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| 1 | Synergistic Effects of Chuanxiong-Chishao Herb-Pair on Promoting Angiogenesis at Network Pharmacological and Pharmacodynamic Levels显示文摘Objective: To investigate the synergistic effects of Chuanxiong-Chishao herb-pair(CCHP) on promoting angiogenesis in silico and in vivo. Methods: The mechanisms of action of an herb-pair, ChuanxiongChishao, were investigated using the network pharmacological and pharmacodynamic strategies involving computational drug target prediction and network analysis, and experimental validation. A set of network pharmacology methods were created to study the herbs in the context of targets and diseases networks, including prediction of target profiles and pharmacological actions of main active compounds in Chuanxiong and Chishao. Furthermore, the therapeutic effects and putative molecular mechanisms of Chuanxiong-Chishao actions were experimentally validated in a chemical-induced vascular insufficiency model of transgenic zebrafish in vivo. The m RNA expression of the predicted targets were further analyzed by real-time polymerase chain reaction(RT-PCR). Results: The computational prediction results found that the compounds in Chuanxiong have antithrombotic, antihypertensive, antiarrhythmic, and antiatherosclerotic activities, which were closely related to protecting against hypoxic-ischemic encephalopathy, ischemic stroke, myocardial infarction and heart failure. In addition, compounds in Chishao were found to participate in anti-inflammatory effect and analgesics. Particularly, estrogen receptor α(ESRα) and hypoxia-inducible factor 1-α(HIF-1α) were the most important potential protein targets in the predicted results. In vivo experimental validation showed that post-treatment of tetramethylpyrazine hydrochloride(TMP·HCl) and paeoniflorin(PF) promoted the regeneration of new blood vessels in zebrafish involving up-regulating ESRα m RNA expression. Co-treatment of TMP·HCl and PF could enhance the vessel sprouting in chemical-induced vascular insufficiency zebrafish at the optimal compatibility proportion of PF 10 μmol/L with TMP·HCl 1 μmol/L. Conclusions: The network pharmacological strategies combining drug target prediction and network analysis identified some putative targets of CCHP. Moreover, the transgenic zebrafish experiments demonstrated that the Chuanxiong-Chishao combination synergistically promoted angiogenic activity, probably involving ESRα signaling pathway. | WANG Yan GUO Gang YANG Bin-rui XIN Qi-qi LIAO Qi-wen LEE Simon Ming-Yuen HU Yuan-jia CHEN Ke-ji CONG Wei-hong | 2017 | Chinese Journal of Integrative Medicine2017，23，9： | 19 |
| 2 | Essential oil of Curcuma wenyujin induces apoptosis in human hepatoma cells显示文摘AIM: To investigate the effects of the essential oil of Curcuma wenyujin (CWO) on growth inhibition and on the induction of apoptosis in human HepG2 cancer cells. METHODS: The cytotoxic effect of drugs on HepG2 cells was measured by 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetra-zolium bromide (MTT) assay. DNA fragmentation was visualized by agarose gel electrophoresis. Cell cycle and mitochondrial transmembrane potential (△Ψm) were determined by flow cytometry (FCM). Cytochrome C immunostaining was evaluated by fluorescence microscopy. Caspase-3 enzymatic activity was assayed by the cleavage of Ac-DEVD-R110. Cleaved PARP and active caspase-3 protein levels were measured by FCM using BD? CBA Human Apoptosis Kit. RESULTS: Treatment with CWO inhibited the growth of HepG2 cells in a dose-dependent manner, and the IC50 of CWO was approximately 70 μg/mL. CWO was found to inhibit the growth of HepG2 cells by inducing a cell cycle arrest at S/G2. DNA fragmentation was evidentlyobserved at 70 μg/mL after 72 h of treatment. During the process, cytosolic HepG2 cytochrome C staining showed a markedly stronger green fluorescence than in control cells in a dose-dependent fashion, and