IQGAP1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation by Akt activation

Chen, Feng,Zhu, Hai-Hong,Zhou, Lin-Fu,Wu, Shan-Shan,Wang, Jing,Chen, Zhi Korean Society for Biochemistry and Molecular Bion 2010 Experimental and molecular medicine Vol.42 No.7

The scaffold protein IQGAP1 shows elevated levels in several cancer types, but its expression in hepatocellular carcinoma is unknown. We found that 58% of human hepatocellular carcinoma tissue samples had increased IQGAP1 expression compared to adjacent normal tissue. Overexpressing IQGAP1 raised the in vivo tumorigenicity of hepatocellular carcinoma cells, and forced overexpression of IQGAP1 in vitro stimulated cell proliferation. Cell growth was reduced by knockdown or mutation of IQGAP1, or by treatment of cells with a phosphotidylinositol 3-kinase inhibitor. To determine the mechanism by which IQGAP1 overexpression affected hepatocellular carcinoma cells, we confirmed its interaction in these cells with mammalian target of rapamycin (mTOR), a serine/threonine kinase that integrates signals about nutrient and energy status with downstream effectors that influence cell division. In addition, we discovered a new interaction involving IQGAP1, mTOR and Akt, which is a downstream target of mTOR. Akt phosphorylation on Ser-473, which is catalyzed by mTOR and required for Akt activation, increased with increasing amounts of IQGAP1, and decreased with IQGAP1 mutation. We hypothesize that IQGAP1 is a scaffold that facilitates mTOR and Akt interaction.

IQGAP1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation by Akt activation

Feng Chen,Zhi Chen,Hai-Hong Zhu,Lin-Fu Zhou,Shan-Shan Wu,Jing Wang 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.7

The scaffold protein IQGAP1 shows elevated levels in several cancer types, but its expression in hepatocellular carcinoma is unknown. We found that 58%of human hepatocellular carcinoma tissue samples had increased IQGAP1 expression compared to adjacent normal tissue. Overexpressing IQGAP1 raised the in vivo tumorigenicity of hepatocellular carcinoma cells, and forced overexpression of IQGAP1 in vitro stimulated cell proliferation. Cell growth was reduced by knockdown or mutation of IQGAP1, or by treatment of cells with a phosphotidylinositol 3-kinase inhibitor. To determine the mechanism by which IQGAP1 overexpression affected hepatocellular carcinoma cells,we confirmed its interaction in these cells with mammalian target of rapamycin (mTOR), a serine/threonine kinase that integrates signals about nutrient and energy status with downstream effectors that influence cell division. In addition, we discovered a new interaction involving IQGAP1, mTOR and Akt, which is a downstream target of mTOR. Akt phosphorylation on Ser-473, which is catalyzed by mTOR and required for Akt activation, increased with increasing amounts of IQGAP1, and decreased with IQGAP1 mutation. We hypothesize that IQGAP1 is a scaffold that facilitates mTOR and Akt interaction.

A Portable Wireless EEG System for Neurofeedback: Design and Implementation

Chen, Hai-Feng,Ye, Dong-Hee,Kang, Young-Ho,Lee, Jung-Tae The Korean Society of Medical and Biological Engin 2007 의공학회지 Vol.28 No.4

Human can learn how to shape their brain electrical activity in a desired direction through continuous feedback of the electroencephalogram (EEG), and this technique is known as Neurofeedback (or EEG biofeedback), which has been used since the late 1960s in clinical applications. In this study, a portable wireless EEG (named wEEG) has been designed and implemented, which consists of a mobile station (a wireless two-channel EEG acquisition device) and a base station (a bridge between mobile station and computer). Moreover, a SensoriMotor Rhythm (SMR) training system was also implemented with the wEEG for enhancing attention with virtual environment. Experiment results based on 16 volunteers' (8 females and 8 males, average age is $27{\pm}4$) were reported in this paper. The results show that the SMR ratio of 87.5% subjects increased about 0.7% in training status than that in the stable status. With the proposed system, many training protocol scan be designed easily and can be done at home in our daily life conveniently. Additionally, the proposed system will be useful for disabled and aged people.

