1.Study on lipid-lowering traditional Chinese medicines based on pharmacophore technology and patent retrieval.
Xiao-qian HUO ; Yu-su HE ; Lian-sheng QIAO ; Zhi-yi SUN ; Yan-ling ZHANG
China Journal of Chinese Materia Medica 2014;39(24):4839-4843
The combined application of statins that inhibit HMG-CoA reductase and fibrates that activate PPAR-α can produce a better lipid-lowering effect than the simple application, but with stronger adverse reactions at the same time. In the treatment of hyperlipidemia, the combined administration of TCMs and HMG-CoA reductase inhibitor in treating hyperlipidemia shows stable efficacy and less adverse reactions, and provides a new option for the combined application of drugs. In this article, the pharmacophore technology was used to search chemical components of TCMs, trace their source herbs, and determine the potential common TCMs that could activate PPAR-α. Because there is no hyperlipidemia-related medication reference in modern TCM classics, to ensure the high safety and efficacy of all selected TCMs, we selected TCMs that are proved to be combined with statins in the World Traditional/Natural Medicine Patent Database, analyzed corresponding drugs in pharmacophore results based on that, and finally obtained common TCMs that can be applied in PPAR-α and combined with statins. Specifically, the pharmacophore model was based on eight receptor-ligand complexes of PPAR-α. The Receptor-Ligand Pharmacophore Generation module in the DS program was used to build the model, optimize with the Screen Library module, and get the best sub-pharmacophore, which consisted of two hydrogen bond acceptor, three hydrophobic groups and 19 excluded volumes, with the identification effectiveness index value N of 2. 82 and the comprehensive evaluation index CAI value of 1. 84. The model was used to screen the TCMD database, hit 5,235 kinds of chemical components and 1 193 natural animals and plants, and finally determine 62 TCMs. Through patent retrieval, we found 38 TCMs; After comparing with the virtual screening results, we finally got seven TCMs.
Acyl Coenzyme A
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metabolism
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Animals
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Databases, Factual
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Drugs, Chinese Herbal
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chemistry
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pharmacology
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Hydrophobic and Hydrophilic Interactions
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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chemistry
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pharmacology
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Lipid Metabolism
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drug effects
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Lipids
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blood
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Medicine, Chinese Traditional
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Models, Molecular
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Quantitative Structure-Activity Relationship
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Technology
2.Virtual screening for natural CETP inhibitors by structure-based pharmacophore.
Xiao-qian HUO ; Lian-sheng QIAO ; Lu-di JIANG ; Yu-su HE ; Gong-yu LI ; Yan-ling ZHANG
China Journal of Chinese Materia Medica 2015;40(15):3063-3067
Cholesterol ester transfer protein (CETP) is a key regulator of high density lipoprotein (HDL). Owing to its important role in the reverse of cholesterol transport, CETP has become a hotspot target in modulating lipid drug design. In this paper, structure based pharmacophore (SBP) models for CETP inhibitors were built based on the protein structure 4F2A from Protein Database (PDB). The best pharmacophore contained six hydrophobic features, one hydrogen bond acceptor feature and nine excluded volume features, with the N and CAI value was 3.33 and 2.31 respectively. Then the model was used to search the traditional Chinese medicine database (TCMD) and 629 compounds originated from 315 TCM herbs were obtained. Molecular docking was also used to validate SBP by analyzing the critical amino acid residue and the interaction between potential active compounds and receptor. In this study, several TCM herbs, like Lycii Frutus and Schisandrae chinensis fructus, which contained more optimal SBP based screening results, have been reported hypolipidemic effect, and need to be studied deeply in a more focused research on herbal active constituents. Therefore, this study could provide reliable fundamental data for exploring the action mechanisms of TCM, and be applicable to identify lead candidates, which can be utilized as starting scaffolds for natural CETP inhibitors.
Cholesterol Ester Transfer Proteins
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antagonists & inhibitors
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Drug Evaluation, Preclinical
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methods
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Medicine, Chinese Traditional
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Molecular Docking Simulation
3.HPLC determination of two phenylpropanoid amides in solani melongenae radix from different cultivation regions.