CWO also caused mitochondrial transmembrane depolarization. Furthermore, the results clearly demonstrated that both, activity of caspase-3 enzyme and protein levels of cleaved PARP, significantly increased in a dose- dependent manner after treatment with CWO. CONCLUSION: CWO exhibits an antiproliferative effect in HepG2 cells by inducing apoptosis. This growth inhibition is associated with cell cycle arrest, cytochrome C translocation, caspase 3 activation, Poly- ADP-ribose polymerase (PARP) degradation, and loss of mitochondrial membrane potential. This process involves a mitochondria-caspase dependent apoptosis pathway. As apoptosis is an important anti-cancer therapeutic target, these results suggest a potential of CWO as a chemotherapeutic agent. | YU Xiao Feng-Qing Yang Shao-Ping Li Guang Hu Simon Ming-Yuen Lee Yi-Tao Wang | 2008 | World Journal of Gastroenterology2008，14，27： | 13 |
| 3 | Genomic Analyses Yield Markers for Identifying Agronomically Important Genes in Potato显示文摘野土豆种类有实质的 phenotypic 和生理的差异。这里,我们基于茄属节 Petota 的 201 就职的 genomic 分析报导对野、栽培的土豆种类的一个全面评价。我们定序这 201 就职的染色体并且识别了 6 ? 487 ? 从在 clade 的 167 就职的 006 高质量的单个核苷酸多型性(SNP ) 4 茄属节 Petota,包括 146 野并且有宽广地理分布的 21 栽培双土豆就职。染色体宽的基因变化分析比栽培土豆,和在农学地重要的疾病抵抗的高得多的基因差异,基因在野土豆被观察的证明野土豆的差异高。由关于已知的量的特点 loci (QTL ) 利用信息,而且,我们在选择下面识别了 609 基因,包括那些在 tubers 与痛苦的损失相关,那些在 tuberization 包含了,土豆的二个主要驯养的特点。种系发生的分析在 clade 揭示了所有种类的一个纵贯的部门 4,不是就那些在 S.? brevicaule 建筑群,和进一步支持的 S。是的 candolleanum 栽培土豆和在南部的秘鲁的栽培土豆的 monophyletic 起源的祖先。另外,我们分析了 S. 的染色体 ? candolleanum 并且鉴别 529 基因在栽培土豆输了。一起,在这研究产生的分子的标记为为土豆繁殖有用的农学地重要的基因的鉴定提供一个珍贵资源。 | Yangping Li Christophe Colleoni Junjie Zhang Qiqi Liang Yufeng Hu Holly Ruess Reinhard Simon Yinghong Liu Hanmei Liu Guowu Yu Eric Schmitt Ghloe Ponitzki Guangjian Liu Huanhuan Huang Feilong Zhan Lin Chen Yubi Huang David Spooner Binquan Huang | 2018 | Molecular Plant2018，11，3： | 8 |
| 4 | Accelerated design and characterization of non-uniform cellular materials via a machine-learning based framework显示文摘Cellular materials,widely found in engineered and nature systems,are highly dependent on their geometric arrangement.A nonuniform arrangement could lead to a significant variation of mechanical properties while bringing challenges in material design.Here,this proof-of-concept study demonstrates a machine-learning based framework with the capability of accelerated characterization and pattern generation.Results showed that the proposed framework is capable of predicting the mechanical response curve of any given geometric pattern within the design domain under appropriate neural network architecture and parameters.Additionally,the framework is capable of generating matching geometric patterns for a targeted response through a databank constructed from our machine learning model.The accuracy of the predictions was verified with finite element simulations and the sources of errors were identified.Overall,our machine-learning based framework can boost the design efficiency of cellular materials at unit level,and open new avenues for the programmability of function at system level. | Chunping Ma Zhiwei Zhang Benjamin Luce Simon Pusateri Binglin Xie Mohammad H.Rafiei Nan Hu | 2020 | npj Computational Materials2020，，1： | 3 |
| 5 | Why 90%of clinical drug development fails and how to improve it?显示文摘Ninety percent of clinical drug development fails despite implementation of many successful strategies,which raised the question whether certain aspects in target validation and drug optimization are overlooked?Current drug optimization overly emphasizes potency/specificity using structure-activityrelationship(SAR)but overlooks tissue exposure/selectivity in disease/normal tissues using structure-tissue exposure/selectivity—relationship(STR),which may mislead the drug candidate selection and impact the balance of clinical dose/efficacy/toxicity.We propose structure-tissue exposure/selectivity—activity relationship(STAR)to improve drug optimization,which