<i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;"> is an emerging ubiquitous and opportunistic pathogen that cur...<i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;"> is an emerging ubiquitous and opportunistic pathogen that currently contaminates a wide spectrum of foods including powdered milk and poses a lethal threat to neonates, the elderly and persons with immune deficiencies. They cause life threatening neonatal meningitis, septicemia, and necrotizing enterocolitis. A total of 360 samples of powdered infant formula were collected from postnatal hospital attendees reconstituting the PIF for their children in the North Central region of Nigeria where cases of infant mortality </span><span style="font-family:Verdana;">are </span><span style="font-family:""><span style="font-family:Verdana;">very high and presenting as enterocolitis and diarrhea. Pre-enriched samples were cultured in chromogenic </span><i><span style="font-family:Verdana;">Cronobacter</span></i><span style="font-family:Verdana;"> broth and were then further sub-cultured into a chromogenic </span><i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;"> agar. They were positive, exhibiting yellowish cultures typical of </span><i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;">. Biochemical tests of the isolates were also carried out and indicated the presence of </span><i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;">. The isolates were then characterized molecularly using specie specific PCR detection of </span><i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;">. The targeted genes of interest were </span><i><span style="font-family:Verdana;">ompA</span></i><span style="font-family:Verdana;"> gene and </span><i><span style="font-family:Verdana;">CPA</span></i><span style="font-family:Verdana;"> gene. The isolates tested showed bands for </span><i><span style="font-family:Verdana;">ompA</span></i><span style="font-family:Verdana;"> gene on electrophoresis imager and were confirmed as </span><i><span style="font-family:Verdana;">Cronobacter sakazakii.</span></i><span style="font-family:Verdana;"> In Nigeria, majority of infants are still fed with PIF. There is no existing data on the detection of </span><i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;"> previously reported in the North central region of Nigeria hence the need to carry out the present study. The result of the study demonstrated the need for effective prevention and control measures as contamination of PIF with </span><i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;"> constituted potential public health risk to neonates and infants.展开更多
目的探究人偏肺病毒感染的发病机制,并基于逆向网络药理学思维对其进行中药组方预测。方法于Genecards数据库和OMIM数据库中获取人偏肺病毒的靶点,将所得靶点导入STRING数据库构建蛋白互作网络,利用Cytoscape 3.9.0软件结合R软件获得关...目的探究人偏肺病毒感染的发病机制,并基于逆向网络药理学思维对其进行中药组方预测。方法于Genecards数据库和OMIM数据库中获取人偏肺病毒的靶点,将所得靶点导入STRING数据库构建蛋白互作网络,利用Cytoscape 3.9.0软件结合R软件获得关键靶点。根据GO和KEGG富集分析明确其发病机制与通路。根据度值选取核心靶点,通过Uniprot数据库将核心靶点转换后于traditional Chinese medicine SP数据库逆向收集中药成分及中药。使用Cytoscape 3.9.0软件构建关键靶点-有效成分-中药网络关系图。利用STBYL-2.0软件将核心靶点与核心成分进行分子对接验证,最后确定度值较高中药并分析整理其性、味、归经。结果共获取人偏肺病毒靶点209个,根据度值得到26个关键靶点。GO富集分析主要得出1866个条目,KEGG富集分析显示88条信号通路。根据度值选取的8个核心靶点于traditional Chinese medicine SP数据库中共匹配到29种入血成分及298种中药。将8个核心靶点蛋白与度值较高的4种核心成分进行分子对接验证,结果稳定且良好。整理度值≥10的中药共69种,主要为苦参、连翘、余甘子、半枝莲、木蝴蝶、银杏叶等,以寒性药、苦味药居多,其次为温性药、辛味药,并且肝、肺二经居多。结论运用逆向网络药理学思维及分子对接技术对人偏肺病毒进行靶点、通路、成分和中药预测,为临床治疗及研究提供新思路和理论依据。展开更多
OBJECTIVE:To evaluate the efficacy of Renshen Sanqi Chuanxiong formula(RSCF)for preventing vascular aging,and to investigate the possible molecular mechanism underlying the actions of RSCF.METHODS:Potentially active c...OBJECTIVE:To evaluate the efficacy of Renshen Sanqi Chuanxiong formula(RSCF)for preventing vascular aging,and to investigate the possible molecular mechanism underlying the actions of RSCF.METHODS:Potentially active components and their relatively direct targets were identified by combining drug-likeness(DL)screening using a target identification process.Vascular aging-associated targets for RSCF were obtained