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Assessment of Biomarkers in Acetaminophen-Induced Hepatic Toxicity by siRNA

  • Kang, Jin-Seok;Yum, Young-Na;Kim, Joo-Hwan;Park, Sue-Nie
    • Biomolecules & Therapeutics
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    • v.17 no.4
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    • pp.438-445
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    • 2009
  • We investigated global gene expression from both mouse liver and mouse hepatic cell lines treated with acetaminophen (APAP) in order to compare in vivo and in vitro profiles and to assess the feasibility of the two systems. During our analyses of gene expression profiles, we picked up several down-regulated genes, such as the cytochrome P450 family 51 (Cyp51), sulfotransferase family cytosolic 1C member 2 (Sult1c2), 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgcs1), and several genes that were up-regulated by APAP, such as growth arrest and DNA-damage-inducible 45 alpha (Gadd45a), transformation related protein 53 inducible nuclear protein 1 (Trp53inp1) and zinc finger protein 688 (Zfp688). For validation of gene function, synthesized short interfering RNAs (siRNAs) for these genes were transfected in a mouse hepatic cell line, BNL CL.2, for investigation of cell viability and mRNA expression level. We found that siRNA transfection of these genes induced down-regulation of respective mRNA expression and decreased cell viability. siRNA transfection for Cyp51 and others induced morphological alterations, such as membrane thickening and nuclear condensation. Taken together, siRNA transfection of these six genes decreased cell viability and induced alteration in cellular morphology, along with effective inhibition of respective mRNA, suggesting that these genes could be associated with APAP-induced toxicity. Furthermore, these genes may be used in the investigation of hepatotoxicity, for better understanding of its mechanism.

Measuring the Seriousness of Adverse Drug Reactions : Comparisons between Korean Experts and WHO Working Group Members (의약품 부작용의 심각도 조사 비교분석)

  • Rhee, Jin-Nie;Park, Se-Young;Heo, Ji-Haeng;Park, Mi-Hae;Ha, Ji-Hye;Lee, Eui-Kyung
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.3
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    • pp.237-242
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    • 2011
  • This study measures seriousness of adverse drug reactions (ADRs) among Korean physicians and pharmacists using two times surveys based on Delphi technique. Each participant scored 20 ADR terms on a scale of one to ten (10 being the most serious). We repeated the exercise for the 49 first survey respondents and 32 re-evaluated score. We compared the results of our survey with those of WHO CIOMS (Council for International Organization of Medical Sciences) working groups members conducted in 1995. The overall mean ADR seriousness score was 6.49 for Koreans and 5.12 for WHO CIOMS members, presenting Korean experts perceived more seriously for each ADR. Mean score changes for the same respondents showed similar trends regardless of access to the first survey results. There were no statistically significant score differences between the physicians and the pharmacists. The high consensus of seriousness for each ADR between the Korean experts and the WHO CIOMS members implies that the similar results are reproducible, suggesting the possibility of developing standardized tools for measuring the seriousness of individual ADRs in the future.

Clenbuterol Inhibits SREBP-1c Expression by Activating CREB1

  • Zhou, Lei;Li, Yixing;Nie, Tao;Feng, Shengqiu;Yuan, Jihong;Chen, Huaping;Yang, Zaiqing
    • BMB Reports
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    • v.40 no.4
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    • pp.525-531
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    • 2007
  • As a $\beta_2$-adrenergic agonist, clenbuterol decreases body fat, but the molecular mechanism underlying this process is unclear. In the present study, we treated 293T and L-02 cells with clenbuterol and found that clenbuterol downregulates SREBP-1c expression and upregulates CREB1 expression. Considering SREBP-1c has the function of regulating the transcription of several lipogenic enzymes, we considered that the downregulation of SREBP-1c is responsible for body fat reduction by clenbuterol. Many previous studies have found that clenbuterol markedly increases intracellular cAMP levels, therefore, we also investigated whether CREB1 is involved in this process. The data from our experiments indicate that CREB1 overexpression inhibits SREBP-1c transcription, and that this action is antagonized by CREB2, a competitive inhibitor of CREB1. Furthermore, since PPARs are able to repress SREBP-1c transcription, we investigated whether clenbuterol and CREB1 function via a pathway involving PPAR activation. However, our results showed that clenbuterol or CREB1 overexpression suppressed PPARs transcription in 293T and L-02 cells, which suggested that they impair SREBP-1c expression in other ways.

