Objective:To investigate the mutagenic potential of Trois using the bacterial reverse mutation assay(Ames test)and in vitro chromosomal aberration test.Methods:The ability of Trois to induce reverse mutations was eval...Objective:To investigate the mutagenic potential of Trois using the bacterial reverse mutation assay(Ames test)and in vitro chromosomal aberration test.Methods:The ability of Trois to induce reverse mutations was evaluated in Salmonella lyphimurium(TA 98,TA100,TAI535 and TA1537)and Escherichia coli(WP2 uvrA)with and without metabolic activation system(S9 mix)at the dose range of 313 to 5000μg/plate.Chromosomal aberrations were evaluated in Chinese hamster lung(CHL)cell line at the dose levels of 15,7.5,3.7,1.9 and 0.9 mg/mL in the absence and presence of S9 mix.Results:There were no increases in the number of revertant colonies at any concentrations of Trois used in the study with and without S9 mix in all tester strains.Trois did not produce any structural aberration in CHL cells in the presence or absence of S9 mix.Conclusions:Results of this study suggest that Trois is non-mutagenic.展开更多
Objective:Menage a trois 1(MAT1)is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA repair.Its dysregulat...Objective:Menage a trois 1(MAT1)is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA repair.Its dysregulation is responsible for diseases including cancers.To further explore the role of MAT1 in breast cancer,we investigated the pathways in which MAT1 might be involved,the association between MAT1 and molecular subtypes,and the role of MAT1 in clinical outcomes of breast cancer patients.Methods:We conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer cells.Also,we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis,correlation analysis and prognosis analysis on public databases.Results:MAT1 was involved in multiple pathways including normal physiology signaling and disease-related signaling.Furthermore,MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor,and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both m RNA and protein levels.Correlation analysis revealed significant association between MAT1 m RNA amount and epithelial markers,mesenchymal markers,cancer stem cell markers,apoptosis markers,transcription markers and oncogenes.Consistently,the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor,vimentin,sex determining region Y-box 2 and sine oculis homeobox homolog 1.Importantly,Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free survival.Conclusions:MAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients.展开更多
TROY(TNFRSF expressed on the mouse embryo)是近年新发现的表达于小鼠胚胎的肿瘤坏死因子受体超家族成员。TROY在体内分布广泛,尤其高表达于胚胎和成熟的中枢神经系统。研究表明,TROY能与髓鞘抑制因子Nogo NgR1及脑内神经再生抑制因子...TROY(TNFRSF expressed on the mouse embryo)是近年新发现的表达于小鼠胚胎的肿瘤坏死因子受体超家族成员。TROY在体内分布广泛,尤其高表达于胚胎和成熟的中枢神经系统。研究表明,TROY能与髓鞘抑制因子Nogo NgR1及脑内神经再生抑制因子(LINGO-1)形成功能受体复合物,参与中枢神经系统轴突生长抑制因子的信号转导;TROY还能诱导细胞副凋亡,促进某些细胞的增殖分化。本文就TROY在上述相关领域的研究进展作一综述。展开更多
Gastric cancer(GC) is one of the leading causes of cancerrelated mortality worldwide.Cancer stem cells(CSCs),which were first identified in acute myeloid leukemia and subsequently in a large array of solid tumors,play...Gastric cancer(GC) is one of the leading causes of cancerrelated mortality worldwide.Cancer stem cells(CSCs),which were first identified in acute myeloid leukemia and subsequently in a large array of solid tumors,play important roles in cancer initiation,dissemination and recurrence.CSCs are often transformed tissue-specific stem cells or de-differentiated transit amplifying progenitor cells.Several populations of multipotent gastric stem cells(GSCs) that reside in the stomach have been determined to regulate physiological tissue renewal and injury repair.These populations include the Villin+ and Lgr5+ GSCs in the antrum,the Troy+ chief cells in the corpus,and the Sox2+ GSCs that are found in both the antrum and the corpus.The disruption of tumor suppressors in Villin+ or Lgr5+ GSCs leads to GC in mouse models.In addition to residing GSCs,bone marrow-derived cells can initiate GC in a mouse model of chronic Helicobacter infection.Furthermore,expression of the cell surface markers CD133 or CD44 defines gastric CSCs in mouse models and in human primary GC tissues and cell lines.Targeted elimination of CSCs effectively reduces tumor size and grade in mouse models.In summary,the recent identification of normal GSCs and gastric CSCs has greatly improved our understanding of the molecular and cellular etiology of GC and will aid in the development of effective therapies to treat patients.展开更多