IL-33 promotes IL-10 production in macrophages: a role for IL-33 in macrophage foam cell formation

Hai-Feng Zhang,Mao-Xiong Wu,Yong-Qing Lin,Shuang-Lun Xie,Tu-Cheng Huang,Pin-Ming Liu,Ru-Qiong Nie,Qin-Qi Meng,Nian-Sang Luo,Yang-Xin Chen,Jing-Feng Wang 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and sitespecific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the − 2000 to − 1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the − 1997 to − 1700 and − 1091 to − 811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.

An Investigation of Surface Roughness in Ultrasonic Assisted Dry Grinding of 12Cr2Ni4A with Large Diameter Grinding Wheel

Hai-Feng Chen,Jin-Yuan Tang,Wen Shao,Bo Zhao 한국정밀공학회 2018 International Journal of Precision Engineering and Vol.19 No.6

Ultrasonic assisted dry grinding (UADG) is a novel green manufacturing technology for decreasing the negative environment impact of cutting fluids and improving the surface characteristics. In this study, the influences of the ultrasonic amplitude, grinding depth and grinding velocity on the surface roughness in ultrasonic assisted dry grinding of 12Cr2Ni4A with a large CBN grinding wheel were investigated. Due to the Poisson effect, the ultrasonic assisted dry grinding using a large diameter grinding wheel is the combination of axial ultrasonic assisted grinding and radial ultrasonic assisted grinding. The results indicated that the main axial ultrasonic component tended to smooth the surface topography by increasing the interaction overlap of the adjacent cutting traces, but it would result in more side flow/ploughing on the surface at a larger ultrasonic amplitude; the radial ultrasonic component exerted a function on the increase of the surface roughness through deepening the individual grinding trajectories. Thus, the surface roughness decreased first and then increased with the increase of grinding depth due to the combined contribution of axial and radial vibrations. However, the improving effect of ultrasonic vibration on the surface roughness gradually weakened with the increase of grinding velocity. Under proper operating parameters, surface roughness obtained in ultrasonic assisted dry grinding can be reduced up to 30% compared with that of common dry grinding.

Molecular Biology and Omics : Direct Evaluation of the Effect of Gene Dosage on Secretion of Protein from Yeast Pichia pastoris by Expressing EGFP

( Hai Long Liu ),( Yu Feng Qin ),( Yuan Kai Huang ),( Yao Sheng Chen ),( Pei Qing Cong ),( Zu Yong He ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.2

Increasing the gene copy number has been commonly used to enhance the protein expression level in the yeast Pichia pastoris. However, this method has been shown to be effective up to a certain gene copy number, and a further increase of gene dosage can result in a decrease of expression level. Evidences indicate the gene dosage effect is product-dependent, which needs to be determined when expressing a new protein. Here, we describe a direct detection of the gene dosage effect on protein secretion through expressing the enhanced green fluorescent protein (EGFP) gene under the direction of the α-factor preprosequence in a panel of yeast clones carrying increasing copies of the EGFP gene (from one to six copies). Directly examined under fluorescence microscopy, we found relatively lower levels of EGFP were secreted into the culture medium at one copy and two copies, substantial improvement of secretion appeared at three copies, plateau happened at four and five copies, and an apparent decrease of secretion happened at six copies. The secretion of EGFP being limiting at four and five copies was due to abundant intracellular accumulation of proteins, observed from the fluorescence image of yeast and confirmed by western blotting, which significantly activated the unfolded protein response indicated by the up-regulation of the BiP (the KAR2 gene product) and the protein disulfide isomerase. This study implies that tagging a reporter like GFP to a specific protein would facilitate a direct and rapid determination of the optimal gene copy number for high-yield expression.