Jing SUN ; Yu-Fan GU ; Man-Man LI ; Xiao-Qin SU ; Hui-Xi HUO ; Jing ZHANG ; Zheng HUANG ; Qian ZHANG ; Yun-Fang ZHAO ; Jun LI ; Peng-Fei TU
China Journal of Chinese Materia Medica 2014;39(12):2300-2304
A quantitative HPLC-DAD method was developed for simultaneous determination of N-trans-p-coumaroyloctopamine and N-trans-p-coumaroyltyramine in Solani Melongenae Radix from different cultivation regions in China The separation was performed on an Agilent Eclipse XDB C18 column (4.6 mm x 250 mm, 5 microm) at 30 degrees C with a gradient elution of methanol and 0.1% formic acid in water as mobile phase. The flow rate was set at 1.0 mL x min(-1) and the detection wavelength was 300 nm. The calibration curves of N-trans-p-coumaroyloctopamine and N-trans-p-coumaroyltyramine were linear over the ranges of 2.84-68.16, 3.10-74.40 mg x L(-1), and the average recoveries (n = 9) were 99.30% and 102.8%, respectively. The developed method was successfully applied for the analysis of sixteen samples from different cultivation regions in China, which indicated that the method is simple, rapid, accurate, and reliable for quality evaluation of Solani Melongenae Radix.
Amides
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analysis
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China
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Chromatography, High Pressure Liquid
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methods
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Drugs, Chinese Herbal
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analysis
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Plant Roots
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chemistry
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Solanaceae
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chemistry
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classification
4.Effects of high glucose exposure on permeability of brain microvascular endothelial cells
Dan LOU ; Yi-jie SHA ; Yi SHUAI ; Qian HUO ; Chen LI ; Ping XIAO ; Gong-hua TAO
Shanghai Journal of Preventive Medicine 2020;32(1):71-
Objective To investigate the permeability of brain microvascular endothelial cells under the condition of high glucose exposure. Methods The bEnd.3 cell line was chosen to detect the value of trans- endothelial electrical resistance (TEER), the activity of alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT).Hence, the characteristics of blood-brain barrier in cell model were identified.The permeability of brain microvascular endothelial cells on high glucose exposure was evaluated by cell morphology, cell viability, intracellular lactate dehydrogenase activity and relative expression of
5.Genetic analysis of a child with atypical Williams-Beuren syndrome presenting as supravalvular aortic stenosis.
Dong WU ; Mengting ZHANG ; Yue GAO ; Xiaodong HUO ; Hai XIAO ; Qian ZHANG ; Bing KANG ; Xin WANG ; Shixiu LIAO
Chinese Journal of Medical Genetics 2020;37(4):475-478
OBJECTIVE:
To explore the genetic basis for a child with supravalvular aortic stenosis.
METHODS:
The child and his parents were subjected to conventional G-banding karyotyping, array comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) analysis.
RESULTS:
No karyotypic abnormality was detected in the child and his parents. aCGH has identified a de novo 278 kb deletion encompassing the ELN gene in 7q11.23, which overlapped with the critical region of Williams-Beuren syndrome (WBS). MLPA has confirmed above findings.
CONCLUSION
The proband was diagnosed with atypical WBS. Deletion of the ELN gene may predispose to supravalvular aortic stenosis in the proband.
Aortic Stenosis, Supravalvular
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genetics
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Child
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Chromosome Banding
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Chromosomes, Human, Pair 7
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genetics
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Comparative Genomic Hybridization
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Gene Deletion
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Genetic Testing
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Humans
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Williams Syndrome
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complications
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genetics
6.NaFeEDTA fortified soy sauce showed higher iron absorption rate in Chinese females.
Jun-Sheng HUO ; Xiao-Guang YANG ; Jian-Hua PIAO ; Jun-Quan GAO ; Hong MIAO ; Bo YU ; Cheng-Qian LU ; Jun-Shi CHEN
Biomedical and Environmental Sciences 2007;20(2):126-130
OBJECTIVENaFeEDTA was considered as a promising iron fortificant for controlling iron deficiency anemia. Soy sauce is a suitable food carrier for iron fortification and is a popular condiment in China. Iron absorption rates of NaFeEDTA and FeSO4 were observed and compared in adult female subjects.
