检索结果-南通市图书馆

HCS strategy targeting dysregulation of the VHL/HIF pathway for drug discovery

Advances in Bioscience and Biotechnology 2013年第3期4卷 398-405页

作者： Bastien Cautain Nuria de Pedro Maria Munoz de Escalona Jose R.Tormo Olga Genilloud Francisca Vicente screening and target validation department Fundacion MedinaGranadaSpain

One-third of top-selling drugs are derived from natural products. When only a fraction of the bioactive natural products diversity has been explored, huge opportunities still remain for discovering novel leads for the development of new drugs. Clear cell renal cell carcinoma (ccRCC) is a highly vascular tumour arising from epithelial elements. Mutations in the Von Hippel-Lindau (VHL) gene are responsible for VHL disease and arise in the majority of Renal Cell Carcinoma (RCC) as well as in other types of cancer. Renal carcinoma cell lines with naturally occurring VHL mutations (RCC4 VA) and their genetically matched wild-type VHL (RCC4 VHL) counterparts were seeded onto 96-well plates and allowed to attach overnight. Fungal extracts were tested on both cell lines. Clinically useful antitumor agents were used as positive controls and as reference points to establish the efficacy and selectivity of the new compounds. Renal cell carcinoma cell lines expressing VHL or not were treated with Carboxyfluorescein succinimidyl ester (CFSE). The day after cell inoculation, extracts were added and during the following days of incubation, fluorescence intensity was measured as a surrogate marker for cell viability. The most promising extracts selectively inhibited growth of pVHL-defi- cient cells but not of wild-type VHL cells. We used High Content Bio-imaging, a complete cellular imaging workflow that integrates instruments and software to acquire and analyze images, to evaluate their effect. Cell imaging can reveal effects that would be overlooked by other cell assay approaches. This target-based whole cell screen is a new strategy, which ensures cell permeability and target selectivity especially in natural product screening where natural product purification is a labour of extensive work. This approach permitted a dynamic study where fluorescence was measured without affecting cell viability and enabling a better detection of cytotoxic effects such as autophagy, senescence or

关键词： High Content screening Natural Products HIF Drug Discovery

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Antihyperuricemic effect of mangiferin aglycon derivative J99745 by inhibiting xanthine oxidase activity and urate transporter 1 expression in mice

引用

Acta Pharmaceutica Sinica B 2018年第2期8卷 306-315页

作者： Zhizhen Qin Shoubao Wang Yihuang Lin Ying Zhao Shengqian Yang Junke Song Tao Xie Jinlong Tian Song Wu Guanhua Du Beijing Key Laboratory of Drug target and screening Research department of New Drug R&D Institute of Materia Medica Chinese Academy of Medical Science and Peking Union Medical College

A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase(XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7 th day to induce hyperuricemia. Meanwhile, J99745(3, 10, and 30 mg/kg), allopurinol(20 mg/kg) or benzbromarone(20 mg/kg) were orally administered to mice for 7 days. On the 7 th day,uric acid and creatinine in serum and urine, blood urea nitrogen(BUN), malondialdehyde(MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin(H&E) staining. Hepatic XOD, renal urate transporter 1(URAT1), glucose transporter type 9(GLUT9), organic anion transporter 1(OAT1) and ATP-binding cassette transporter G2(ABCG2) were detected by Western blot and real time polymerase chain reaction(PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid(FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our resultssuggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent.

关键词： Antihyperuricemic effect Mangiferin aglycon Derivative Xanthine oxidase Urate transporter 1

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and anti-inflammation

引用

Chinese Journal of Natural Medicines 2018年第3期16卷 184-193页

作者： ZHANG Wen SONG Jun-Ke ZHANG Xue ZHOU Qi-Meng HE Guo-Rong XU Xiao-Na Yan Rong ZHOU Wen-Xia DU Guan-Hua Beijing Key Laboratory of Drug target Identification and Drug screening Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College department of Neuroimmunopharmacology Beijing Institute of Pharmacology and Toxicology State Key Laboratory of Toxicology and Medical Countermeasures

Salvianolic acid A （SAA） is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier （BBB） through matrix metallopeptidase 9 （MMP-9） inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion （MCAO） for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 ***-l. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 （TIMP-1） to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.