Structural Maintenance of Chromosomes 4 is a Predictor of Survival and a Novel Therapeutic Target in Colorectal Cancer

Feng, Xiao-Dong,Song, Qi,Li, Chuan-Wei,Chen, Jian,Tang, Hua-Mei,Peng, Zhi-Hai,Wang, Xue-Chun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Background: Structural maintenance of chromosomes 4 (SMC-4) is a chromosomal ATPase which plays an important role in regulate chromosome assembly and segregation. However, the role of SMC-4 in the incidence of malignancies, especially colorectal cancer is still poorly understood. Materials and Methods: We here used quantitative PCR and Western blot analysis to examine SMC-4 mRNA and protein levels in primary colorectal cancer and paired normal colonic mucosa. SMC-4 clinicopathological significance was assessed by immunohistochemical staining in a tissue microarray (TMA) in which 118 cases of primary colorectal cancer were paired with noncancerous tissue. The biological function of SMC-4 knockdown was measured by CCK8 and plate colony formation assays. Fluorescence detection has been used to detect cell cycling and apoptosis. Results: SMC-4 expression was significantly higher in colorectal cancer and associated with T stage, N stage, AJCC stage and differentiation. Knockdown of SMC-4 expression significantly suppressed the proliferation of cancer cells and degraded its malignant degree. Conclusions: Our clinical and experimental data suggest that SMC-4 may contribute to the progression of colorectal carcinogenesis. Our study provides a new therapeutic target for colorectal cancer treatment.

TobpreproHypSys-A Gene Expression and Defense Protein Activity in the Tobacco Wounding Response

( Feng Ren ),( Hai Jiang Lian ),( Liang Chen ) 한국식물학회 2008 Journal of Plant Biology Vol.51 No.1

Efficacy of Pap Test in Combination with ThinPrep Cytological Test in Screening for Cervical Cancer

Chen, Hua,Shu, Hui-Min,Chang, Zhou-Lin,Wang, Zhi-Feng,Yao, Hai-Hong,Zhu, Hong-Mei,Lu, Tian-Mei,Ma, Qiang-Yan,Yang, Bin-Lie Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Background: Our aim was to investigate the efficacy of the Pap test in combination with the ThinPrep cytological test (TCT) in screening for cervical cancer in China. Design: From March 2006 to October 2008, 988 women with the mean age $46.4{\pm}10.5$ years (range, 23-80 years) were recruited to receive cervical cancer screening. Pap test results ${\geq}$ grade III and TCT findings ${\geq}$ ASCUS/AGUS were considered abnormal. Subjects with a Pap test result ${\geq}$ grade IIb received TCT. Colposcopy and biopsies were performed in all participants, and final diagnosis was based on pathological findings. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Youden index for predicting CIN I or above were determined. Results: The sensitivity, specificity, PPV, NPV and Youden index of the Pap test were 43.1%, 97.2%, 70.0%, 91.9%, and 40.3%, respectively. The same values for TCT in predicting CIN were 80.0%, 63.2%, 16.0%, 97.3%, and 43.2%, respectively. The two tests in combination gave values for predicting CIN of 64.8%, 87.6%, 43.6%, 94.4%, and 53.5%, respectively. Combined testing exhibited the highest Youden index (53.4%). Conclusion: The Pap test with a reduced threshold in combination with the TCT has high sensitivity and high specificity in screening for cervical cancer.

Modal parameter identification of civil structures using symplectic geometry mode decomposition

Feng Hu,Lun-hai Zhi,Zhixiang Huang,Bo Chen 한국풍공학회 2023 Wind and Structures, An International Journal (WAS Vol.36 No.1

In this article, a novel structural modal parameters identification methodology is developed to determine the natural frequencies and damping ratios of civil structures based on the symplectic geometry mode decomposition (SGMD) approach. The SGMD approach is a new decomposition algorithm that can decompose the complex response signals with better decomposition performance and robustness. The novel method firstly decomposes the measured structural vibration response signals into individual mode components using the SGMD approach. The natural excitation technique (NExT) method is then used to obtain the free vibration response of each individual mode component. Finally, modal natural frequencies and damping ratios are identified using the direct interpolating (DI) method and a curve fitting function. The effectiveness of the proposed method is demonstrated based on numerical simulation and field measurement. The structural modal parameters are identified utilizing the simulated non-stationary responses of a frame structure and the field measured non-stationary responses of a supertall building during a typhoon. The results demonstrate that the developed method can identify the natural frequencies and damping ratios of civil structures efficiently and accurately.