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Phosphorylated protein chip combined with artificial intelligence tools for precise drug screening
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作者 Katsuhisa Horimoto Yuki Suyama +7 位作者 Tadamasa Sasaki Kazuhiko Fukui Lili Feng Meiling Sun Yamin Tang Yixuan Zhang Dongyin Chen Feng Han 《Journal of Biomedical Research》 CAS CSCD 2024年第3期195-205,共11页
We have developed a protein array system,named"Phospho-Totum",which reproduces the phosphorylation state of a sample on the array.The protein array contains 1471 proteins from 273 known signaling pathways.Ac... We have developed a protein array system,named"Phospho-Totum",which reproduces the phosphorylation state of a sample on the array.The protein array contains 1471 proteins from 273 known signaling pathways.According to the activation degrees of tyrosine kinases in the sample,the corresponding groups of substrate proteins on the array are phosphorylated under the same conditions.In addition to measuring the phosphorylation levels of the 1471 substrates,we have developed and performed the artificial intelligence-assisted tools to further characterize the phosphorylation state and estimate pathway activation,tyrosine kinase activation,and a list of kinase inhibitors that produce phosphorylation states similar to that of the sample.The Phospho-Totum system,which seamlessly links and interrogates the measurements and analyses,has the potential to not only elucidate pathophysiological mechanisms in diseases by reproducing the phosphorylation state of samples,but also be useful for drug discovery,particularly for screening targeted kinases for potential drug kinase inhibitors. 展开更多
关键词 Phospho-Totum protein array signal transduction pathways artificial intelligence tools drug screening
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An Experimental Model for Screening Anti-AIDS Drugs with Bovine Immunodeficiency Virus
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作者 王岱 刘淑红 +3 位作者 陈启民 耿运琪 徐为人 魏月芳 《Journal of Chinese Pharmaceutical Sciences》 CAS 1997年第1期35-39,共5页
The assays for bovine immunodeficiency virus (BIV) induced syncytium formation and BIV long terminal repeat (LTR) directed luciferase (Luc) gene expression were applied to screen and evaluate anti AIDS drugs. Frequen... The assays for bovine immunodeficiency virus (BIV) induced syncytium formation and BIV long terminal repeat (LTR) directed luciferase (Luc) gene expression were applied to screen and evaluate anti AIDS drugs. Frequency of the syncytium formation and BIV LTR directed Luc activity were in proportion to the number of input BIV infected cells. AZT inhibited the syncytium formation and the BIV LTR directed Luc gene expression level. Its inhibitory effects were dosedependent with the IC 50 being 0.24 and 0.052 mmol / L, respectively. 展开更多
关键词 Acquired immunodeficiency syndrome (AIDS) Drug screening Bovine immunodeficiency virus (BIV) SYNCYTIUM Long terminal repeat (LTR) 3′ Azido 2′ 3′ dide oxythymidine (AZT)
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Brain organoids are new tool for drug screening of neurological diseases 被引量:2
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作者 Jin-Qi Zhou Ling-Hui Zeng +5 位作者 Chen-Tao Li Da-Hong He Hao-Duo Zhao Yan-Nan Xu Zi-Tian Jin Chong Gao 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第9期1884-1889,共6页
At the level of in vitro drug screening,the development of a phenotypic analysis system with highcontent screening at the core provides a strong platform to support high-throughput drug screening.There are few systema... At the level of in vitro drug screening,the development of a phenotypic analysis system with highcontent screening at the core provides a strong platform to support high-throughput drug screening.There are few systematic reports on brain organoids,as a new three-dimensional in vitro model,in terms of model stability,key phenotypic fingerprint,and drug screening schemes,and particula rly rega rding the development of screening strategies for massive numbers of traditional Chinese medicine monomers.This paper reviews the development of brain organoids and the advantages of brain organoids over induced neurons or cells in simulated diseases.The paper also highlights the prospects from model stability,induction criteria of brain organoids,and the screening schemes of brain organoids based on the characteristics of brain organoids and the application and development of a high-content screening system. 展开更多
关键词 brain organoids disease modeling high-content system multiple omic analysis network pharmacology NEURODEGENERATION phenotypic fingerprint psychiatric diseases stem cells traditional Chinese medicine drug screening