by selecting common genes not only from potential targets but also from human vascular aging-associated genes.Cytoscape 3.2.1 software was employed to visualize the complex compound-target and target-function networks.Biological process and molecular function were assessed,and the Kyoto Encyclopedia of Genes and Genomes and pathway enrichment analyses were performed using Clue GO.Pathways directly associated with vascular aging were integrated into a"vascular aging-related"pathway.RESULTS:Altogether,122 potentially active components of RSCF were identified through DL screening,and their corresponding 692 direct targets were retrieved via target prediction and identification.We identified 49 vascular aging-associated targets for RSCF by overlapping the 692 potential targets with 146 human vascular aging-associated genes.The results from the compound-target network indicated that most components acted on common targets and displayed synergistic action,which showed that the magnifying effects of RSCF were based on these common targets.The target-function network revealed that each target was involved in multiple function modules,suggesting that RSCF was multi-functional during treatment of vascular aging.The results of the Clue GO analysis indicated that most of the targets were associated with the hypoxia-inducible factor 1(HIF-1)signaling pathway.The results from the pathway analysis also indicated that an integrative vascular aging-related pathway mainly included an angiogenesis regulation module,cell-survival module,and oxidative stress-resistance module.CONCLUSION:Our results suggested that many components act synergistically on common targets to delay vascular aging,and each target is involved in multiple functional modules.The Clue GO analysis indicated that most of the targets were connected to the HIF-1 signaling pathway,FOXO signaling pathway,and thyroid hormone signaling pathway.展开更多
In 1805, Thomas Young was the first to propose an equation(Young's equation) to predict the value of the equilibrium contact angle of a liquid on a solid. On the basis of our predecessors, we further clarify that ...In 1805, Thomas Young was the first to propose an equation(Young's equation) to predict the value of the equilibrium contact angle of a liquid on a solid. On the basis of our predecessors, we further clarify that the contact angle in Young's equation refers to the super-nano contact angle. Whether the equation is applicable to nanoscale systems remains an open question. Zhu et al. [College Phys. 4 7(1985)] obtained the most simple and convenient approximate formula, known as the Zhu–Qian approximate formula of Young's equation. Here, using molecular dynamics simulation, we test its applicability for nanodrops. Molecular dynamics simulations are performed on argon liquid cylinders placed on a solid surface under a temperature of 90 K, using Lennard–Jones potentials for the interaction between liquid molecules and between a liquid molecule and a solid molecule with the variable coefficient of strength a. Eight values of a between 0.650 and 0.825 are used. By comparison of the super-nano contact angles obtained from molecular dynamics simulation and the Zhu–Qian approximate formula of Young's equation, we find that it is qualitatively applicable for nanoscale systems.展开更多
目的基于网络药理学方法研究连芩解毒方的免疫调节作用机制。方法通过中药系统药理学数据库与分析平台(Troditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)和GeneCards数据库,分别获取连芩解毒...目的基于网络药理学方法研究连芩解毒方的免疫调节作用机制。方法通过中药系统药理学数据库与分析平台(Troditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)和GeneCards数据库,分别获取连芩解毒方的活性成分及其潜在靶点、免疫调节相关靶点,取交集靶点进行分析。构建蛋白互作(protein-protein interaction,PPI)网络和化合物-靶点网络,筛选关键活性成分和核心作用靶点。采用分子对接技术验证关键活性成分与核心靶点的结合活性,并利用DAVID(The Database for Annotation,Visualization,and Integrated Discovery)数据库对交集靶点进行基因本体论(Gene Ontology,GO)功能及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。结果连芩解毒方共有143个成分和164个靶点,其中有130个成分、79个靶点与免疫调节有关,占比分别为90.91%和48.17%;其中关键化合物13个,核心靶基因18个,Degree值排名前4位的核心靶点与排名前3位的关键化合物体现较好的结合性。连芩解毒方参与免疫调节主要影响272个生物学过程,58条通路。结论连芩解毒方可能通过槲皮素、山奈酚、β-谷甾醇等关键化合物作用于肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-6(interleukin-6,IL-6)等核心靶点,影响蛋白质磷酸化、细胞质、细胞核等生物学过程,调节代谢途径等关键通路来发挥其免疫调节作用,本研究为后续免疫性疾病的治疗提供了参考依据。展开更多
