The aim of present study was to prepare buccal tablets of fluconazole for oral candidiasis.The dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so ...The aim of present study was to prepare buccal tablets of fluconazole for oral candidiasis.The dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so as to reduce the frequency of administration and to overcome the side effects of systemic treatment.The buccal tablets were prepared by using Carbopol 71G and Noveon AA-1 by direct compression method.Microcry stalline cellulose was used as the filler and its effect was also studied.The prepared dosage forms were evaluated for physicochemical properties,in vitro release studies and mucoadhesive properties using sheep buccal mucosa as a model tissue.Tablets containing 50% of polymers(Carbopol & Noveon) were found to be the best with moderate swelling along with favorable bioadhesion force,residence time and in vitro drug release.The in vitro drug release studies revealed that drug released for 8 h,which in turn may reduce dosing frequency and improved patient compliance in oral candidiasis patients.展开更多
目的运用网络药理学方法研究半夏泻心汤治疗慢性萎缩性胃炎(CAG)的作用机制。方法运用中药系统药理学数据库和分析平台(TCMSP)获取半夏泻心汤化合物及靶标,以口服生物利用度(OB)≥30%和类药性(DL)≥0.18为阈值进行化合物筛选,将靶标输入...目的运用网络药理学方法研究半夏泻心汤治疗慢性萎缩性胃炎(CAG)的作用机制。方法运用中药系统药理学数据库和分析平台(TCMSP)获取半夏泻心汤化合物及靶标,以口服生物利用度(OB)≥30%和类药性(DL)≥0.18为阈值进行化合物筛选,将靶标输入Uniprot获取靶标对应的基因Symbol;从人类基因数据库(Gene Card:The Human Gene Database)获取CAG疾病基因,并筛选出与半夏泻心汤靶标基因的交集基因;运用Cytoscape3.7.1软件绘制"疾病-中药-化合物-交集靶标(基因)"网络图、STRING构建蛋白互作(PPI)网络、利用分子对接技术对关键靶点和化合物的相互作用进行验证。G∶Profiler数据分析平台进行GO富集以及KEGG通路富集分析。结果通过设置OB和DL值筛选得到半夏泻心汤化合物189种,在获得交集基因80个后,剔除不含交集基因(靶标)的化学成分后,最终筛得化合物148种,GO富集分析后共获得符合筛选标准的条目1188条,其中分子功能59条、生物过程1086条、细胞组成43条,KEGG富集分析共获得97条。槲皮素、黄芩素、汉黄芩素、小檗碱等为半夏泻心汤的主要活性成分,STAT3、TNF、AKT1、HSP90AA1、TP53等为主要作用靶标。分子对接结果显示,筛选的化合物和核心靶点HSP90AA1、潜在靶点EGFR之间均能较好的结合,涉及氮化合物的代谢、氧化反应、细胞凋亡等生物过程,调控PI3K-Akt信号通路、IL-17信号通路、胃癌通路、幽门螺旋杆菌感染的上皮细胞通路。结论半夏泻心汤的主要活性成分有槲皮素、黄芩素、汉黄芩素、小檗碱,通过多靶点多通路发挥治疗慢性萎缩性胃炎作用。展开更多
[目的]通过网络药理学及分子对接分析木防己汤治疗慢性心力衰竭(chronic heart failure,CHF)的具体机制并进行验证。[方法]使用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analys...[目的]通过网络药理学及分子对接分析木防己汤治疗慢性心力衰竭(chronic heart failure,CHF)的具体机制并进行验证。[方法]使用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)获取木防己汤的主要有效成分及治疗靶点,同时使用人类基因数据库(Human Gene Database,GeneCards)数据库、药物靶标数据库(Therapeutic Target Database,TTD)、人类孟德尔遗传在线(Online Mendelian Inheritance in Man,OMIM)数据库、药品数据与药物靶点(DrugBank)、遗传药理学与药物基因组学数据库(Pharmacogenetics and Pharmacogenomics Knowledge Base,PharmGkb)等数据库获取CHF的相关基因,并通过Cytoscape 3.9软件构建木防己汤-靶点-CHF网络;对获取的治疗靶点分别进行蛋白互作(protein-protein interaction,PPI)分析、基因本体(gene ontology,GO)富集分析及京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析,最后使用AutoDockVina、PyMol软件对木防己汤治疗CHF主要成分及核心靶点进行分子对接验证。[结果]共获取木防己汤主要有效成分32个,治疗靶点326个,CHF相关基因10693个,木防己汤治疗CHF靶点104个。KEGG分析显示脂质与动脉粥样硬化、肿瘤受体激活、神经活性配体与受体相互作用、阿尔茨海默病、钙信号通路排名靠前。拓扑分析结果显示木防己汤治疗CHF核心靶点为热休克蛋白90α家族A类成员1(heat shock protein 90ɑfamily class A member 1,HSP90AA1)、前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)。分子对接结果显示木防己汤治疗CHF关键靶点与主要活性成分对接良好。[结论]木防己汤治疗CHF具有多靶点、多通路的特点,其治疗机制涉及HSP90AA1、PTGS2等蛋白,本研究为CHF相关生物实验研究及新药开发提供了临床支持及理论参考。展开更多
