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NHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma

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Cancer Communications 2024年第2期44卷 251-272页

作者： Yue Yao Yi Xu Liang Yu Ting-Mao Xue Zhi-Jie Xiao Pui-Chi Tin Hiu-Ling Fung Hoi-Tang Ma Jing-ping Yun judy wai ping yam Department of Pathology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongP.R.China Department of Endocrinology and Metabolism Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China Department of Hepatopancreatobiliary Surgery Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China State Key Laboratory of Oncology in South China Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Hepatobiliary Surgery II Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China Scientific Research Center The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdongP.R.China State Key Laboratory of Liver Research The University of Hong KongHong KongP.R.China Department of Pathology Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China

Background:Small extracellular vesicles(sEVs)mediate intercellular commu-nication that contributes to hepatocellular carcinoma(HCC)progression via multifaceted *** success of cell entry determines the effect of sEV on recipient ***,we aimed to delineate the mechanisms underlying the uptake of sEV in ***:AF,Alexa Fluor;ANOVA,analysis of variance;ATP9A,ATPase Phospholipid Transporting 9A;BCECF-AM,2’,7’-bis-(2-barboxyethyl)-5-(and-6)-carboxyfluorescein,acetoxymethyl ester;BSA,bovine serum albumin;CCMR,Centre for Comparative Medicine Research;CRISPR,clustered regularly interspaced short palindromic repeats;CTL,ctrl;CXCR4,C-X-C Chemokine Receptor Type 4;DAPI,4′,6-diamidino-2-phenylindole;DFS,disease-free survival;DMEM,Dulbecco’s Modified Eagle Medium;DMSO,dimethyl sulfoxide;Dox,doxycycline;EEA1,early endosome antigen 1;EIPA,5-(N-ethyl-N-isopropyl)-amiloride;FBS,fetal bovine serum;FITC,fluorescein isothiocyanate;GAPDH,glyceraldehyde-3-phosphate dehydrogenase;GM130,Golgi matrix protein 130;HCC,hepatocellular carcinoma;HEPES,4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;HPRT1,hypoxanthine phosphoribosyltransferase 1;H-score,histoscore;IAA,indole-3-acetic acid;KD,knockdown;KO,knockout;mAID,mini-auxin-inducible degron;MTT,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide;NHE7,Na(+)/H(+)exchanger 7;ns,non-significant;OD,optical density;OS,overall survival;PBS,phosphate-buffered saline;PCR,polymerase chain reaction;pHe,endosomal pH;pHi,intracellular pH;PKH67,Paul Karl Horan 67;Rab21,Ras-associated binding protein 21;RIPA,radioimmunoprecipitation assay;SAM,synergistic activation mediator;SEMs,standard error of the means;sEVs,small extracellular vesicles;sgRNA,single-guide RNA;shRNA,short-hairpin RNA;SLC9,solute carrier gene 9;SLiCE,Seamless Ligation Cloning Extract;TCGA,The Cancer Genome Atlas;TCL,total cell lysates;TGN,trans-Golgi network;TMA,tissue microarray;TMR,tetramethyl rhodamine;TSG101,tumor susceptibility gene *** Yao an

关键词： hepatocellular carcinoma small extracellular vesicles macropinocytosis pH regulation sodium-hydrogen exchanger

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Role of Small Extracellular Vesicles in Liver Diseases:Pathogenesis,Diagnosis,and Treatment

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1176-1185页

作者： Tingmao Xue judy wai ping yam Department of Hepatobiliary Surgery II Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdongChina Department of Pathology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongChinaReceived

Extracellular vesicles(EVs)are vesicular bodies that bud off from the cell membrane or are secreted virtually by all cell *** EVs(sEVs or exosomes)are key mediators of cell-cell communication by delivering their cargo,including proteins,lipids,or RNAs,to the recipient cells where they induce changes in signaling pathways and phenotypic *** findings have revealed the pivotal involve-ment of sEVs in the pathogenesis of various *** the bright side,they are rich sources of biomarkers for diag-nosis,prognosis,treatment response,and disease *** have high stability,biocompatibility,targetability,low toxicity,and are immunogenic in *** intrinsic properties make sEVs an ideal delivery vehicle to be loaded with cargo for therapeutic *** diseases are a major global health *** review aims to focus on the roles and mechanisms of sEVs in the pathogenesis of liver diseases,liver injury,liver failure,and liver *** are released not only by hepatocytes but also by stromal and immune cells in the *** detection of liver disease determines the chance for cura-tive treatment and high survival of *** review focuses on the potential of circulating sEV cargo as specific and sensitive noninvasive biomarkers for the early detection and prognosis of liver *** addition,the therapeutic use of sEVs derived from various cell types is ***-though sEVs hold promise for clinical applications,there are still challenges to be overcome by further research to bring utilization of sEVs into clinical practice.

关键词： Small extracellular vesicles Liver injury Liver fibrosis Liver fail-ure Hepatocellular carcinoma Biomarkers.