目的:通过网络药理学和实验验证,探讨益肾祛浊方治疗多囊卵巢综合征(polycystic ovary syndrome,PCOS)合并胰岛素抵抗(insulin resistance,IR)的作用机制。方法:检索中药系统药理学数据库与分析平台(TCMSP)数据库筛选益肾祛浊方的活性...目的:通过网络药理学和实验验证,探讨益肾祛浊方治疗多囊卵巢综合征(polycystic ovary syndrome,PCOS)合并胰岛素抵抗(insulin resistance,IR)的作用机制。方法:检索中药系统药理学数据库与分析平台(TCMSP)数据库筛选益肾祛浊方的活性成分及作用靶点;利用GeneCards、OMIM、DrugBank等数据库筛选PCOS-IR疾病靶点;构建药物-成分-靶点网络;通过STRING和DAVID进行蛋白质-蛋白质互作(protein-protein interaction,PPI)网络分析、基因本体(Gene Ontology,GO)功能及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析;使用AutodockTools 1.5.7软件进行分子对接。高脂饲料联合来曲唑构建PCOS-IR大鼠模型,检测血清性激素、糖代谢指标,并利用蛋白质印迹和实时荧光定量聚合酶链反应验证关键靶点表达。结果:检索到益肾祛浊方主要有效成分136个,靶点406个。选出山柰酚、槲皮素、β-谷甾醇等5种核心化学成分。核心网络中的靶点按照度值进行排名,筛选到白细胞介素-6(interleukin-6,IL-6)、信号转导及转录活化因子3(signal transducer and activator of transcription 3,STAT3)、蛋白激酶B1(protein kinase B1,AKT1)、热休克蛋白90(heat shock protein 90,HSP90)、肿瘤蛋白53(tumor protein 53,TP53)等10个关键靶点。富集于晚期糖基化终末产物-晚期糖基化终末产物受体(advanced glycation end product-receptor for advanced glycation end product,AGE-RAGE)、磷脂酰肌醇3激酶(phosphoinositide 3-kinase,PI3K)-AKT等信号通路。动物实验表明,益肾祛浊方可降低PCOS-IR大鼠血清黄体生成素(luteinizing hormone,LH)、睾酮、空腹胰岛素(fasting insulin,FINS)及稳态模型评估胰岛素抵抗指数(HOMA-IR)水平,差异均有统计学意义(均P<0.05),下调PCOS-IR大鼠卵巢组织STAT3、表皮生长因子受体(epidermal growth factor receptor,EGFR)、HSP90蛋白及基因表达,上调AKT1、TP53蛋白及基因表达,差异均有统计学意义(均P<0.05)。结论:益肾祛浊方通过多成分、多靶点、多通路改善PCOS-IR内分泌异常及糖代谢紊乱。展开更多
文摘<i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;"> is an emerging ubiquitous and opportunistic pathogen that currently contaminates a wide spectrum of foods including powdered milk and poses a lethal threat to neonates, the elderly and persons with immune deficiencies. They cause life threatening neonatal meningitis, septicemia, and necrotizing enterocolitis. A total of 360 samples of powdered infant formula were collected from postnatal hospital attendees reconstituting the PIF for their children in the North Central region of Nigeria where cases of infant mortality </span><span style="font-family:Verdana;">are </span><span style="font-family:""><span style="font-family:Verdana;">very high and presenting as enterocolitis and diarrhea. Pre-enriched samples were cultured in chromogenic </span><i><span style="font-family:Verdana;">Cronobacter</span></i><span style="font-family:Verdana;"> broth and were then further sub-cultured into a chromogenic </span><i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;"> agar. They were positive, exhibiting yellowish cultures typical of </span><i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;">. Biochemical tests of the isolates were also carried out and indicated the presence of </span><i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;">. The isolates were then characterized molecularly using specie specific PCR detection of </span><i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;">. The targeted genes of interest were </span><i><span style="font-family:Verdana;">ompA</span></i><span style="font-family:Verdana;"> gene and </span><i><span style="font-family:Verdana;">CPA</span></i><span style="font-family:Verdana;"> gene. The isolates tested showed bands for </span><i><span style="font-family:Verdana;">ompA</span></i><span style="font-family:Verdana;"> gene on electrophoresis imager and were confirmed as </span><i><span style="font-family:Verdana;">Cronobacter sakazakii.</span></i><span style="font-family:Verdana;"> In Nigeria, majority of infants are still fed with PIF. There is no existing data on the detection of </span><i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;"> previously reported in the North central region of Nigeria hence the need to carry out the present study. The result of the study demonstrated the need for effective prevention and control measures as contamination of PIF with </span><i><span style="font-family:Verdana;">Cronobacter sakazakii</span></i><span style="font-family:Verdana;"> constituted potential public health risk to neonates and infants.