目的:通过高通量转录组测序和相对定量血清蛋白组学技术筛选肝癌转移相关的关键基因.方法:利用Ion Proton.测序仪比较人肝癌细胞株(Smmc-7721)和正常人肝细胞株(L-02)的差异表达基因,对差异表达基因进行聚类分析、GO功能注释和富集分析...目的:通过高通量转录组测序和相对定量血清蛋白组学技术筛选肝癌转移相关的关键基因.方法:利用Ion Proton.测序仪比较人肝癌细胞株(Smmc-7721)和正常人肝细胞株(L-02)的差异表达基因,对差异表达基因进行聚类分析、GO功能注释和富集分析,获得肝癌细胞转移相关基因;收集10例肝细胞癌(hepatocellular carcinoma,HCC)患者血清及匹配10例正常人血清,通过相对和绝对定量的同位素标记(isobaric tags for relative and absolute quantitation,iTRAQ)联合基质辅助激光解吸电离串联飞行时间质谱(ma t r ixassisted laser desorption/ionization tandemtime of flight mass spectrometry,MALDITOF/MS)检测肝癌与正常对照组血清差异表达蛋白;将两组学结果进行交集分析,确定肝癌转移关键基因,并在76例HCC和癌旁组织中进行免疫组织化学验证.结果:对肝癌细胞及正常肝细胞进行转录组测序分析,共得到肝癌细胞差异表达基因618个,生物信息学分析差异表达基因主要聚集在转移相关、转录因子相关、氧化还原过程等14个分子功能,其中转移相关功能基因所占比例最大,达15.05%(93/618);血清蛋白组学分析共得到69个肝癌血清差异表达蛋白,其中在肝癌组上调33个,下调36个;将转录组测序筛选的与转移功能相关基因与蛋白质组学进行交集分析,发现有3个共同交集的差异因子,其中差异最明显的是肝癌中表达上调的热休克蛋白90 AA1(heat shock protein 90 AA1,HSP90AA1);免疫组织化学验证结果显示,HSP90α表达强阳性在门脉转移和无门脉转移HCC组织中的比例分别为66.7%(16/24)和25%(13/52)(P<0.005),HSP90α在有门脉转移的肝癌组织表达明显增高.结论:利用转录组结合血清蛋白组策略,发现HSP90AA1可能是在肝癌转移重要基因.展开更多
Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevan...Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in HPSCC.Methods:In a preceding investigation,HSP90AA1,a differential gene,was discovered through transcriptome sequencing of HPSCC tissues,considering both the presence and absence of LM.Validation of HSP90AA1 expression was accomplished via qRT-PCR,western-blotting(WB),and immunohistochemistry(IHC),while its prognostic significance was assessed employing Kaplan–Meier survival analysis(KMSA),log-rank test(LR),and Cox’s regression analysis(CRA).Bioinformatics techniques facilitated the prediction and analysis of its plausible mechanisms in LM,further substantiated by in vitro and in vivo experiments utilizing FaDu cell lines.Results:HSP90AA1 is substantially upregulated in HPSCC with LM and is identified as an independent prognostic risk determinant.The down-regulation of HSP90AA1 can achieve inhibition of tumor cell proliferation,migration and invasion.Both in vivo experiments and Bioinformatics exploration hint at promoting LM by Epithelial-mesenchymal transition(EMT),regulated by HSP90AA1.Conclusions:HSP90AA1,by controlling EMT,can foster LM in HPSCC.This finding sets the foundation for delving into new therapeutic targets for HPSCC.展开更多
文摘The aim of present study was to prepare buccal tablets of fluconazole for oral candidiasis.The dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so as to reduce the frequency of administration and to overcome the side effects of systemic treatment.The buccal tablets were prepared by using Carbopol 71G and Noveon AA-1 by direct compression method.Microcry stalline cellulose was used as the filler and its effect was also studied.The prepared dosage forms were evaluated for physicochemical properties,in vitro release studies and mucoadhesive properties using sheep buccal mucosa as a model tissue.Tablets containing 50% of polymers(Carbopol & Noveon) were found to be the best with moderate swelling along with favorable bioadhesion force,residence time and in vitro drug release.The in vitro drug release studies revealed that drug released for 8 h,which in turn may reduce dosing frequency and improved patient compliance in oral candidiasis patients.