关键词： Salvianolic acid A Ischemia MCAO Blood brain barrier NF-κB MMP-9

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Norlichexanthone purified from plant endophyte prevents postmenopausal osteoporosis by targeting ERa to inhibit RANKL signaling

引用

Acta Pharmaceutica Sinica B 2021年第2期11卷 442-455页

作者： Keqi Wang Yongyan Chen Shuo Gao Maosi Wang Mengmeng Ge Qian Yang Mingkai Liao Lin Xu Junjie Chen Zhiping Zeng Haifeng Chen Xiao-kun Zhang Ting Lin Hu Zhou School of Pharmaceutical Sciences Fujian Provincial Key Laboratory of Innovative Drug Target ResearchXiamen UniversityXiamen 361102China High Throughput Drug screening Platform Xiamen UniversityXiamen 361102China

Although different types of drugs are available for postmenopausal osteoporosis,the limitations of the current therapies including drug resistances and adverse effects require identification of novel anti-osteoporosis ***,we defined that norlichexanthone(NOR),a natural product,is a ligand of estrogen receptor-alpha(ERα)and revealed its therapeutic potential for postmenopausal *** used mammalian-one hybrid assay to screen for ERαmodulators from crude extracts of several plant *** a result,NOR purified from the extract of endophyte ARL-13 was identified as a selective ERα*** directly bound to ERαwith an affinity in nanomolar range,revealing that it is a natural ligand of ERα.NOR induced osteoblast formation in MC3T3-E1 precursor ***,NOR inhibited receptor activator of nuclear factor-kappa B ligand(RANKL)-induced osteoclast formation in both RAW264.7 macrophages and mouse primary ***,NOR inhibited RANKL-induced association of ERαand TRAF6 to prevent ERα-mediated TRAF6 activation via Lys63-linked ***,NOR exhibited potent anti-osteoporosis efficacy in an ovariectomized mouse *** to estrogen,NOR was of much less capability in stimulating endometrial hyperplasia and promoting mammalian cancer cell *** together,our study identified NOR as a natural and high affinity ligand of ERαwith substantial anti-osteoporosis but less estrogenic activity.

关键词： Norlichexanthone Osteoporosis Osteoclast RANKL signaling TRAF6 ERa

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Pharmacokinetic study of salvianolic acid D after oral and intravenous administration in rats

引用

Acta Pharmaceutica Sinica B 2015年第3期5卷 246-253页

作者： Junke Song Wen Zhang Jialin Sun Xiaona Xu Xue Zhang Li Zhang Zhangying Feng Guan-hua Du State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing Key Laboratory of Drug Target Identification and Drug ScreeningInstitute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical College Pharmacy department of the Affiliated Hospital of Medical College of Qingdao University The Fourth Hospital of Hebei Medical University

A sensitive, specific and rapid LC-MS method was developed and validated for the determination of salvianolic acid D (SAlD) in rat plasma. This method used a single quadrupole mass spectrometer with an electrospray ionization (ESI) source. A single ion monitoring scanning (SIM) mode was employed. it showed good linearity over the concentration range from 3.3 to 666.7 ngfint. for the determination of Sala The R.S.D.% of intra-day and inter-day precision values were no more than 7.69%, and the accuracy was within 91%-104% at all quality control Levels. This LC MS method was applied to the pharmacokinetic study of SaID in rats. A two-compartmental model analysis was employed. The plasma concentrations at 2 mm (C-2min) were 5756.06 +/- 719.61, 11,073.01 +/- 1783.46 and 21,077.58 +/- 5581.97 nit, for 0.25, 0.5 and I mg/kg intravenous injection, respectively. The peak plastna concentration (C-max) was 333.08 +/- 61.21 pg/L for 4 mg/kg oral administration. The area under curve (AUC(0-t)) was 14,384.379 +/- 8443.t84. 22,813.369 +/- 11,860.823, 46,406.122 +/- 27,592.645 and 8201.740+4711.961 mu g/L.h for intravenous injection (0.25, 0.5 and 1 mg/kg) and oral administration (4 mg/kg), respectively. The bioavailability of SalD) was calculated to be 4.159% +/- 0.517%. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia IMedica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

关键词： Salvianolic acid D LC-MS Pharmacokinetics Bioavilability Dose proportiionality salvia miltiorrhiza Danshen Analysis method

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Cocrystal virtual screening based on the XGBoost machine learning model

