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A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential targets of Bioactive Compounds from a Herbal Prescription Based on the Therapeutic Efficacy of Yinchenhao Tang for Jaundice Syndrome

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Engineering 2021年第9期7卷 1293-1305页

作者： Hui Xiong Ai-Hua Zhang Ya-Jing Guo Xiao-Hang Zhou Hui Sun Le Yang Heng Fang Guang-Li Yan Xi-Jun Wang National Chinmedomics Research Center&National TCM Key Laboratory of Serum Pharmacochemistry Department of Pharmaceutical AnalysisHeilongjiang University of Chinese MedicineHarbin 150040China State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyMacao 999078China National Engineering Laboratory for the Development of Southwestern Endangered Medicinal Materials Guangxi Botanical Garden of Medicinal PlantNanning 530023China

A herbal prescription in traditional Chinese medicine(TCM)has great complexity,with multiple components and multiple targets,making it extremely challenging to determine its bioactive *** Tang(YCHT)has been extensively used for the treatment of jaundice *** many studies have examined the efficacy and active ingredients of YCHT,there is still a lack of an in-depth systematic analysis of its effective components,mechanisms,and potential targets—especially one based on clinical *** study established an innovative strategy for discovering the potential targets and active compounds of YCHT based on an integrated clinical and animal experiment *** serum metabolic profiles and constituents of YCHT in vivo were determined by ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry(UPLC-Q-ToF-MS)-based metabolomics combined with a serum pharmacochemistry ***,a compound–target–pathway network was constructed and analyzed by network pharmacology and ingenuity pathway analysis(IPA).We found that eight active components could modulate five key *** key targets were further verified by enzyme-linked immunosorbent assay(ELISA),which indicated that YCHT exerts therapeutic effects by targeting cholesterol 7a-hydroxylase(CYP7A1),multidrug-resistance-associated protein 2(ABCC2),multidrug-resistance-associated protein 3(ABCC3),uridine diphosphate glucuronosyl transferase 1A1(UGT1A1),and farnesoid X receptor(FXR),and by regulating metabolic pathways including primary bile acid biosynthesis,porphyrin and chlorophyll metabolism,and biliary *** main effective compounds were discovered and correlated with the key targets and *** this way,we demonstrate that this integrated strategy can be successfully applied for the effective discovery of the active compounds and therapeutic targets of an herbal prescription.

关键词： Efficacy Bioactive compound Small molecule targets Herbal medicine Metabolomics

The function and potential drug targets of tumour-associated Tregs for cancer immunotherapy

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Science China(Life Sciences) 2019年第2期62卷 179-186页

作者： Shanshan Yan Yaguang Zhang Bing Sun State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences University of Chinese Academy of Sciences School of Life Sciences University of Science and Technology of China University of Chinese Academy of Sciences

Regulatory T cells(Tregs) play an important role in maintaining self-tolerance and immune homeostasis, but they also play a negative role in evoking effective antitumour immune responses. There is ample evidence indicating that the depletion of Tregs or the inhibition of Treg function will enhance antitumour effects. However, it is unclear which surface molecules of Tregs are suitable targets for tumour immunotherapy with minimal toxic side effects, which is a central theme in the field of Treg-targeted immunotherapy. In this review, we focus on the regulatory mechanisms of Tregs, including intrinsic and extrinsic factors within the tumour microenvironment, and we address potential drug targets on Tregs for immunotherapy.

关键词： tumour-associated tregs regulation targets immunotherapy

Possible mechanisms underlying treatment of Alzheimer’s disease with Traditional Chinese Medicine: active components, potential targets and synthetic pathways of Bulao Elixir

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Journal of Traditional Chinese Medicine 2020年第3期40卷 484-496页

作者： Ren Beida Cheng Fafeng Wang Xueqian Wan Yuxiang Ji Wenting Du Xin Zhang Shuang Liu Shilling Ma Chongyang Xiong Yiliang Hao Gaoting Wang Qingguo School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China The Third Affiliated Hospital Beijing University of Chinese MedicineBeijing 100029China School of Chinese Classics Beijing University of Chinese MedicineBeijing 100029China Affiliated Hospital of Shanxi University of Traditional Chinese Medicine Taiyuan 030000China

