Genetically-engineered <i>Salmonella typhimurium</i> expressing TIMP-2 as a therapeutic intervention in an orthotopic glioma mouse model

Wen, Min,Zheng, Jin Hai,Choi, Jin Myung,Pei, Jian,Li, Chun-Hao,Li, Song-Yuan,Kim, In-Young,Lim, Sa-Hoe,Jung, Tae-Young,Moon, Kyung-Sub,Min, Jung-Joon,Jung, Shin Elsevier 2018 Cancer letters Vol.433 No.-

<P><B>Abstract</B></P> <P>Glioma is one of the most devastating and refractory cancers. The main factors underlying therapeutic failure include extremely invasive characteristics and lack of effective methods for drug delivery. Attenuated <I>Salmonella</I> strains presented a high concentration of tumor targets in various types of cancer models, suggesting a role as potential vectors for drug delivery. In this study, we genetically engineered an attenuated strain of <I>Salmonella</I> as an anti-invasive vector for the targeted delivery and expression of tissue inhibitor of metalloproteinases 2 (TIMP-2) in an orthotopic nude mouse model of glioma. The bioluminescence signals related to tumor size significantly declined in the TIMP-2-expressing <I>Salmonella</I> (SLpTIMP-2)-treated group compared with the control group. Compared with the control group with a survival rate of an average of 33 days, the SLpTIMP-2 group showed an extended survival rate by nearly 60% and lasted an average period of 53 days with TIMP-2 induction. These results indicated the promising therapeutic potential of <I>S. typhimurium</I> for targeted delivery and secretion of TIMP-2 in glioma.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Intracranial injection of <I>Salmonella</I> has been demonstrated to be a more effective than tail vein injection. </LI> <LI> Treatment with TIMP-2-expressing bacteria showed down regulation of MMP-2 in orthotopic glioma. </LI> <LI> TIMP-2-expressing bacteria significantly inhibited tumor growth and elongated animal survive. </LI> </UL> </P>

Risk Control of Theme Park

LI Jian-min,ZHENG Ya-nan 인하대학교 정석물류통상연구원 2009 인하대학교 정석물류통상연구원 학술대회 Vol.2009 No.10

As one kind of leisure and tourist attractions, Theme Parks bring enormous business opportunities to the society. Meanwhile, it also has great latent risk for its huge investment. According to statistics, 2,500 theme parks had been built up by 2007 in China, which cost about RMB 150 billion. But there were 70% percent of the parks in loss. The article attempted to generalize the present situation and hidden risks of the theme parks of Chian and look into the causes of external and internal. Through case studies, this article wanted to seek implementing suitable measures to reduce the risk of theme parks from the mutualism point of view and make suggestions further to the risk control of Chinese theme parks.

Combined Expression of Metastasis Related Markers Naa10p, SNCG and PRL-3 and its Prognostic Value in Breast Cancer Patients

Min, Li,Ma, Ruo-Lan,Yuan, Hua,Liu, Cai-Yun,Dong, Bing,Zhang, Cheng,Zeng, Yan,Wang, Li,Guo, Jian-Ping,Qu, Li-Ke,Shou, Cheng-Chao Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

Combinations of multiple biomarkers representing distinct aspects of metastasis may have better prognostic value for breast cancer patients, especially those in late stages. In this study, we evaluated the protein levels of N-${\alpha}$-acetyltransferase 10 protein (Naa10p), synuclein-${\gamma}$ (SNCG), and phosphatase of regenerating liver-3 (PRL-3) in 365 patients with breast cancer by immunohistochemistry. Distinct prognostic subgroups of breast cancer were identified by combination of the three biomarkers. The Naa10p+SNCG-PRL-3-subgroup showed best prognosis with a median distant metastasis-free survival (DMFS) of 140 months, while the Naa10p-SNCG+PRL-3+subgroup had the worst prognosis with a median DMFS of 60.5 months. Multivariate analysis indicated Naa10p, SNCG, PRL-3, and the TNM classification were all independent prognostic factors for both DMFS and overall survival (OS). The three biomarker combination of Naa10p, SNCG and PRL-3 performed better in patients with lymph node metastasis, especially those with more advanced tumors than other subgroups. In conclusion, the combined expression profile of Naa10p, SNCG and PRL-3, alone or in combination with the TNM classification system, may provide a precise estimate of prognosis of breast cancer patients.