The Troyan horse served here as a sufficiently vivid picture to enter into the history conflicts of an archetypal symbol of treachery and robbery, a metaphor for domination, a monad of violence and its justification...The Troyan horse served here as a sufficiently vivid picture to enter into the history conflicts of an archetypal symbol of treachery and robbery, a metaphor for domination, a monad of violence and its justification. The body of terrorism rests not on ideology/beliefs/religions-it is purely a practical idea, behind which there is only one thing: terra nova-the habitat. It is necessary to look for other reasons for the massacres and public executions of modern times, because no religion calls for open murder-only dogmatists armed with faith, craved crusaders hikes, and therefore cannot be recognized and accepted as responsible for the murder. This is the search for the guilty, but only the person is guilty-the fault is his area of responsibility. The Utopians of Thomas More, who revered Mithra, acted like him: like Greek gods, they interfered in human wars, descending from heaven, and restored justice by waging war beyond their state borders, as if protecting the inviolability of their territory and their laws, whose rejection, like, and encroachment on them, led to armed conflicts, the purpose of allowing them was the introduction of forced disciplina (established order), sanctioned by Mithra himself. It is this identity that allows us to consider Utopia as an extended invective for the entire social order, regardless of time and place, and in particular the state as a paramilitary mechanism for the improvement of the human hostel, based on regulations that allow and, more often, provoke its violation, since destabilization is the driving force of existence. This polar involvement of Mithra in the war lies hidden in the very aporia of the world-war, which turns the god of treaties into the chthonic deity of destruction and murder.展开更多
目的研究缺血预处理(IPC)对局灶性脑缺血的保护作用以及对TNFRSF expressed on the mouse embryo(TROY)表达的影响。方法33只雄性成年SD大鼠,随机分为预处理6 h组(IPC-6组,11只)、预处理72 h组(IPC-72组,11只)和缺血组(CI组,11只)。利...目的研究缺血预处理(IPC)对局灶性脑缺血的保护作用以及对TNFRSF expressed on the mouse embryo(TROY)表达的影响。方法33只雄性成年SD大鼠,随机分为预处理6 h组(IPC-6组,11只)、预处理72 h组(IPC-72组,11只)和缺血组(CI组,11只)。利用线栓法建立大脑中动脉栓塞(MCAO)致局灶性脑缺血模型。MCAO 10 min作为IPC,IPC-6和IPC-72组分别在IPC后6 h和72 h制作短暂性局灶性脑缺血模型。再灌注24h后,对所有动物行神经功能缺损评分(NDS),并处死大鼠取脑.应用2%TTC染色测定梗死容积、TUNEL染色研究细胞凋亡情况和免疫组化观察TROY表达变化。结果与CI组比较,IPC-72组显著改善局灶性脑缺血24h后大鼠神经功能损害[两组评分分别为2(1.5-3),1(0-2)],减少脑梗死容积[(299.33±70.98)mm^3,(69.25±47.66)mm^3],抑制细胞凋亡和增强TROY的表达(阳性细胞数分别为42±11,87±17)(P<0.01)。结论IPC对其后局灶性脑缺血有明显的保护作用,能诱导脑缺血耐受,可能与TROY表达上调相关。展开更多
基金supported by Venus Medicine Research Centre,Werne,Germany(Grant No.VPG-115-2012)
文摘Objective:To investigate the mutagenic potential of Trois using the bacterial reverse mutation assay(Ames test)and in vitro chromosomal aberration test.Methods:The ability of Trois to induce reverse mutations was evaluated in Salmonella lyphimurium(TA 98,TA100,TAI535 and TA1537)and Escherichia coli(WP2 uvrA)with and without metabolic activation system(S9 mix)at the dose range of 313 to 5000μg/plate.Chromosomal aberrations were evaluated in Chinese hamster lung(CHL)cell line at the dose levels of 15,7.5,3.7,1.9 and 0.9 mg/mL in the absence and presence of S9 mix.Results:There were no increases in the number of revertant colonies at any concentrations of Trois used in the study with and without S9 mix in all tester strains.Trois did not produce any structural aberration in CHL cells in the presence or absence of S9 mix.Conclusions:Results of this study suggest that Trois is non-mutagenic.
