• Title/Summary/Keyword: J-lead

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Inhibition of HBV replication and gene expression in vitro and in vivo with a single AAV vector delivering two shRNA molecules

  • Li, Zhi;He, Ming-Liang;Yao, Hong;Dong, Qing-Ming;Chen, Yang-Chao;Chan, Chu-Yan;Zheng, Bo-Jian;Yuen, Kwok-Yung;Peng, Ying;Sun, Qiang;Yang, Xiao;Lin, Marie C.;Sung, Joseph J.Y.;Kung, Hsiang-Fu
    • BMB Reports
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    • v.42 no.1
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    • pp.59-64
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    • 2009
  • Hepatitis B virus (HBV) infection is highly prevalent worldwide. The major challenge for current antiviral treatment is the elevated drug resistance that occurs via rapid viral mutagenesis. In this study, we developed AAV vectors to simultaneously deliver two or three shRNAs targeting different HBV-related genes. These vectors showed markedly better antiviral effects than ones that delivered a single shRNA in vitro. A dual shRNA expression vector (AAV-157i/1694i), which simultaneously expressed two shRNAs targeted the S and X genes of HBV, reduced HBsAg, HBeAg and HBV DNA levels by $87{\pm}4$, $80.3{\pm}2.6$ and $86.2{\pm}7%$ respectively, eight days post-transduction. In a mouse model of prophylactic treatment, HBsAg and HBeAg were reduced to undetectable levels and the serum HBV DNA level was reduced by at least 100 fold. These results indicate that AAV-157i/1694i generates potent anti-HBV effects and that the strategy of constructing multi-shRNA expression vectors may lead to enhanced anti-HBV efficacy and overcome the evading mechanism of the virus and thus the development of drug resistance.

Association between Polymorphisms of MSTN and MYF5 Genes and Growth Traits in Three Chinese Cattle Breeds

  • Zhang, R.F.;Chen, H.;Lei, C.Z.;Zhang, C.L.;Lan, X.Y.;Zhang, Y.D.;Zhang, H.J.;Bao, B.;Niu, H.;Wang, X.Z.
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.12
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    • pp.1798-1804
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    • 2007
  • The objective of this study was to assess the association of polymorphisms in MSTN and MYF5 genes with growth traits in three Chinese cattle breeds. Only one homozygous animal with BB genotype at MSTN locus was observed in Jiaxian population which was at Hardy-Weinberg disequilibrium (p<0.05). The frequencies of allele A at MSTN locus and allele B at MYF5 locus in the three Chinese breeds were 0.9550/0.9730/0.9720 and 0.8275/0.7581/0.7523, respectively. Allele A at MSTN locus and allele B at MYF5 locus were dominant in these three populations. No statistically significant differences in growth traits were observed between the genotypes of the Jiaxian breed at MSTN and MYF5 loci and the Nanyang breed at MYF5 locus. However, there were statistically significant differences between the genotypes at MSTN locus of the Nanyang breed for WH, HG, HGI and HGBLR (p<0.05), and of the Qinchuan breed for BLI (p<0.05). The SNP in MYF5 had significant effects on WH and HHC of Qinchuan animals (p<0.05). These results suggest that MSTN and MYF5 are strong candidate genes that influence growth traits in cattle. Other SNPs of MSTN and MYF5 or other linked genes should also be studied, which could lead to the development of selection plans to improve the performance of Chinese cattle and also promote the breeding of genuine beef cattle in China.

