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21.
Qiyan Wang Jian Bai Amir Abliz Ying Liu Kenan Gong Jingjing Li Wenjie Shi Yaqi Pan Fangfang Liu Shujuan Lai Haijun Yang Changdong Lu Lixin Zhang Wei Chen Ruiping Xu Hong Cai Yang Ke Changqing Zeng 《基因组蛋白质组与生物信息学报(英文版)》2015,13(4):258-270
Esophageal squamous cell carcinoma(ESCC) has a high mortality rate. To determine the molecular basis of ESCC development, this study sought to identify characteristic genome-wide alterations in ESCC, including exonic mutations and structural alterations. The clinical implications of these genetic alterations were also analyzed. Exome sequencing and verification were performed for nine pairs of ESCC and the matched blood samples, followed by validation with additional samples using Sanger sequencing. Whole-genome SNP arrays were employed to detect copy number alteration(CNA) and loss of heterozygosity(LOH) in 55 cases, including the nine ESCC samples subjected to exome sequencing. A total of 108 non-synonymous somatic mutations(NSSMs) in102 genes were verified in nine patients. The chromatin modification process was found to be enriched in our gene ontology(GO) analysis. Tumor genomes with TP53 mutations were significantly more unstable than those without TP53 mutations. In terms of the landscape of genomic alterations, deletion of 9p21.3 covering CDKN2A/2B(30.9%), amplification of 11q13.3 covering CCND1(30.9%), and TP53 point mutation(50.9%) occurred in two-thirds of the cases. These results suggest that the deregulation of the G1 phase during the cell cycle is a key event in ESCC.Furthermore, six minimal common regions were found to be significantly altered in ESCC samples and three of them, 9p21.3, 7p11.2, and 3p12.1, were associated with lymph node metastasis. With the high correlation of TP53 mutation and genomic instability in ESCC, the amplification of CCND1, the deletion of CDKN2A/2B, and the somatic mutation of TP53 appear to play pivotal roles via G1 deregulation and therefore helps to classify this cancer into different genomic subtypes.These findings provide clinical significance that could be useful in future molecular diagnoses and therapeutic targeting. 相似文献
22.
Evidence has emerged that mesenchymal stem cells (MSCs) represent a promising cell population for supporting new clinical
cellular therapies. Currently, bone marrow represents the main source of MSCs, but their differentiation capacity declines
with age. We have identified possible novel multilineage mesenchymal cells from human placenta. In addition to their multilineage
differentiation, they have a direct immunosuppressive effect on proliferation of T lymphocytes from human adult peripheral
blood (PB) and umbilical cord blood (UCB) in vitro. This immunoregulatory feature strongly implies that they have a potential
application in allograft transplantation. Since placenta and UCB can be obtained from the same donor, placenta is an attractive
source of MSCs for co-transplantation in conjunction with UCB-derived hematopoietic stem cells to reduce the potential of
graft-versus-host disease in recipients. However, the way that they modulate the immune system is unclear. In this investigation,
we have addressed the effects of human placental MSCs on various subtypes of UCB-derived and PB-derived T lymphocytes.
This study was supported by a grant from the National Natural Science Foundation (no. 30571949), by the Beijing Nova Star
program, by the Beijing Elitist Fund (20051D0301029), and by the Beijing Obstetrics and Gynecology Hospital. 相似文献
23.
Avenin—like基因是近年来发现的一类新基因。根据小麦avenin-like基因的保守序列,设计合成了一对特异性引物,对拟斯卑尔脱山羊草(Aegilops spehoides,ss)的基因组DNA进行avenin-like基因扩增、克隆、序列测定和表达分析,发现了一个新型avenin—like基因。基因长855bp,编码284个氨基酸残基,分子量约为33kD。Souchern blot结果表明其属于多基因家族。RT—PCR证实了avenin-like基因在籽粒胚乳中特异性表达。其对应的氨基酸序列含有18个半胱氨酸残基,可以形成7对分子内二硫键。研究表明Avenin-like蛋白是一类新型的储藏蛋白。这为小麦加工品质的改良提供了理论依据和遗传资源。 相似文献
24.