文摘目的运用网络药理学方法研究半夏泻心汤治疗慢性萎缩性胃炎(CAG)的作用机制。方法运用中药系统药理学数据库和分析平台(TCMSP)获取半夏泻心汤化合物及靶标,以口服生物利用度(OB)≥30%和类药性(DL)≥0.18为阈值进行化合物筛选,将靶标输入Uniprot获取靶标对应的基因Symbol;从人类基因数据库(Gene Card:The Human Gene Database)获取CAG疾病基因,并筛选出与半夏泻心汤靶标基因的交集基因;运用Cytoscape3.7.1软件绘制"疾病-中药-化合物-交集靶标(基因)"网络图、STRING构建蛋白互作(PPI)网络、利用分子对接技术对关键靶点和化合物的相互作用进行验证。G∶Profiler数据分析平台进行GO富集以及KEGG通路富集分析。结果通过设置OB和DL值筛选得到半夏泻心汤化合物189种,在获得交集基因80个后,剔除不含交集基因(靶标)的化学成分后,最终筛得化合物148种,GO富集分析后共获得符合筛选标准的条目1188条,其中分子功能59条、生物过程1086条、细胞组成43条,KEGG富集分析共获得97条。槲皮素、黄芩素、汉黄芩素、小檗碱等为半夏泻心汤的主要活性成分,STAT3、TNF、AKT1、HSP90AA1、TP53等为主要作用靶标。分子对接结果显示,筛选的化合物和核心靶点HSP90AA1、潜在靶点EGFR之间均能较好的结合,涉及氮化合物的代谢、氧化反应、细胞凋亡等生物过程,调控PI3K-Akt信号通路、IL-17信号通路、胃癌通路、幽门螺旋杆菌感染的上皮细胞通路。结论半夏泻心汤的主要活性成分有槲皮素、黄芩素、汉黄芩素、小檗碱,通过多靶点多通路发挥治疗慢性萎缩性胃炎作用。
文摘[目的]通过网络药理学及分子对接分析木防己汤治疗慢性心力衰竭(chronic heart failure,CHF)的具体机制并进行验证。[方法]使用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)获取木防己汤的主要有效成分及治疗靶点,同时使用人类基因数据库(Human Gene Database,GeneCards)数据库、药物靶标数据库(Therapeutic Target Database,TTD)、人类孟德尔遗传在线(Online Mendelian Inheritance in Man,OMIM)数据库、药品数据与药物靶点(DrugBank)、遗传药理学与药物基因组学数据库(Pharmacogenetics and Pharmacogenomics Knowledge Base,PharmGkb)等数据库获取CHF的相关基因,并通过Cytoscape 3.9软件构建木防己汤-靶点-CHF网络;对获取的治疗靶点分别进行蛋白互作(protein-protein interaction,PPI)分析、基因本体(gene ontology,GO)富集分析及京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析,最后使用AutoDockVina、PyMol软件对木防己汤治疗CHF主要成分及核心靶点进行分子对接验证。[结果]共获取木防己汤主要有效成分32个,治疗靶点326个,CHF相关基因10693个,木防己汤治疗CHF靶点104个。KEGG分析显示脂质与动脉粥样硬化、肿瘤受体激活、神经活性配体与受体相互作用、阿尔茨海默病、钙信号通路排名靠前。拓扑分析结果显示木防己汤治疗CHF核心靶点为热休克蛋白90α家族A类成员1(heat shock protein 90ɑfamily class A member 1,HSP90AA1)、前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)。分子对接结果显示木防己汤治疗CHF关键靶点与主要活性成分对接良好。[结论]木防己汤治疗CHF具有多靶点、多通路的特点,其治疗机制涉及HSP90AA1、PTGS2等蛋白,本研究为CHF相关生物实验研究及新药开发提供了临床支持及理论参考。
