameters exhibited substantial differences between different sex and age groups, even after indexation by body surface area. The normal ranges of 3D-LV and 3D-LA volume and function differed from those recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, presented by the World Alliance Societies of Echocardiography (WASE) study, and from the 2D values in the EMINCA study. The normal reference values of 3D echocardiography-derived LV and LA volume and function were established for the first time in healthy Han Chinese adults. Normal ranges of 3D-LV and 3D-LA echocardiographic measurements stratified with sex, age, and race should be recommended for clinical applications.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"649-663"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957061","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 RNA-seq reveals the transcriptional program underlying tumor progression and metastasis in neuroblastoma. 单细胞 RNA 序列分析揭示了神经母细胞瘤肿瘤进展和转移的转录程序。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-08-01 Epub Date: 2024-07-17 DOI: 10.1007/s11684-024-1081-7

Zhe Nian, Dan Wang, Hao Wang, Wenxu Liu, Zhenyi Ma, Jie Yan, Yanna Cao, Jie Li, Qiang Zhao, Zhe Liu

{"title":"Single-cell RNA-seq reveals the transcriptional program underlying tumor progression and metastasis in neuroblastoma.","authors":"Zhe Nian, Dan Wang, Hao Wang, Wenxu Liu, Zhenyi Ma, Jie Yan, Yanna Cao, Jie Li, Qiang Zhao, Zhe Liu","doi":"10.1007/s11684-024-1081-7","DOIUrl":"10.1007/s11684-024-1081-7","url":null,"abstract":"Neuroblastoma (NB) is one of the most common childhood malignancies. Sixty percent of patients present with widely disseminated clinical signs at diagnosis and exhibit poor outcomes. However, the molecular mechanisms triggering NB metastasis remain largely uncharacterized. In this study, we generated a transcriptomic atlas of 15 447 NB cells from eight NB samples, including paired samples of primary tumors and bone marrow metastases. We used time-resolved analysis to chart the evolutionary trajectory of NB cells from the primary tumor to the metastases in the same patient and identified a common 'starter' subpopulation that initiates tumor development and metastasis. The 'starter' population exhibited high expression levels of multiple cell cycle-related genes, indicating the important role of cell cycle upregulation in NB tumor progression. In addition, our evolutionary trajectory analysis demonstrated the involvement of partial epithelial-to-mesenchymal transition (p-EMT) along the metastatic route from the primary site to the bone marrow. Our study provides insights into the program driving NB metastasis and presents a signature of metastasis-initiating cells as an independent prognostic indicator and potential therapeutic target to inhibit the initiation of NB metastasis.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"690-707"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626441","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

Epigenetics and environmental health. 表观遗传学与环境健康。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-08-01 Epub Date: 2024-05-28 DOI: 10.1007/s11684-023-1038-2

Min Zhang, Ting Hu, Tianyu Ma, Wei Huang, Yan Wang

{"title":"Epigenetics and environmental health.","authors":"Min Zhang, Ting Hu, Tianyu Ma, Wei Huang, Yan Wang","doi":"10.1007/s11684-023-1038-2","DOIUrl":"10.1007/s11684-023-1038-2","url":null,"abstract":"Epigenetic modifications including DNA methylation, histone modifications, chromatin remodeling, and RNA modifications complicate gene regulation and heredity and profoundly impact various physiological and pathological processes. In recent years, accumulating evidence indicates that epigenetics is vulnerable to environmental changes and regulates the growth, development, and diseases of individuals by affecting chromatin activity and regulating gene expression. Environmental exposure or induced epigenetic changes can regulate the state of development and lead to developmental disorders, aging, cardiovascular disease, Alzheimer's disease, cancers, and so on. However, epigenetic modifications are reversible. The use of specific epigenetic inhibitors targeting epigenetic changes in response to environmental exposure is useful in disease therapy. Here, we provide an overview of the role of epigenetics in various diseases. Furthermore, we summarize the mechanism of epigenetic alterations induced by different environmental exposures, the influence of different environmental exposures, and the crosstalk between environmental variation epigenetics, and genes that are implicated in the body's health. However, the interaction of multiple factors and epigenetics in regulating the initiation and progression of various diseases complicates clinical treatments. We discuss some commonly used epigenetic drugs targeting epigenetic modifications and methods to prevent or relieve various diseases regulated by environmental exposure and epigenetics through diet.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"571-596"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161407","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 the potential of bispecific ADCs for targeted cancer therapy. 释放双特异性 ADC 在癌症靶向治疗中的潜力。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-08-01 Epub Date: 2024-07-23 DOI: 10.1007/s11684-024-1072-8

