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Superenhancers as master gene regulators and novel therapeutic targets in brain tumors
Zhuang Hai-Hui,Qu Qiang,Teng Xin-Qi,Dai Ying-Huan,Qu Jian 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Transcriptional deregulation, a cancer cell hallmark, is driven by epigenetic abnormalities in the majority of brain tumors, including adult glioblastoma and pediatric brain tumors. Epigenetic abnormalities can activate epigenetic regulatory elements to regulate the expression of oncogenes. Superenhancers (SEs), identified as novel epigenetic regulatory elements, are clusters of enhancers with cell-type specificity that can drive the aberrant transcription of oncogenes and promote tumor initiation and progression. As gene regulators, SEs are involved in tumorigenesis in a variety of tumors, including brain tumors. SEs are susceptible to inhibition by their key components, such as bromodomain protein 4 and cyclin-dependent kinase 7, providing new opportunities for antitumor therapy. In this review, we summarized the characteristics and identification, unique organizational structures, and activation mechanisms of SEs in tumors, as well as the clinical applications related to SEs in tumor therapy and prognostication. Based on a review of the literature, we discussed the relationship between SEs and different brain tumors and potential therapeutic targets, focusing on glioblastoma.
( Jian Ping Li ),( Yu Li Lin ),( Hong Qin Zhuang ),( Zi Chun Hua ) 한국미생물 · 생명공학회 2013 Journal of microbiology and biotechnology Vol.23 No.9
Urokinase (uPA) and its receptor (uPAR) play an important role in tumor growth and metastasis. Targeting the excessive activation of this system as well as the proliferation of the tumor vascular endothelial cell would be expected to prevent tumor neovasculature and halt the tumor development. In this regard, the amino-terminal fragment (ATF) of urokinase has been confirmed as effective to inhibit the proliferation, migration, and invasiveness of cancer cells via interrupting the interaction of uPA and uPAR. Previous studies indicated that ATF expressed in Escherichia coli was mainly contained in inclusion bodies and also lacked posttranslational modifications. In this study, the biologically active and soluble ATF was cloned and expressed in Pichia pastoris. The recombinant protein was purified to be homogenous and confirmed to be biologically active. The yield of the active ATF was about 30 mg/l of the P. pastoris culture medium. The recombinant ATF (rATF) could efficiently inhibit angiogenesis, endothelial cell migration, and tumor cell invasion in vitro. Furthermore, it could inhibit in vivo xenograft tumor growth and prolong the survival of tumor-bearing mice significantly by competing with uPA for binding to cell surfaces. Therefore, P. pastoris is a highly efficient and cost-effective expression system for large-scale production of biologically active rATFs for potential therapeutic application.
A SANDWICH-INJECTION METHOD FOR MICROCHIP ELECTROPHORESIS
JIAN-LONG ZHAO,GANG LI,GUI-SHENG ZHUANG,HONG-BO ZHOU,YUAN-SEN XU 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2007 NANO Vol.2 No.6
In microchip electrophoresis (μ-CE), sample injection is generally achieved through cross, double-T, or T-form injector structures. In these reported approaches, the separation efficiency and detection sensitivity of μ-CE is significantly influenced by the shape and size of the sample plug introduced into the separation channel or sample leakage in separation phase. Here, we present a sandwich-injection method for controlling discrete sample injection in μ-CE. This method involves four accessory arm channels in which symmetrical potentials are loaded to form a unique parallel electric field distribution at the intersection of sample and separation channels. The parallel electric field effectuate a virtual wall to confine the shape of a sample plug and depress the spreading of the sample plug at the junction of sample and separation channels, and also prevent sample leakage during separation step. The key features of this method are the ability to inject well-defined sample plugs at the original sample concentration and the ability to control the sample plug size. The virtues of the novel injection technique were demonstrated with numerical models and validated with fluorescence visualizations of electrophoretic experiments.
