Background Xinfuli Granule （XG）, a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and t...Background Xinfuli Granule （XG）, a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with dox- orubicin-induced cardiotoxicity. Methods Sprague-Dawley rats were treated with intraperitoneal injection of Doxorubicin （DOX, 2.5 mg/kg per week） for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline （control group） or different dosage of XG （0.675 g/kg per day, 1.35 g/kg per day, and 2.7g/kg per day, respectively） for six weeks. Transtho- racic echocardiography was performed to evaluate the left ventricular fractional shortening （LVFS） and left ventricular ejection fraction （LVEF） before and after the XG treatment and histopathologic changes were also examined. Myocardial cell apoptosis was detected by TUNEL staining. The expression of related genes and proteins were analyzed using immunohistochemical staining. Results Compared to those in the control group, rats in XG treated groups showed significantly improved cardiac function and milder cardiac histopathological changes, lower cardiomyocyte apoptosis index, higher expression of Bcl-2 and lower expression of Bax. Conclusions Administration of XG improves cardiac function and histopathological changes in rats with doxorubicin-induced cardiotoxicity. These effects are associated with inhibition of cardiomyocyte apoptosis, perhaps via regulation of Bcl-2 and Bax protein expression.展开更多
利用GenBank中的数据,通过聚合酶链式反应(polymerase chain reaction,PCR)从人的cDNA文库中克隆得到功能基因TOX(thymocyte selection-associated high mobility group box),运用生物信息学分析其结构特性,并通过逆转录PCR(reverse tra...利用GenBank中的数据,通过聚合酶链式反应(polymerase chain reaction,PCR)从人的cDNA文库中克隆得到功能基因TOX(thymocyte selection-associated high mobility group box),运用生物信息学分析其结构特性,并通过逆转录PCR(reverse transcription PCR,RT-PCR)分析TOX在细胞系中的表达;利用荧光显微镜观察其亚细胞定位情况;使用细胞生长曲线实验和流式细胞术分析TOX对细胞增殖及细胞周期的影响.结果表明:TOX基因定位于人8号染色体q12.1上,全长4 131bp,编码526个氨基酸,该蛋白质分子质量约为57ku,含有9个外显子和8个内含子,其编码蛋白为高迁移率蛋白家族成员,能参与基因调控等生理过程;TOX基因在白血病细胞系Jurkat和Raji中高表达,并定位于细胞核中;对细胞生长曲线绘制及细胞周期分析表明,TOX能够使细胞生长速度加快,且S期细胞比例明显上升.说明TOX参与了细胞增殖调控,有可能研究开发为药物靶标或疾病标志物.展开更多
为了解析与胸腺细胞选择相关的高迁移率族蛋白4(tox high mobility group box family member 4,TOX4)在尼罗罗非鱼(Oreochromis niloticus)响应无乳链球菌(Streptococcus agalactiae)感染过程中的功能,利用聚合酶链式反应(PCR)克隆和鉴...为了解析与胸腺细胞选择相关的高迁移率族蛋白4(tox high mobility group box family member 4,TOX4)在尼罗罗非鱼(Oreochromis niloticus)响应无乳链球菌(Streptococcus agalactiae)感染过程中的功能,利用聚合酶链式反应(PCR)克隆和鉴定尼罗罗非鱼TOX4基因(GenBank登录号:XP003458812)的开放阅读框(open reading frame,ORF)序列,对推导的TOX4氨基酸序列进行生物信息学分析,分析其亚细胞定位特征,以及在尼罗罗非鱼头肾淋巴细胞亚群的分布特征,并利用荧光定量PCR(qRT-PCR)技术分析TOX4基因在健康鱼各组织及响应无乳链球菌感染过程中的表达模式。结果表明:尼罗罗非鱼TOX4基因的ORF全长为2004 bp,编码667个氨基酸,预测TOX4蛋白的相对分子质量为69060,理论等电点为4.69,无信号肽序列及跨膜结构,具有一个HMG保守结构域;亚细胞定位结果显示,TOX4蛋白主要表达于细胞核中;多序列比对及系统进化分析均显示,尼罗罗非鱼与斑马拟丽鱼(Maylandia zebra)TOX4氨基酸序列的同源性最高;qRT-PCR分析显示,TOX4基因在健康尼罗罗非鱼各组织中均有表达,且在血液中表达量最高;单细胞转录组数据分析显示,TOX4基因主要在尼罗罗非鱼非特异性细胞毒性细胞(nonspecific cytotoxic cell,NCC)和巨噬细胞(macrophage,Mφ)中表达;经无乳链球菌感染后,尼罗罗非鱼脑、头肾、肠道和脾脏中TOX4基因的表达量显著上调,并在感染后12 h(脑、头肾、肠道)和48 h(脾脏)达到峰值。研究表明,TOX4可能参与尼罗罗非鱼响应细菌感染的免疫应答过程。展开更多