基金supported by the National Natural Science Foundation of China (Grant No.81572608 and 81172422)the Wuhan Science and Technology Bureau (Grant No.2017060201010170)
文摘Objective:Menage a trois 1(MAT1)is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA repair.Its dysregulation is responsible for diseases including cancers.To further explore the role of MAT1 in breast cancer,we investigated the pathways in which MAT1 might be involved,the association between MAT1 and molecular subtypes,and the role of MAT1 in clinical outcomes of breast cancer patients.Methods:We conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer cells.Also,we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis,correlation analysis and prognosis analysis on public databases.Results:MAT1 was involved in multiple pathways including normal physiology signaling and disease-related signaling.Furthermore,MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor,and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both m RNA and protein levels.Correlation analysis revealed significant association between MAT1 m RNA amount and epithelial markers,mesenchymal markers,cancer stem cell markers,apoptosis markers,transcription markers and oncogenes.Consistently,the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor,vimentin,sex determining region Y-box 2 and sine oculis homeobox homolog 1.Importantly,Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free survival.Conclusions:MAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients.
文摘TROY(TNFRSF expressed on the mouse embryo)是近年新发现的表达于小鼠胚胎的肿瘤坏死因子受体超家族成员。TROY在体内分布广泛,尤其高表达于胚胎和成熟的中枢神经系统。研究表明,TROY能与髓鞘抑制因子Nogo NgR1及脑内神经再生抑制因子(LINGO-1)形成功能受体复合物,参与中枢神经系统轴突生长抑制因子的信号转导;TROY还能诱导细胞副凋亡,促进某些细胞的增殖分化。本文就TROY在上述相关领域的研究进展作一综述。
基金Supported by Fundamental Research Funds for the Central Universities lzujbky-2013-221China’s National Science and Technology Program for Public Wellbeing Grant No.2012GS620101Major Science and Technology Projects of Gansu Province Grant No.1102FKDA006
文摘Gastric cancer(GC) is one of the leading causes of cancerrelated mortality worldwide.Cancer stem cells(CSCs),which were first identified in acute myeloid leukemia and subsequently in a large array of solid tumors,play important roles in cancer initiation,dissemination and recurrence.CSCs are often transformed tissue-specific stem cells or de-differentiated transit amplifying progenitor cells.Several populations of multipotent gastric stem cells(GSCs) that reside in the stomach have been determined to regulate physiological tissue renewal and injury repair.These populations include the Villin+ and Lgr5+ GSCs in the antrum,the Troy+ chief cells in the corpus,and the Sox2+ GSCs that are found in both the antrum and the corpus.The disruption of tumor suppressors in Villin+ or Lgr5+ GSCs leads to GC in mouse models.In addition to residing GSCs,bone marrow-derived cells can initiate GC in a mouse model of chronic Helicobacter infection.Furthermore,expression of the cell surface markers CD133 or CD44 defines gastric CSCs in mouse models and in human primary GC tissues and cell lines.Targeted elimination of CSCs effectively reduces tumor size and grade in mouse models.In summary,the recent identification of normal GSCs and gastric CSCs has greatly improved our understanding of the molecular and cellular etiology of GC and will aid in the development of effective therapies to treat patients.
文摘The Troyan horse served here as a sufficiently vivid picture to enter into the history conflicts of an archetypal symbol of treachery and robbery, a metaphor for domination, a monad of violence and its justification. The body of terrorism rests not on ideology/beliefs/religions-it is purely a practical idea, behind which there is only one thing: terra nova-the habitat. It is necessary to look for other reasons for the massacres and public executions of modern times, because no religion calls for open murder-only dogmatists armed with faith, craved crusaders hikes, and therefore cannot be recognized and accepted as responsible for the murder. This is the search for the guilty, but only the person is guilty-the fault is his area of responsibility. The Utopians of Thomas More, who revered Mithra, acted like him: like Greek gods, they interfered in human wars, descending from heaven, and restored justice by waging war beyond their state borders, as if protecting the inviolability of their territory and their laws, whose rejection, like, and encroachment on them, led to armed conflicts, the purpose of allowing them was the introduction of forced disciplina (established order), sanctioned by Mithra himself. It is this identity that allows us to consider Utopia as an extended invective for the entire social order, regardless of time and place, and in particular the state as a paramilitary mechanism for the improvement of the human hostel, based on regulations that allow and, more often, provoke its violation, since destabilization is the driving force of existence. This polar involvement of Mithra in the war lies hidden in the very aporia of the world-war, which turns the god of treaties into the chthonic deity of destruction and murder.