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The potential role of the three-dimensional-bioprinting model in screening and developing drugs
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作者 Chao-Lin Deng Bin Wu 《World Journal of Gastroenterology》 SCIE CAS 2022年第47期6788-6790,共3页
Recently,we have read with great interest the original article used different spatial configuration models of colorectal cancer(CRC)for validating the antitumor efficacy with Diiminoquinone.We feel obliged to provide ... Recently,we have read with great interest the original article used different spatial configuration models of colorectal cancer(CRC)for validating the antitumor efficacy with Diiminoquinone.We feel obliged to provide new insight into the drug screening models by integrating and analyzing the original method and result.These comments may provide comprehensive insights into threedimensional drug screening models and the difference between pathologic subtypes in CRC. 展开更多
关键词 Colorectal cancer three-dimensional-bioprinting Mucinous adenocarcinoma Drug screening models
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A robust luminescent assay for screening alkyladenine DNA glycosylase inhibitors to overcome DNA repair and temozolomide drug resistance
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作者 Ying-Qi Song Guo-Dong Li +5 位作者 Dou Niu Feng Chen Shaozhen Jing Vincent Kam Wai Wong Wanhe Wang Chung-Hang Leung 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2023年第5期514-522,共9页
Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical resection.However,despite its effectiveness,at least 50%of patients do not respond to TMZ,which ... Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical resection.However,despite its effectiveness,at least 50%of patients do not respond to TMZ,which is associated with repair and/or tolerance of TMZ-induced DNA lesions.Studies have demonstrated that alkyladenine DNA glycosylase(AAG),an enzyme that triggers the base excision repair(BER)pathway by excising TMZ-induced N3-methyladenine(3meA)and N7-methylguanine lesions,is overexpressed in glioblastoma tissues compared to normal tissues.Therefore,it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in glioblastomas.Herein,we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic methods.As a proof-of-concept,this assay was used to screen 1440 food and drug administration-approved drugs against AAG,resulting in the repurposing of sunitinib as a potential AAG inhibitor.Sunitinib restored glioblastoma(GBM)cancer cell sensitivity to TMZ,inhibited GBM cell proliferation and stem cell characteristics,and induced GBM cell cycle arrest.Overall,this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background. 展开更多
关键词 Drug screening Alkyladenine DNA glycosylase N3-methyladenine GLIOBLASTOMA TEMOZOLOMIDE SUNITINIB
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An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening
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作者 Biao Wang Bang-Shun He +6 位作者 Xiao-Lan Ruan Jiang Zhu Rui Hu Jie Wang Ying Li Yun-Huang Yang Mai-Li Liu 《Military Medical Research》 SCIE CAS CSCD 2023年第3期325-341,共17页
Background:Tumor cell heterogeneity mediated drug resistance has been recognized as the stumbling block of cancer treatment.Elucidating the cytotoxicity of anticancer drugs at single-cell level in a high-throughput wa... Background:Tumor cell heterogeneity mediated drug resistance has been recognized as the stumbling block of cancer treatment.Elucidating the cytotoxicity of anticancer drugs at single-cell level in a high-throughput way is thus of great value for developing precision therapy.However,current techniques suffer from limitations in dynamically characterizing the responses of thousands of single cells or cell clones presented to multiple drug conditions.Methods:We developed a new microfluidics-based“SMART”platform that is Simple to operate,able to generate a Massive single-cell array and Multiplex drug concentrations,capable of keeping cells Alive,Retainable and Trackable in the microchambers.These features are achieved by integrating a Microfluidic chamber Array(4320 units)and a sixConcentration gradient generator(MAC),which enables highly efficient analysis of leukemia drug effects on single cells and cell clones in a high-throughput way.Results:A simple procedure produces 6 on-chip drug gradients to treat more than 3000 single cells or single-cell derived clones and thus allows an efficient and precise analysis of cell heterogeneity.The statistic results reveal that Imatinib(Ima)and Resveratrol(Res)combination treatment on single cells or clones is much more efficient than Ima or Res single drug treatment,indicated by the markedly reduced half maximal inhibitory concentration(IC50).Additionally,single-cell derived clones demonstrate a higher IC_(50) in each drug treatment compared to single cells.Moreover,primary cells isolated from two leukemia patients are also found with apparent heterogeneity upon drug treatment on MAC.Conclusions:This microfluidics-based“SMART”platform allows high-throughput single-cell capture and culture,dynamic drug-gradient treatment and cell response monitoring,which represents a new approach to efficiently investigate anticancer drug effects and should benefit drug discovery for leukemia and other cancers. 展开更多