Substituent Effects of Accelerator on Nitroxide-Mediated Radical Polymerization
Jian-ying Huang,Jia-ming Zhuang,You-si Zou 한국고분자학회 2011 Macromolecular Research Vol.19 No.8
The acceleration effect of various agents on the rate of styrene bulk polymerization in 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) mediated polymerization was investigated, including dimethyl malonate (DMM), diethyl methyl malonate (DEMM), diethyl tert-butylmalonate (DEBM), diethyl diethylmalonate (DEDEM), 3-methyl-2,4-pentanedione (MPD), acetyl malononitrile (Ac-MN), and dimethyl malononitrile (DM-MN). Polymerization with the additive proceeded in a living manner, as indicated by keeping a low polydispersity and increasing the molecular weight with the reaction time and conversion. The structure of the styrene polymerization did not change in the presence of these additives. The monomer conversion efficiency was approximately 99% and maintained a relatively narrow polydispersity of 1.29 with the optimal [Ac-MN]/[TEMPO] molar ratios of 4 in 1.5 h. With the accelerator,dipole/dipole interactions led to a weakening of the C-ON bond and an acceleration of the reaction. There is a trend for a higher polymerization rate with more electron-withdrawing substituents.
Ze-Jian Wang,Xingzi Zhang,Ping Wang,Zhiwei Sui,Meijin Guo,Siliang Zhang,Yingping Zhuang 한국생물공학회 2020 Biotechnology and Bioprocess Engineering Vol.25 No.3
The effects of different oxygen uptake rates (OUR) on the physiological metabolism of Rhodobacter sphaeroides were investigated systematically in 50 L fermenters due to the significant influence on industrial coenzyme Q10 production under oxygen supply limitation. Meanwhile, the seriously decreased oxygen transfer rate caused by the increased broth viscosity was successfully prevented with OUR-directed continuous ammonium sulfate feeding in the late fermentation phase. The statistical analysis results showed that controlling OUR constantly at 45 ± 2.2 mmol/L/h by the oxygen supply level adjustment and the continuous ammonium sulfate feeding could greatly enhance Q10 production. This OUR-Stat controlling strategy successfully achieved the maximal coenzyme Q10 production (2584 ± 82 mg/L), which was 15.4% higher than that of the control. The highest specific CoQ10 content was 25.9 mg/(g DCW)), and the yield of CoQ10 to glucose consumption was up to 19.37 mg/g. These results demonstrated that the optimal OUR-Stat controlling strategy would be effective and economical for improving the industrial CoQ10 production.
Zhu, Jian,Chu, Bing-Feng,Yang, Yi-Peng,Zhang, Sheng-Lai,Zhuang, Ming,Lu, Wen-Jie,Liu, Ying-Bin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5
Objective: This study aimed to investigate the expression of B7-H4 in human thyroid cancer and determine any association with patient clinicopathological parameters and survival. Methods: B7-H4 expression in 64 clinical thyroid cancer specimens was assessed with immunohistochemistry. Moreover, B7-H4 mRNA expression in 10 fresh resected specimens were evaluated by the reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical staining of CD3 was performed to assess the number of tumor infiltrating T lymphocytes (TILs) in thyroid cancers. Results: Positive B7-H4 immunohistochemical staining was observed in 61 out of 64 (95.3%) specimens of thyroid cancer tissues. Significantly more B7-H4 mRNA copies were found in thyroid cancer tissue than that adjacent normal tissue. Moreover, B7-H4 expression in human thyroid cancer tissues was significantly correlated with patient TNM stages and extrathyroidal extension (P<0.05), being inversely correlated with the number of TILs (P<0.05). The overall survival rate of the patients with higher B7-H4 expression was significantly worse than that of the patients with lower B7-H4 expression. Conclusions: This present study suggests that high B7-H4 expression is associated with cancer progression, reduced tumor immunosurveillance and worse patient outcomes in human thyroid cancer.
Jiangzhou Zhuang,Xiaoyin Jin,Xianlin Shen,Junjun Tan,Longhui Nie,Jian Xiong,Bing Hu 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.7
A series of catalysts, ionic liquid-modified SBA-15 (denoted ILSBA) doped with H5PMo10V2O40 (HPMoV2) have been synthesized and characterized by XRD, FT-IR, 1H NMR, TG-DTA, and TEM. The catalyst was used for the removal of dibenzothiophene (DBT) in model oil combined with hydrogen peroxide (the oxidant) and acetonitrile (the phase-transfer agent). It was observed that the sulfur content of DBT can be reduced from 500 to 2 ppm by adjusting the amount of catalyst, the reaction temperatures and the reaction time. Besides, the catalyst activity for different sulfur compounds showed a huge difference which may be mainly affected by the electron densities of sulfur atom. Moreover, the catalyst can be recycled seven times without a significant loss in activity, which could be ascribed to the strong electrostatic interaction between ILSBA and HPMoV2. In addition, a postulated mechanism was proposed to reveal the oxidative desulfurization process.