Genetic Variation of Taenia Pisiformis Collected from Sichuan, China, Based on the Mitochondrial Cytochrome b gene

  • Yang, Deying;Ren, Yongjun;Fu, Yan;Xie, Yue;Nie, Huaming;Nong, Xiang;Gu, Xiaobin;Wang, Shuxian;Peng, Xuerong;Yang, Guangyou
    • Parasites, Hosts and Diseases
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    • v.51 no.4
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    • pp.449-452
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    • 2013
  • Taenia pisiformis is one of the most important parasites of canines and rabbits. T. pisiformis cysticercus (the larval stage) causes severe damage to rabbit breeding, which results in huge economic losses. In this study, the genetic variation of T. pisiformis was determined in Sichuan Province, China. Fragments of the mitochondrial cytochrome b (cytb) (922 bp) gene were amplified in 53 isolates from 8 regions of T. pisiformis. Overall, 12 haplotypes were found in these 53 cytb sequences. Molecular genetic variations showed 98.4% genetic variation derived from intra-region. $F_{ST}$ and Nm values suggested that 53 isolates were not genetically differentiated and had low levels of genetic diversity. Neutrality indices of the cytb sequences showed the evolution of T. pisiformis followed a neutral mode. Phylogenetic analysis revealed no correlation between phylogeny and geographic distribution. These findings indicate that 53 isolates of T. pisiformis keep a low genetic variation, which provide useful knowledge for monitoring changes in parasite populations for future control strategies.

Production and Prophylactic Efficacy Study of Human Papillomavirus-like Particle Expressing HPV16 L1 Capsid Protein

  • Park, Jie-Yun;Pyo, Hyun-Mi;Yoon, Sun-Woo;Baek, Sun-Young;Park, Sue-nie;Kim, Chul-Joong;Haryoung Poo
    • Journal of Microbiology
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    • v.40 no.4
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    • pp.313-318
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    • 2002
  • To perform the prophylactic study of a vaccine derived from human papillomavirus (HPV) using Balb/c mice, we produced virus like particles consisting of HPV capsid protein L1 which has been reported to induce significant humoral and cellular immunity using various animal model systems. In order to produce HPV16 VLPs, the cDNA of L1 capsid protein in HPV type 16, obtained by polymerase chain reaction, was inserted into yeast expression vector, YEG$\alpha$-HIR525 under the control of GAL10 promoter. The transformation of YEG$\alpha$-HPV16 L1 was performed into the yeast Saccharomyces cerevisiae Y2805 by the lithium acetate method and the yeast clone expressing the highest level of L1 capsid protein of human papillomavirus type 16 was selected by Western blot analysis using anti-HPV16 L1 antibody. The purification of HPV16 VLP has been performed by the ultracentrifugation and gel-filtration methods. To validate the vaccine efficacy of the purified HPV16 VLPs and investigate the properties of HPV16 VLPs to induce humoral immunity, ELISA assay was performed. A significantly increased production of anti-HPV16 VLP antibodies was observed in sera from immunized mice. The neutralization activity of antibodies in the sera from the vaccinated mice was demonstrated by a rapid and simple assay to detect hemagglutihation inhibition activity.

Development of a Screening System for Drugs Against Human Papillomavirus-Associated Cervical Cancer: Based On E7-Rb Binding

  • Cho, Young-Sik;Cho, Cheong-Weon;Kang, Jeong-Woo;Cho, Min-Chul;Lee, Kyung-Ae;Shim, Jung-Hyun;Kwon, Our-Han;Choe, Yong-Kyung;Park, Sue-Nie;Yoon, Do-Young
    • BMB Reports
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    • v.34 no.1
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    • pp.80-84
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    • 2001
  • The human papillomavirus E7 protein can form a specific complex with a retinoblastoma tumor suppressor gene product (p105-Rb) that results in the release of the E2F transcription factor, which is critical for the growth-deregulation and transforming properties of the viral E7 oncoprotein. In an attempt to apply interaction between the E7 oncoprotein and a target cellular protein Rb for an in vitro screening system for drugs against human papillomavirus infection, we primarily investigated the E7Rb binding through a pull down assay and enzyme-linked immunosorbent assay. The pull down assay showed that both glutathione S-transferase-tagged E7 and His-tagged E7 immobilized on resins specifically produced complexes with bacterially expressed Rb in a dose-dependent manner, as determined by immunoblot analyses. This result coincided with that of an enzyme-linked immunosorbent assay, which is a useful system for the mass screening of potential drugs. Taken together, this screening system (based on the interaction between E7 and Rb) can be a promising system in the development of drugs against cervical cancers caused by human papillomavirus infection.

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Contraction Behavior of Collagen Gel and Fibroblats Activity in Dermal Equivalent Model

