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Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl_4-induced liver injury

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Chinese Journal of Natural Medicines 2017年第7期15卷 525-533页

作者： GUO Qing zhang qian-qian CHEN Jia-Qing zhang Wei QIU Hong-Cong zhang Zun-Jian LIU Bu-Ming XU Feng-Guo MOE Key Laboratory of Drug Quality Control and Pharmacovigilance China Pharmaceutical University Nanjing 210009 China State key laboratory of natural medicine China Pharmaceutical University Nanjing 210009 China State Key Laboratory for Quality Research in Chinese Medicines Macao University of Science & Technology Avenida Wai Long Taipa Macao China Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards Nanning 530022 China

Phyllanthus Urinaria L.(PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl_4-induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl_4 and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl_4-induced liver injury were screened out using nonparametric test and Pearson's correlation analysis(OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl_4-induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria.

关键词： Metabolomics Hepatic protection Phyllanthus Urinaria Carbon tetrachloride

Characterization of laccase gene StLAC6 and its involvement in the pathogenicity and peroxisome function in Setosphaeria turcica

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Journal of Integrative Agriculture 2022年第7期21卷 2019-2030页

作者： LIU Ning zhang qian-qian JIA Hui ZHAO Bin ZHU Zi-ping CAO Zhi-yan DONG Jin-gao State Key Laboratory of North China Crop Improvement and Regulation/Key Laboratory of Hebei Province for Plant Physiology and Molecular Pathology Baoding 071001P.R.China College of Plant Protection Hebei Agricultural UniversityBaoding 071001P.R.China College of Life Sciences Hebei Agricultural UniversityBaoding 071001P.R.China Langfang Academy of Agriculture and Forestry Science Langfang 065000P.R.China

Laccases, as a kind of multicopper oxidase, play an important role in pigment synthesis and growth in fungi and are involved in their interactions with host plants. In Setosphaeria turcica, 9 laccase-like multicopper oxidases have been identified, and StLAC2 is involved in the synthesis of the melanin that accumulates in the cell wall. The function of another major laccase gene, StLAC6, was studied here. The knockout of StLAC6 had no effect on the growth, morphology or invasion ability of S. turcica, but the morphology and function of peroxisomes of knockout mutants were abnormal. The knockout of the StLAC6 gene resulted in increased contents of phenolic compounds and melanin and the sensitivity to fungicides increased compared with wild type strains. In the mutants of StLAC6, there is a significant change of the expression levels of other laccase genes. This study provides a new insight into laccase functions and the relationship of the laccase gene family in plant pathogenic fungi.

关键词： Setosphaeria turcica laccase StLAC6 peroxisome fungicides

Genotoxicity and Embryotoxicity Study of Bicyclol Methyl Ether, Main Impurity in Bicyclol

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Chinese Journal of Integrative Medicine 2019年第10期25卷 743-749页

作者： zhang qian-qian LI qiang DONG Lin LI Wan-fang LI Chao WANG Ai-ping WEI Jin-feng JIN Hong-tao New Drug Safety Evaluation Center Institute of Materia Medica Chinese Academy of Medical Sciences Beijing (100050) China Beijing Union Pharm aceutical Factory Beijing (100026) China Beijing Union-Genious Pharmaceutical Technology Ltd. Beijing (100176) China

Objective: To assess the genotoxicity and embryotoxicity of bicyclol methyl ether(BME), the main impurity in bicyclol. Methods: Five concentrations of BME(0.5, 5, 50, 500 and 5000 μg/plate) were used in the Ames test to detect gene mutation. In the chromosome aberration test, Chinese hamster lung cells were used to detect chromosomal aberration of BME(15, 30, 60, 120 μg/m L) with or without S9 mixture. Embryotoxicity test was also conducted to determine any embryotoxicity of BME(7.5, 22.5, 67.5 μg/L) using zebrafish embryos. Results: No significant differences were observed in the Ames test and the chromosome aberration test in the BME groups compared with the vehicle control group. The zebrafish embryos toxicity test also showed no embryo development toxicity of BME, including hatching rate, body length, pericardial area and yolk sac area. Conclusions: Bicyclol methyl ether has no genotoxicity in vitro and embryotoxicity in zebrafish embryos, and the impurity in bicyclol is qualified.