classifies drug candidates based on drug’s potency/selectivity,tissue exposure/selectivity,and required dose for balancing clinical efficacy/toxicity.ClassⅠdrugs have high specificity/potency and high tissue exposure/selectivity,which needs low dose to achieve superior clinical efficacy/safety with high success rate.ClassⅡdrugs have high specificity/potency and low tissue exposure/selectivity,which requires high dose to achieve clinical efficacy with high toxicity and needs to be cautiously evaluated.ClassⅢdrugs have relatively low(adequate)specificity/potency but high tissue exposure/selectivity,which requires low dose to achieve clinical efficacy with manageable toxicity but are often overlooked.ClassⅣdrugs have low specificity/potency and low tissue exposure/selectivity,which achieves inadequate efficacy/safety,and should be terminated early.STAR may improve drug optimization and clinical studies for the success of clinical drug development. | Duxin Sun Wei Gao Hongxiang Hu Simon Zhou | 2022 | Acta Pharmaceutica Sinica B2022，12，7： | 3 |
| 6 | Randomized Trial of Endoscopic Sphincterotomy With Balloon Dilation Versus Endoscopic Sphincterotomy Alone for Removal of Bile Duct Stones显示文摘 | Anthony Yuen Bun Teoh Frances Ka Yin Cheung Bing Hu Ya Min Pan Larry Hin Lai Philip Wai Yan Chiu Simon Kin Hung Wong Francis Ka Leung Chan James Yun Wong Lau | 2013 | Gastroenterology2013，，： | 2 |
| 7 | Neurological Deficit and Extent of Neuronal Necrosis Attributable to Middle Cerebral Artery Occlusion in Rats: Statistical Validation显示文摘 | Julio H. Garcia Simone Wagner Kai-Feng Liu Xiao-jiang Hu | 1995 | Stroke A Journal of Cerebral Circulation1995，，4： | 2 |
| 8 | Levels of soluble interleukin-2 receptor-alpha are elevated in serum and ascitic fluid from epithelial ovarian cancer patients显示文摘 | Huteau JA Simon HU Kurman C | 1994 | Am J Obstet Gynecol1994，170，3： | 1 |
| 9 | Roleof reactive oxygenspecies (ROS)in apoptosisinduction 显示文摘 | Simon HU Haj-Yehia A Levi-Schaffer F | 2000 | Apoptosis2000，5，5： | 1 |
| 10 | Mathematical modeling of the regulation of cspase-3 activilion and degredation显示文摘 | Stucki JW Simon Hu | 2005 | J Thor Biol2005，234，1： | 1 |
| 11 | Use of an anti-interleukin-5 antibody in the hypereosinophilic syndrome with eosino- philic dermatitis显示文摘 | Plotz SG Simon HU Darsow U | 2003 | N Engl J Med2003，349，24： | 1 |
| 12 | Neutrophil tethering on E-selectin activates beta 2 integrin binding to ICAM-1 through a mitogenactivated protein kinase signal transduction pathway显示文摘 | Simon SI Hu Y Vestweber D | 2000 | J Immunol2000，164，8： | 1 |
| 13 | Clinical and immunologicaleffects of low-dose IFN-alpha treatment in patients with corticosteroid-resistant asthma显示文摘 | Simon HU Seelbach H Ehmann R | 2003 | Allergy2003，58，12： | 1 |
| 14 | Role of ocular melanin in ophthalmic physiology and pathology 显示文摘 | Hu DN Simon JD Sarna T | 2008 | Photochem Photobiol2008，84，： | 1 |
| 15 | Protective role of autophagy and autophagy-related protein 5 in early tumorigenesis显示文摘 | Liu H He Z Simon HU | 2015 | J Mol Med (Berl)2015，93，2： | 1 |
| 16 | Autophagy suppresses melanoma tumorigenesis by inducing senescence 显示文摘 | Liu H He Z Simon HU | 2013 | Autophagy2013，10，2： | 1 |
| 17 | Life and death parlners apoptosis, autophagy and the cross-talk belween them显示文摘 | Eisenherg Lerner A Bialik S Simon HU | 2009 | Cell Death Differ2009，16，7： | 1 |
| 18 | Neutrophil tethering on E-selectin activates bata 2 integrin binding to ICAM-1 through a mitogen-activated protein kinase signal transduction pathway显示文摘 | Simon SI Hu Y Vestweber D | 2000 | J Immunol2000，164，： | 1 |
| 19 | Neutrophil apoptosis pathways and their moditications in inflammation 显示文摘 | Simon HU | 2003 | Immunol Rev2003，193，： | 1 |
| 20 | Life and death partners: apoptosis,autophagy and the cross-talk between them 显示文摘 | Eisenberg-Lerner A Bialik S Simon HU | 2009 | Cell Death Differ2009，16，7： | 1 |
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