BACKGROUND Heart diseases are the primary cause of death all over the world.Following myocardial infarction,billions of cells die,resulting in a huge loss of cardiac function.Stem cell-based therapies have appeared as...BACKGROUND Heart diseases are the primary cause of death all over the world.Following myocardial infarction,billions of cells die,resulting in a huge loss of cardiac function.Stem cell-based therapies have appeared as a new area to support heart regeneration.The transcription factors GATA binding protein 4(GATA-4)and myocyte enhancer factor 2C(MEF2C)are considered prominent factors in the development of the cardiovascular system.AIM To explore the potential of GATA-4 and MEF2C for the cardiac differentiation of human umbilical cord mesenchymal stem cells(hUC-MSCs).METHODS hUC-MSCs were characterized morphologically and immunologically by the presence of specific markers of MSCs via immunocytochemistry and flow cytometry,and by their potential to differentiate into osteocytes and adipocytes.hUC-MSCs were transfected with GATA-4,MEF2C,and their combination to direct the differentiation.Cardiac differentiation was confirmed by semiquant itative real-time polymerase chain reaction and immunocytochemistry.RESULTS hUC-MSCs expressed specific cell surface markers CD105,CD90,CD44,and vimentin but lack the expression of CD45.The transcription factors GATA-4 and MEF2C,and their combination induced differentiation in hUC-MSCs with significant expression of cardiac genes i.e.,GATA-4,MEF2C,NK2 homeobox 5(NKX2.5),MHC,and connexin-43,and cardiac proteins GATA-4,NKX2.5,cardiac troponin T,and connexin-43.CONCLUSION Transfection with GATA-4,MEF2C,and their combination effectively induces cardiac differentiation in hUC-MSCs.These genetically modified MSCs could be a promising treatment option for heart diseases in the future.展开更多
Objective Recent studies have shown abnormal expression of octamer-binding transcription factor 4(OCT4) and interleukin-18(IL-18) to be related to cancer. However, the molecular mechanisms by which the IL-18 and OCT4 ...Objective Recent studies have shown abnormal expression of octamer-binding transcription factor 4(OCT4) and interleukin-18(IL-18) to be related to cancer. However, the molecular mechanisms by which the IL-18 and OCT4 gene polymorphisms are associated with prostate cancer remain unclear. In this study, we aimed to determine whether the presence of IL-18 and OCT4 polymorphisms were associated with size, grade, tumor, nodes and metastasis(TNM) stage, or survival in patients with prostate cancer.Methods Polymorphisms in OCT4 and IL-18 genes were evaluated to determine susceptibility to prostate cancer in 120 patients. A control group consisted of 125 Chinese participants. Genotyping was performed using TaqMan allelic discrimination assays, and statistical analysis was performed using SPSS. Results No association was found between OCT4 and IL-18 gene polymorphisms and prostate cancer susceptibility. For OCT4 AA and IL-18-607 CC genotypes, there was a significant association with higher tumor grade(P = 0.03 and P = 0.025) and stage(P = 0.04 and P = 0.001). The OCT4 and IL-18-137 GG genotype was correlated with higher tumor grade(P = 0.028) and stage(P = 0.008). Furthermore, OCT4 AA was significantly more frequent in patients with lymph node metastasis(P = 0.02) and distant metastasis(P = 0.01). The Cox proportional hazard model showed that tumor grade and stage grouping were independent prognostic factors but IL-18 and OCT4 polymorphisms were not. Conclusion The OCT4 gene may have a profound effect on prostate cancer risk. Polymorphism variants in the IL-18(IL-18-607 and IL-18-137) and OCT4 genes may be associated with poor prognoses for individuals with prostate cancer.展开更多
