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Progress in drug delivery system for fibrosis therapy

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Asian Journal of Pharmaceutical Sciences 2021年第1期16卷 47-61页

作者： Lei Xing Xin Chang Lijun Shen Chenglu Zhang yatong fan Chongsu Cho Zhiqi Zhang Hulin Jiang State Key Laboratory of Natural Medicines Department of PharmaceuticsChina Pharmaceutical UniversityNanjing 210009China Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences Seoul National UniversitySeoul 08826Korea Department of General Surgery Shanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200081China

Fibrosis is a necessary process in the progression of chronic disease to cirrhosis or even cancer,which is a serious disease threatening human *** studies have shown that the early treatment of fibrosis is turning point and particularly ***,how to reverse fibrosis has become the focus and research hotspot in recent *** far,the considerable progress has been made in the development of effective anti-fibrosis drugs and targeted drug ***,the existing research results will lay the foundation for more breakthrough delivery systems to achieve better anti-fibrosis ***,this review summaries anti-fibrosis delivery systems focused on three major organ fibrotic diseases such as liver,pulmonary,and renal fibrosis accompanied by the elaboration of relevant pathological mechanisms,which will provide inspiration and guidance for the design of fibrosis drugs and therapeutic systems in the future.

关键词： Fibrotic disease Liver fibrosis Lung fibrosis Kidney fibrosis Anti-fibrosis Drug delivery system

CD24调节Ly6C^hi巨噬细胞和胆管结扎所致肝纤维化的实验研究

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中华微生物学和免疫学杂志 2019年第3期39卷 161-167页

作者：郑鉴项杰张华樊亚童肖俊张学军天津医科大学基础医学院免疫学系天津市细胞和分子免疫重点实验室天津医科大学免疫微环境与疾病省部共建教育部重点实验室300070 山东省立医院西院济南250022 天津医科大学总医院空港医院检验科 300300

目的探讨CD24分子对肝内Ly6C^hi巨噬细胞的调节作用及其对胆管结扎(BDL)诱导的小鼠胆汁淤积型肝纤维化的影响。方法建立小鼠胆管结扎诱导肝纤维化模型,H&E染色观察肝组织形态学变化,天狼星红(Sirius Red)染色观察肝纤维化程度,血清学方... 详细信息

目的探讨CD24分子对肝内Ly6C^hi巨噬细胞的调节作用及其对胆管结扎(BDL)诱导的小鼠胆汁淤积型肝纤维化的影响。方法建立小鼠胆管结扎诱导肝纤维化模型,H&E染色观察肝组织形态学变化,天狼星红(Sirius Red)染色观察肝纤维化程度,血清学方法检测转氨酶改变,real-time PCR检测肝纤维化相关指标以及TGF-β1的mRNA表达,免疫荧光观察肝组织中α-SMA表达,流式细胞术检测肝内巨噬细胞比例和数量变化以及TGF-β1的分泌。结果在BDL诱导的小鼠肝纤维化模型中,CD24敲除(CD24^-/-)小鼠与野生型小鼠(WT)相比,H&E结果显示肝脏炎性浸润增多,汇管区胆管增生更为严重。同时,血清学结果显示谷丙转氨酶(ALT)表达水平明显升高。Sirius Red染色结果表明CD24^-/-小鼠肝纤维化程度明显大于WT小鼠,肝纤维化相关指标的mRNA表达也显著升高。流式细胞术分析发现,肝内巨噬细胞高表达CD24分子,WT小鼠造模后肝内的巨噬细胞比例和数量明显少于CD24^-/-小鼠,进一步分析发现CD24^-/-小鼠的肝内Ly6C^hi巨噬细胞比例明显高于WT小鼠,其Ly6Clo巨噬细胞比例无明显差异。Real-time PCR结果显示,CD24^-/-小鼠肝组织中TGF-β1的表达高于WT小鼠。细胞内染色后进行流式分析发现,造模后CD24^-/-小鼠肝脏中的Ly6C^hi巨噬细胞比WT小鼠分泌更多的TGF-β1。结论CD24分子可能通过调节Ly6C^hi巨噬细胞在肝中的比例和其TGF-β1的分泌,从而减轻了BDL诱导的肝纤维化。