Hongye Zeng, Wenjing Ning, Xue Liu, Wenxin Luo, Ningshao Xia

引用次数: 0

Regulations of m⁶A and other RNA modifications and their roles in cancer. m6A 和其他 RNA 修饰的调节及其在癌症中的作用。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-08-01 Epub Date: 2024-06-22 DOI: 10.1007/s11684-024-1064-8

Xin-Hui Chen, Kun-Xiong Guo, Jing Li, Shu-Hui Xu, Huifang Zhu, Guang-Rong Yan

{"title":"Regulations of m6A and other RNA modifications and their roles in cancer.","authors":"Xin-Hui Chen, Kun-Xiong Guo, Jing Li, Shu-Hui Xu, Huifang Zhu, Guang-Rong Yan","doi":"10.1007/s11684-024-1064-8","DOIUrl":"10.1007/s11684-024-1064-8","url":null,"abstract":"RNA modification is an essential component of the epitranscriptome, regulating RNA metabolism and cellular functions. Several types of RNA modifications have been identified to date; they include N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), N6,2'-O-dimethyladenosine (m6Am), N4-acetylcytidine (ac4C), etc. RNA modifications, mediated by regulators including writers, erasers, and readers, are associated with carcinogenesis, tumor microenvironment, metabolic reprogramming, immunosuppression, immunotherapy, chemotherapy, etc. A novel perspective indicates that regulatory subunits and post-translational modifications (PTMs) are involved in the regulation of writer, eraser, and reader functions in mediating RNA modifications, tumorigenesis, and anticancer therapy. In this review, we summarize the advances made in the knowledge of different RNA modifications (especially m6A) and focus on RNA modification regulators with functions modulated by a series of factors in cancer, including regulatory subunits (proteins, noncoding RNA or peptides encoded by long noncoding RNA) and PTMs (acetylation, SUMOylation, lactylation, phosphorylation, etc.). We also delineate the relationship between RNA modification regulator functions and carcinogenesis or cancer progression. Additionally, inhibitors that target RNA modification regulators for anticancer therapy and their synergistic effect combined with immunotherapy or chemotherapy are discussed.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"622-648"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436720","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

Acquired immune thrombotic thrombocytopenic purpura (TTP) associated with inactivated COVID-19 vaccine CoronaVac. 与 COVID-19 灭活疫苗 CoronaVac 相关的获得性免疫血栓性血小板减少性紫癜 (TTP)。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-08-01 Epub Date: 2024-07-03 DOI: 10.1007/s11684-023-1054-2

Zhangbiao Long, Suyu Jiang, Honglei Xin, Lu Zhang, Ruinan Lu, Fengqi Liu, Yong Xu, Linv Wang, Jun Wang, Xuezhong Zhang, Hui Liao, Jinning Shi, Xue Yan, Xiang Zhu, Ruonan Shao, Zijian Li, Yilin Zhu, Han Yan, Jiao Wu, Chao Fang, Xiaodong Xi, Xiaofeng Shi

{"title":"Acquired immune thrombotic thrombocytopenic purpura (TTP) associated with inactivated COVID-19 vaccine CoronaVac.","authors":"Zhangbiao Long, Suyu Jiang, Honglei Xin, Lu Zhang, Ruinan Lu, Fengqi Liu, Yong Xu, Linv Wang, Jun Wang, Xuezhong Zhang, Hui Liao, Jinning Shi, Xue Yan, Xiang Zhu, Ruonan Shao, Zijian Li, Yilin Zhu, Han Yan, Jiao Wu, Chao Fang, Xiaodong Xi, Xiaofeng Shi","doi":"10.1007/s11684-023-1054-2","DOIUrl":"10.1007/s11684-023-1054-2","url":null,"abstract":"Corona virus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has affected the whole world. Acquired thrombotic thrombocytopenic purpura (TTP) has been reported after administration of mRNA- or adenoviral vector-based COVID-19 vaccines, including Ad26.COV2-S, BNT162b2, mRNA-1273, and ChAdOx1 nCov-19. However, whether inactivated vaccines, such as CoronaVac, could cause TTP and whether the symptoms in TTPs caused by inactivated vaccines are different from previously reported cases are unknown. In this study, two cases were reported. Both cases developed TTP after the second CoronaVac vaccination shot, but not the first. They demonstrated symptoms of fever, neurological abnormalities, renal dysfunction, thrombocytopenia, and hemolysis. Both patients achieved complete remission through several sessions of plasma exchanges and immune suppression. The incidence of TTP in Nanjing area was analyzed. The number of patients with TTP was 12 in 2019, 6 in 2020, 16 in 2021, and 19 in 2022. To the authors' knowledge, this report is the first report of TTP associated with inactivated COVID-19 vaccine (CoronaVac). The rarity and delayed onset may be due to the relatively milder immune response caused by the inactivated vaccines than mRNA-based ones. Timely plasma exchange is a vital treatment for CoronaVac-related TTP, similar to activated vaccine-related TTP.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"744-751"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491627","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