OBJECTIVE: To elucidate the mechanisms underlying the treatment of Alzheimer’s disease(AD) with Traditional Chinese Medicine(TCM), by examining the active components, potential targets and synthetic pathways of Bulao Elixir(BLE).METHODS: The Absorption, Distribution, Metabolism, Excretion(ADME)/Toxicology(T) calculation was used to screen the active components of Bulao Elixir. Based on the TCM Systems Pharmacology Analysis Platform(TCMSP database) and a text mining tool(GoPubMed database), we predicted and screened the active components of Bulao Elixir and its therapeutic targets for AD. Using the Database for Annotation, Visualization and Integrated Discovery(DAVID), we obtained the targets for AD. Cytoscape software was used to establish a network map of the active component-target and target-pathway of Bulao Elixir. Gene function, related biological processes and signaling pathways were analyzed using the DAVID ***: Twelve active components were selected from 196 components of Bulao Elixir. Among 2209 targets, 102 effective targets were selected, and 30 important targets were identified via matching with the disease targets. After further analysis, 14 core targets were identified. Enrichment analysis revealed that most of these important targets were involved in multiple biological processes, including apoptosis, inflammatory reactions, and cell regulation cycles. The synthetic pathways for AD treatment were identified after analyzing and confirming the relevant pathways, providing potentially useful information for diagnosis and treatment methods for ***: The current study elucidated the potential treatment mechanisms of Bulao Elixir in AD using network pharmacology, providing a foundation for further clarification of its treatment targets.

关键词： Alzheimer disease Pharmacology Components targets Pathway Bulao Elixir

The mechanism and relevant mediators associated with neuronal apoptosis and potential therapeutic targets in subarachnoid hemorrhage

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Neural Regeneration Research 2023年第2期18卷 244-252页

作者： Qi Tian Sheng Liu Shou-Meng Han Wei Zhang Xian-Yao Qin Jun-Hui Chen Cheng-Li Liu Yu-Jia Guo Ming-Chang Li Department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal *** previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this *** them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after *** apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative ***,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal *** there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of *** this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.

关键词： blood-brain barrier mechanism mediators neuronal apoptosis pathways subarachnoid hemorrhage targets treatment

Radiation force on absorbing targets and power measurements of a high intensity focused ultrasound (HIFU) source

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Science China(Physics,Mechanics & Astronomy) 2010年第10期53卷 1780-1787页

作者： QIAN ZuWen ZHU ZheMin YE ShiGong JIANG WenHua ZHU HouQing YU JinShen Institute of Acoustics Chinese Academy of SciencesBeijing 100190China Beijing YUANDE Biological Technology Development Company Beijing 100176China

Based on the analytic expressions for the radiated field of a circular concave piston given by Hasegawa et al.,an integral for calculation of the radiation force on a plane absorbing target in a spherically focused field is derived.A general relation between acoustic power P and normal radiation force Fn is obtained under the condition of kr *** computation is carried out by using the symbolic computation program for practically focused sources and absorbing circular *** results show that,for a given source,there is a range of target positions where the radiation force is independent of the target's position under the assumption that the contribution of the acoustic field behind the target to the radiation force can be *** experiments are carried out and confirm that there is a range of target positions where the measured radiation force is basically independent of the target's position even at high acoustic power (up to 700 W).It is believed that when the radiation force method is used to measure the acoustic power radiated from a focused source,the size of the target must be selected in such a way that no observable sound can be found in the region behind the target.

关键词： Radiation force targets power measurements high intensity focused ultrasound

Detection of small targets with adaptive binarization threshold in infrared video sequences

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Chinese Optics Letters 2006年第3期4卷 152-154页

作者：杨磊杨杰 Institute of Image Processing and Pattern Recognition Shanghai Jiao Tong University Shanghai 200240

An additive discussion for the validity of using the weighted information entropy to evaluate the complex degree of infrared （IR） backgronnds is given, Since small targets can be temporarily lost in actual infrared video sequences, an adaptive binarization threshold for small targets detection is presented. Experimental results show the robustness of our method,