关键词： CD24分子胆管结扎(BDL) 肝纤维化 Ly6C^hi巨噬细胞 TGF-β1

CD24分子调节四氯化碳诱导小鼠肝纤维化的实验研究

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中华微生物学和免疫学杂志 2017年第3期37卷 171-177页

作者：项杰李雄飞海蕾樊亚童郑鉴张华张学军天津医科大学基础医学院免疫学系天津市细胞和分子免疫重点实验室天津医科大学免疫微环境与疾病省部共建教育部重点实验室300070

目的探究CD24分子对四氯化碳（carbon tetrachloride，CCl4）诱导的小鼠肝纤维化发生的调节作用及其细胞学基础。方法建立CCl4诱导的小鼠肝纤维化模型，HE染色观察小鼠肝组织损伤情况，血清学方法检测谷丙转氨酶（ALT）表达水平。Sirius... 详细信息

目的探究CD24分子对四氯化碳（carbon tetrachloride，CCl4）诱导的小鼠肝纤维化发生的调节作用及其细胞学基础。方法建立CCl4诱导的小鼠肝纤维化模型，HE染色观察小鼠肝组织损伤情况，血清学方法检测谷丙转氨酶（ALT）表达水平。Sirius Red染色法检测小鼠肝纤维化的程度，real-time PCR方法检测肝脏组织中α-SMA、Col1a1、TGF-β1及其CD24分子的表达。Western blot检测肝组织中α-SMA、CD24分子蛋白水平的表达。比较野生型（WT）小鼠和CD24基因敲除小鼠（CD24^-/-）注射CCl4后，小鼠肝纤维化的程度。流式细胞术检测模型鼠肝内巨噬细胞的变化。ELISA方法检测M1、M2型巨噬细胞上清中TGF-β1的表达。结果在CCl4诱导的小鼠肝纤维化模型中，肝组织中CD24 mRNA表达水平明显升高，同时，Western blot检测CD24分子也升高。HE染色观察到CD24^-/-小鼠肝中炎性细胞浸润明显多于WT小鼠，血清中ALT表达水平也明显升高。Sirius Red染色结果显示CD24^-/-小鼠肝组织中纤维化严重程度高于WT小鼠，α-SMA、Col1a1等肝纤维化指标都有明显升高。流式细胞术分析表明纤维化发生后，CD24^-/-小鼠的巨噬细胞明显多于WT小鼠。Real-time PCR检测发现CD24^-/-小鼠肝组织中TGF-β1 mRNA的表达明显高于WT小鼠。ELISA检测结果发现CD24^-/-的M2型巨噬细胞上清中，TGF-β1的分泌量多于WT的M2型巨噬细胞上清，而M1型巨噬细胞上清中无明显变化。结论CD24分子减轻了CCl4诱导的小鼠肝纤维化，机制可能通过调节肝内M2型巨噬细胞分泌的促纤维化细胞因子TGF-β1，进而改变肝星状细胞（HSCs）的活性以减轻肝的纤维化。

关键词： CD24分子四氯化碳肝纤维化巨噬细胞 TGF-β1

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6个欧洲李品种果实品质的综合评价

食品与发酵工业 2025年第1期51卷 280-289页

作者：杨芬芬王亚铜李勤勤周嫣然耿文娟张展闳樊国全章世奎新疆农业大学园艺学院新疆维吾尔自治区乌鲁木齐830000 新疆农业科学院轮台果树资源圃新疆维吾尔自治区轮台841600

以6个不同品种欧洲李果实为试材,对其描述性表型、外观数量性表型、不同组织部位内在品质、抗氧化活性等指标进行测定和差异分析,基于相关性分析和主成分分析方法筛选决定品质的关键成分因子,根据得分对6个品种进行排序,为欧洲李品种筛... 详细信息