m⁶A reader YTHDF1 promotes cardiac fibrosis by enhancing AXL translation. m6A 读者 YTHDF1 通过增强 AXL 翻译促进心脏纤维化。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2024-06-01 Epub Date: 2024-05-28 DOI: 10.1007/s11684-023-1052-4

Han Wu, Weitao Jiang, Ping Pang, Wei Si, Xue Kong, Xinyue Zhang, Yuting Xiong, Chunlei Wang, Feng Zhang, Jinglun Song, Yang Yang, Linghua Zeng, Kuiwu Liu, Yingqiong Jia, Zhuo Wang, Jiaming Ju, Hongtao Diao, Yu Bian, Baofeng Yang

{"title":"m6A reader YTHDF1 promotes cardiac fibrosis by enhancing AXL translation.","authors":"Han Wu, Weitao Jiang, Ping Pang, Wei Si, Xue Kong, Xinyue Zhang, Yuting Xiong, Chunlei Wang, Feng Zhang, Jinglun Song, Yang Yang, Linghua Zeng, Kuiwu Liu, Yingqiong Jia, Zhuo Wang, Jiaming Ju, Hongtao Diao, Yu Bian, Baofeng Yang","doi":"10.1007/s11684-023-1052-4","DOIUrl":"10.1007/s11684-023-1052-4","url":null,"abstract":"Cardiac fibrosis caused by ventricular remodeling and dysfunction such as post-myocardial infarction (MI) can lead to heart failure. RNA N6-methyladenosine (m6A) methylation has been shown to play a pivotal role in the occurrence and development of many illnesses. In investigating the biological function of the m6A reader YTHDF1 in cardiac fibrosis, adeno-associated virus 9 was used to knock down or overexpress the YTHDF1 gene in mouse hearts, and MI surgery in vivo and transforming growth factor-β (TGF-β)-activated cardiac fibroblasts in vitro were performed to establish fibrosis models. Our results demonstrated that silencing YTHDF1 in mouse hearts can significantly restore impaired cardiac function and attenuate myocardial fibrosis, whereas YTHDF1 overexpression could further enhance cardiac dysfunction and aggravate the occurrence of ventricular pathological remodeling and fibrotic development. Mechanistically, zinc finger BED-type containing 6 mediated the transcriptional function of the YTHDF1 gene promoter. YTHDF1 augmented AXL translation and activated the TGF-β-Smad2/3 signaling pathway, thereby aggravating the occurrence and development of cardiac dysfunction and myocardial fibrosis. Consistently, our data indicated that YTHDF1 was involved in activation, proliferation, and migration to participate in cardiac fibrosis in vitro. Our results revealed that YTHDF1 could serve as a potential therapeutic target for myocardial fibrosis.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"499-515"},"PeriodicalIF":8.1,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161420","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

A distinct "repair" role of regulatory T cells in fracture healing. 调节性 T 细胞在骨折愈合中的独特 "修复 "作用。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2024-06-01 Epub Date: 2024-03-16 DOI: 10.1007/s11684-023-1024-8

Tingting Wu, Lulu Wang, Chen Jian, Zhenhe Zhang, Ruiyin Zeng, Bobin Mi, Guohui Liu, Yu Zhang, Chen Shi

