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.

Molecular Cloning and Bioinformatic Analysis of SPATA4 Gene

Liu, Shang-Feng,Ai, Chao,Ge, Zhong-Qi,Liu, Hai-Luo,Liu, Bo-Wen,He, Shan,Wang, Zhao Korean Society for Biochemistry and Molecular Biol 2005 Journal of biochemistry and molecular biology Vol.38 No.6

Full-length cDNA sequences of four novel SPATA4 genes in chimpanzee, cow, chicken and ascidian were identified by bioinformatic analysis using mouse or human SPATA4 cDNA fragment as electronic probe. All these genes have 6 exons and have similar protein molecular weight and do not localize in sex chromosome. The mouse SPATA4 sequence is identified as significantly changed in cryptorchidism, which shares no significant homology with any known protein in swissprot databases except for the homologous genes in various vertebrates. Our searching results showed that all SPATA4 proteins have a putative conserved domain DUF1042. The percentages of putative SPATA4 protein sequence identity ranging from 30% to 99%. The high similarity was also found in 1 kb promoter regions of human, mouse and rat SPATA4 gene. The similarities of the sequences upstream of SPATA4 promoter also have a high proportion. The results of searching SymAtlas (http://symatlas.gnf.org/SymAtlas/) showed that human SPATA4 has a high expression in testis, especially in testis interstitial, leydig cell, seminiferous tubule and germ cell. Mouse SPATA4 was observed exclusively in adult mouse testis and almost no signal was detected in other tissues. The pI values of the protein are negative, ranging from 9.44 to 10.15. The subcellular location of the protein is usually in the nucleus. And the signal peptide possibilities for SPATA4 are always zero. Using the SNPs data in NCBI, we found 33 SNPs in human SPATA4 gene genomic DNA region, with the distribution of 29 SNPs in the introns. CpG island searching gives the data about CpG island, which shows that the regions of the CpG island have a high similarity with each other, though the length of the CpG island is different from each other.This research is a fundamental work in the fields of the bioinformational analysis, and also put forward a new way for the bioinformatic analysis of other genes.

Molecular Cloning and Bioinformatic Analysis of SPATA4 Gene

Shang Feng Liu,Chao Ai,Zhong Qi Ge,Hai Luo Liu,Bo Wen Liu,Shan He,Zhao Wang 한국생활환경학회 2005 BMB Reports Vol.38 No.6

Multiple Impairments in Male Reproduction 1 (mimr1), a Novel Male-Sterile Mutant of Arabidopsis thaliana, Shows Several Defects in Male Reproductive Development

Hai-Yan Chen,Yue-Feng Guan,Xue-Yong Huang,Yu-Ting Wu,Fen-Fei Wang,Ju-Fang Gao,Que Zhou,Zhong-Nan Yang,Jia-Yao Liu,Hong-Xia Zhang 한국식물학회 2012 Journal of Plant Biology Vol.55 No.3

We have characterized a new male-sterile mutant in Arabidopsis that exhibits conditional sterility but has restored fertility when drought-stressed. This mutant,multiple impairments in male reproduction 1 (mimr1),shows pleiotropic defects in both vegetative and reproductive development. Examination with dissecting and scanning electron microscopes revealed that its pollen grains are not effectively released from the anther locule after dehiscence, and anther differentiation is defective. Growth of the style and stamen filaments are also abnormal. Histological analysis demonstrated that these phenomena are due not only to a noticeably reduced extension of the stamen but also greater elongation of the pistil. Genetic analysis indicated that mimr1 is a single locus recessive nuclear mutant. The mutation can be mapped to a locus strongly linked to a 1200-kb region on Chromosome 3. Meta-analysis of expression patterning presented several candidate genes in that region. No mutants with similar phenotypes have previously been reported, suggesting that mimr1 is a novel male-sterile locus. Characterization of MIMR1 will provide further insights into the molecular basis for the development of plant reproductive organs.

Enhanced x-ray irradiation-induced cancer cell damage by gold nanoparticles treated by a new synthesis method of polyethylene glycol modification

Liu, Chi-Jen,Wang, Chang-Hai,Chien, Chia-Chi,Yang, Tsung-Yeh,Chen, Shin-Tai,Leng, Wei-Hua,Lee, Cheng-Feng,Lee, Kuen-Ho,Hwu, Y,Lee, Yao-Chang,Cheng, Chia-Liang,Yang, Chung-Shi,Chen, Y J,Je, J H,Margari IOP Pub 2008 Nanotechnology Vol.19 No.29

<P>We explored a very interesting gold nanoparticle system—pegylated gold in colloidal solution—and analyzed its uptake by mice colorectal adenocarcinoma CT26 tumor cells and the impact on the cell’s response to x-ray irradiation. We found that exposure to polyethylene glycol (PEG) modified (‘pegylated’) 4.7 ± 2.6 nm gold nanoparticles synthesized by a novel synchrotron-based method enhances the response of CT26 cells to x-ray irradiation. Transmission electron microscopy (TEM) and confocal microscopy revealed that substantial amounts of such nanoparticles are taken up and absorbed by the cells and this conclusion is supported by quantitative induced coupled plasma (ICP) results. Standard tests indicated that the internalized particles are highly biocompatible but strongly enhance the cell damage induced by x-ray irradiation. Synchrotron radiation Fourier transform infrared (SR-FTIR) spectromicroscopy analyzed the chemical aspects of this phenomenon: the appearance of C = O stretching bond spectral features could be used as a marker for cell damage and confirmed the enhancement of the radiation-induced toxicity for cells.</P>

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.