引用

Chinese Chemical Letters 2023年第8期34卷 398-403页

作者： Dezhi Yang Li Wang Penghui Yuan Qi An Bin Su Mingchao Yu Ting Chen Kun Hu Li Zhang Yang Lu Guanhua Du Beijing City Key Laboratory of Polymorphic Drugs Center of Pharmaceutical PolymorphsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Shandong Soteria Pharmaceutical Co. Ltd.Laiwu 271100China Beijing City Key Laboratory of Drug target and screening Research National Center for Pharmaceutical ScreeningInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Co-crystal formation can improve the physicochemical properties of a compound,thus enhancing its ***,artificial intelligence-based co-crystal virtual screening in the early stage of drug development has attracted extensive attention from ***,the complexity of developing and applying algorithms hinders it wide *** study presents a data-driven co-crystal prediction method based on the XGBoost machine learning model of the scikit-learn *** simplified molecular input line entry specification(SMILES)information of two compounds is simply inputted to determine whether a co-crystal can be *** data set includs the co-crystal records presented in the Cambridge Structural Database(CSD)and the records of no co-crystal formation from extant literature and *** molecular descriptors are adopted as the features of a compound in the data *** developed model shows excellent performance in the proposed co-crystal training and validation sets with high accuracy,sensitivity,and F1 *** prediction success rate of the model exceeds 90%.The model therefore provides a simple and feasible scheme for designing and screening co-crystal drugs efficiently and accurately.

关键词： Cocrystal Machine learning XGBoost Molecular descriptor Praziquantel Nefiracetam

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Combination therapy with miR34a and doxorubicin synergistically inhibits Doxresistant breast cancer progression via downregulation of Snail through suppressing Notch/NF-kB and RAS/RAF/MEK/ERK signaling pathway

引用

Acta Pharmaceutica Sinica B 2021年第9期11卷 2819-2834页

作者： Xiaoxia Yang Pengfei Shang Bingfang Yu Qiuyang Jin Jing Liao Lei Wang Jianbo Ji Xiuli Guo department of Pharmacology Key Laboratory of Chemical Biology(Ministry of Education)Drug Screening UnitPlatformSchool of Pharmaceutical SciencesShandong UniversityJinan 250012China

Resistance to breast cancer(BCa) chemotherapy severely hampers the patient’s *** provide a potential therapeutic prospect for *** this study,the reversal function of microRNA34 a(miR34 a) on doxorubicin(Dox) resistance of BCa and the possible mechanism was *** found that the relative level of miR34 a was significantly decreased in Dox-resistant breast cancer cell MCF-7(MCF-7/A) compared with Dox-sensitive MCF-7 *** with miR34 a significantly suppressed the invasion,migration,adhesion of MCF-7/A cells without inhibiting their growth *** combination of miR34 a and Dox could significantly inhibit the proliferation,migration,invasion and induce the apoptosis of MCF-7/A *** synergistic effect of this combination on resistant MCF-7/A cells has no obvious relation with the expressions of classical drug-resistant proteins P-GP,MRP and GST-π,while closely related with the down-regulation on TOP2 A and ***,we found both protein and mRNA expression of Snail were significantly up-regulated in MCF-7/A cells in comparison with MCF-7 *** with small interfering RNA(siRNA) of Snail could inhibit the invasion,migration and adhesion of drug-resistant MCF-7/A cells,while highexpression of Snail could remarkably promote the invasion,migration and adhesion of MCF-7 cells,which might be related with regulation of N-cadherin and *** with miR34 a in MCF-7/A cells induced a decrease of Snail *** potential binding sites of miR34 a with 3’UTR of Snail were predicted by miRDB target prediction software,which was confirmed by luciferase reporter gene *** showed that the relative activity of luciferase was reduced in MCF-7/A cells after co-transfection of miR34 a and wild type(wt)-Snail,while did not change by co-transfection with miR34 a and 3’ UTR mutant type(mut) *** of miR34 a and Dox induced a stronger decrease of Snail in MCF-7/A cells in comparison

关键词： Breast cancer miR34a Dox Drug resistance Snail Notch/NF-kB RAS/RAF/MEK/ERK Therapy

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Nanotechnology in retinal drug delivery

引用

International Journal of Ophthalmology(English edition) 2018年第6期11卷 1038-1044页

作者： Sibo Jiang Yesenia L Franco Yan Zhou Jianjun Chen department of Pharmaceutics University of Florida department of Pharmaceutics University of Minnesota School of Pharmaceutical Sciences Guangdong Provincial Key Laboratory of New Drug Screening Southern Medical University

Retinal diseases, including age-related macular degeneration （AMD） and diabetic retinopathy （DR） are the leading causes of blindness in adults over the age of 50 years in the US. While most of those conditions do not have a cure, currently available treatment options attempt to prevent further vision loss. For many ophthalmic drugs, an efficient delivery system to provide maximum therapeutic efficacy and promote patient compliance remains an unmet medical need. An exploration of literature via PubMed spanning from 2007 to 2017 was conducted to identify studies that have evaluated nanotechnology as platforms for delivering therapeutic agents to the posterior segment of the eye where the retina is located. Until now, four routes that have been utilized for retinal drug delivery are the intravitreal, periocular, subretinal, and systemic routes. Intravitreal injections are now widely used in clinical practice due to their ability to directly target the back of the eye but are highly invasive procedures that may cause several complications, particularly with repeated uses over a short timespan. Nanotechnology shows great promise to revolutionize retinal drug delivery, offering many advantages such as a targeted delivery system towards the specific site of the retina as well as sustained delivery of therapeutic agents. In this review, specific eye anatomy and constraints on ocular drug administration are illustrated. Further, we list and highlight several examples of nanosystems, such as hydrogels, liposomes, dendrimers, and micelles, used via different drug delivery routes to treat various retinal diseases.