以6个不同品种欧洲李果实为试材,对其描述性表型、外观数量性表型、不同组织部位内在品质、抗氧化活性等指标进行测定和差异分析,基于相关性分析和主成分分析方法筛选决定品质的关键成分因子,根据得分对6个品种进行排序,为欧洲李品种筛选及开发利用提供一定理论依据。结果表明,不同品种的果实在品质间存在显著差异(P<0.05)。单果鲜重、果实纵径、横径、侧径最大的是‘总统’;不同组织的物质成分分布不同,果皮的可溶性糖含量、维生素C含量、可滴定酸含量高于果肉;‘法兰西’可溶性糖最高;‘塔城酸梅’可滴定酸最高;果皮、果肉中清除DPPH自由基能力最强的分别是‘理查德早生’、‘女神’;清除羟自由基能力最强的是‘塔城酸梅’。维生素C、类黄酮与果实自由基清除效果呈显著相关性。经主成分分析提取出5个特征值大于1的公因子,综合得分排名前3的是‘女神’、‘法兰西’、‘斯泰勒’。分析结果显示果皮色泽、可溶性固形物含量较高的品种是‘法兰西’、‘女神’,适宜鲜食;单果重、硬度、果皮及果肉L*、可食率等第一主成分得分最高的品种是‘女神’、‘斯泰勒’,适宜长途运输销售;抗氧化活性较高的品种是‘法兰西’、‘总统’、‘女神’、‘塔城酸梅’,适宜加工为抗衰功能的保健产品。

关键词：欧洲李果实品质抗氧化活性主成分分析综合评价

Genetic diversity,population structure,and relationships of apricot(Prunus)based on restriction site-associated DNA sequencing

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Horticulture Research 2020年第1期7卷 1928-1940页

作者： Wenwen Li Liqiang Liu Yanan Wang Qiuping Zhang Guoquan fan Shikui Zhang yatong Wang Kang Liao College of Horticulture and Forestry Xinjiang Agricultural UniversityUrumqiXinjiang 830052China Xiongyue National Germplasm Resources Garden of the Liaoning Institute of Pomology XiongyueShenyang 115009China Luntai National Fruit Germplasm Resources Garden of Xinjiang Academy of Agricultural Sciences LuntaiXinjiang 841600China

Single-nucleotide polymorphisms(SNPs)are the most abundant form of genomic polymorphisms and are widely used in population genetics ***,high-throughput sequencing was used to examine the genome-level diversity,population structure,and relationships of apricot,which are important for germplasm conservation and molecular *** site-associated DNA sequencing(RAD-seq)was adopted to sequence 168 Prunus *** distributed in five ecological groups,including 74 accessions of cultivated Prunus armeniaca *** 94 accessions of wild apricots(*** *** Prunus sibirica L.),which generated 417,961 high-quality *** used cluster,genetic structure,and principal component analyses to examine the genetic diversities and genetic relationships of the 168 *** Dzhungar-Ili ecological group accessions showed the highest genetic diversity in terms of private allele number,observed heterozygosity,and nucleotide *** speculate that the Central Asian ecological group accessions were domesticated from the Dzhungar-Ili ecological group *** population structure and gene flow of the North China and European ecological group accessions suggested a genetic background of *** argue that the two groups should be considered hybrid swarms connected to *** by continuous and extensive gene *** originated in Northwest China(Ili Valley),subsequently spread throughout Central Asia,and eventually spread to *** addition,selective sweep signatures in *** during domestication from wild to cultivated apricots,combined with differentially expressed genes,underlie distinct fruit traits,including sugars,aromas,organic acids,and *** study provides substantive and valuable genomic resources that will significantly advance apricot improvement and effective utilization.

