Potential molecular mechanisms underlying the effect of arsenic on angiogenesis

Juan Zhang,Yue Zhang,Weiyan Wang,Zhiyi Zhang 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.11

Arsenic is a potent chemotherapeutic drug thatis applied as a treatment for cancer; it exerts its functionsthrough multiple pathways, including angiogenesis inhibition. As angiogenesis is a critical component of the progressionof many diseases, arsenic is a feasible treatmentoption for patients with other angiogenic diseases, includingrheumatoid arthritis and psoriasis, among others. However,arsenic is also a well-known carcinogen, demonstrating apro-angiogenesis effect. This review will focus on the dualeffects of arsenic on neovascularization and the relevantmechanisms underlying these effects, aiming to provide arational understanding of arsenic treatment. In particular, weexpect to provide a comprehensive overview of the currentknowledge of the mechanisms by which arsenic influencesangiogenesis.

HIST1H2BN induced cell proliferation and EMT phenotype in prostate cancer via NF-κB signal pathway

Zhang Juan,Chang Yuhan,Xia Haiyan,Xu Luwei,Wei Xiaowei 한국유전학회 2021 Genes & Genomics Vol.43 No.11

Background The potential role of HIST1H2BN in prostate cancer remains unclear. Objective To evaluate the carcinogenic role of HIST1H2BN in prostate cancer. Methods The expression of HIST1H2BN in prostate cancer was analyzed using TCGA database and clinical samples. The roles and mechanisms of HIST1H2BN were investigated in DU145 and PC3 cells. Results HIST1H2BN was signifcantly upregulated in prostate cancer. HIST1H2BN knockdown inhibited cell proliferation, migration and EMT phenotype in prostate cancer cells. Downregulating HIST1H2BN diminished the expression and binding activity of NF-κB p65, then infuenced the expression of MMP2 and MMP9. Conclusion This is the frst study to elaborate a HIST1H2BN-NF-κB-EMT regulatory axis in oncogenesis, indicating that HIST1H2BN might be potential therapeutic target for prostate cancer.

Dissipative Analysis for Nonlinear Singular Systems with Time-delay

Juan Zhou,Qing-Ling Zhang,Yue Zhang,Bo Men 제어·로봇·시스템학회 2017 International Journal of Control, Automation, and Vol.15 No.6

This paper is concerned with the dissipative control problem for a class of nonlinear singular systemswith time-delay. The quadratic supply rate with coefficient matrix Q > 0 and Q 0 are both discussed. Basedon the Lyapunov stability theory, sufficient conditions are given to guarantee that the system is strictly dissipativevia linear matrix inequality technique. Then congruent transformation method and Schur complement lemma arerespectively used to determine corresponding proportional and derivative feedback controller for Q > 0 andQ 0. At last, two examples involve a practical example are given to verify the effectiveness of the method proposed inthis paper.

The Structure-preserving Doubling Numerical Algorithm of the Continuous Coupled Algebraic Riccati Equation

Juan Zhang,Shifeng Li 제어·로봇·시스템학회 2020 International Journal of Control, Automation, and Vol.18 No.7

In the paper, we apply a structure-preserving doubling algorithm to solve the continuous coupled algebraic Riccati equation (CCARE). Using the existence and uniqueness of the CCARE, we show that the iteration solution of the CCARE are positive semi-definite, symmetric, and unique. Further, we discuss the convergent analysis of the structure-preserving doubling algorithm. Moreover, we present two modified structure-preserving doubling algorithms. Finally, we offer corresponding numerical examples to illustrate the effectiveness of the derived numerical algorithms.

Discovery, semisynthesis, biological activities, and metabolism of ocotillol-type saponins

Juan Liu,Yangrong Xu,Jingjing Yang,Wenzhi Wang,Jianqiang Zhang,Renmei Zhang,Qingguo Meng 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.3

Ocotillol-type saponins are one kind of tetracyclic triterpenoids, sharing a tetrahydrofuran ring. Natural ocotillol-type saponins have been discovered in Panax quinquefolius L., Panax japonicus, Hana mina, and Vietnamese ginseng. In recent years, the semisynthesis of 20(S/R)-ocotillol-type saponins has been reported. The biological activities of ocotillol-type saponins include neuroprotective effect, antimyocardial ischemia, antiinflammatory, antibacterial, and antitumor activities. Owing to their chemical structure, pharmacological actions, and the stereoselective activity on antimyocardial ischemia, ocotillol-type saponins are subjected to extensive consideration. In this review, we sum up the discovery, semisynthesis, biological activities, and metabolism of ocotillol-type saponins.