  • Yang, Eun-Kyung;Lee, Doo-Hoon;Park, Sue-Nie;Choe, Tae-Boo;Park, Jung-Keug
    • Journal of Microbiology and Biotechnology
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    • v.7 no.4
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    • pp.267-271
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    • 1997
  • We developed a dermal equivalent (DE) which was engineered using human dermal fibroblasts and a matrix of collagen gel. The in vitro construction of the DE was accomplished by casting a porcine collagen type I solution plus concentrated medium with isolated and cultured fibroblasts. These constructs were attached to culture dishes or left floating in culture medium. Contraction of attached gels results in decreased gel thickness without a change in gel diameter, and contraction of floating gels results in decreased gel thickness and diameter. After contraction, there was no increase in cell number in floating gels, but cells in attached gels began to increase after about 4 days of the lag phase in cell growth curve. At this lag phase, addition of fibroblast growth factor (FGF) at a concentration of $0.1{\mu}$/ml promoted cell proliferation in the attached collagen gels, but no effect in floating gels. These results indicate that the method of contraction had an influence on the extracellular matrix (ECM) organization, and this influenced not only cell growth but also fibroblast responsiveness to FGF. This suggests that attached collagen gel is more suitable as a dermal equivalent than the floating gel. And the final contracted area of attached gel is much larger than that of the floating gel since floating gel is contracted in all directions but attached gel is contracted only vertically.

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3D Markov chain based multi-priority path selection in the heterogeneous Internet of Things

  • Wu, Huan;Wen, Xiangming;Lu, Zhaoming;Nie, Yao
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.13 no.11
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    • pp.5276-5298
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    • 2019
  • Internet of Things (IoT) based sensor networks have gained unprecedented popularity in recent years. With the exponential explosion of the objects (sensors and mobiles), the bandwidth and the speed of data transmission are dwarfed by the anticipated emergence of IoT. In this paper, we propose a novel heterogeneous IoT model integrated the power line communication (PLC) and WiFi network to increase the network capacity and cope with the rapid growth of the objects. We firstly propose the mean transmission delay calculation algorithm based the 3D Markov chain according to the multi-priority of the objects. Then, the attractor selection algorithm, which is based on the adaptive behavior of the biological system, is exploited. The combined the 3D Markov chain and the attractor selection model, named MASM, can select the optimal path adaptively in the heterogeneous IoT according to the environment. Furthermore, we verify that the MASM improves the transmission efficiency and reduce the transmission delay effectively. The simulation results show that the MASM is stable to changes in the environment and more applicable for the heterogeneous IoT, compared with the other algorithms.

Design and Analysis of High-Speed Unmanned Aerial Vehicle Ground Directional Rectifying Control System

  • Yin, Qiaozhi;Nie, Hong;Wei, Xiaohui;Xu, Kui
    • International Journal of Aeronautical and Space Sciences
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    • v.18 no.4
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    • pp.623-640
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    • 2017
  • The full nonlinear equations of an unmanned aerial vehicle ground taxiing mathematical dynamic model are built based on a type of unmanned aerial vehicle data in LMS Virtual.Lab Motion. The flexible landing gear model is considered to make the aircraft ground motion more accurate. The electric braking control system is established in MATLAB/Simulink and the experiment of it verifies that the electric braking model with the pressure sensor is fitted well with the actual braking mechanism and it ensures the braking response speediness. The direction rectification control law combining the differential brake and the rudder with 30% anti-skid brake is built to improve the directional stability. Two other rectifying control laws are demonstrated to compare with the designed control law to verify that the designed control is of high directional stability and high braking efficiency. The lateral displacement increases by 445.45% with poor rectification performance under the only rudder rectifying control relative to the designed control law. The braking distance rises by 36m and the braking frequency increases by 85.71% under the control law without anti-skid brake. Different landing conditions are simulated to verify the good robustness of the designed rectifying control.

Experimental Study on Sustained-release 5-Fluorouracil Implantation in Canine Peritoneum and Para-aortic Abdominalis

  • Wei, Guo;Nie, Ming-Ming;Shen, Xiao-Jun;Xue, Xu-Chao;Ma, Li-Ye;Du, Cheng-Hui;Wang, Shi-Liang;Bi, Jian-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.407-411
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    • 2014
  • Objective: To observe local and systemic toxicity after sustained-release 5-fluorouracil (5-Fu) implantation in canine peritoneum and para-aortic abdominalis and the changes of drug concentration in the local implanted tissue with time. Methods: 300 mg sustained-release 5-Fu was implanted into canine peritoneum and para-aorta abdominalis. Samples were taken 3, 5, 7 and 10 days after implantation for assessment of changes and systemic reactions. High performance liquid chromatography was applied to detect the drug concentrations of peritoneal tissue at different distances from the implanted site, lymphatic tissue of para-aortic abdominalis, peripheral blood and portal venous blood. Results: 10 days after implantation, the drug concentrations in the peritoneum, lymphatic tissue and portal vein remained relatively high within 5 cm of the implanted site. There appeared inflammatory reaction in the local implanted tissue, but no visible pathological changes such as cell degeneration and necrosis, and systemic reaction like anorexia, nausea, vomiting and fever. Conclusions: Sustained-release 5-Fu implantation in canine peritoneum and para-aortic abdominalis can maintain a relatively high tumour-inhibiting concentration for a longer time in the local implanted area and portal vein, and has mild local and systemic reactions. Besides, it is safe and effective to prevent or treat recurrence of gastrointestinal tumours and liver metastasis.