关键词： bicyclol methyl ether genotoxicity embryotoxicity Ames test chromosome aberration test zebrafish

GKK1032B from endophytic Penicillium citrinum induces the apoptosis of human osteosarcoma MG63 cells through caspase pathway activation

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Chinese Journal of Natural Medicines 2022年第1期20卷 67-73页

作者： LIU Na SONG Mei-Na zhang qian-qian WU Cong ZHU Kong-Kai SUN Yu-Lin LI Meng-Ru YANG Feng-Ying FENG Run-Liang zhang Yu-Ying zhang Hua School of Biological Science and Technology University of JinanJinan 250022China

Chemical investigation of the culture extract of an endophytic Penicillium citrinum from Dendrobium officinale,afforded nine citrinin derivatives(1–9)and one peptide-polyketide hybrid GKK1032B(10).The structures of these compounds were determined by spectroscopic *** absolute configurations of 1 and 2 were determined for the first time by calculation of electronic circular dichroism(ECD)*** them,GKK1032B(10)showed significant cytotoxicity against human osteosarcoma cell line MG63 with an IC50 value of 3.49μmol·L–1,and a primary mechanistic study revealed that it induced the apoptosis of MG63 cells via caspase pathway activation.

关键词： Penicillium citrinum Endophytic GKK1032B Anti-proliferation Apoptosis

Determination of the Number of SSR Alleles Necessary for the Analysis of Genetic Relationships Between Maize Inbred Lines

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Agricultural Sciences in China 2010年第12期9卷 1713-1725页

作者： WU Cheng-lai, LI Sheng-fu, DONG Bing-xue, zhang qian-qian and zhang Chun-qing State Key Laboratory of Crop Biology/College of Agriculture, Shandong Agricultural University, Tai’an 271018, P.R.China State Key Laboratory of Crop Biology/College of Agriculture Shandong Agricultural University Tai'an 271018 P.R.China

The amount of molecular marker information has considerable impact on the results of studies of crop germplasm genetic relationships in crop. The number of alleles required to reveal genetic relationship in maize inbred lines is a theoretical issue that needs to be addressed. In this study, 112 pairs of SSR （simple sequence repeat） primers and 97 maize inbred lines were selected to study the relationship between the number of inbred lines and the number of SSR primers and alleles required for a stable cluster. The results showed that the number of SSR primers is not tightly associated with the stability of the cluster analysis results, while an increase in the number of alleles can significantly improve the stability of cluster analysis results. The number of inbred lines （X） is significantly associated with the number of alleles required for stable cluster analysis （Y）, and the regression equation is Y- 600.8xe（-15.9/x）. This equation can be used to calculate the number of SSR alleles required for a genetic relationship study of maize inbred lines. These results provide a reference for determining of SSR alleles number in genetic relationship analysis of maize inbred line and other crop germplasm.

关键词： maize inbred line SSR number of alleles genetic relationship

Effects of insulin-like growth factor binding protein-related protein 1 in mice with hepatic fibrosis induced by thioacetamide

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Chinese Medical Journal 2010年第18期123卷 2521-2526页

作者： LIU Li-xin zhang Hai-yan zhang qian-qian GUO Xiao-hong Experimental Center of Science and Research of the First Teaching Hospital of Shanxi Medical University Institute of Liver Disease and Key Laboratory of Cell Physiology Provincial Department of the Ministry of Education of Shanxi Medical University Taiyuan Shanxi 030001 China