This work was conducted for radiolabeling of an anticancer antibiotic, i.e. doxorubicin with 61Cu for production of possible tracer used in PET oncology. 61Cu was prepared with natural zinc target and 22 MeV150 μA pr...This work was conducted for radiolabeling of an anticancer antibiotic, i.e. doxorubicin with 61Cu for production of possible tracer used in PET oncology. 61Cu was prepared with natural zinc target and 22 MeV150 μA protons via natZn(p, xn)61Cu reaction with a yield of 123.2 MBq·μA-1·h-1. Optimization reactions were performed for pH, temperature and concentration. Biodistribution of the tracer was studied in normal and fibrosarcoma bearing mice. At the optimized conditions, ITLC showed that radiochemical purity was over 97% with a specific activity of 2.22× 103MBq ·mmol-1·L-1. This was kept unchanged even with presence of human serum as well as room temperature for 5 h. Biodistribution of the tracer in fibrosarcoma bearing mice demonstrated significant tumor uptake after 2 h. This tracer can be used in the detection of various tumors responding to doxorubicin chemotherapy using PET scan and/or determination of tumor therapy response to doxorubicin chemotherapy.展开更多
Doxorubicin （DXR） was entrapped in liposomes coated with themonoclonal antibody,MGb<sub>2</sub>,against human gastric cancer.Negative-stain electronmicroscopy showed the diameter of liposomes was 105.6&#...Doxorubicin （DXR） was entrapped in liposomes coated with themonoclonal antibody,MGb<sub>2</sub>,against human gastric cancer.Negative-stain electronmicroscopy showed the diameter of liposomes was 105.6±21.1nm.The drugentrapment efficiency was 47.6±8.1%.There were about 5667 drug moleculesentrapped and 48 antibody molecules incorporated per liposome.It was confirmedby ELISA and binding assay that the immunoliposomes could bind selectively andcarry their contents to human gastric cancer cell line,BGC-823.Theimmunoliposomes showed specific cytotoxicity to BGC-823,2.3-fold more effectivethan free DXR and 56.7-fold more effective than non-specific liposomes,but only1/25 of toxicity to normal human embryonic lung cell line,SL<sub>7</sub>,as comparedwith free DXR.This study indicates that the immunoliposomes could deliverDXR selectively to the target cells and might be useful in targeting chemotherapyof human gastric cancer.展开更多
基金This study was supported by the grants from the ＂Ten Chinese Medicine for Ten Diseases＂ Project of Beijing,China （SBSY2013-005）, National Science Foundation of China （81541010） and Capital Medical Development Scien- tific Research Fund （2014-4-4035）.
文摘Background Xinfuli Granule （XG）, a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with dox- orubicin-induced cardiotoxicity. Methods Sprague-Dawley rats were treated with intraperitoneal injection of Doxorubicin （DOX, 2.5 mg/kg per week） for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline （control group） or different dosage of XG （0.675 g/kg per day, 1.35 g/kg per day, and 2.7g/kg per day, respectively） for six weeks. Transtho- racic echocardiography was performed to evaluate the left ventricular fractional shortening （LVFS） and left ventricular ejection fraction （LVEF） before and after the XG treatment and histopathologic changes were also examined. Myocardial cell apoptosis was detected by TUNEL staining. The expression of related genes and proteins were analyzed using immunohistochemical staining. Results Compared to those in the control group, rats in XG treated groups showed significantly improved cardiac function and milder cardiac histopathological changes, lower cardiomyocyte apoptosis index, higher expression of Bcl-2 and lower expression of Bax. Conclusions Administration of XG improves cardiac function and histopathological changes in rats with doxorubicin-induced cardiotoxicity. These effects are associated with inhibition of cardiomyocyte apoptosis, perhaps via regulation of Bcl-2 and Bax protein expression.