关键词： nanotechnology nanoparticle drug delivery retina age-related macular degeneration diabetic retinopathy

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Structural landscape on a series of rhein:Berberine cocrystal salt solvates:The formation,dissolution elucidation from experimental and theoretical investigations

引用

Chinese Chemical Letters 2022年第6期33卷 3207-3211页

作者： Dezhi Yang Hongjuan Wang Qiwen Liu Penghui Yuan Ting Chen Li Zhang Shiying Yang Zhengzheng Zhou Yang Lu Guanhua Du Beijing City Key Laboratory of Polymorphic Drugs Center of Pharmaceutical PolymorphsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China department of Hygiene Inspection and Quarantine Science School of Public HealthSouthern Medical University(Guangdong Provincial Key Laboratory of Tropical Disease ResearchNMPA Key Laboratory for Safety Evaluation of Cosmetics)Guangzhou 510515China Beijing City Key Laboratory of Drug target and screening Research National Center for Pharmaceutical ScreeningInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

The specific crystalline form of a compound remarkably affects its physicochemical ***,a detailed analysis of the structural features and intermolecular interactions of a multi-component crystal is feasible to understand the relationships among the structure,physicochemical properties and the formation *** the present study,three novel cocrystal salt solvates of rhein and berberine were reported for the first *** solid characterizations and theoretical computations based on density functional theory(DFT)were carried out to demonstrate the intermolecular *** theoretical computation shows that the strongest interaction existed between berberine cation and rhein anion,and the electrostatic interaction play a dominant ***,no salt bond was observed between *** intrinsic dissolution rate analysis in water shows that the monohydrate exhibits 17 times enhancement in comparison with *** rhein and berberine combined in ionic state in cocrystal salt is the main reason for the solubility *** paper suggests that the interactions between the different components can be visualized and qualitatively and quantitatively analyzed by theoretical computation,which is helpful to understand the relationship between stereochemical structure and physicochemical properties of multi-component complex.

关键词： Cocrystal Rhein Berberine Theoretical computation Energy decomposition analysis Solubility

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Alisol B 23-acetate-induced HepG2 hepatoma cell death through mTOR signaling-initiated G_1 cell cycle arrest and apoptosis: A quantitative proteomic study

引用

Chinese Journal of Cancer Research 2019年第2期31卷 375-388页

作者： Ji Xia Qiang Luo Shengbin Huang Fuquan Jiang Lin Wang Guanghui Wang Jingjing Xie Jie Liu Yang Xu School of Pharmaceutical Sciences Fujian Provincial Key Laboratory of Innovative Drug Target Research Xiamen University department of Oncology Zhongshan Hospital of Xiamen University Institute of Gastrointestinal Oncology Medical College of Xiamen University

Objective: The present study aimed to investigate the molecular events in alisol B 23-acetate(ABA) cytotoxic activity against a liver cancer cell ***: First, we employed a quantitative proteomics approach based on stable isotope labeling by amino acids in cell culture(SILAC) to identify the different proteins expressed in HepG2 liver cancer cells upon exposure to ABA. Next, bioinformatics analyses through DAVID and STRING on-line tools were used to predict the pathways involved. Finally, we applied functional validation including cell cycle analysis and Western blotting for apoptosis and mTOR pathway-related proteins to confirm the bioinformatics ***: We identified 330 different proteins with the SILAC-based quantitative proteomics approach. The bioinformatics analysis and the functional validation revealed that the mTOR pathway, ribosome biogenesis, cell cycle, and apoptosis pathways were differentially regulated by ABA. G1 cell cycle arrest, apoptosis and mTOR inhibition were ***: ABA, a potential mTOR inhibitor, induces the disruption of ribosomal biogenesis. It also affects the mTOR-MRP axis to cause G1 cell cycle arrest and finally leads to cancer cell apoptosis.

关键词： Alisol B 23-acetate apoptosis cell cycle mTOR ribosome proteins

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：