关键词 MICROFLUIDICS Single-cell analysis LEUKEMIA High-throughput drug screening Single-cell cloning
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Tumor cell membrane-coated continuous electrochemical sensor for GLUT1 inhibitor screening
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作者 Jiaqian Zhao Yuqiao Liu +5 位作者 Ling Zhu Junmin Li Yanhui Liu Jiarui Luo Tian Xie Dajing Chen 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2023年第6期673-682,共10页
Glucose transporter 1(GLUT1)overexpression in tumor cells is a potential target for drug therapy,but few studies have reported screening GLUT1 inhibitors from natural or synthetic compounds.With current analysis techn... Glucose transporter 1(GLUT1)overexpression in tumor cells is a potential target for drug therapy,but few studies have reported screening GLUT1 inhibitors from natural or synthetic compounds.With current analysis techniques,it is difficult to accurately monitor the GLUT1 inhibitory effect of drug molecules in real-time.We developed a cell membrane-based glucose sensor(CMGS)that integrated a hydrogel electrode with tumor cell membranes to monitor GLUT1 transmembrane transport and screen for GLUT1 inhibitors in traditional Chinese medicines(TCMs).CMGS is compatible with cell membranes of various origins,including different types of tumors and cell lines with GLUT1 expression knocked down by small interfering RNA or small molecules.Based on CMGS continuous monitoring technique,we investigated the glucose transport kinetics of cell membranes with varying levels of GLUT1 expression.We used CMGS to determine the GLUT1-inhibitory effects of drug monomers with similar structures from Scutellaria baicalensis and catechins families.Results were consistent with those of the cellular glucose uptake test and molecular-docking simulation.CMGS could accurately screen drug molecules in TCMs that inhibit GLUT1,providing a new strategy for studying transmembrane protein-receptor interactions. 展开更多
关键词 Glucose transporter 1 inhibitor Electrochemical sensor Drug screen Traditional Chinese medicine
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3D bioprinting of in vitro porous hepatoma models:establishment,evaluation,and anticancer drug testing
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作者 Xiaoyuan Wang Zixian Liu +7 位作者 Qianqian Duan Boye Zhang Yanyan Cao Zhizhong Shen Meng Li Yanfeng Xi Jianming Wang Shengbo Sang 《Bio-Design and Manufacturing》 SCIE EI CAS CSCD 2024年第2期137-152,共16页
Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study desc... Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study describes the use of threedimensional(3D)bioprinting technology to construct a 3D model with human hepatocarcinoma SMMC-7721 cells(3DP-7721)by combining gelatin methacrylate(GelMA)and poly(ethylene oxide)(PEO)as two immiscible aqueous phases to form a bioink and innovatively applying fluorescent carbon quantum dots for long-term tracking of cells.The GelMA(10%,mass fraction)and PEO(1.6%,mass fraction)hydrogel with 3:1 volume ratio offered distinct pore-forming characteristics,satisfactorymechanical properties,and biocompatibility for the creation of the 3DP-7721 model.Immunofluorescence analysis and quantitative real-time fluorescence polymerase chain reaction(PCR)were used to evaluate the biological properties of the model.Compared with the two-dimensional culture cell model(2D-7721)and the 3D mixed culture cell model(3DM-7721),3DP-7721 significantly improved the proliferation of cells and expression of tumor-related proteins and genes.Moreover,we evaluated the differences between the three culture models and the effectiveness of antitumor drugs in the three models and discovered that the efficacy of antitumor drugs varied because of significant differences in resistance proteins and genes between the three models.In addition,the comparison of tumor formation in the three models found that the cells cultured by the 3DP-7721 model had strong tumorigenicity in nude mice.Immunohistochemical evaluation of the levels of biochemical indicators related to the formation of solid tumors showed that the 3DP-7721 model group exhibited pathological characteristics of malignant tumors,the generated solid tumors were similar to actual tumors,and the deterioration was higher.This research therefore acts as a foundation for the application of 3DP-7721 models in drug development research. 展开更多