关键词： Entropy Experiments targets

CALORIMETRY DETERMINATION OF ^(210)Po IN targets

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Nuclear Science and Techniques 1993年第2期4卷 125-128页

作者：冯跟胜 China Institute of Atomic Energy Beijing 102413 China

The polonium-210 activity in raw material targets which was used to make the start neutron source rods of Qinshan Nuclear Power Station was determined in calorimetry. The calorimeter used is a twin-cup isothermal one. It works at room temperature and does not need any device of constant temperature. The instruments used for calorimetry are simple and have good properties. The background is from -1μV to + 2 μ V when the room temperature changs between 16℃ and 28 ℃. The data gotten in calorimetry are in correspondence within ±3.4 % with those from liquid scintillation method after the targets were dissolved, additionally in correspondence within ±1.7% with the data given by Amersham Laboratories for 241Am determination.

关键词： Calorimetry determination Polonium-210 Raw material targets Radioactivity Start neutron source rods

Leishmaniasis:Current status of available drugs and new potential drug targets

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Asian Pacific Journal of Tropical Medicine 2012年第6期5卷 485-497页

作者： Nisha Singh Manish Kumar Rakesh Kumar Singh Molecular Immunology Laboratory Department of BiochemistryFaculty of ScienceBanaras Hindu UniversityVaranasi-221 005India Department of Chemistry Bose InstituteAPC RoadKolkata-700009India

The control of Leishmania infection relies primarily on chemotherapy till *** to pentavalent antimonials,which have been the recommended drugs to treat cutaneous and visceral leishmaniasis,is now widespread in Indian *** drug formulations like amphotericin B,its lipid formulations,and miltefosine have shown great efGcacy to treat leishmaniasis but their high cost and therapeutic complications limit their *** addition, irregular and inappropriate uses of these second line drugs in endemic regions like state of Bihar, India threaten resistance development in the *** context to the limited drug options and unavailability of either preventive or prophylactic candidates,there is a pressing need to develop true antileishmanial drugs to reduce the disease burden of this debilitating endemic *** significant progress of leishmanial research during last few decades, identification and characterization of novel drugs and drug targets are far from *** review will initially describe current drug regimens and later will provide an overview on few important biochemical and enzymatic machineries that could be utilized as putative drug targets for generation of true antileishmanial drugs.

关键词： Leishmaniasis Drug resistance Drug targets Drugs

MicroRNAs and liver cancer associated with iron overload:Therapeutic targets unravelled

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World Journal of Gastroenterology 2013年第32期19卷 5212-5226页

作者： Catherine M Greene Robert B Varley Matthew W Lawless Respiratory Research Division Department of MedicineEducation and Research CentreRoyal College of Surgeons In IrelandBeaumont Hospital Experimental Medicine UCD School of Medicine and Medical ScienceMater Misericordiae University Hospital

Primary liver cancer is a global disease that is on the *** carcinoma(HCC)accounts for most primary liver cancers and has a notably low survival rate,largely attributable to late diagnosis,resistance to treatment,tumour recurrence and ***(miRNAs/miRs)are regulatory RNAs that modulate protein *** are involved in several biological and pathological processes including the development and progression of *** the poor outcomes with current HCC treatments,miRNAs represent an important new target for therapeutic *** studies have demonstrated their role in HCC development and *** many risk factors underlie the development of HCC,one process commonly altered is iron *** overload occurs in several liver diseases associated with the development of HCC including Hepatitis C infection and the importance of miRNAs in iron homeostasis and hepatic iron overload is well *** miRNA expression in hepatic fibrosis and injury response have been reported,as have dysregulated miRNA expression patterns affecting cell cycle progression,evasion of apoptosis,invasion and ***2009,miR-26a delivery was shown to prevent HCC progression,highlighting its therapeutic *** studies have since investigated the clinical potential of other miRNAs with one drug,Miravirsen,currently in phaseⅡclinical *** also have potential as biomarkers for the diagnosis of HCC and to evaluate treatment *** studies and clinical trials suggest miRNA-based treatments and diagnostic methods will have novel clinical applications for HCC in the coming years,yielding improved HCC survival rates and patient outcomes.

关键词： MicroRNAs Liver cancer Iron regulation Hepatitis C Therapeutic targets