文摘为了解析与胸腺细胞选择相关的高迁移率族蛋白4(tox high mobility group box family member 4,TOX4)在尼罗罗非鱼(Oreochromis niloticus)响应无乳链球菌(Streptococcus agalactiae)感染过程中的功能,利用聚合酶链式反应(PCR)克隆和鉴定尼罗罗非鱼TOX4基因(GenBank登录号:XP003458812)的开放阅读框(open reading frame,ORF)序列,对推导的TOX4氨基酸序列进行生物信息学分析,分析其亚细胞定位特征,以及在尼罗罗非鱼头肾淋巴细胞亚群的分布特征,并利用荧光定量PCR(qRT-PCR)技术分析TOX4基因在健康鱼各组织及响应无乳链球菌感染过程中的表达模式。结果表明:尼罗罗非鱼TOX4基因的ORF全长为2004 bp,编码667个氨基酸,预测TOX4蛋白的相对分子质量为69060,理论等电点为4.69,无信号肽序列及跨膜结构,具有一个HMG保守结构域;亚细胞定位结果显示,TOX4蛋白主要表达于细胞核中;多序列比对及系统进化分析均显示,尼罗罗非鱼与斑马拟丽鱼(Maylandia zebra)TOX4氨基酸序列的同源性最高;qRT-PCR分析显示,TOX4基因在健康尼罗罗非鱼各组织中均有表达,且在血液中表达量最高;单细胞转录组数据分析显示,TOX4基因主要在尼罗罗非鱼非特异性细胞毒性细胞(nonspecific cytotoxic cell,NCC)和巨噬细胞(macrophage,Mφ)中表达;经无乳链球菌感染后,尼罗罗非鱼脑、头肾、肠道和脾脏中TOX4基因的表达量显著上调,并在感染后12 h(脑、头肾、肠道)和48 h(脾脏)达到峰值。研究表明,TOX4可能参与尼罗罗非鱼响应细菌感染的免疫应答过程。
文摘This work was conducted for radiolabeling of an anticancer antibiotic, i.e. doxorubicin with 61Cu for production of possible tracer used in PET oncology. 61Cu was prepared with natural zinc target and 22 MeV150 μA protons via natZn(p, xn)61Cu reaction with a yield of 123.2 MBq·μA-1·h-1. Optimization reactions were performed for pH, temperature and concentration. Biodistribution of the tracer was studied in normal and fibrosarcoma bearing mice. At the optimized conditions, ITLC showed that radiochemical purity was over 97% with a specific activity of 2.22× 103MBq ·mmol-1·L-1. This was kept unchanged even with presence of human serum as well as room temperature for 5 h. Biodistribution of the tracer in fibrosarcoma bearing mice demonstrated significant tumor uptake after 2 h. This tracer can be used in the detection of various tumors responding to doxorubicin chemotherapy using PET scan and/or determination of tumor therapy response to doxorubicin chemotherapy.
文摘Doxorubicin （DXR） was entrapped in liposomes coated with themonoclonal antibody,MGb<sub>2</sub>,against human gastric cancer.Negative-stain electronmicroscopy showed the diameter of liposomes was 105.6±21.1nm.The drugentrapment efficiency was 47.6±8.1%.There were about 5667 drug moleculesentrapped and 48 antibody molecules incorporated per liposome.It was confirmedby ELISA and binding assay that the immunoliposomes could bind selectively andcarry their contents to human gastric cancer cell line,BGC-823.Theimmunoliposomes showed specific cytotoxicity to BGC-823,2.3-fold more effectivethan free DXR and 56.7-fold more effective than non-specific liposomes,but only1/25 of toxicity to normal human embryonic lung cell line,SL<sub>7</sub>,as comparedwith free DXR.This study indicates that the immunoliposomes could deliverDXR selectively to the target cells and might be useful in targeting chemotherapyof human gastric cancer.