关键词 3D bioprinting Hepatoma tumor models Drug screening Antitumor drug development
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Strategic insights into the cultivation of pancreatic cancer organoids from endoscopic ultrasonography-guided biopsy tissue
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作者 Jia-Li Yang Jun-Feng Zhang +4 位作者 Jian-You Gu Mei Gao Ming-You Zheng Shi-Xiang Guo Tao Zhang 《World Journal of Gastroenterology》 SCIE CAS 2024年第42期4532-4543,共12页
BACKGROUND The frequent suboptimal efficacy of endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB)to culture pancreatic cancer(PC)organoids(PCOs)poses a major challenge in the advancement of personalized medicine... BACKGROUND The frequent suboptimal efficacy of endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB)to culture pancreatic cancer(PC)organoids(PCOs)poses a major challenge in the advancement of personalized medicine for advanced PC.AIM To explore how to obtain appropriate puncture tissues from EUS-FNB and optimize the strategy for efficiently constructing PCOs,providing an efficient tool for the advancement of personalized medicine.METHODS Patients who underwent EUS-FNB for the diagnosis of PC tissue were prospectively enrolled.We refined the endoscopic biopsy procedures and organoid cultivation techniques.All tissue specimens verified by on-site pathological assessment were cultured in a semi-suspended medium in a microfluidic environment.We assessed differences in PCOs cultured beyond and below five generations examining patient demographics,specimen and organoid attributes,and the sensitivity of organoids to a panel of clinical drugs through cell viability assays.RESULTS In this study,16 patients with PC were recruited,one sample was excluded because onsite cytopathology showed no tumor cells.Successful organoid generation occurred in 93.3%(14 of 15)of the EUS-FNB specimens,with 60%(9 of 15)sustaining over five generations.Among these patients,those with a history of diabetes,familial cancer,or larger tumors exhibited enhanced PCO expandability.The key factors influencing longterm PCOs expansion included initial needle sample quality(P=0.005),rapid initiation of organoid culture postisolation(P≤0.001),and high organoid activity(P=0.031).Drug sensitivity analysis revealed a partial response in two patients following therapeutic intervention and surgery and stable disease in four patients,indicating a moderate correlation between organoid response and clinical outcomes.CONCLUSION Optimal initial needle sampling,rapid and precise biopsy sample processing,process isolated samples as soon as possible,and sufficient cellular material are crucial for successful cultivating PCOs.High organoid activity is an important factor in maintaining their long-term expansion,which is essential for shortening the time of drug sensitivity analysis and is the basis of PC research. 展开更多
关键词 Endoscopic ultrasound-guided fine-needle biopsy Pancreatic cancer organoid Puncture technique Cultivation optimization strategy Drug screening
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Conversion therapy in advanced perihilar cholangiocarcinoma based on patient-derived organoids:A case report
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作者 Yong-Gang He Ling-Yu Zhang +4 位作者 Jing Li Zheng Wang Chong-Yu Zhao Lu Zheng Xiao-Bing Huang 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第10期4274-4280,共7页
BACKGROUND Patient-derived organoids(PDOs)have been demonstrated to predict the response to drugs in multiple cancer types.However,it remains unclear about its application in cholangiocarcinoma.CASE SUMMARY A 59-year-... BACKGROUND Patient-derived organoids(PDOs)have been demonstrated to predict the response to drugs in multiple cancer types.However,it remains unclear about its application in cholangiocarcinoma.CASE SUMMARY A 59-year-old woman was admitted to the hospital due to upper abdominal pain for over 8 months.According to relevant examinations,she was diagnosed as perihilar cholangiocarcinoma(pCCA)with intrahepatic metastasis and perihilar lymphatic metastasis.After multidisciplinary team discussion,percutaneous transhepatic cholangiodrainage was performed to relieve biliary obstruction,and puncture biopsy was conducted to confirm the pathological diagnosis.Transarterial chemoembolization with nab-paclitaxel was used in combination with toripalimab and lenvatinib,but the levels of tumor markers including alpha fetal protein,carcinoembryonic antigen,carbohydrate antigen 15-3 and cancer antigen 125 were still raised.The PDO for drug screening showed sensitive to gemcitabine and cisplatin.Accordingly,the chemotherapy regimen was adjusted to gemcitabine and cisplatin in combination with toripalimab and lenvatinib.After 4 cycles of treatment,the tumor was assessed resectable,and radical surgical resection was performed successfully.One year after surgery,the patient was still alive,and no recurrence or occurred.CONCLUSION PDOs for drug sensitivity contribute to screening effective chemotherapy drugs for advanced pCCA,promoting conversion therapy and improving the prognosis. 展开更多