Selective miRNA Expression Profile in Chronic Myeloid Leukemia K562 Cell-derived Exosomes

Feng, Dan-Qin,Huang, Bo,Li, Jing,Liu, Jing,Chen, Xi-Min,Xu, Yan-Mei,Chen, Xin,Zhang, Hai-Bin,Hu, Long-Hua,Wang, Xiao-Zhong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of hematopoietic stem cell scarrying the Philadelphia (Ph) chromosome and an oncogenic BCR-ABL1 fusion gene. The tyrosine kinase inhibitor (TKI) of BCR-ABL1 kinase is a treatment of choice for control of CML. Objective: Recent studies have demonstrated that miRNAs within exosomes from cancer cells play crucial roles in initiation and progression. This study was performed to assess miRNAs within exosomes of K562 cells. Methods: miRNA microarray analysis of K562 cells and K562 cell-derived exosomes was conducted with the 6th generation miRCURYTM LNA Array (v.16.0). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also carried out. GO terms and signaling pathways were categorized into 66 classes (including homophilic cell adhesion, negative regulation of apoptotic process, cell adhesion) and 26 signaling pathways (such as Wnt). Results: In exosomes, 49 miRNAs were up regulated as compared to K562 cells, and two of them were further confirmed by quantitative real-time PCR. There are differentially expressed miRNAs between K562 cell derived-exosomes and K562 cells. Conclusion: Selectively expressed miRNAs in exosomes may promote the development of CML via effects on interactions (e.g. adhesion) of CML cells with their microenvironment.

Whole Brain Radiotherapy Plus Chemotherapy in the Treatment of Brain Metastases from Lung Cancer: A Meta-analysis of 19 Randomized Controlled Trails

Liu, Wen-Jing,Zeng, Xian-Tao,Qin, Hai-Feng,Gao, Hong-Jun,Bi, Wei-Jing,Liu, Xiao-Qing Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Objective: To evaluate the efficacy and safety of whole brain radiotherapy (WBRT) plus chemotherapy versus WBRT alone for treating brain metastases (BM) from lung cancer by performing a meta-analysis based on randomized controlled trials (RCTs). Methods: The PubMed, Embase, CENTRAL, ASCO, ESMO, CBM, CNKI, and VIP databases were searched for relevant RCTs performed between January 2000 and March 2012. After quality assessment and data extraction, the meta-analysis was performed using the RevMan 5.1 software, with funnel plot evaluation of publication bias. Results: 19 RCTs involving 1,343 patients were included. The meta-analyses demonstrated that compared to WBRT alone, WBRT plus chemotherapy was more effective with regard to the objective response rate (OR = 2.30, 95% CI = 1.79 - 2.98; P < 0.001); however, the incidences of gastrointestinal reactions (RR = 3.82, 95% CI = 2.33 - 6.28, P <0.001), bone marrow suppression (RR = 5.49, 95% CI = 3.65 - 8.25, P < 0.001), thrombocytopenia (RR = 5.83, 95% CI = 0.39 - 86.59; P = 0.20), leukopenia (RR = 3.13, 95% CI = 1.77 - 5.51; P < 0.001), and neutropenia (RR = 2.75, 95% CI = 1.61 - 4.68; P < 0.001) in patients treated with WBRT plus chemotherapy were higher than with WBRT alone. There was no obvious publication bias detected. Conclusion: WBRT plus chemotherapy can obviously improve total efficacy rate, butalso increases the incidence of adverse reactions compared to WBRT alone. From the limitations of this study, more large-scale, high-quality RCTs are suggested for further verification.

Roles of Signaling Pathways in the Epithelial-Mesenchymal Transition in Cancer

Liu, Xia,Yun, Fen,Shi, Lin,Li, Zhe-Hai,Luo, Nian-Rong,Jia, Yong-Feng Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

The epithelial-mesenchymal transition (EMT) is a cellular process though which an epithelial phenotype can be converted into a phenotype of mesenchymal cells. Under physiological conditions EMT is important for embryogenesis, organ development, wound repair and tissue remodeling. However, EMT may also be activated under pathologic conditions, especially in carcinogenesis and metastatic progression. Major signaling pathways involved in EMT include transforming growth factor ${\beta}(TGF-{\beta})$, Wnt, Notch, Hedgehog and other signaling pathways. These pathways are related to several transcription factors, including Twist, Smads and zinc finger proteins snail and slug. These interact with each other to provide crosstalk between the relevant signaling pathways. This review lays emphasis on studying the relationship between EMT and signaling pathways in carcinogenesis and metastatic progression.

Adaptive Gaussian Mechanism Based on Expected Data Utility under Conditional Filtering Noise

( Hai Liu ),( Zhenqiang Wu ),( Changgen Peng ),( Feng Tian ),( Laifeng Lu ) 한국인터넷정보학회 2018 KSII Transactions on Internet and Information Syst Vol.12 No.7

Differential privacy has broadly applied to statistical analysis, and its mainly objective is to ensure the tradeoff between the utility of noise data and the privacy preserving of individual’s sensitive information. However, an individual could not achieve expected data utility under differential privacy mechanisms, since the adding noise is random. To this end, we proposed an adaptive Gaussian mechanism based on expected data utility under conditional filtering noise. Firstly, this paper made conditional filtering for Gaussian mechanism noise. Secondly, we defined the expected data utility according to the absolute value of relative error. Finally, we presented an adaptive Gaussian mechanism by combining expected data utility with conditional filtering noise. Through comparative analysis, the adaptive Gaussian mechanism satisfies differential privacy and achieves expected data utility for giving any privacy budget. Furthermore, our scheme is easy extend to engineering implementation.