The Effects of Dietary Caloric Distribution on Insulin Secretion and Insulin Resistance in Sprague Dawley Rats (백서에서 식이내 열량 영양소의 배분이 인슐린 분비능과 인슐린 저항성에 미치는 영향)

  • Park, Sun-Min;Ahn, Seoung-Hee;Choi, Mi-Kyung;Kim, Young-Hee;Park, Chun-Hee;Choi, Soo-Bong
    • Journal of Nutrition and Health
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    • v.34 no.5
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    • pp.485-492
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    • 2001
  • The prevalence of type 2 diabetes mellitus has been rapidly increased in parallel with the westernization of eating behavior in Korea. Increased consumption of animal fat and simple sugar can be potential contributors for insulin resistance. The purpose of the study was to determine whether Western-(WD) and Korean-style(KD) diets altered insulin secretion and insulin resistance in male Sprague Dawley rats. Rats weighing 98$\pm$5g were provided by KD(77 En% of starch, 5 En% of corn oil and 13 En% of gluten plus 5 En% of casein), WD(42 En% of starch, 40 En% of butter and 18% of casein) or control diet(62 En% of starch, 20 En% of corn oil and 18% of casein) for 12 weeks. Body weights were lower in KD compared to WD. Fasting blood glucose levels were not different among diets. Insulin secretion from the beta cells was higher by 2.2$\pm$0.4 folds in WD than KD at baseline. In hyperglycemic clamp insulin secretion was higher in WD than KD and CD. Whole body glucose disposal rates referred to the state of insulin sensitivity were lowest in WD among groups. Glycogen deposits in soleus and quadriceps muscles were lowest in WD among all groups, but their triglyceride contents were highest. GLUT4 contents and glycogen synthase were lowest in WD in both muscles. In conclusions, westernization of diets needed more insulin to normalization of blood glucose levels due to increased insulin resistance. Thus, WD would lead to increased prevalence of diabetes mellitus when increased insulin resistance could not be compensated by insulin secretion in the case of elevated blood glucose levels. (Korean J Nutriton 34(5) : 485~492, 2001)

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Effects of Newly Synthesized Recombinant Human Amyloid-β Complexes and Poly-Amyloid-β Fibers on Cell Apoptosis and Cognitive Decline

  • Park, Soojin;Huh, Jae-Won;Eom, Taekil;Park, Naeun;Lee, Youngjeon;Kim, Ju-Sung;Kim, Sun-Uk;Shim, Insop;Lee, Sang-Rae;Kim, Ekyune
    • Journal of Microbiology and Biotechnology
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    • v.27 no.11
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    • pp.2044-2051
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    • 2017
  • The main pathological hallmark of Alzheimer's disease is the deposition of amyloid-beta ($A{\beta}$) peptides in the brain. $A{\beta}$ has been widely used to mimic several aspects of Alzheimer's disease. However, several characteristics of amyloid-induced Alzheimer's disease pathology are not well established, especially in mice. The present study aimed to develop a new Alzheimer's disease model by investigating how $A{\beta}$ can be effectively aggregated using prokaryotes and eukaryotes. To express the $A{\beta}42$ complex in HEK293 cells, we cloned the $A{\beta}42$ region in a tandem repeat and incorporated the resulting construct into a eukaryotic expression vector. Following transfection into HEK293 cells via lipofection, cell viability assay and western blotting analysis revealed that exogenous $A{\beta}42$ can induce cell death and apoptosis. In addition, recombinant His-tagged $A{\beta}42$ was successfully expressed in Escherichia coli BL21 (DE3) and not only readily formed $A{\beta}$ complexes, but also inhibited the proliferation of SH-SY5Y cells and E. coli. For in vivo testing, recombinant His-tagged $A{\beta}42$ solution ($3{\mu}g/{\mu}l$ in $1{\times}PBS$ containing $1mM\;Ni^{2+}$) was injected stereotaxically into the left and right lateral ventricles of the brains of C57BL/6J mice (n = 8). Control mice were injected with $1{\times}PBS$ containing $1mM\;Ni^{2+}$ following the same procedure. Ten days after the sample injection, the Morris water maze test confirmed that exogenous $A{\beta}$ caused an increase in memory loss. These findings demonstrated that $Ni^{2+}$ is capable of complexing the 50-kDa amyloid and that intracerebroventricular injection of $A{\beta}42$ can lead to cognitive impairment, thereby providing improved Alzheimer's disease models.

Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study

  • Peter, Aniekan Imo;Naidu, Edwin CS;Akang, Edidiong;Ogedengbe, Oluwatosin O;Offor, Ugochukwu;Rambharose, Sanjeev;Kalhapure, Rahul;Chuturgoon, Anil;Govender, Thirumala;Azu, Onyemaechi O
    • Toxicological Research
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    • v.34 no.3
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    • pp.221-229
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    • 2018
  • Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman's space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.

Preparation of PZT Powders by Hydrothermal Synthesis : Effects of Starting Materials and the Agitation of Substrate on Powder Characteristics (수열합성법에 의한 PZT 분말제조 : 출발물질과 기질의 교반이 분말특성에 미치는 영향)

  • Jung, S.T.;Lee, K.J.;Seo, K.W.
    • Applied Chemistry for Engineering
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    • v.8 no.2
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    • pp.292-300
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    • 1997
  • In this study PZT powders were prepared with shapes of cubic by hydrothermal synthesis with various starting materials, and the sintering characteristics of the powders were investigated. The particle shapes were cubic regardless of starting materials, but the mean size of particles formed using $Pb(NO_3)_2$, $Ti(OC_4H_9)_4$ and $Zr(OC_4H_9)_4$ was relatively smaller than that of particles prepared from other starting materials. Agitation of the feedstock during hydrothermal reaction results in decreasing the required reaction temperature for the formation of nuclei, and in increasing the size of product particles. XRD results showed that the major phase of PZT crystal powders was a tetragonal phase at the Zr to Ti ratio of 40 to 60, or a rhombohedral phase at its ratio of 60 to 40. The density of a sintered body made from the hydrothermal powders in PbO surrounding varied with sintering temperatures and with periods of sintering time. The experimental results also showed that the optimum sintering condition was at $1150^{\circ}C$ for a 2hr sintering, and that the density of a sintered body was $7.6g/cm^3$.

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Effect of N-BACK Program for Cognition, Visual-Perception, Depression, Anxiety, Activity of Daily Living in Stroke Patients (N-BACK 프로그램이 뇌졸중 환자의 인지, 시지각, 우울, 불안과 일상생활활동에 미치는 효과)

  • Kim, S.Y.;Kwon, S.N.;Kim, J.H.
    • Journal of rehabilitation welfare engineering & assistive technology
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    • v.9 no.3
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    • pp.185-193
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    • 2015
  • The purpose of this study was to demonstrate clinical effects on cognition, visual perception, depression, anxiety, and activities of daily living by applying the N-BACK program, a brain stimulated training program, which is used for the clinical purpose. To prove this, subjects suspected of cognitive impairment with 18-23 points in a Korean version of mental status examination (MMSE-K) were recruited among the population who had been diagnosed with stroke duration and suffered from it for six months of duration, and 10 of the subjects were selected into the experimental group and the control group, respectively. A total of 20 sessions were carried out for 30 minutes per day 5 times for 4 weeks. As a result, the experimental group who has been applied the N-BACK program showed positive results in the improvement of cognition, visual perception, depression, anxiety, and daily living skills. The results obtained from this study expect us that applying the N-BACK program for the improvement of cognition, visual perception, depression, and anxiety to stroke patients has a positive effect on the rehabilitation of patients and will lead them to improve daily living activities more independently.

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Effects of Temperature and Mechanical Deformation on the Microhardness of Lead free and Composite Solders (무연 복합 솔더의 미소경도에 미치는 기계적 변형과 온도의 영향)