关键词 Patient-derived organoids Perihilar cholangiocarcinoma Conversion therapy Drug screening Intrahepatic metastasis Case report
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Visualization analysis of research hotspots and trends on gastrointestinal tumor organoids
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作者 Gang Wang Tao Liu Wen-Ting He 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第6期2826-2841,共16页
BACKGROUND Gastrointestinal tumor organoids serve as an effective model for simulating cancer in vitro and have been applied in basic biology and preclinical research.Despite over a decade of development and increasin... BACKGROUND Gastrointestinal tumor organoids serve as an effective model for simulating cancer in vitro and have been applied in basic biology and preclinical research.Despite over a decade of development and increasing research achievements in this field,a systematic and comprehensive analysis of the research hotspots and future trends is lacking.AIM To address this problem by employing bibliometric tools to explore the publication years,countries/regions,institutions,journals,authors,keywords,and references in this field.METHODS The literature was collected from Web of Science databases.CiteSpace-6.2R4,a widely used bibliometric analysis software package,was used for institutional analysis and reference burst analysis.VOSviewer 1.6.19 was used for journal cocitation analysis,author co-authorship and co-citation analysis.The‘online platform for bibliometric analysis(https://bibliometric.com/app)’was used to assess the total number of publications and the cooperation relationships between countries.Finally,we employed the bibliometric R software package(version R.4.3.1)in R-studio,for a comprehensive scientific analysis of the literature.RESULTS Our analysis included a total of 1466 publications,revealing a significant yearly increase in articles on the study of gastrointestinal tumor organoids.The United States(n=393)and Helmholtz Association(n=93)have emerged as the leading countries and institutions,respectively,in this field,with Hans Clevers and Toshiro Sato being the most contributing authors.The most influential journal in this field is Gastroenterology.The most impactful reference is"Long term expansion of epithelial organs from human colon,adenoma,adenocarcinoma,and Barrett's epithelium".Keywords analysis and citation burst analysis indicate that precision medicine,disease modeling,drug development and screening,and regenerative medicine are the most cutting-edge directions.These focal points were further detailed based on the literature.CONCLUSION This bibliometric study offers an objective and quantitative analysis of the research in this field,which can be considered as an important guide for next scientific research. 展开更多
关键词 Gastrointestinal tumor organoids Bibliometric analysis Drug development and screening Model CiteSpace
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Drug Screening Experiment in vitro of Fox Eperythrozoon
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作者 高光平 高桂生 +1 位作者 史秋梅 张艳英 《Agricultural Science & Technology》 CAS 2013年第11期1639-1641,共3页
[Objective] The research aimed to make the drug screening experiment in vitro of eperythrozoon of fox. [Method] RPMI-1640 was used as the basic culture medium and 30% calf serum was added. Using Berenil, oxytetracycli... [Objective] The research aimed to make the drug screening experiment in vitro of eperythrozoon of fox. [Method] RPMI-1640 was used as the basic culture medium and 30% calf serum was added. Using Berenil, oxytetracycline, al icin, doxy-cycline,imidocarb,florfenicol,Fuhongjuesha,primaquine phosphate and other drug powder,the drug screening experiment in vitro of fox eperythrozoon was made under the conditions of 37.3 ℃, 5% CO2. [Result] The effects of Fuhongjuesha was the best,and that of primaquine phosphate and Berenil was the next. And imidocarb,al-licin and florfenicol were effective. [Conclusion] The research provided scientific and theoretical basis for the clinical treatment of eperythrozoonosis. 展开更多
关键词 EPERYTHROZOON Fox in vitro Drug screening