METHODSThe stable isotope tracer method was used in Chinese females consuming a typical Chinese diet. Ten healthy young Chinese women were selected as subjects in the 15-day study. A plant-based diet was used based on the dietary pattern of adult women in the 1992 National Nutrition Survey. Six milligram of 54Fe in 54FeSO4 soy sauce and 3 mg 58Fe in Na58FeEDTA soy sauce were given to the same subjects in two days. Food samples and fecal samples were collected and analyzed.
RESULTSIron absorption rates of NaFeEDTA and FeSO4 were 10.51% +/- 2.83 and 4.73% +/- 2.15 respectively. The 58Fe (NaFeEDTA) absorption was significantly higher than that of 54Fe (FeSO4) (P < 0.01). The iron absorption rate from NaFeEDTA was 1.2 times higher than that from FeSO4 in Chinese adult women consuming a typical Chinese diet.
CONCLUSIONThe higher absorption rate of NaFeEDTA suggested that NaFeEDTA would be a better iron fortificant used in soy sauce for the controlling of iron deficiency anemia in China.
Adolescent ; Adult ; China ; Edetic Acid ; pharmacokinetics ; Female ; Ferric Compounds ; pharmacokinetics ; Ferrous Compounds ; pharmacokinetics ; Food, Fortified ; Humans ; Iron ; pharmacokinetics ; Soy Foods
7.X-ray guided internal urethroplasty with PlasmaKinetic electrodes for urethratresia.
Yan-Xin DONG ; Yun-Cheng QIAN ; Jun-Chang YANG ; Xiao-Kang GAO ; Shuang-Jin HUO ; Dong LI ; Hou-Yong ZHOU
National Journal of Andrology 2009;15(7):636-638
OBJECTIVETo evaluate endourethral surgery for urethratresia under the X-ray guide.
METHODSWe performed transurethral urethroplasty for 11 patients with urethratresia using the PlasmaKinetic electrodes under the guidance of C arm xanthippe.
RESULTSIn the 11 cases, operations were all successful, 9 achieved smooth urination and 2 needed regular urethral dilation.
CONCLUSIONX-ray guided internal urethroplasty with PlasmaKinetic electrodes is a simple and efficient treatment for urethratresia.
Adult ; Aged ; Electrodes ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Urethra ; injuries ; Urethral Obstruction ; surgery ; X-Rays
8.UPLC-TOF/MS based chemical profiling approach to evaluate toxicity-attenuated chemical composition in combination of ginseng and radix aconiti praeparata.
Zeng-Chun MA ; Si-Si ZHOU ; Qian-De LIANG ; Chao HUO ; Yu-Guang WANG ; Hong-Ling TAN ; Cheng-Rong XIAO ; Yue GAO
Acta Pharmaceutica Sinica 2011;46(12):1488-1492
In the present study, an ultra performance liquid chromatography coupled with time-of-fight mass spectrometry (UPLC-TOF/MS) based chemical profiling approach was used to evaluate chemical constitution between co-decoction and mixed decoction of ginseng and Radix Aconiti Praeparata. Two different kinds of decoctions, namely co-decoction of ginseng and Radix Aconiti Praeparata: water extract of mixed two herbs, and mixed decoction of ginseng and Radix Aconiti Praeparata: mixed water extract of each individual herbs, were prepared. Batches of these two kinds of decoction samples were subjected to UPLC-TOF/MS analysis. The datasets of t(R) m/z pairs, ion intensities and sample codes were processed with supervised partial least squared discriminant analysis (OPLS-DA) to holistically compare the difference between these two decoction samples. Significant difference between the two decoction samples was showed in the results of positive ion mode. The contents of hypaconitine and deoxyaconitine decreased, while that of benzoylmesaconine, benzoylhypaconine and dehydrated benzoylmesaconine increased in the samples of co-decoction of ginseng and Radix Aconiti Praeparata. The content of diester-diterpenoid alkaloids decreased, while that of monoester-diterpenoid alkaloids increased, which is probably the basis of toxicity-attenuated action when combined ginseng with Radix Aconiti Praeparata.