Meihua Zheng Weili Qiao Jie Cui Lei Liu Hong Liu Zhirong Wang Changdong Yan 《Molecular and cellular biochemistry》2014,393(1-2):59-67
The present study was designed to investigate the effect of hydrogen sulfide on cellular senescence of human umbilical vascular endothelial cells (HUVECs CC-2517) and its underlying mechanism. The premature senescence-like phenotype HUVECs (the fourth passage) was induced by treatment with nicotinamide (NAM, an inhibitor of SIRT1, 5 mmol/L, 12 h). Cells were cultured with sodium hydrosulfide (NaHS, 12.5, 25, 50 and 100 μmol/L) for 48 h in premature senescence-like phenotype HUVECs. The fourth passage of HUVECs was considered as young group. Senescence-associated (SA)-β-galactosidase activities were detected to evaluate cell senescence, and the expression of SA heterochromatin foci (SAHF) was visualized by DAPI DNA staining. The mRNA and protein levels of SIRT1 were detected using RT-PCR and western blotting analysis, respectively. The results showed that β-galactosidase positive cells and the formation of SAHF were markedly increased after treatment with NAM (5 mmol/L) for 12 h. We also found that NaHS (12.5 μmol/L) had no effect on the percentage of SA β-gal positive cells and the expression of SAHF, and the hallmarks decreased at the concentration of 25 and 50 μmol/L, reaching the minimum at 50 μmol/L, while the percentage of SA β-gal positive cells and the expression of SAHF increased at the concentration of 100 μmol/L. Furthermore, we found that both on protein and mRNA levels of SIRT1 in the Y+N+S50 group was significantly increased compared with that in Y+N group. In conclusion, NaHS delays senescence of HUVECs induced by NAM via upregulation of SIRT1 expression. 相似文献
25.
目的研究Bmi-1对MCF-7细胞阿霉素敏感性的影响及机制。方法阿霉素处理MCF-7/Bmilsi、MCF-7/GFPsi和MCF一7细胞株,M1Tr法检测阿霉素的IC50;DAPI检测阿霉素处理后细胞的凋亡,计算凋亡指数(apoptosisindex,AI);Western印迹检测相关蛋白P53,phospho—Akt(Ser473)(pAkt),totle—Akt(tAkt),Bcl-2,Bax的表达。结果阿霉素处理72h的MCF-7/Bmi.1si组生长抑制率明显高于MCF-7和MCF-7/GFPsi组,MCF-7/Bmilsi组的IC50为(0.15±0.02)μg/ml,而MCF-7组和MCF-7/GFPsi组的IC50分别为(0.87±0.06)μg/ml和(0.81±0.02)μg/ml(P〈0.05)。阿霉素处理48h后用DAPI检测凋亡发现,MCF-7/Bmi.lsi+doxorubiein组可见大量凋亡细胞,而MCF-7+doxorubicin和MCF-7/GFPsi+doxo—rubicin组出现较少的凋亡细胞,MCF-7/Bmi-1si+doxorubicin组凋亡指数明显高于对照组(P〈0.05)。进一步研究发现:MCF-7/Bmi.1si+doxorubicin组与MCF-7+doxorubiein及MCF-7/GFPsi+doxorubiein组相比,P53表达量增加,tAkt表达未发生改变,而pAkt的表达明显减少,另外,Bcl-2表达量减少而Bax表达量增加,差异具有显著性(P〈0.05)。结论沉默Bmi—l基因表达能增加MCF-7细胞对阿霉素的敏感性,增加阿霉素引起的凋亡。 相似文献
26.