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Bioprinting of novel 3D tumor array chip for drug screening 被引量:10
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作者 Mingjun Xie Qing Gao +2 位作者 Jianzhong Fu Zichen Chen Yong He 《Bio-Design and Manufacturing》 SCIE CSCD 2020年第3期175-188,共14页
Biomedical field has been seeking a feasible standard drug screening system consisting of 3D tumor model array for drug researching due to providing sufficient samples and simulating actual in vivo tumor growth situat... Biomedical field has been seeking a feasible standard drug screening system consisting of 3D tumor model array for drug researching due to providing sufficient samples and simulating actual in vivo tumor growth situation,which is still a challenge to rapidly and uniformly establish though.Here,we propose a novel drug screening system,namely 3D tumor array chip with“layer cake”structure,for drug screening.Accurate gelatin methacryloyl hydrogel droplets(~0.1μL)containing tumor cells can be automatically deposited on demand with electrohydrodynamic 3D printing.Transparent conductive membrane is introduced as a chip basement for preventing charges accumulation during fabricating and convenient observing during screening.Culturing chambers formed by stainless steel and silicon interlayer is convenient to be assembled and recycled.As this chip is compatible with the existing 96-well culturing plate,the drug screening protocols could keep the same as convention.Important properties of this chip,namely printing stability,customizability,accuracy,microenvironment,tumor functionalization,are detailly examined.As a demonstration,it is applied for screening of epirubicin and paclitaxel with breast tumor cells to confirm the compatibility of the proposed screening system with the traditional screening methods.We believe this chip will potentially play a significant role in drug evaluation in the future. 展开更多
关键词 3D tumor array chip(3D-TAC) Gelatin methacryloyl(GelMA) Drug screening In vitro model BIOPRINTING
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Screening compounds against HCV based on MAVS/IFN-β pathway in a replicon model 被引量:2
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作者 Qiu-Xia Fu Li-Cui Wang +7 位作者 Shuai-Zheng Jia Bo Gao Yong Zhou Juan Du Ying-Li Wang Xiao-Hui Wang Jian-Chun Peng Lin-Sheng Zhan 《World Journal of Gastroenterology》 SCIE CAS CSCD 2010年第44期5582-5587,共6页
AIM:To develop a sensitive assay for screening compounds against hepatitis C virus (HCV).METHODS:The proteolytic cleavage of NS3/4A on enhanced yellow fluorescent protein (eYFP)-mitochondrial antiviral signaling prote... AIM:To develop a sensitive assay for screening compounds against hepatitis C virus (HCV).METHODS:The proteolytic cleavage of NS3/4A on enhanced yellow fluorescent protein (eYFP)-mitochondrial antiviral signaling protein (MAVS) was examined by reporter enzyme secreted placental alkaline phosphatase (SEAP),which enabled us to perform ongoing monitoring of anti-HCV drugs through repeated chemiluminescence.Subcellular localization of eYFP-MAVS was assessed by fluorescence microscopy.Cellular localization and protein levels were examined by Western blotting.RESULTS:HCV NS3/4A protease cleaved eYFP-MAVSfrom mitochondria to block the activation of interferon (IFN)-β promoter,thus resulting in downregulation of SEAP activity.The decrease in SEAP activity was proportional to the dose of active NS3/4A protease.Also this reporter assay was used to detect anti-HCV activity of IFN-α and cyclosporine A.CONCLUSION:Our data show that this reporter system is a sensitive and quantitative reporter of anti-HCV inhibitors.This system will constitute a new tool to allow the efficient screening of HCV inhibitors. 展开更多
关键词 Mitochondrial antiviral signaling protein Hepatitis C virus INTERFERON-Β Drug screening
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Current Status of Targets and Assays for Anti-HIV Drug Screening 被引量:1
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作者 Ren-rong TIAN Qing-jiao LIAO Xu-lin CHEN 《Virologica Sinica》 SCIE CAS CSCD 2007年第6期476-485,共10页
HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent,treat and to better understand the disease,it is one of the main causes of morbidity a... HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent,treat and to better understand the disease,it is one of the main causes of morbidity and mortality worldwide. Currently,there are 30 drugs or combinations of drugs approved by FDA. Because of the side-effects,price and drug resistance,it is essential to discover new targets,to develop new technology and to find new anti-HIV drugs. This review summarizes the major targets and assays currently used in anti-HIV drug screening. 展开更多