Aconitine
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analogs & derivatives
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analysis
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Aconitum
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chemistry
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Alkaloids
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analysis
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Chromatography, High Pressure Liquid
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methods
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Drug Combinations
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Drugs, Chinese Herbal
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chemistry
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Panax
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chemistry
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Plants, Medicinal
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chemistry
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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methods
9.Screen p53 mutations in hepatocellular carcinoma by FASAY: a novel splicing mutation.
Xiao-mo WU ; Jing-geng FU ; Wang-zhong GE ; Jiang-yan ZHU ; Jun-yong WANG ; Wei ZHANG ; Wei QIAN ; Ke-ke HUO
Journal of Zhejiang University. Science. B 2007;8(2):81-87
OBJECTIVETo establish a routine procedure for the detection of p53 mutations in hepatocellular carcinoma (HCC) surgical resections using the FASAY (functional analysis of separated alleles of p53 on yeast) procedure.
METHODSp53 status was analyzed by FASAY and cDNA sequencing in 50 cases of HCC. After the extraction of RNA from the frozen tumor and corresponding normal tissues, reverse transcription RT-PCR was carried out using these samples. The assay can detect mutations of p53 mRNA between codons 67 and 347 by the DNA-binding activity of the protein and reveal them as red colonies.
RESULTSOf the 50 specimens, 29 (58%) were positive (mutant) by FASAY. Sequencing analysis confirmed that all 29 FASAY positive tumors harbored mutations, and that no mutations were detectable in any FASAY negative tumors. In 29 p53 mutations, 22 mutations were point missense mutation, 5 were deletions and 2 were splicing mutations. A novel splice mutation on splice donor of intron 6 was reported, which could produce two different mRNAs, respectively using the nearest upstream and downstream recessive splice donor sites.
CONCLUSIONFASAY is a sensitive method for detecting the various types of p53 mutations in HCC, suggesting that the yeast functional assay for the detection of p53 mutations may be essential for elucidating their clinical significance.
Alternative Splicing ; genetics ; Carcinoma, Hepatocellular ; genetics ; DNA Mutational Analysis ; methods ; Gene Frequency ; Genetic Testing ; Humans ; Liver Neoplasms ; genetics ; Mutation ; Reproducibility of Results ; Sensitivity and Specificity ; Tumor Suppressor Protein p53 ; genetics
10.Quantitative evaluation on the effectiveness of prevention and control measures against pandemic influenza A (H1N1) in Beijing, 2009
Xiao-Li WANG ; Peng YANG ; Zhi-Dong CAO ; Da-Jun ZENG ; Jiang WU ; Yi ZHANG ; Hai-Kun QIAN ; Xiao-Min PENG ; Hui-Jie LIANG ; Xing-Huo PANG ; Ying DENG ; Xiong HE ; Quan-Yi WANG
Chinese Journal of Epidemiology 2010;31(12):1374-1378
Objective To quantitatively evaluate the effectiveness of prevention and control measures against pandemic influenza A (H1N1) in Beijing, 2009 and to provide evidence for developing and adjusting strategies for prevention and control of the disease. Methods Considering the seasonality and the number of vaccination on pandemic influenza A (H1N1) , data regarding pandemic influenza A (H1N1) in Beijing were collected and analyzed. Based on the dynamics of infectious disease transmission, a quantitative model for evaluation of prevention and control measures was developed. Results Both latency and infectious periods of pandemic influenza A (H1N1) were estimated to be 1.82 days and 2.08 days, respectively. The effective reproduction numbers of the three periods were 1.13,1.65 and 0.96, respectively. Thanks to the implementation of a series of measures to prevent and control pandemic influenza A (H1N1), the cumulative number of laboratory-confirmed cases of pandemic influenza A (H1N1) was reduced, making it much smaller than what would have been under the natural situation. Specifically, the program on pandemic (H1N1) 2009 vaccination reduced the cumulative number of laboratory-confirmed cases by 24.08% and postponed the peak time. Conclusion Measures that had been taken during this period, had greatly contributed to the successful prevention and control of pandemic influenza A (H1N1). The 2009 Pandemic (H1N1)vaccination was confirmed to have contributed to the decrease of cumulative number of laboratoryconfirmed cases and postponed the peak arrival time.