  • Lee Joo Won;Kang Sung K.;Lee Hyuck Mo
    • Journal of the Microelectronics and Packaging Society
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    • v.12 no.2 s.35
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    • pp.121-128
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    • 2005
  • Solder joints in microelectronic devices are frequently operated at an elevated temperature in service. They also experience plastic deformation caused by temperature excursion and difference in thermal expansion coefficients. Deformed solders can go through a recovery and recrystallization process at an elevated temperature, which would alter their microstructure and mechanical properties. In this study, to predict the changes in mechanical properties of Pb-free solder joints at high temperatures, the high temperature microhardness of several Pb-free and composite solders was measured as a function of temperature, deformation, and annealing condition. Solder alleys investigated include pure Sn, Sn-0.7Cu, Sn-3.5Ag, Sn-3.8Ag-0.7Cu, Sn-2.8Ag-7.0Cu (composite), and Sn-2.7Ag-4.9Cu-2.9Ni (composite). Numbers are all in wt.$\%$ unless specified otherwise. Solder pellets were cast at two cooling rates (0.4 and $7^{\circ}C$/s). The pellets were compressively deformed by $30\%$ and $50\%$ and annealed at $150^{\circ}C$ for 2 days. The microhardness was measured as a function of indentation temperature from 25 to $130^{\circ}C$. Their microstructure was also evaluated to correlate with the changes in microhardness.

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Protective effect of Korean Red Ginseng against FK506-induced damage in LLC-PK1 cells

  • Lee, Dahae;Kang, Ki Sung;Yu, Jae Sik;Woo, Jung-Yoon;Hwang, Gwi Seo;Eom, Dae-Woon;Baek, Seung-Hoon;Lee, Hye Lim;Kim, Ki Hyun;Yamabe, Noriko
    • Journal of Ginseng Research
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    • v.41 no.3
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    • pp.284-289
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    • 2017
  • Background: Compound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated. Methods: LLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay. Results: The reduction in LLC-PK1 cell viability by $60{\mu}M$ FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with $60{\mu}M$ FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by $60{\mu}M$ FK506 treatment, whereas it was decreased after cotreatment with KRG. Conclusion: Taken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.

A Study on the Economic Efficiency of Capital Market (자본시장(資本市場)의 경제적(經濟的) 효율성(效率性)에 관한 연구(硏究))

  • Nam, Soo-Hyun
    • The Korean Journal of Financial Management
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    • v.2 no.1
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    • pp.55-75
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    • 1986
  • This article is to analyse the economic efficiency of capital market, which plays a role of resource allocation in terms of financial claims such as stock and bond. It provides various contributions to the welfare theoretical aspects of modern capital market theory. The key feature that distinguishes the theory described here from traditional welfare theory is the presence of uncertainty. Securities has time dimensions and the state and outcome of the future are really uncertain. This problem resulting from this uncertainty can be solved by complete market, but it has a weak power to explain real stock market. Capital Market is faced with the uncertainity because it is a kind of incomplete market. Individuals and firms in capital market made their consumption-investment decision by their own criteria, i. e. the maximization of expected utility form intertemporal consumption and the maximization of the market value of firm. We noted that allocative decisions that had to be made in the economy could be naturally subdivided into two groups. One set of decisions concerned the allocation of first-period resources among consumption $C_i$, investment in risky firms $I_j$, and riskless investment M. The other decisions concern the distribution among individuals of income available in the second period $Y_i(\theta)$. Corresponing to this grouping, the theoretical analysis of efficiency has also been dichotomized. The optimality of the distribution of output in the second period is distributive efficiency" and the optimality of the allocation of first-period resources is 'the efficiency of investment'. We have found in the distributive efficiency that the conditions for attainability is the same as the conditions for market optimality. The necessary and sufficient conditions for attainability or market optimality is that (1) all utility functions are such that -$\frac{{U_i}^'(Y_i)}{{U_i}^"(Y_i)}={\mu}_i+{\lambda}Y_i$-linear risk tolerance function where the coefficients ${\mu}_i$ and $\lambda$ are independent of $Y_i$, and (2) there are homogeneous expectations, i. e. ${\Large f}_i(\theta)={\Large f}(\theta)$ for every i. On the other hand, the efficiency of investment has disagreement about optimal investment level. The investment level for market rule will not generally lead to Pareto-optimal allocation of investment. This suboptimality is caused by (1)the difference of Diamond's decomposable production function and mean-variance valuation model and (2) the selection of exelusive investment or competitive investment. In conclusion, this article has made an analysis of conditions and processes of Pareto-optimal allocation of resources in capital marker and tried to connect with significant issues in modern finance.

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