关键词 ANTI-HIV TARGETS Assays Drug screening
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A high‑throughput three‑dimensional cell culture platform for drug screening 被引量:2
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作者 Jingyu Ock Wei Li 《Bio-Design and Manufacturing》 CSCD 2020年第1期40-47,共8页
Traditional two-dimensional(2D)cell cultures lack the extracellular matrix(ECM)-like structure or dynamic fluidic microenvironment for cells to maintain in vivo functionality.Three-dimensional(3D)tissue scaffolds,on t... Traditional two-dimensional(2D)cell cultures lack the extracellular matrix(ECM)-like structure or dynamic fluidic microenvironment for cells to maintain in vivo functionality.Three-dimensional(3D)tissue scaffolds,on the other hand,could provide the ECM-like microenvironment for cells to reformulate into tissue or organoids that are highly useful for in vitro drug screening.In this study,a high-throughput two-chamber 3D microscale tissue model platform is developed.Porous scaffolds are selectively foamed on a commercially available compact disk using laser.Perfusion of cell culture medium is achieved with centrifugal force-driven diffusion by disk rotation.Experimental studies were conducted on the fabrication process under various gas saturation and laser power conditions.Cell cultures were performed with two types of human cell lines:M059K and C3A-sub28.It is shown that the structure of microscale porous scaffolds can be controlled with laser foaming parameters and that coating with polydopamine these scaffolds are inducive for cell attachment and aggregation,forming a 3D network.With many such two-chamber models fabricated on a single CD and perfusion driven by the centrifugal force from rotation,the proposed platform provides a simple solution to the high-cost and lengthy drug development process with a high-throughput and physiologically more relevant tissue model system. 展开更多
关键词 High-throughput screening Three-dimensional tissue model Drug screening Centrifugal force-driven diffusion Laser foaming
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INTRODUCTION OF THE HIGH THROUGHPUT SCREENING SYSTEM
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作者 李元 《Chinese Medical Sciences Journal》 CAS CSCD 2001年第3期179-181,共3页
In this article, we introduce the system of high throughput screening (HTS). Its role in new drug study and current development is described. The relationship between research achievements of genome study and new type... In this article, we introduce the system of high throughput screening (HTS). Its role in new drug study and current development is described. The relationship between research achievements of genome study and new type screening model of new drugs is emphasized. The personal opinions of current problems about HTS study in China are raised. 展开更多
关键词 high throughput screening new drug screening recombinant protein target automatic analysis
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Four FDA-approved drugs exhibited inhibition effect on severe fever with thrombocytopenia syndrome virus in vitro
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作者 WANG Tian-tian YIN Zhi-yun +11 位作者 DENG Ya-li ZHU Qiong ZHOU Min HU Si-jing Wu Qiao-li JIN Jia-yin ZHANG Dan-na LIU Xi-jia JIANG Bo-yong SHEN Shu DENG Fei SHI Jun-ming 《Journal of Hainan Medical University》 2022年第23期11-17,共7页
Objective:To screen the anti-SFTSV drugs from 1430 FDA-approved drugs via mini-genome system,and to investigate which stage of the infection process could be suppressed by the identified drugs.Methods:The SFTSV mini-g... Objective:To screen the anti-SFTSV drugs from 1430 FDA-approved drugs via mini-genome system,and to investigate which stage of the infection process could be suppressed by the identified drugs.Methods:The SFTSV mini-genome system was used to screen drugs with inhibitory effect on SFTSV replication and transcription,and the 50%inhibitory concentration(IC_(50))of each drug was calculated by drug concentration gradient inhibition experiment.Drugs were used to pre-incubate with virus and then incubate with cells,to incubate with virus and cells simultaneously,to incubate with cells after virus invading into cells,or to incubate during the whole infection process,and then qRT-PCR was used to measure the viral RNA copies in the culture supernatant.These experiments were performed to quantitatively determine the inhibition effects of drugs on SFTSV indifferent stages of the whole process including virion stability,entry and post-entry stages,so as to clarify the inhibition mechanism of these drugs.Results:Four drugs including Mycophenolate mofetil,Mycophenolic acid,Nitazoxanide,and Vidofludimus were identified having efficient inhibitory effects on SFTSV RNA replication via minigenome system,with the IC_(50) of 0.014μmol/L,0.627μmol/L,1.283μmol/L,and 0.059μmol/L,respectively.All four drugs showed effective inhibition when adding during the whole SFTSV infection process as well as the post-entry stage.Conclusion:Mycophenolate mofetil,Mycophenolic acid,Nitazoxanide and Vidofludimus show efficient anti-viral effects on SFTSV infection. 展开更多