Wu X Liu X Sengupta J Bu Y Yi F Wang C Shi Y Zhu Y Jiao Q Song F 《Indian journal of experimental biology》2011,49(2):105-112
The oncogene Bmi-1 is highly up-regulated in breast carcinoma and is found to be efficient in preventing apoptosis of the cancer cells. Doxorubicin is an important chemotherapeutic agent against breast carcinoma. However, the effective therapeutic response to doxorubicin is often associated with severe toxicity. The present study is targetted at developing a strategy to increase doxorubicin sensitivity to lower doses without compromising its efficacy. A stable cell line with a persistent silencing of Bmi-1 was established. MTT assay was performed to evaluate 50% inhibitory concentration (IC50) values of doxorubicin. Apoptosis was detected by FCM and the expression of related genes [phosphor-Akt (pAkt), totle-Akt (tAkt), Bcl-2 and Bax] was studied by Western blot. In vivo, the sensitivity of the tumor tissues against doxorubicin was evaluated by transplanted MCF-7 nude mice model and the apoptosis of tissue cells was detected by TUNEL assay. The expression of pAkt and Bcl-2 was down-regulated, whereas Bax was up-regulated in Bmi-1 silencing cells. The results obtained indicated that silencing of Bmi-1 can render MCF-7 cells more sensitive to doxorubicin which induced a significantly higher percentage of apoptosis cells in vitro and in vivo. All together these results clearly demonstrate that Bmi-1 siliencing combined treatment of doxorubicin might be a new strategy for biological treatment on breast cancer. 相似文献
27.
Yueru Sun Shuhui Yin Yitao Feng Jie Li Jiahai Zhou Changdong Liu Guang Zhu Zhihong Guo 《The Journal of biological chemistry》2014,289(22):15867-15879
The serine-histidine-aspartate triad is well known for its covalent, nucleophilic catalysis in a diverse array of enzymatic transformations. Here we show that its nucleophilicity is shielded and its catalytic role is limited to being a specific general base by an open-closed conformational change in the catalysis of (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (or MenH), a typical α/β-hydrolase fold enzyme in the vitamin K biosynthetic pathway. This enzyme is found to adopt an open conformation without a functional triad in its ligand-free form and a closed conformation with a fully functional catalytic triad in the presence of its reaction product. The open-to-closed conformational transition involves movement of half of the α-helical cap domain, which causes extensive structural changes in the α/β-domain and forces the side chain of the triad histidine to adopt an energetically disfavored gauche conformation to form the functional triad. NMR analysis shows that the inactive open conformation without a triad prevails in ligand-free solution and is converted to the closed conformation with a properly formed triad by the reaction product. Mutation of the residues crucial to this open-closed transition either greatly decreases or completely eliminates the enzyme activity, supporting an important catalytic role for the structural change. These findings suggest that the open-closed conformational change tightly couples formation of the catalytic triad to substrate binding to enhance the substrate specificities and simultaneously shield the nucleophilicity of the triad, thus allowing it to expand its catalytic power beyond the nucleophilic catalysis. 相似文献
28.
Shiyang Chen Yajuan Zheng Xiaojuan Ran Hui Du Hua Feng Lei Yang Yating Wen Changdong Lin Shihui Wang Mengwen Huang Zhanjun Yan Dianqing Wu Hongyan Wang Gaoxiang Ge An Zeng Yi Arial Zeng Jianfeng Chen 《Cell research》2021,(12):1291-1307
Intestinal stem cell (ISC) differentiation is regulated precisely by a niche in the crypt,where lymphocytes may interact with stem and transient amplifying (TA)... 相似文献
29.
Hydrobiologia - Exploring species-environment relationships to identify essential habitat areas is recognized as an effective way for resource conservation and management. Because of ecological and... 相似文献
30.
Hydrobiologia - The small-scale whelk (Rapana venosa) and Asian paddle crab (Charybdis japonica) pot fishery are of great socio-economic importance to coastal communities of the Yellow Sea, China.... 相似文献