关键词： Prunus cultivated structure

Functional and binding studies of gallic acid showing platelet aggregation inhibitory effect as a thrombin inhibitor

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Chinese Herbal Medicines 2022年第2期14卷 303-309页

作者： Yuxin Zhang Xing Wang Binan Lu Yanbin Gao Yanling Zhang yatong Li Hongjuan Niu Lu fan Zongran Pang Yanjiang Qiao Key Laboratory of Ethnomedicine of Ministry of Education School of PharmacyMinzu University of ChinaBeijing 100081China Beijing Key Lab of Traditional Chinese Medicine Collateral Disease Theory Research School of Traditional Chinese MedicineCapital Medical UniversityBeijing 100069China Key Laboratory of TCM-Information Engineer of State Administration of TCM School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 100029China

Objective:This study was devoted to identifying natural thrombin inhibitors from traditional Chinese medicine(TCM)and evaluating its biological activity in vitro and binding ***:A combination strategy containing molecular docking,thrombin inhibition assay,surface plasmon resonance(SPR)and molecular dynamics simulation were applied to verify the study ***:Gallic acid was confirmed as a direct thrombin inhibitor with IC;of 9.07μmol/L and showed a significant inhibitory effect on thrombin induced platelet ***-based binding studies demonstrated that gallic acid interacted with thrombin with a KDvalue of 8.29μmol/*** dynamics and binding free energy analysis revealed that thrombin-gallic acid system attained equilibrium rapidly with very low fluctuations,the calculated binding free energies was-14.61 kcal/***230,Glu232,Ser235,Gly258 and Gly260 were the main amino acid residues responsible for thrombin inhibition by gallic acid,providing a mechanistic basis for further ***:This study proved that gallic acid is a direct thrombin inhibitor with platelet aggregation inhibitory effect,which could provide a basis for the follow-up research and development for novel thrombin inhibitors.

关键词： gallic acid molecular dynamics natural thrombin inhibitor platelet aggregation surface plasmon resonance

The effect of polymorphisms in STX4 on Warfarin dosage in Chinese cardiovascular disease patients

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Journal of Chinese Pharmaceutical Sciences 2016年第9期25卷 683-689页

作者： yatong Zhang Xi Liang fan Dong Zihui Zheng Xin Hu Department of Pharmacy National Center of Gerontology Beijing Hospital Beijing 100730 China Department of Pharmacy Beijing Luhe Hospital Tongzhou Beijing 101149 China

VKORC1 and CYP2C9 have been shown to be strongly associated with Warfarin dosing. However, it is still unclear whether other common genetic variants also contribute to the variation in Warfarin dosing. In the present study, we aim to investigate possible effects of single nucleotide polymorphisms （SNPs） in other candidate genes （CYP4F2, CACNAIC and STX4）, as well as several factors, on stable daily Warfarin dosage （DWMD） in Chinese cardiovascular disease patients. 207 cardiovascular disease patients treated with Warfarin were recruited from Beijing Hospital. DNA was extracted from the blood samples collected one day after Warfarin administration. Nine SNPs （i.e. rs9923231, rs9934438, rs7294, rs1799853, rs1057910, rs4086116, rs2108622, rs216013 and rs10871454 in five genes （i.e. VKORC1, CYP2Cg, CYP4F2, CACNA1C and STX4） were analyzed using ligase detection reactions （LDR）. Univariate analyses and multiple linear regression analyses were performed to analyze the associations between SNPs and other factors （i.e. body surface area （BSA）, Statin medication） and DWMD. Four SNPs （i.e. rs9923231, rs9934438, rs7294 in VKORC1 and rsi0871454 in STX4） had significant statistically effects on DWMD. The multiple linear regression model showed that rs10871454 in STX4, BSA, statin medication, and rs1057910 in CYP2C9 were the significant independent covariates of DWMD. SNP （rs10871454） in STX4 had the strongest effect on Warfarin dosing among the examined candidate genes, indicating that it might serve as a key genetic factor for prediciting the Warfarin maintenance dose in Chinese patients.