A New Ferulic Acid Ester and Other Constituents from Dracocephalum peregrinum

Li-Min Dai,Chun-Chao Zhao,Hui-zi Jin,Yun-Heng Shen,Hui-Liang Li,Cai-Yun Peng,Jian Tang,Wei-Dong Zhang 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.10

A new ferulic acid ester, 1'-methyl-2'-hydroxyethyl ferulate (1), together with methylcaffeate (2), 4- hydroxy cinnamic acid (3), ferulic acid (4), caffeic acid (5), diosmetin (6), luteolin (7), 5,3',4'-trihydroxy- 3,7-dimethoxyflavone (8), eriodictyol (9), kaempferol (10), quercetin (11), acacetin-7-Oglcopyranoside (12), 4-(β-glucopyranosyloxy) benzoic acid (13), luteolin-7-O-(6''-feruloyl) glucopyranoside (14), luteolin-7-O-glucopyranoside (15), kaempferide-3-O-rhamnopyranoside (16), quercitrin (17), kaempferol-3-O-glucopyranoside (18), prunasin (19), quercetin-7-O-glucopyranoside (20), quercetin-3-O-glucopyranoside (21), plantaginin (22), linarin (23), luteolin-7-O-rutinoside (24), and chlorogenic acid (25) were isolated from the aerial parts of Dacocephalum peregrinum. The structure of 1 was elucidated on the basis of spectroscopic and HR-ESI-MS analyses. In addition, compound 1 exhibited mild inhibitory effect on NO production in LPS-stimulated RAW264.7 cells.

EBV-miR-BHRF1-1 Targets p53 Gene: Potential Role in Epstein-Barr Virus Associated Chronic Lymphocytic Leukemia

Dan-Min Xu,Yi-Lin Kong,Li Wang,Hua-Yuan Zhu,Jia-Zhu Wu,Yi Xia,Yue Li,Shu-Chao Qin,Lei Fan,Jian-Yong Li,Jin-Hua Liang,Wei Xu 대한암학회 2020 Cancer Research and Treatment Vol.52 No.2

Purpose The purpose of this study was to investigate the prognostic impact of Epstein-Barr virus (EBV)–microRNA (miRNA, miR)-BHRF1-1 with chronic lymphocytic leukemia (CLL) as well as role of EBV-miR-BHRF1-1 in p53 gene. Materials and Methods Quantitative reverse transcription–polymerase chain reaction and western blotting were used to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL. Results p53 aberration was associated with the higher expression level of EBV-miR-BHRF1-1 (p < 0.001) which was also an independent prognostic marker for overall survival (p=0.028; hazard ratio, 5.335; 95% confidence interval, 1.193 to 23.846) in 97 newly-diagnosed CLL patients after adjusted with International Prognostic Index for patients with CLL. We identified EBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressed luciferase reporter activity by specific interaction with the seed region within the p53 3- untranslated region. Discordance of p53 messenger RNA and protein expression was associated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1- 1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosis and decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53 protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferation in cell lines. Conclusion This study supported the role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our results support the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLL with p53 gene aberration.

A New Ferulic Acid Ester and Other Constituents from Dracocephalum peregrinum

Dai, Li-Min,Zhao, Chun-Chao,Jin, Hui-Zi,Tang, Jian,Shen, Yun-Heng,Li, Hui-Liang,Peng, Cai-Yon,Zhang, Wei-Dong 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.10

A new ferulic acid ester, 1'-methyl-2'-hydroxyethyl ferulate (1), together with methylcaffeate (2), 4-hydroxy cinnamic acid (3), ferulic acid (4), caffeic acid (5), diosmetin (6), luteolin (7), 5,3',4'-trihydroxy-3,7-dimethoxyflavone (8), eriodictyol (9), kaempferol (10), quercetin (11), acacetin-7-O-glcopyranoside (12), 4-($\beta$-glucopyranosyloxy) benzoic acid (13), luteolin-7-O-(6"-feruloyl) glucopyranoside (14), luteolin-7-O-glucopyranoside (15), kaempferide-3-O-rhamnopyranoside (16), quercitrin (17), kaempferol-3-O-glucopyranoside (18), prunasin (19), quercetin-7-O-glucopyranoside (20), quercetin-3-O-glucopyranoside (21), plantaginin (22), linarin (23), luteolin-7-O-rutinoside (24), and chlorogenic acid (25) were isolated from the aerial parts of Dacocephalum peregrinum. The structure of 1 was elucidated on the basis of spectroscopic and HR-ESI-MS analyses. In addition, compound 1 exhibited mild inhibitory effect on NO production in LPS-stimulated RAW264.7 cells.

Comprehensive Bioinformation Analysis of the MRNA Profile of Fascin Knockdown in Esophageal Squamous Cell Carcinoma

Wu, Bing-Li,Luo, Lie-Wei,Li, Chun-Quan,Xie, Jian-Jun,Du, Ze-Peng,Wu, Jian-Yi,Zhang, Pi-Xian,Xu, Li-Yan,Li, En-Min Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Background: Fascin, an actin-bundling protein forming actin bundles including filopodia and stress fibers, is overexpressed in multiple human epithelial cancers including esophageal squamous cell carcinoma (ESCC). Previously we conducted a microarray experiment to analyze fascin knockdown by RNAi in ESCC. Method: In this study, the differentially expressed genes from mRNA expression profilomg of fascin knockdown were analyzed by multiple bioinformatics methods for a comprehensive understanding of the role of fascin. Results: Gene Ontology enrichment found terms associated with cytoskeleton organization, including cell adhesion, actin filament binding and actin cytoskeleton, which might be related to fascin function. Except GO categories, the differentially expressed genes were annotated by 45 functional categories from the Functional Annotation Chart of DAVID. Subpathway analysis showed thirty-nine pathways were disturbed by the differentially expressed genes, providing more detailed information than traditional pathway enrichment analysis. Two subpathways derivated from regulation of the actin cytoskeleton were shown. Promoter analysis results indicated distinguishing sequence patterns and transcription factors in response to the co-expression of downregulated or upregulated differentially expressed genes. MNB1A, c-ETS, GATA2 and Prrx2 potentially regulate the transcription of the downregulated gene set, while Arnt-Ahr, ZNF42, Ubx and TCF11-MafG might co-regulate the upregulated genes. Conclusions: This multiple bioinformatic analysis helps provide a comprehensive understanding of the roles of fascin after its knockdown in ESCC.

