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Epigenetic dysregulation in hepatocellular carcinoma: focus on polycomb group proteins

null

《医学前沿(英文)》 2013年 第7卷 第2期   页码 231-241 doi: 10.1007/s11684-013-0253-7

摘要:

Hepatocellular carcinoma (HCC) development is characterized by the presence of epigenetic alterations, including promoter DNA hypermethylation and post-translational modifications of histone, which profoundly affect expression of a wide repertoire of genes critical for cancer development. Emerging data suggest that deregulation of polycomb group (PcG) proteins, which are key chromatin modifiers repressing gene transcription during developmental stage, plays a causative role in oncogenesis. PcG proteins assemble into polycomb repressive complex 1 (PRC1) and polycomb repressive complex 2 (PRC2) to impose the histone H3 lysine 27 trimethylation (H3K27me3) modification for repression. In this review, we will first recapitulate the mechanisms of two key epigenetic pathways: DNA methylation and histone modifications. Specifically, we will focus our discussion on the molecular roles of PcG proteins. Next, we will highlight recent findings on PcG proteins, their clinicopathological implication and their downstream molecular consequence in hepatocarcinogenesis. Last but not least, we will consider the therapeutic potential of targeting enhancer of zeste homolog 2 (EZH2) as a possible treatment for HCC. Improving our understanding on the roles of PcG proteins in hepatocarcinogenesis can benefit the development of epigenetic-based therapy.

关键词: liver cancer     epigenetics     histone modifications     polycomb group proteins     enhancer of zeste homolog 2 (EZH2)    

Spatiotemporal expression of Ezh2 in the developing mouse cochlear sensory epithelium

null

《医学前沿(英文)》 2016年 第10卷 第3期   页码 330-335 doi: 10.1007/s11684-016-0459-6

摘要:

The enhancer of zeste 2 polycomb repressive complex 2 subunit (Ezh2) is a histone-lysine N-methyltransferase enzyme that participates in DNA methylation. Ezh2 has also been reported to play crucial roles in stem cell proliferation and differentiation. However, the detailed expression profile of Ezh2 during mouse cochlear development has not been investigated. Here, we examined the spatiotemporal expression of Ezh2 in the cochlea during embryonic and postnatal development. Ezh2 expression began to be observed in the whole otocyst nuclei at embryonic day 9.5 (E9.5). At E12.5, Ezh2 was expressed in the nuclei of the cochlear prosensory epithelium. At E13.5 and E15.5, Ezh2 was expressed from the apical to the basal turns in the nuclei of the differentiating cochlear epithelium. At postnatal day (P) 0 and 7, the Ezh2 expression was located in the nuclei of the cochlear epithelium in all three turns and could be clearly seen in outer and inner hair cells, supporting cells, the stria vascularis, and spiral ganglion cells. Ezh2 continued to be expressed in the cochlear epithelium of adult mice. Our results provide the basic Ezh2 expression pattern and might be useful for further investigating the detailed role of Ezh2 during cochlear development.

关键词: polycomb repressive complex     Ezh2     expression     inner ear     cochlea     development    

Disabled homolog 2 is required for migration and invasion of prostate cancer cells

null

《医学前沿(英文)》 2015年 第9卷 第3期   页码 312-321 doi: 10.1007/s11684-015-0401-3

摘要:

Disabled homolog 2 (DAB2) is frequently deleted or epigenetically silenced in many human cancer cells. Therefore, DAB2 has always been regarded as a tumor suppressor gene. However, the role of DAB2 in tumor progression and metastasis remains unclear. In this study, DAB2 expression was upregulated along with human prostate cancer (PCa) progression. DAB2overexpression or knockdown effects in LNCaP and PC3 cell lines were verified to address the biological functions of DAB2 in PCa progression and metastasis. LNCaP and PC3 cell lines were generated from human PCa cells with low and high metastatic potentials, respectively. The results showed that DAB2 shRNA knockdown can inhibit the migratory and invasive abilities of PC3 cells, as well as the tumorigenicity, whereas DAB2 overexpression enhanced LNCaP cell migration and invasion. Further investigation showed that DAB2 regulated the cell migration associated genes in PC3 cells, and the differential DAB2 expression between LNCaP and PC3 cells was partly regulated by histone 4 acetylation. Therefore, DAB2 may play an important role in PCa progression and metastasis.