Background Insulin-like growth factor binding protein-related protein 1 （IGFBPrP1） can activate hepatic stellate cells and increase extracellular matrix （ECM） in vitro. However, the effects of IGFBPrP1 in mice with hepatic fibrosis, and the mechanisms of these effects, are currently unknown. We aim to address these issues in this study. Methods Intraperitoneal injection of thioacetamide （TAA） is a classic method for establishing a mouse model of hepatic fibrosis. Using this model, we administered anti-IGFBPrP1 antibody, again via intraperitoneal injection. The morphological changes of liver fibrosis were observed with both HE and Masson stainning. The immunohistochemical assays and Western blotting were used to measure changes in IGFBPrP1, a-smooth muscle actin （a-SMA） and ECM in liver tissues, and the expression of transforming growth factor-β1 （TGF-β1） and Smad3. Data were statistically analyzed using one-way analysis of variance （ANOVA）, the SNK-q test for inter-group differences. Results The Masson staining analysis showed that compared with normal control group, content of collagen fiber in TAA5w group was significantly increased （P 〈0.01）, and it was significantly decreased in TAA5w/alGFBPrP1 group compared with in TAA5w group （P 〈0.01）. The expression of hepatic IGFBPrP1, a-SMA, TGF-β1, Smad3, collagen 1 and fibronectin （FN） was significantly up-regulated in the TAA5w group （P 〈0.01）. Anti-IGFBPrP1 treatment reversed these changes （P 〈0.01）. Conclusions IGFBPrP1 plays an important role in the development of hepatic fibrosis. Anti-IGFBPrP1 prevents fibrosis in mice by suppressing the activation of hepatic stellate cells, inhibiting the synthesis of major components of the ECM （namely, collagen I and FN）. The mechanism for this suppression of fibrosis is associated with the TGF-β1/Smad3 signaling pathways.

关键词： insulin-like growth factor binding protein-related protein 1 hepatic fibrosis extracellular matrix Smad3 protein transforming growth factor beta 1

Expression of surface markers on peripheral CD4＋CD25^high T cells in patients with atopic asthma： role of inhaled corticosteroid

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Chinese Medical Journal 2008年第3期 205-212页

作者： zhang qian qian Fen-hong LIU Hua ZHOU Lin-fu HUANG Mao zhang Xi-long YIN Kai-sheng Department of Respiratory Medicine First Affiliated HospitalNanjing.Medical University Nanjing Jiangsu 210029 China

Background CD4^＋CD25^＋ regulatory T cells （Tregs） mediate immune suppression through cell-cell contact with surface molecules, particularly cytotoxic T lymphocyte-associated antigen 4 （CTLA-4）, glucocorticoid-induced tumor necrosis factor receptor family-related protein （GITR）, and transforming growth factor β （TGF-β）, but little is known about the exact role of Tregs in the pathogenesis of asthma. This study sought to characterize the expression of surface markers on peripheral blood mononuclear cells-derived Tregs in patients with atopic asthma and healthy subjects, and to investigate the effect of inhaled corticosteroid on them. Methods The expression of surface molecules on CD4^＋CD25^high Tregs was detected by flow cytometry. The effect of inhaled corticosteroid on expression of the surface molecules on Tregs was determined in vivo and in vitro. Total serum immunoglobulin E （IgE） and high-sensitivity C-reactive protein were measured by enzyme linked immunosorbent assay and latex enhanced immunoturbidimetric assay, respectively. Results Equivalent numbers of peripheral Tregs were found in patients with atopic asthma （stable and acute） and healthy subjects. Tregs preferentially expressed CTLA-4, GITR, toll-like receptor 4 （TLR4）, latency-associated peptide （LAP/FGF-β1）, and forkhead box P3 （FOXP3）. Patients with acute asthma had decreased numbers of CD4^＋CD25^highLAP^＋ T cells compared to healthy subjects and stable asthmatics. Inhaled corticosteroid enhanced the percentage of Tregs expressing LAP in vivo and in vitro dose-dependently. Furthermore, the percentages of Tregs expressing LAP were negatively correlated with total serum IgE levels and severity of asthma, but positively correlated with forced expiratory volume in one second percentage of the predicted value in patients with asthma. Conclusions The results suggest that membrane-bound TGF-β1 is a potential candidate for predicting the severity of asthma, and may contribute to the sustained remission of