Protein-protein Interaction Network Analyses for Elucidating the Roles of LOXL2-delta72 in Esophageal Squamous Cell Carcinoma

Wu, Bing-Li,Zou, Hai-Ying,Lv, Guo-Qing,Du, Ze-Peng,Wu, Jian-Yi,Zhang, Pi-Xian,Xu, Li-Yan,Li, En-Min Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase (LOX) family, is a copper-dependent enzyme that catalyzes oxidative deamination of lysine residues on protein substrates. LOXL2 was found to be overexpressed in esophageal squamous cell carcinoma (ESCC) in our previous research. We later identified a LOXL2 splicing variant LOXL2-delta72 and we overexpressed LOXL2-delta72 and its wild type counterpart in ESCC cells following microarray analyses. First, the differentially expressed genes (DEGs) of LOXL2 and LOXL2-delta72 compared to empty plasmid were applied to generate protein-protein interaction (PPI) sub-networks. Comparison of these two sub-networks showed hundreds of different proteins. To reveal the potential specific roles of LOXL2- delta72 compared to its wild type, the DEGs of LOXL2-delta72 vs LOXL2 were also applied to construct a PPI sub-network which was annotated by Gene Ontology. The functional annotation map indicated the third PPI sub-network involved hundreds of GO terms, such as "cell cycle arrest", "G1/S transition of mitotic cell cycle", "interphase", "cell-matrix adhesion" and "cell-substrate adhesion", as well as significant "immunity" related terms, such as "innate immune response", "regulation of defense response" and "Toll signaling pathway". These results provide important clues for experimental identification of the specific biological roles and molecular mechanisms of LOXL2-delta72. This study also provided a work flow to test the different roles of a splicing variant with high-throughput data.

AN EMPIRICAL EXAMINATION OF THE PEER INFLUENCE ON CROWDFUNDING MARKETS

Yuho Chung,Yiwei Li,Jian-min Jia 글로벌지식마케팅경영학회 2016 Global Marketing Conference Vol.2016 No.7

Crowdfunding has recently emerged as a novel way for people to collect monetary donation from large numbers of internet users. Since 2009, the volume of crowdfunding has increased exponentially, reaching 16.2 billion in 2014. A growing number of literature starts to investigate social influence in crowdfunding that occurs when former backers, who make contribution to fund a project at an earlier stage of fund-raising period, make influences of the contribution decision of latter backers. Crowdfunding can be classified into four categories, namely, lending-based, equity-based, reward-based, and donation-based. The primary goal of lending-based and equity-based crowdfunding is to raise capital and borrow money from a number of investors or lenders in exchange for interest payment or equity share of a company. In contrast, reward-based crowdfunding or donation-based crowdfunding requires a project initiator to create a project, which raise fund to develop a new product (e.g., private good) or enhance the public interest (e.g., public good). In this study, we focus on the two most popular crowdfunding type: reward-based and donation-based crowdfunding projects. In reward-based crowdfunding, backers (or contributors) give a small amount of money in return for a reward such as a copy of creative work or pre-sell products. In donation-based crowdfunding, backers donate to projects for gratitude and the pleasure of giving and expect no compensation in exchange

Molecular Cloning, Identification and Characteristics of a Novel Isoform of Carbamyl Phosphate Synthetase 1 in Human Testis

( Ran Huo ),( Hui Zhu ),( Li Lu ),( Lan Lan Ying ),( Min Xu ),( Zhi Yang Xu ),( Jian Min Li ),( Zuo Min Zhou ),( Jia Hao Sha ) 생화학분자생물학회 2005 BMB Reports Vol.38 No.1

A gene coding a novel isoform of carbamyl phosphate synthetase I (CPSI) was cloned from a human testicular library. As shown by cDNA microarray hybridization, this gene was expressed at a higher level in human adult testes than in fetal testes. The full length of its cDNA was 3831 bp, with a 3149 bp open reading frame, encoding a 1050-amino-acid protein. The cDNA sequence was deposited in the GenBank (AY317138). Sequence analysis showed that it was homologous to the human CPS1 gene. The putative protein contained functional domains composing the intact large subunit of carbamoyl phosphate synthetase, thus indicated it has the capability of arginine biosynthesis. A multiple tissue expression profile showed high expression of this gene in human testis, suggesting the novel alternative splicing form of CPS1 may be correlated with human spermatogenesis.