关键词: DAB2     prostate cancer     migration     invasion     acetylation    

第三届环境、工业和能源工程国际会议(EI2E 2019)

会议日期: 2019年09月19日

会议地点: 宁夏银川

主办单位: APISE

第四届设计、机械和材料工程国际会议(D2ME 2019)

会议日期: 2019年09月26日

会议地点: 釜山,韩国

主办单位: HKSME

第四届设计、机械和材料工程国际会议(D2ME 2019)

会议日期: 2019年09月26日

会议地点: 釜山,韩国

主办单位: HKSME

Influence of short chain ceramides and lipophilic penetration enhancers on the nano-structure of stratum corneum model membranes studied using neutron diffraction

Annett SCHROETER, Tanja ENGELBRECHT, Reinhard H. H. NEUBERT

《化学科学与工程前沿(英文)》 2013年 第7卷 第1期   页码 29-36 doi: 10.1007/s11705-013-1302-0

摘要: Oriented stratum corneum model lipid membranes were used to study the influence of the short chain ceramides (CER)[NP] and [AP] as well as the impact of the lipophilic penetration enhancer molecules oleic acid (OA) and isopropyl myristate (IPM) on the lipid nanostructure. The influence of the enhancer molecules were studied using specifically deuterated OA and IPM and neutron diffraction. H NMR spectroscopy was used to study the impact of the ceramides’ degree of order within the stratum corneum model lipid membranes. It was found that CER[NP] forms two very stable phases with high resistance against temperature increase. Phase B showed unusual hydration behavior as no water uptake of this phase was observed. The H NMR spectroscopic measurements showed that CER[NP] based ternary model system had a higher state of lamellar order in comparison to CER[AP] based lipid matrix. The studies confirmed that the short chain ceramides, particularly CER[NP], have a very high impact on the integrity of the Stratum corneum lipid bilayers. The penetration enhancer OA has not influenced the repeat distance of the model membrane based on CER[AP], and was not able to induce a phase separation in the investigated lipid matrix. However, a disorder and a fluidisation of the model membranes were observed when OA was incorporated. IPM showed the same effect but two phases (assigned as phase A and B) appeared, when IPM was used as penetration enhancer and incorporated into the model membrane. Furthermore, two arrangements of IPM were identified in phase A using deuterated IPM. A model of the nanostructure of the Stratum corneum lipid membranes is presented.

关键词: nano-structure of the stratum corneum     ceramide     penetration enhancer     model membrane     neutron diffraction     2H NMR spectroscopy    

2届智能医疗与图像处理国际会议(IMIP 2020)

会议日期: 2020年04月23日

会议地点: 天津

主办单位: IMIP 2020

标题 作者 时间 类型 操作

Epigenetic dysregulation in hepatocellular carcinoma: focus on polycomb group proteins

null

期刊论文

Spatiotemporal expression of Ezh2 in the developing mouse cochlear sensory epithelium

null

期刊论文

Disabled homolog 2 is required for migration and invasion of prostate cancer cells

null

期刊论文

第三届环境、工业和能源工程国际会议(EI2E 2019)

2019年09月19日

会议信息

第四届设计、机械和材料工程国际会议(D2ME 2019)

2019年09月26日

会议信息

肖永红:临床高耐药与高毒性病原体共进化(2023年2月22日)

2023年03月10日

会议视频

第四届设计、机械和材料工程国际会议(D2ME 2019)

2019年09月26日

会议信息

赵家军:2型糖尿病患者的身体活动、久坐行为与心血管疾病风险的关系:MlDiab研究(2023年2月21日)

2023年03月02日

会议视频

Influence of short chain ceramides and lipophilic penetration enhancers on the nano-structure of stratum corneum model membranes studied using neutron diffraction

Annett SCHROETER, Tanja ENGELBRECHT, Reinhard H. H. NEUBERT

期刊论文

沈世钊:大跨结构(2018年6月2日)

2021年04月22日

会议视频

Jian Li:iScience and Interdisciplinary Research(2020年4月2日)

2022年04月18日

会议视频

金涌:化学反应规模的扩大(2018年6月2日)

2021年04月22日

会议视频

徐銤院士解读中国核能(2018年6月2日)

2021年04月22日

会议视频

孙金生:中国油气开采(2018年6月2日)

2021年04月15日

会议视频

2届智能医疗与图像处理国际会议(IMIP 2020)

2020年04月23日

会议信息