Histone Deacetylase Inhibitor Trichostatin A Enhances Antitumor Effects of Docetaxel or Erlotinib in A549 Cell Line

Zhang, Qun-Cheng,Jiang, Shu-Juan,Zhang, Song,Ma, Xiao-Bin Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

Multi-armed Bandit Online Learning Based on POMDP in Cognitive Radio

Juan Zhang,Hesong-Jiang,Hong Jiang,Chunmei Chen 보안공학연구지원센터 2014 International Journal of Smart Home Vol.8 No.3

Human Embryonic Stem Cells - a Potential Vaccine for Ovarian Cancer

Zhang, Zu-Juan,Chen, Xin-Hua,Chang, Xiao-Hong,Ye, Xue,Li, Yi,Cui, Heng Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.9

Objective: To investigate the therapeutic potential of human embryonic stem cells (hESCs) as a vaccine to induce an immune response and provide antitumor protection in a rat model. Methods: Cross-reactivity of antigens between hESCs and tumour cells was screened by immunohistochemistry. Fischer 344 rats were divided into 7 groups, with 6 rats in each, immunized with: Group 1, hESC; Group 2, pre-inactivated mitotic NuTu-19; Group 3 PBS; Group 4, hESC; Group 5, pre-inactivated mitotic NuTu-19; Group 6, PBS; Group 7, hESC only. At 1 (Groups 1-3) or 4 weeks (Groups 4-6) after the last vaccination, each rat was challenged intraperitoneally with NuTu-19. Tumor growth and animal survival were closely monitored. Rats immunized with H9 and NuTu-19 were tested by Western blot analysis of rat orbital venous blood for cytokines produced by Th1 and Th2 cells. Results: hESCs presented tumour antigens, markers, and genes related to tumour growth, metastasis, and signal pathway interactions. The vaccine administered to rats in Group 1 led to significant antitumor responses and enhanced tumor rejection in rats with intraperitoneal inoculation of NuTu-19 cells compared to control groups. In contrast, rats in Group 4 did not display any elevation of antitumour responses. Western blot analysis found cross-reactivity among antibodies generated between H9 and NuTu-19. However, the cytokines did not show significant differences, and no side effects were detected. Conclusion: hESC-based vaccination is a promising modality for immunotherapy of ovarian cancer.

Synthesis and biological evaluation of glucagon-like peptide-1 receptor agonists

Zhang, Yu-Juan,Shen, Liu-Lan,Cheon, Hyae-Gyeong,Xu, Yong-Nan,Jeong, Jin-Hyun 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.5

In this study, a series of fused-heterocyclic derivatives were systematically designed and synthesized using an efficient route, and evaluated in terms of GLP-1R agonist activity. We employed short synthetic steps and reactions that are tolerant of the presence of various functional groups and suitable for parallel operations to enable the rapid generation of libraries of diverse and structurally complex small molecules. Of the compounds synthesized, 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a] pyridin-2-yl)phenyl methanesulfonate (8e) was the most potent agonist with an $EC_{50}$ of $7.89{\mu}M$, and thus is the compound with the greatest potential for application. These findings represent a valuable starting point for the design and discovery of small-molecule GLP-1R agonists that can be administered orally.

Darapladib, a Lipoprotein-Associated Phospholipase A2 Inhibitor, Reduces Rho Kinase Activity in Atherosclerosis

Juan Zhang,Dong-Ling Xu,Xiao-Bo Liu,Shao-jie Bi,Tong Zhao,Shu-Jian Sui,Xiao-Ping Ji,Qing-Hua Lu 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.2

Purpose: Increased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and Rho kinase activity may be associated with atherosclerosis. The principal aim of this study was to examine whether darapladib (a selective Lp-PLA2 inhibitor) could reduce the elevated Lp-PLA2 and Rho kinase activity in atherosclerosis. Materials and Methods: Studies were performed in male Sprague-Dawley rats. The atherosclerosis rats were prepared by feeding them with a high-cholesterol diet for 10 weeks. Low-dose darapladib (25 mg·kg-1·d-1) and high-dose darapladib (50 mg·kg-1·d-1) interventions were then administered over the course of 2 weeks. Results: The serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoproteincholesterol (HDL-C), high-sensitivity C-reactive protein (hs-CRP), and Lp-PLA2, significantly increased in atherosclerosis model groups, as did Rho kinase activity and cardiomyocyte apoptosis (p<0.05 vs. sham group), whereas nitric oxide (NO) productionwas reduced. Levels of TC, LDL-C, CRP, Lp-PLA2, and Rho kinase activity were respectively reduced in darapladib groups, whereas NO production was enhanced. When compared to the low-dose darapladib group, the reduction of the levels of TC, LDL-C, CRP, and Lp-PLA2 was more prominent in the high-dose darapladib group (p<0.05), and the increase of NO productionwas more prominent (p<0.05). Cardiomyocyte apoptosis of the high-dose darapladib group was also significantly reduced compared to the low-dose darapladib group (p<0.05). However, there was no significant difference in Rho kinase activity between the low-dose darapladib group and the high-dose darapladib group (p>0.05). Conclusion: Darapladib, a Lp-PLA2 inhibitor, leads to cardiovascular protection that might be mediated by its inhibition of both Rho kinase and Lp-PLA2 in atherosclerosis.