关键词 Severe fever with thrombocytopenia syndrome virus Drug screening Antiviral effect Inhibition phase
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Development of glioblastoma organoids and their applications in personalized therapy 被引量:2
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作者 Can Xu Xiaoye Yuan +4 位作者 Pengyu Hou Ziru Li Changsheng Wang Chuan Fang Yanli Tan 《Cancer Biology & Medicine》 SCIE CAS CSCD 2023年第5期353-368,共16页
Glioblastomas(GBMs)are the brain tumors with the highest malignancy and poorest prognoses.GBM is characterized by high heterogeneity and resistance to drug treatment.Organoids are 3-dimensional cultures that are const... Glioblastomas(GBMs)are the brain tumors with the highest malignancy and poorest prognoses.GBM is characterized by high heterogeneity and resistance to drug treatment.Organoids are 3-dimensional cultures that are constructed in vitro and comprise cell types highly similar to those in organs or tissues in vivo,thus simulating specific structures and physiological functions of organs.Organoids have been technically developed into an advanced ex vivo disease model used in basic and preclinical research on tumors.Brain organoids,which simulate the brain microenvironment while preserving tumor heterogeneity,have been used to predict patients’therapeutic responses to antitumor drugs,thus enabling a breakthrough in glioma research.GBM organoids provide an effective supplementary model that reflects human tumors’biological characteristics and functions in vitro more directly and accurately than traditional experimental models.Therefore,GBM organoids are widely applicable in disease mechanism research,drug development and screening,and glioma precision treatments.This review focuses on the development of various GBM organoid models and their applications in identifying new individualized therapies against drug-resistant GBM. 展开更多
关键词 GLIOBLASTOMA ORGANOIDS glioma stem cell drug screening
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3D-bioprinted cholangiocarcinoma-on-a-chip model for evaluating drug responses 被引量:1
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作者 Qiong Liu Luis SMille +9 位作者 Cesar Villalobos Ingrid Anaya Matthias Vostatek Sili Yi Wanlu Li Junlong Liao Huanghui Wu Yongteng Song Lize Xiong Yu Shrike Zhang 《Bio-Design and Manufacturing》 SCIE EI CAS CSCD 2023年第4期373-389,共17页
Cholangiocarcinoma(CCA)is characterized by heterogeneous mutations and a refractory nature.Thus,the development of a model for effective drug screening is urgently needed.As the established therapeutic testing models ... Cholangiocarcinoma(CCA)is characterized by heterogeneous mutations and a refractory nature.Thus,the development of a model for effective drug screening is urgently needed.As the established therapeutic testing models for CCA are often ineffective,we fabricated an enabling three-dimensional(3D)-bioprinted CCA-on-a-chip model that to a good extent resembled the multicellular microenvironment and the anatomical microstructure of the hepato-vascular-biliary system to perform high-content antitumor drug screening.Specifically,cholangiocytes,hepatocytes,and vascular endotheliocytes were employed for 3D bioprinting of the models,allowing for a high degree of spatial and tube-like microstructural control.Interestingly,it was possible to observe CCA cells attached to the surfaces of the gelatin methacryloyl(GelMA)hydrogelembedded microchannels and overgrown in a thickening manner,generating bile duct stenosis,which was expected to be analogous to the in vivo configuration.Over 4000 differentially expressed genes were detected in the CCA cells in our 3D coculture model compared to the traditional two-dimensional(2D)monoculture.Further screening revealed that the CCA cells grown in the 3D traditional model were more sensitive to the antitumoral prodrug than those in the 2D monoculture due to drug biotransformation by the neighboring functional hepatocytes.This study provides proof-of-concept validation of our bioprinted CCA-on-a-chip as a promising drug screening model for CCA treatment and paves the way for potential personalized medicine strategies for CCA patients in the future. 展开更多
关键词 Tumor-on-a-chip Biliary tumor 3D bioprinting Tumor microenvironment Drug screening
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