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Ferroptosis:From Basic Research to Clinical Therapeutics in Hepatocellular Carcinoma

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Journal of Clinical and Translational Hepatology 2023年第1期11卷 207-218页

作者： Ziyue Huang Haoming Xia Yunfu Cui judy wai ping yam Yi Xu Department of Hepatopancreatobiliary Surgery Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina Department of Pathology Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina Key Laboratory of Myocardial Ischemia Harbin Medical UniversityMinistry of EducationHarbinHeilongjiangChina

Hepatocellular carcinoma(HCC)is one of the most common and highly heterogeneous malignancies *** the rapid development of multidisciplinary treatment and personalized precision medicine strategies,the overall survival of HCC patients remains *** limited survival benefit may be attributed to difficulty in early diagnosis,the high recurrence rate and high tumor ***,a novel mode of cell death driven by iron-dependent lipid peroxidation,has been implicated in the development and therapeutic response of various tumors,including *** this review,we discuss the regulatory network of ferroptosis,describe the crosstalk between ferroptosis and HCCrelated signaling pathways,and elucidate the potential role of ferroptosis in various treatment modalities for HCC,such as systemic therapy,radiotherapy,immunotherapy,interventional therapy and nanotherapy,and applications in the diagnosis and prognosis of HCC,to provide a theoretical basis for the diagnosis and treatment of HCC to effectively improve the survival of HCC patients.

关键词： Hepatocellular carcinoma Ferroptosis Sorafenib Cancer therapy Molecular targets

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Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1170-1183页

作者： Xudong Zhao Yudan Wang Haoming Xia Shuqiang Liu Ziyue Huang Risheng He Liang Yu Nanfeng Meng Hang Wang Junqi You Jinglin Li judy wai ping yam Yi Xu Yunfu Cui Department of Hepatopancreatobiliary Surgery Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina Department of Pathology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina Key Laboratory of Basic Pharmacology of Ministry of Education Zunyi Medical UniversityZunyiGuizhouChina Key Laboratory of Functional and Clinical Translational Medicine Fujian Province UniversityXiamen Medical CollegeXiamenFujianChina Jiangsu Province Engineering Research Center of Tumor Targeted Nano Diagnostic and Therapeutic Materials Yancheng Teachers UniversityYanchengJiangsuChina Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang province HangzhouZhejiangChina Key Laboratory of Gastrointestinal Cancer(Fujian Medical University) Ministry of EducationSchool of Basic Medical SciencesFujian Medical UniversityFuzhouFujianChina State Key Laboratory of Chemical Oncogenomics Key Laboratory of Chemical GenomicsPeking University Shenzhen Graduate SchoolShenzhenGuangdongChina Key Laboratory of Intelligent Pharmacy and Individualized Therapy of Huzhou Department of PharmacyChangxing People’s HospitalChangxingZhejiangChina

Hepatocellular carcinoma(HCC)being a leading cause of cancer-related death,has high associated mortality and recurrence *** has been of great necessity and urgency to find effective HCC diagnosis and treatment *** have shown that microvascular invasion(MVI)is an independent risk factor for poor prognosis after *** abnormal expression of biomacromolecules such as circ-RNAs,lncRNAs,STIP1,and PD-L1 in HCC patients is strongly correlated with *** of several markers mentioned in this review affects the proliferation,invasion,metastasis,EMT,and anti-apoptotic processes of HCC cells through multiple complex ***,these biomarkers may have an important clinical role and serve as promising interventional targets for *** this review,we provide a comprehensive overview on the functions and regulatory mechanisms of MVI-related biomarkers in HCC.

关键词： Hepatocellular carcinoma Microvascular invasion Biomarkers Progress Molecular mechanism

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人参山药挤压膨化工艺优化及其理化性质研究

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食品工业科技 2020年第21期41卷 193-198,207页

作者：宋欢张瑞逄世峰王英平吉林农业大学中药材学院人参新品种选育与开发国家地方联合工程研究中心吉林长春130118 中国农业科学院特产研究所吉林长春130112

采用双螺杆挤压膨化工艺制备人参、山药膨化制品,并研究其最佳工艺条件及其膨化前后理化性质的变化。以生晒参、山药饮片为实验材料,将生晒参粉与山药饮片粉按1∶1比例混合,在单因素的基础上,以膨化制品的径向膨化率为考察指标,根据L9(3... 详细信息

采用双螺杆挤压膨化工艺制备人参、山药膨化制品,并研究其最佳工艺条件及其膨化前后理化性质的变化。以生晒参、山药饮片为实验材料,将生晒参粉与山药饮片粉按1∶1比例混合,在单因素的基础上,以膨化制品的径向膨化率为考察指标,根据L9(3~4)正交表进行正交试验,确定人参、山药复合粉挤压膨化的最佳工艺参数,并对膨化前后的营养品质、物理化特性、有效成分进行比较分析。结果显示:人参、山药复合挤压膨化的最佳工艺参数为:螺杆转速为250 r/min,Ⅲ区温度160℃,物料水分含量24%,在此条件下得到疏松多孔的膨化制品,产品径向膨化率达到最大值为2.43。人参、山药复合粉挤膨化后与膨化前营养化学成分相比,粗灰分含量差异不大(P>0.05),粗脂肪、TDF、IDF、粗蛋白质、可溶性蛋白质、总淀粉、支链淀粉含量均降低(Pwai均有提高;人参、山药复合粉基本营养化学成分与物理特性相关性分析表明,膨化前后的糊化度变化率与淀粉含量变化率、支链淀粉含量变化率呈显著负相关(Pwai值的变化率与IDF呈极显著正相关(P<0.01),WSI值与支链淀粉、脂肪、TDF、IDF含量变化率呈显著负相关(P<0.05)。膨化前后人参总皂苷由5.50%下降到5.15%,差异显著(P<0.05)。结论:通过挤压膨化技术的应用,使人参、山药复合粉的理化性质得到了改善,为进一步研究奠定理论基础。

关键词：人参山药挤压膨化正交优化理化性质

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