文摘目的探究人偏肺病毒感染的发病机制,并基于逆向网络药理学思维对其进行中药组方预测。方法于Genecards数据库和OMIM数据库中获取人偏肺病毒的靶点,将所得靶点导入STRING数据库构建蛋白互作网络,利用Cytoscape 3.9.0软件结合R软件获得关键靶点。根据GO和KEGG富集分析明确其发病机制与通路。根据度值选取核心靶点,通过Uniprot数据库将核心靶点转换后于traditional Chinese medicine SP数据库逆向收集中药成分及中药。使用Cytoscape 3.9.0软件构建关键靶点-有效成分-中药网络关系图。利用STBYL-2.0软件将核心靶点与核心成分进行分子对接验证,最后确定度值较高中药并分析整理其性、味、归经。结果共获取人偏肺病毒靶点209个,根据度值得到26个关键靶点。GO富集分析主要得出1866个条目,KEGG富集分析显示88条信号通路。根据度值选取的8个核心靶点于traditional Chinese medicine SP数据库中共匹配到29种入血成分及298种中药。将8个核心靶点蛋白与度值较高的4种核心成分进行分子对接验证,结果稳定且良好。整理度值≥10的中药共69种,主要为苦参、连翘、余甘子、半枝莲、木蝴蝶、银杏叶等,以寒性药、苦味药居多,其次为温性药、辛味药,并且肝、肺二经居多。结论运用逆向网络药理学思维及分子对接技术对人偏肺病毒进行靶点、通路、成分和中药预测,为临床治疗及研究提供新思路和理论依据。
基金Supported by the National Nature Science Foundation of China(the Mechamism research of Vascular Aging Induced by High Glucose from AMPK/m TOR Pathway and the Interfering Effects of Yiqi Huoxue Chinese Herbal Medicine,No.81673822,the Molecular Mechamism Research of Yiqi Huoxue Fang Postponing Vascular Endothelial Cell Senescence by SIRT1-autophagy Pathway,No.81503448)the Independent Topic Program of China Academy of Chinese Medical Sciences(Effect of Intestinal Microflora on High Glucose-induced Vascular Aging and Internention of Extracts from Radix Ginseng Radix Notoginseng and Rhizoma Chanxiong,No.ZZ2017011)
文摘OBJECTIVE:To evaluate the efficacy of Renshen Sanqi Chuanxiong formula(RSCF)for preventing vascular aging,and to investigate the possible molecular mechanism underlying the actions of RSCF.METHODS:Potentially active components and their relatively direct targets were identified by combining drug-likeness(DL)screening using a target identification process.Vascular aging-associated targets for RSCF were obtained by selecting common genes not only from potential targets but also from human vascular aging-associated genes.Cytoscape 3.2.1 software was employed to visualize the complex compound-target and target-function networks.Biological process and molecular function were assessed,and the Kyoto Encyclopedia of Genes and Genomes and pathway enrichment analyses were performed using Clue GO.Pathways directly associated with vascular aging were integrated into a"vascular aging-related"pathway.RESULTS:Altogether,122 potentially active components of RSCF were identified through DL screening,and their corresponding 692 direct targets were retrieved via target prediction and identification.We identified 49 vascular aging-associated targets for RSCF by overlapping the 692 potential targets with 146 human vascular aging-associated genes.The results from the compound-target network indicated that most components acted on common targets and displayed synergistic action,which showed that the magnifying effects of RSCF were based on these common targets.The target-function network revealed that each target was involved in multiple function modules,suggesting that RSCF was multi-functional during treatment of vascular aging.The results of the Clue GO analysis indicated that most of the targets were associated with the hypoxia-inducible factor 1(HIF-1)signaling pathway.The results from the pathway analysis also indicated that an integrative vascular aging-related pathway mainly included an angiogenesis regulation module,cell-survival module,and oxidative stress-resistance module.CONCLUSION:Our results suggested that many components act synergistically on common targets to delay vascular aging,and each target is involved in multiple functional modules.The Clue GO analysis indicated that most of the targets were connected to the HIF-1 signaling pathway,FOXO signaling pathway,and thyroid hormone signaling pathway.