关键词： asthma atopy glucocorticoids regulatory T cells transforming growth factor β

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基于高光谱的牛奶中真蛋白质含量反演

光谱学与光谱分析 2015年第12期35卷 3436-3439页

作者：张倩倩谭琨江苏省资源环境信息工程重点实验室(中国矿业大学) 江苏徐州221116

牛奶蛋白质的分析和监测是奶制品行业中不可或缺的环节利用可见光/近红外反射光谱（350~2 500nm）进行纯牛奶中真蛋白质含量的快速定量反演。分别通过ASD地物光谱仪和CEM真蛋白质测定仪采集牛奶样本的反射光谱数据以及蛋白质含量数据,... 详细信息

牛奶蛋白质的分析和监测是奶制品行业中不可或缺的环节利用可见光/近红外反射光谱（350~2 500nm）进行纯牛奶中真蛋白质含量的快速定量反演。分别通过ASD地物光谱仪和CEM真蛋白质测定仪采集牛奶样本的反射光谱数据以及蛋白质含量数据,对比分析不同的光谱预处理方法和波段筛选方法,得到特征波段,最后利用主成分回归（PCR）和最小二乘支持向量机（LS-SVM）模型建立牛奶反射光谱和蛋白质含量之间的定量校正模型,并对其预测能力进行比较,从而确定最优的牛奶中真蛋白质含量反演模型。实验结果证明：（1）比较不同光谱预处理方法,发现多元散射校正与二阶微分联合使用效果较好;（2）相对于全光谱建模,适当的特征变量优选有助于提高建模精度,缩短建模时间;（3）PCR的验证集决定系数R2P为0.952 2,验证集均方根误差RMSEP为0.048 7,而LS-SVM的R2P为0.958 0,RMSEP为0.048 2,其预测精度要优于PCR。研究表明,可见光/近红外高光谱反射率数据可以为牛奶真蛋白质含量的检测提供一种快速、无损的新方法。

关键词：高光谱牛奶蛋白质定量反演模型

基于卫星和地面观测的2013年以来我国臭氧时空分布及变化特征

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环境科学 2019年第3期40卷 1132-1142页

作者：张倩倩张兴赢国家卫星气象中心北京100081

采用卫星和地面观测臭氧(O_3)浓度,分析2013年以来我国O_3的时空分布和年际变化特征.卫星观测对流层O_3总量和地面观测O_3浓度分布相互印证,我国高浓度O_3主要分布在东部人口密集、经济发达的区域,并且呈现夏季高、冬季低的季节分布趋势... 详细信息

采用卫星和地面观测臭氧(O_3)浓度,分析2013年以来我国O_3的时空分布和年际变化特征.卫星观测对流层O_3总量和地面观测O_3浓度分布相互印证,我国高浓度O_3主要分布在东部人口密集、经济发达的区域,并且呈现夏季高、冬季低的季节分布趋势. 4个重点关注城市(北京、上海、广州、成都) O_3日变化均呈现单峰分布,最高值在每日15:00～16:00.统计分析发现,4个城市除上海市之外,其他3个城市O_3浓度在周末和工作日没有显著差别,表明O_3的"周末效应"减弱. 2013年4月～2018年6月,我国地面观测O_3浓度呈现明显上升趋势. 2014～2017年,北京、上海和成都市近地面O_3浓度分别以2. 36、3. 3和3. 6μg·(m^3·a)^(-1)的速度显著上升. 4个城市2014～2017年O_3超标天数占比分别为17. 2%(北京)、10. 7%(上海)、8. 8%(广州)和11. 2%(成都),北京市O_3超标天数最多、超标期间O_3浓度最高,O_3污染最为严重.

关键词：臭氧中国卫星观测地面观测时空分布变化趋势