Previous studies have shown that octamer-binding transcription factor 4（Oct4） plays a significant role in early embryonic development of mammalian animals, and different Oct4 expression levels induce multi-lineage d...Previous studies have shown that octamer-binding transcription factor 4（Oct4） plays a significant role in early embryonic development of mammalian animals, and different Oct4 expression levels induce multi-lineage differentiation which are regulated by DNA methylation. To explore the relationship between the methylation pattern of Oct4 gene exon 1 and embryonic development, in this work, five different tissues（heart, liver, lung, cerebrum and cerebellum） from three germ layers were chosen from low age（50–60 d） and advanced age（60–70 d） of fetal cattle and the differences between tissues or ages were analyzed, respectively. The result showed that the DNA methylation level of Oct4 gene exon 1 was significant different（P〈0.01） between any two of three germ layers in low age（〈60 d）, but kept steady of advanced age（P〉0.05）（〉60 d）, suggesting that 60-d post coital was an important boundary for embryonic development. In addition, in ectoderm（cerebrum and cerebellum）, there was no significant methylation difference of Oct4 gene exon 1 between low age and advanced age（P〉0.05）, but the result of endoderm（liver and lung） and mesoderm（heart） were on the contrary（P〈0.01）, which indicated the development of ectoderm was earlier than endoderm and mesoderm. The methylation differences from the 3rd, 5th and 9th Cp G-dinucleotide loci of Oct4 gene exon 1 were significantly different between each two of three germ layers（P〈0.05）, indicating that these three loci may have important influence on bovine embryonic development. This study showed that bovine germ layers differentiation was significantly related to the DNA methylation status of Oct4 gene exon 1. This work firstly identified the DNA methylation profile of bovine Oct4 gene exon 1 and its association with germ layers development in fetus and adult of cattle. Moreover, the work also provided epigenetic information for further studying bovine embryonic development and cellular reprogramming.展开更多
目的:观察八聚体结合转录因子4(Oct4)在神经母细胞瘤中的表达情况,并探讨其与神经母细胞瘤转移和侵袭的关系。方法:采用免疫组织化学方法和RT-PCR方法检测神经母细胞瘤组织及癌旁组织中Oct4的表达情况。收集患者临床病理参数,分析Oct4...目的:观察八聚体结合转录因子4(Oct4)在神经母细胞瘤中的表达情况,并探讨其与神经母细胞瘤转移和侵袭的关系。方法:采用免疫组织化学方法和RT-PCR方法检测神经母细胞瘤组织及癌旁组织中Oct4的表达情况。收集患者临床病理参数,分析Oct4表达与神经母细胞瘤临床病理参数之间的关系。采用电穿孔转染法,将Oct4 si RNA转入神经母细胞瘤SK-N-MC细胞中,通过伤口愈合实验和Boyden小室检测Oct4对神经母细胞瘤SK-N-MC细胞转移和侵袭能力的影响。结果:神经母细胞瘤组织中Oct4的表达水平高于癌旁组织(P<0.05)。Oct4的阳性表达率与患者有无淋巴结转移和分化程度密切相关(P<0.01),但与患者性别、年龄、肿瘤大小和临床病理分期均无明显关系(P>0.05);转染Oct4 si RNA可显著抑制神经母细胞瘤SKN-MC细胞的转移和侵袭能力(P<0.01)。结论:Oct4具有促进神经母细胞瘤转移和侵袭的作用,其高表达可能与神经母细胞瘤的发生和发展密切相关。展开更多
基金Supported by the Higher Education Commission(HEC),Pakistan Scholarship for Ph.D.Studies to Razzaq SS,No.520-148390-2BS6-011.
文摘BACKGROUND Heart diseases are the primary cause of death all over the world.Following myocardial infarction,billions of cells die,resulting in a huge loss of cardiac function.Stem cell-based therapies have appeared as a new area to support heart regeneration.The transcription factors GATA binding protein 4(GATA-4)and myocyte enhancer factor 2C(MEF2C)are considered prominent factors in the development of the cardiovascular system.AIM To explore the potential of GATA-4 and MEF2C for the cardiac differentiation of human umbilical cord mesenchymal stem cells(hUC-MSCs).METHODS hUC-MSCs were characterized morphologically and immunologically by the presence of specific markers of MSCs via immunocytochemistry and flow cytometry,and by their potential to differentiate into osteocytes and adipocytes.hUC-MSCs were transfected with GATA-4,MEF2C,and their combination to direct the differentiation.Cardiac differentiation was confirmed by semiquant itative real-time polymerase chain reaction and immunocytochemistry.RESULTS hUC-MSCs expressed specific cell surface markers CD105,CD90,CD44,and vimentin but lack the expression of CD45.The transcription factors GATA-4 and MEF2C,and their combination induced differentiation in hUC-MSCs with significant expression of cardiac genes i.e.,GATA-4,MEF2C,NK2 homeobox 5(NKX2.5),MHC,and connexin-43,and cardiac proteins GATA-4,NKX2.5,cardiac troponin T,and connexin-43.CONCLUSION Transfection with GATA-4,MEF2C,and their combination effectively induces cardiac differentiation in hUC-MSCs.These genetically modified MSCs could be a promising treatment option for heart diseases in the future.