关键词： Warfarin STX4 VKORC1 CYP2C9 Statin

Analysis on the Changes in Fruit Quality of ‘Beishan’ Apricots during Storage at Room Temperature

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Agricultural Biotechnology 2022年第5期11卷 112-115页

作者： Guoquan fan yatong WANG Zhanghu TANG Shaopeng WANG Tasiheng·Jieensi Shikui ZHANG Fruits Germplasm Resources Garden Xinjiang Academy of Agricultural SciencesLuntai 841600China College of Horticulture Xinjiang Agricultural UniversityUrumqi 830052China

[Objectives]This study was conducted to understand the changes in fruit quality during storage of local high-quality apricot variety ‘Beishan’ in Xinjiang at room temperature, and to clarify the suitable storage time of the variety. [Methods] Under normal temperature storage conditions, the changes of fruit weight, firmness, soluble solids, titratable acid, soluble sugar, vitamin C and rot rate were observed every day. [Results] With the increase of storage days at room temperature, the fruit weight and firmness of ‘Beishan’ apricots gradually decreased;the contents of titratable acid and vitamin C decreased gradually;and the contents of soluble solids and soluble sugar increased slightly on the 2^(nd) day of storage, and then gradually decreased. The fruit quality began to decline sharply after the 6^(th) day of storage. The fruit began to rot on the 3^(rd) day of storage, and the rot rate was higher than 60% and increased significantly after the 6^(th) day. After the ‘Beishan’ apricots were stored at room temperature until the 6^(th) day, the fruit quality began to decline sharply, and the rot rate exceeded 60%. The suitable storage time at room temperature was about 6 d. [Conclusions] This study provides data support for the research and promotion of the ‘Beishan’ variety.

关键词： Apricot Fruit Storage at room temperature Quality

基于GC-MS和感官评价鉴定南疆杏仁甜苦性状

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食品工业科技 2023年第21期44卷 293-301页

作者：邢雅阁黄雪樊国全王亚铜张红艳郭玲塔里木大学园艺林学学院新疆阿拉尔843300 新疆生产建设兵团塔里木盆地生物资源保护利用重点实验室新疆阿拉尔843300 新疆农业科学院轮台国家果树资源圃新疆巴音郭楞蒙古自治州841600 华中农业大学园艺林学学院湖北武汉430070

为了鉴定杏仁甜苦筛选鉴定指标,为杏仁选育及深加工提供理论依据。本研究以南疆88份杏仁为实验材料,利用高效液相色谱法和气相色谱-质谱联用技术对其苦杏仁苷和糖组分含量进行了测定分析。结果表明,杏仁中均含有苦杏仁苷,其含量在0.945~... 详细信息

为了鉴定杏仁甜苦筛选鉴定指标,为杏仁选育及深加工提供理论依据。本研究以南疆88份杏仁为实验材料,利用高效液相色谱法和气相色谱-质谱联用技术对其苦杏仁苷和糖组分含量进行了测定分析。结果表明,杏仁中均含有苦杏仁苷,其含量在0.945~36.055 mg/g之间,均值为6.236 mg/g,变异系数为118.289%。通过感官评价,其中有19份苦仁,测定苦杏仁苷含量为10.205~36.055 mg/g,均值为19.047 mg/g;69份甜仁,测定其含量为0.945~12.148 mg/g,均值为2.708 mg/g。杏仁中共检测出7种糖,其中蔗糖含量最高,棉子糖次之,山梨醇含量最低。相关性分析表明杏仁甜苦性状与苦杏仁苷和葡萄糖呈极显著正相关性。主成分分析结果表明总糖、甜度值、蔗糖、苦杏仁苷等因子会影响杏仁甜苦。通过聚类分析将样本聚为Ⅳ类,第Ⅰ类杏仁的苦杏仁苷含量极高,第Ⅱ类杏仁的总糖、蔗糖、棉子糖和甜度值高,第Ⅲ类杏仁的苦杏仁苷、总糖、蔗糖等含量中等,第Ⅳ类杏仁的总糖、蔗糖、棉子糖等含量较低。筛选出总糖含量高、苦杏仁苷含量低、味甜的‘赛买提’、‘托乎提库都’和‘大黄杏’等可用于杏仁加工的种质。

关键词：杏仁气相色谱-质谱联用高效液相色谱苦杏仁苷糖组分