溶质载体家族25成员21(solute carrier 25 member 21,SLC25A21)是氧代二羧酸盐载体,其主要功能是通过反向交换机制将胞浆内的2-氧代己二酸转运至线粒体。前期研究发现,在过表达SLC25A21的3T3-L1细胞中葡萄糖消耗能力显著增加。为进一步...溶质载体家族25成员21(solute carrier 25 member 21,SLC25A21)是氧代二羧酸盐载体,其主要功能是通过反向交换机制将胞浆内的2-氧代己二酸转运至线粒体。前期研究发现,在过表达SLC25A21的3T3-L1细胞中葡萄糖消耗能力显著增加。为进一步挖掘SLC25A21下游关键代谢基因,本研究在3T3-L1细胞中上调SLC25A21表达,利用高通量测序结合生物信息学分析获得差异表达基因,并通过实时荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction,qRT-PCR)验证关键基因表达。结果显示:(1)过表达SLC25A21的脂肪细胞中有26个上调基因,66个下调基因;(2)基因本体论(gene ontology,GO)分析表明,差异表达基因的生物学功能主要涉及脂质合成和代谢过程;京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)和基因集富集分析(gene set enrichment analysis,GSEA)表明,差异表达基因主要富集在鞘脂代谢、胰岛素和胰高血糖素样肽1分泌和合成等信号通路;(3)CytoHubba筛选出GRB2、SOS1、SHC1、CBL、HRAS、SOS2、EGFR、MET、PLCG2和KRAS等10个评分最高的关键基因,主要参与了细胞的糖、脂代谢过程;(4)在脂肪细胞中过表达SLC25A21,qRT-PCR验证结果表明除KRAS表达无明显变化外,其余基因的mRNA表达水平均出现相应的增高。本研究结果将为今后深入研究SLC25A21在糖、脂代谢过程中的作用及机制提供理论依据。展开更多
The research on discovery and development of new treatments for cutaneous leishmaniasis has been declared as priority. Using bioinformatics approaches, this study aimed to identify antileishmanial activity in drugs th...The research on discovery and development of new treatments for cutaneous leishmaniasis has been declared as priority. Using bioinformatics approaches, this study aimed to identify antileishmanial activity in drugs that are currently used as anti-inflammatory and wound healing by such anti-Leishmania activity was validated by in vitro and in vivo assays. In silico analysis identified 153 compounds from which 87 were selected by data mining of DrugBank database, 22 and 44 were detected by PASS （http：//pass.cribi.unipd.it） and BLAST （http：//blast.ncbi.nlm.nih. gov/） alignment, respectively. The majority of identified drugs are used as skin protector, anti-acne, anti-ulcerative （wound healer） or anti-inflammatory and few of them had specific antileishmanial activity. The efficacy as antileishmanial was validated in vitro in 12/23 tested compounds and in all seven compounds that were evaluated in in vivo assays. Notably, this is the first report of antileishmanial activity for adapalene. In conclusion, bioinformatics tools not only can help to reduce time and cost of the drug discovery process but also may increase the chance that candidates identified in silico which have a validated antileishmanial activity by combining different biological properties.展开更多
文摘溶质载体家族25成员21(solute carrier 25 member 21,SLC25A21)是氧代二羧酸盐载体,其主要功能是通过反向交换机制将胞浆内的2-氧代己二酸转运至线粒体。前期研究发现,在过表达SLC25A21的3T3-L1细胞中葡萄糖消耗能力显著增加。为进一步挖掘SLC25A21下游关键代谢基因,本研究在3T3-L1细胞中上调SLC25A21表达,利用高通量测序结合生物信息学分析获得差异表达基因,并通过实时荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction,qRT-PCR)验证关键基因表达。结果显示:(1)过表达SLC25A21的脂肪细胞中有26个上调基因,66个下调基因;(2)基因本体论(gene ontology,GO)分析表明,差异表达基因的生物学功能主要涉及脂质合成和代谢过程;京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)和基因集富集分析(gene set enrichment analysis,GSEA)表明,差异表达基因主要富集在鞘脂代谢、胰岛素和胰高血糖素样肽1分泌和合成等信号通路;(3)CytoHubba筛选出GRB2、SOS1、SHC1、CBL、HRAS、SOS2、EGFR、MET、PLCG2和KRAS等10个评分最高的关键基因,主要参与了细胞的糖、脂代谢过程;(4)在脂肪细胞中过表达SLC25A21,qRT-PCR验证结果表明除KRAS表达无明显变化外,其余基因的mRNA表达水平均出现相应的增高。本研究结果将为今后深入研究SLC25A21在糖、脂代谢过程中的作用及机制提供理论依据。
文摘The research on discovery and development of new treatments for cutaneous leishmaniasis has been declared as priority. Using bioinformatics approaches, this study aimed to identify antileishmanial activity in drugs that are currently used as anti-inflammatory and wound healing by such anti-Leishmania activity was validated by in vitro and in vivo assays. In silico analysis identified 153 compounds from which 87 were selected by data mining of DrugBank database, 22 and 44 were detected by PASS （http：//pass.cribi.unipd.it） and BLAST （http：//blast.ncbi.nlm.nih. gov/） alignment, respectively. The majority of identified drugs are used as skin protector, anti-acne, anti-ulcerative （wound healer） or anti-inflammatory and few of them had specific antileishmanial activity. The efficacy as antileishmanial was validated in vitro in 12/23 tested compounds and in all seven compounds that were evaluated in in vivo assays. Notably, this is the first report of antileishmanial activity for adapalene. In conclusion, bioinformatics tools not only can help to reduce time and cost of the drug discovery process but also may increase the chance that candidates identified in silico which have a validated antileishmanial activity by combining different biological properties.