基金Supported by grants from the China Postdoctoral Science Foundation(No.2014M139951)the Science and Technology Project of Nantong,Jiangsu Province(No.MS22016043)
文摘Objective Recent studies have shown abnormal expression of octamer-binding transcription factor 4(OCT4) and interleukin-18(IL-18) to be related to cancer. However, the molecular mechanisms by which the IL-18 and OCT4 gene polymorphisms are associated with prostate cancer remain unclear. In this study, we aimed to determine whether the presence of IL-18 and OCT4 polymorphisms were associated with size, grade, tumor, nodes and metastasis(TNM) stage, or survival in patients with prostate cancer.Methods Polymorphisms in OCT4 and IL-18 genes were evaluated to determine susceptibility to prostate cancer in 120 patients. A control group consisted of 125 Chinese participants. Genotyping was performed using TaqMan allelic discrimination assays, and statistical analysis was performed using SPSS. Results No association was found between OCT4 and IL-18 gene polymorphisms and prostate cancer susceptibility. For OCT4 AA and IL-18-607 CC genotypes, there was a significant association with higher tumor grade(P = 0.03 and P = 0.025) and stage(P = 0.04 and P = 0.001). The OCT4 and IL-18-137 GG genotype was correlated with higher tumor grade(P = 0.028) and stage(P = 0.008). Furthermore, OCT4 AA was significantly more frequent in patients with lymph node metastasis(P = 0.02) and distant metastasis(P = 0.01). The Cox proportional hazard model showed that tumor grade and stage grouping were independent prognostic factors but IL-18 and OCT4 polymorphisms were not. Conclusion The OCT4 gene may have a profound effect on prostate cancer risk. Polymorphism variants in the IL-18(IL-18-607 and IL-18-137) and OCT4 genes may be associated with poor prognoses for individuals with prostate cancer.
基金supported by the Natural Science Foundation of Shaanxi Province, China (2014JQ3104)the National Natural Science Foundation of China (31000655)China Postdoctoral Science Foundation funded project (2014M560809)
文摘Previous studies have shown that octamer-binding transcription factor 4（Oct4） plays a significant role in early embryonic development of mammalian animals, and different Oct4 expression levels induce multi-lineage differentiation which are regulated by DNA methylation. To explore the relationship between the methylation pattern of Oct4 gene exon 1 and embryonic development, in this work, five different tissues（heart, liver, lung, cerebrum and cerebellum） from three germ layers were chosen from low age（50–60 d） and advanced age（60–70 d） of fetal cattle and the differences between tissues or ages were analyzed, respectively. The result showed that the DNA methylation level of Oct4 gene exon 1 was significant different（P〈0.01） between any two of three germ layers in low age（〈60 d）, but kept steady of advanced age（P〉0.05）（〉60 d）, suggesting that 60-d post coital was an important boundary for embryonic development. In addition, in ectoderm（cerebrum and cerebellum）, there was no significant methylation difference of Oct4 gene exon 1 between low age and advanced age（P〉0.05）, but the result of endoderm（liver and lung） and mesoderm（heart） were on the contrary（P〈0.01）, which indicated the development of ectoderm was earlier than endoderm and mesoderm. The methylation differences from the 3rd, 5th and 9th Cp G-dinucleotide loci of Oct4 gene exon 1 were significantly different between each two of three germ layers（P〈0.05）, indicating that these three loci may have important influence on bovine embryonic development. This study showed that bovine germ layers differentiation was significantly related to the DNA methylation status of Oct4 gene exon 1. This work firstly identified the DNA methylation profile of bovine Oct4 gene exon 1 and its association with germ layers development in fetus and adult of cattle. Moreover, the work also provided epigenetic information for further studying bovine embryonic development and cellular reprogramming.
文摘目的:观察八聚体结合转录因子4(Oct4)在神经母细胞瘤中的表达情况,并探讨其与神经母细胞瘤转移和侵袭的关系。方法:采用免疫组织化学方法和RT-PCR方法检测神经母细胞瘤组织及癌旁组织中Oct4的表达情况。收集患者临床病理参数,分析Oct4表达与神经母细胞瘤临床病理参数之间的关系。采用电穿孔转染法,将Oct4 si RNA转入神经母细胞瘤SK-N-MC细胞中,通过伤口愈合实验和Boyden小室检测Oct4对神经母细胞瘤SK-N-MC细胞转移和侵袭能力的影响。结果:神经母细胞瘤组织中Oct4的表达水平高于癌旁组织(P<0.05)。Oct4的阳性表达率与患者有无淋巴结转移和分化程度密切相关(P<0.01),但与患者性别、年龄、肿瘤大小和临床病理分期均无明显关系(P>0.05);转染Oct4 si RNA可显著抑制神经母细胞瘤SKN-MC细胞的转移和侵袭能力(P<0.01)。结论:Oct4具有促进神经母细胞瘤转移和侵袭的作用,其高表达可能与神经母细胞瘤的发生和发展密切相关。