{"title":"A distinct \"repair\" role of regulatory T cells in fracture healing.","authors":"Tingting Wu, Lulu Wang, Chen Jian, Zhenhe Zhang, Ruiyin Zeng, Bobin Mi, Guohui Liu, Yu Zhang, Chen Shi","doi":"10.1007/s11684-023-1024-8","DOIUrl":"10.1007/s11684-023-1024-8","url":null,"abstract":"Regulatory T cells (Tregs) suppress immune responses and inflammation. Here, we described the distinct nonimmunological role of Tregs in fracture healing. The recruitment from the circulation pool, peripheral induction, and local expansion rapidly enriched Tregs in the injured bone. The Tregs in the injured bone displayed superiority in direct osteogenesis over Tregs from lymphoid organs. Punctual depletion of Tregs compromised the fracture healing process, which leads to increased bone nonunion. In addition, bone callus Tregs showed unique T-cell receptor repertoires. Amphiregulin was the most overexpressed protein in bone callus Tregs, and it can directly facilitate the proliferation and differentiation of osteogenic precursor cells by activation of phosphatidylinositol 3-kinase/protein kinase B signaling pathways. The results of loss- and gain-function studies further evidenced that amphiregulin can reverse the compromised healing caused by Treg dysfunction. Tregs also enriched in patient bone callus and amphiregulin can promote the osteogenesis of human pre-osteoblastic cells. Our findings indicate the distinct and nonredundant role of Tregs in fracture healing, which will provide a new therapeutic target and strategy in the clinical treatment of fractures.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"516-537"},"PeriodicalIF":8.1,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140136","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

Assessment of HER2 status in extramammary Paget disease and its implication for disitamab vedotin, a novel humanized anti-HER2 antibody-drug conjugate therapy. 乳腺外 Paget 病中 HER2 状态的评估及其对新型人源化抗 HER2 抗体-药物共轭疗法迪西他单抗维多汀的影响。

IF 3.9 3区医学

Frontiers of Medicine Pub Date : 2024-06-01 Epub Date: 2024-05-14 DOI: 10.1007/s11684-023-1046-2

Jia Jia, Lili Mao, Jing Lin, Wenyu Li, Pei Yuan, Lei Guo, Jie Dai, Caili Li, Xue Bai, Zhongwu Li, Yu Chen, Jun Guo, Jianming Ying, Lu Si

引用次数: 0

Autophagy in hepatic progenitor cells modulates exosomal miRNAs to inhibit liver fibrosis in schistosomiasis. 肝祖细胞的自噬调节外泌体miRNA，从而抑制血吸虫病的肝纤维化。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2024-06-01 Epub Date: 2024-05-21 DOI: 10.1007/s11684-024-1079-1

Yue Yuan, Jiaxuan Li, Xun Lu, Min Chen, Huifang Liang, Xiao-Ping Chen, Xin Long, Bixiang Zhang, Song Gong, Xiaowei Huang, Jianping Zhao, Qian Chen

{"title":"Autophagy in hepatic progenitor cells modulates exosomal miRNAs to inhibit liver fibrosis in schistosomiasis.","authors":"Yue Yuan, Jiaxuan Li, Xun Lu, Min Chen, Huifang Liang, Xiao-Ping Chen, Xin Long, Bixiang Zhang, Song Gong, Xiaowei Huang, Jianping Zhao, Qian Chen","doi":"10.1007/s11684-024-1079-1","DOIUrl":"10.1007/s11684-024-1079-1","url":null,"abstract":"Schistosoma infection is one of the major causes of liver fibrosis. Emerging roles of hepatic progenitor cells (HPCs) in the pathogenesis of liver fibrosis have been identified. Nevertheless, the precise mechanism underlying the role of HPCs in liver fibrosis in schistosomiasis remains unclear. This study examined how autophagy in HPCs affects schistosomiasis-induced liver fibrosis by modulating exosomal miRNAs. The activation of HPCs was verified by immunohistochemistry (IHC) and immunofluorescence (IF) staining in fibrotic liver from patients and mice with Schistosoma japonicum infection. By coculturing HPCs with hepatic stellate cells (HSCs) and assessing the autophagy level in HPCs by proteomic analysis and in vitro phenotypic assays, we found that impaired autophagy degradation in these activated HPCs was mediated by lysosomal dysfunction. Blocking autophagy by the autophagy inhibitor chloroquine (CQ) significantly diminished liver fibrosis and granuloma formation in S. japonicum-infected mice. HPC-secreted extracellular vehicles (EVs) were further isolated and studied by miRNA sequencing. miR-1306-3p, miR-493-3p, and miR-34a-5p were identified, and their distribution into EVs was inhibited due to impaired autophagy in HPCs, which contributed to suppressing HSC activation. In conclusion, we showed that the altered autophagy process upon HPC activation may prevent liver fibrosis by modulating exosomal miRNA release and inhibiting HSC activation in schistosomiasis. Targeting the autophagy degradation process may be a therapeutic strategy for liver fibrosis during Schistosoma infection.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"538-557"},"PeriodicalIF":8.1,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070808","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