文摘目的:通过高通量转录组测序和相对定量血清蛋白组学技术筛选肝癌转移相关的关键基因.方法:利用Ion Proton.测序仪比较人肝癌细胞株(Smmc-7721)和正常人肝细胞株(L-02)的差异表达基因,对差异表达基因进行聚类分析、GO功能注释和富集分析,获得肝癌细胞转移相关基因;收集10例肝细胞癌(hepatocellular carcinoma,HCC)患者血清及匹配10例正常人血清,通过相对和绝对定量的同位素标记(isobaric tags for relative and absolute quantitation,iTRAQ)联合基质辅助激光解吸电离串联飞行时间质谱(ma t r ixassisted laser desorption/ionization tandemtime of flight mass spectrometry,MALDITOF/MS)检测肝癌与正常对照组血清差异表达蛋白;将两组学结果进行交集分析,确定肝癌转移关键基因,并在76例HCC和癌旁组织中进行免疫组织化学验证.结果:对肝癌细胞及正常肝细胞进行转录组测序分析,共得到肝癌细胞差异表达基因618个,生物信息学分析差异表达基因主要聚集在转移相关、转录因子相关、氧化还原过程等14个分子功能,其中转移相关功能基因所占比例最大,达15.05%(93/618);血清蛋白组学分析共得到69个肝癌血清差异表达蛋白,其中在肝癌组上调33个,下调36个;将转录组测序筛选的与转移功能相关基因与蛋白质组学进行交集分析,发现有3个共同交集的差异因子,其中差异最明显的是肝癌中表达上调的热休克蛋白90 AA1(heat shock protein 90 AA1,HSP90AA1);免疫组织化学验证结果显示,HSP90α表达强阳性在门脉转移和无门脉转移HCC组织中的比例分别为66.7%(16/24)和25%(13/52)(P<0.005),HSP90α在有门脉转移的肝癌组织表达明显增高.结论:利用转录组结合血清蛋白组策略,发现HSP90AA1可能是在肝癌转移重要基因.
基金supported by the National Natural Science Foundation of China(Grant No.82173303)Natural Science Foundation of Chongqing,China(Grant No.cstc2021ycjh-bgzxm0149).
文摘Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in HPSCC.Methods:In a preceding investigation,HSP90AA1,a differential gene,was discovered through transcriptome sequencing of HPSCC tissues,considering both the presence and absence of LM.Validation of HSP90AA1 expression was accomplished via qRT-PCR,western-blotting(WB),and immunohistochemistry(IHC),while its prognostic significance was assessed employing Kaplan–Meier survival analysis(KMSA),log-rank test(LR),and Cox’s regression analysis(CRA).Bioinformatics techniques facilitated the prediction and analysis of its plausible mechanisms in LM,further substantiated by in vitro and in vivo experiments utilizing FaDu cell lines.Results:HSP90AA1 is substantially upregulated in HPSCC with LM and is identified as an independent prognostic risk determinant.The down-regulation of HSP90AA1 can achieve inhibition of tumor cell proliferation,migration and invasion.Both in vivo experiments and Bioinformatics exploration hint at promoting LM by Epithelial-mesenchymal transition(EMT),regulated by HSP90AA1.Conclusions:HSP90AA1,by controlling EMT,can foster LM in HPSCC.This finding sets the foundation for delving into new therapeutic targets for HPSCC.
