BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.Th...BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.展开更多
为研究湿地植物能源化利用潜力,采用全自动甲烷潜力测试系统对不同温度下三种湿地植物厌氧发酵产甲烷特性进行评价,并对产甲烷过程及发酵产物稳定性进行模拟和分析。结果表明:在30 d发酵周期内,中温(37℃)下三种湿地植物巨菌草、狐尾藻...为研究湿地植物能源化利用潜力,采用全自动甲烷潜力测试系统对不同温度下三种湿地植物厌氧发酵产甲烷特性进行评价,并对产甲烷过程及发酵产物稳定性进行模拟和分析。结果表明:在30 d发酵周期内,中温(37℃)下三种湿地植物巨菌草、狐尾藻和水葫芦累积甲烷产量分别达166.5、159.4、236.9 m L·g^(-1)VS,分别比常温(25℃)提高了29.6%、18.3%和39.9%(P<0.01),且中温发酵产气速度更快,发酵周期更短,挥发性固体(VS)去除率更高;采用热重-示差扫描量热法(TG-DSC)对发酵产物稳定性进行分析,TG曲线呈现三个明显失重过程(100℃,250~350℃及400~600℃),全发酵周期总失重率逐渐降低,DSC曲线有两个明显的放热峰,低温区(300℃)放热强度逐渐降低,高温区(400~550℃)狐尾藻峰强度逐渐降低,巨菌草和水葫芦逐渐增加,且峰值右移,表明有机物逐步降解,发酵产物稳定性增加;采用Cheynoweth方程对巨菌草、狐尾藻和水葫芦中温发酵产气过程进行拟合,模型相关系数均大于0.95,产气预测值和实测值差异比分别为1.98%、0.82%和0.32%(P>0.05)。研究表明厌氧发酵制甲烷是湿地植物资源化利用的有效途径,有利于解决人工湿地技术二次污染问题。展开更多
基金National Key Research and Development Program of China,No.2021YFC2701704the National Clinical Medical Research Center for Geriatric Diseases,"Multicenter RCT"Research Project,No.NCRCG-PLAGH-20230010the Military Logistics Independent Research Project,No.2022HQZZ06.
文摘BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.
文摘为研究湿地植物能源化利用潜力,采用全自动甲烷潜力测试系统对不同温度下三种湿地植物厌氧发酵产甲烷特性进行评价,并对产甲烷过程及发酵产物稳定性进行模拟和分析。结果表明:在30 d发酵周期内,中温(37℃)下三种湿地植物巨菌草、狐尾藻和水葫芦累积甲烷产量分别达166.5、159.4、236.9 m L·g^(-1)VS,分别比常温(25℃)提高了29.6%、18.3%和39.9%(P<0.01),且中温发酵产气速度更快,发酵周期更短,挥发性固体(VS)去除率更高;采用热重-示差扫描量热法(TG-DSC)对发酵产物稳定性进行分析,TG曲线呈现三个明显失重过程(100℃,250~350℃及400~600℃),全发酵周期总失重率逐渐降低,DSC曲线有两个明显的放热峰,低温区(300℃)放热强度逐渐降低,高温区(400~550℃)狐尾藻峰强度逐渐降低,巨菌草和水葫芦逐渐增加,且峰值右移,表明有机物逐步降解,发酵产物稳定性增加;采用Cheynoweth方程对巨菌草、狐尾藻和水葫芦中温发酵产气过程进行拟合,模型相关系数均大于0.95,产气预测值和实测值差异比分别为1.98%、0.82%和0.32%(P>0.05)。研究表明厌氧发酵制甲烷是湿地植物资源化利用的有效途径,有利于解决人工湿地技术二次污染问题。