基金Project supported by the National Natural Science Foundation of China(Grant No.11072242)the Key Scientific Studies Program of Hebei Province Higher Education Institute,China(Grant No.ZD2018301)Cangzhou National Science Foundation,China(Grant No.177000001)
文摘In 1805, Thomas Young was the first to propose an equation(Young's equation) to predict the value of the equilibrium contact angle of a liquid on a solid. On the basis of our predecessors, we further clarify that the contact angle in Young's equation refers to the super-nano contact angle. Whether the equation is applicable to nanoscale systems remains an open question. Zhu et al. [College Phys. 4 7(1985)] obtained the most simple and convenient approximate formula, known as the Zhu–Qian approximate formula of Young's equation. Here, using molecular dynamics simulation, we test its applicability for nanodrops. Molecular dynamics simulations are performed on argon liquid cylinders placed on a solid surface under a temperature of 90 K, using Lennard–Jones potentials for the interaction between liquid molecules and between a liquid molecule and a solid molecule with the variable coefficient of strength a. Eight values of a between 0.650 and 0.825 are used. By comparison of the super-nano contact angles obtained from molecular dynamics simulation and the Zhu–Qian approximate formula of Young's equation, we find that it is qualitatively applicable for nanoscale systems.
文摘目的基于网络药理学方法研究连芩解毒方的免疫调节作用机制。方法通过中药系统药理学数据库与分析平台(Troditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)和GeneCards数据库,分别获取连芩解毒方的活性成分及其潜在靶点、免疫调节相关靶点,取交集靶点进行分析。构建蛋白互作(protein-protein interaction,PPI)网络和化合物-靶点网络,筛选关键活性成分和核心作用靶点。采用分子对接技术验证关键活性成分与核心靶点的结合活性,并利用DAVID(The Database for Annotation,Visualization,and Integrated Discovery)数据库对交集靶点进行基因本体论(Gene Ontology,GO)功能及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。结果连芩解毒方共有143个成分和164个靶点,其中有130个成分、79个靶点与免疫调节有关,占比分别为90.91%和48.17%;其中关键化合物13个,核心靶基因18个,Degree值排名前4位的核心靶点与排名前3位的关键化合物体现较好的结合性。连芩解毒方参与免疫调节主要影响272个生物学过程,58条通路。结论连芩解毒方可能通过槲皮素、山奈酚、β-谷甾醇等关键化合物作用于肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-6(interleukin-6,IL-6)等核心靶点,影响蛋白质磷酸化、细胞质、细胞核等生物学过程,调节代谢途径等关键通路来发挥其免疫调节作用,本研究为后续免疫性疾病的治疗提供了参考依据。
文摘目的:通过网络药理学和实验验证,探讨益肾祛浊方治疗多囊卵巢综合征(polycystic ovary syndrome,PCOS)合并胰岛素抵抗(insulin resistance,IR)的作用机制。方法:检索中药系统药理学数据库与分析平台(TCMSP)数据库筛选益肾祛浊方的活性成分及作用靶点;利用GeneCards、OMIM、DrugBank等数据库筛选PCOS-IR疾病靶点;构建药物-成分-靶点网络;通过STRING和DAVID进行蛋白质-蛋白质互作(protein-protein interaction,PPI)网络分析、基因本体(Gene Ontology,GO)功能及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析;使用AutodockTools 1.5.7软件进行分子对接。高脂饲料联合来曲唑构建PCOS-IR大鼠模型,检测血清性激素、糖代谢指标,并利用蛋白质印迹和实时荧光定量聚合酶链反应验证关键靶点表达。结果:检索到益肾祛浊方主要有效成分136个,靶点406个。选出山柰酚、槲皮素、β-谷甾醇等5种核心化学成分。核心网络中的靶点按照度值进行排名,筛选到白细胞介素-6(interleukin-6,IL-6)、信号转导及转录活化因子3(signal transducer and activator of transcription 3,STAT3)、蛋白激酶B1(protein kinase B1,AKT1)、热休克蛋白90(heat shock protein 90,HSP90)、肿瘤蛋白53(tumor protein 53,TP53)等10个关键靶点。富集于晚期糖基化终末产物-晚期糖基化终末产物受体(advanced glycation end product-receptor for advanced glycation end product,AGE-RAGE)、磷脂酰肌醇3激酶(phosphoinositide 3-kinase,PI3K)-AKT等信号通路。动物实验表明,益肾祛浊方可降低PCOS-IR大鼠血清黄体生成素(luteinizing hormone,LH)、睾酮、空腹胰岛素(fasting insulin,FINS)及稳态模型评估胰岛素抵抗指数(HOMA-IR)水平,差异均有统计学意义(均P<0.05),下调PCOS-IR大鼠卵巢组织STAT3、表皮生长因子受体(epidermal growth factor receptor,EGFR)、HSP90蛋白及基因表达,上调AKT1、TP53蛋白及基因表达,差异均有统计学意义(均P<0.05)。结论:益肾祛浊方通过多成分、多靶点、多通路改善PCOS-IR内分泌异常及糖代谢紊乱。
