• Advances in nano research
• /
• v.12 no.3
• /
• pp.301-317
• /
• 2022

Many studies have shown that Mg-Nd-Zn-Zr (abbreviated as JDBM) alloy has good biocompatibility and biodegradability as well as promotion of cell adhesion, proliferation and differentiation, and Wnt/β-catenin signaling pathway may play a unique role in joint tissue by controlling the function of chondrocytes, osteoblasts and synoviocytes. However, it is not clear whether the JDBM alloy induces osteochondral repair through Wnt/β-catenin signaling pathway. This study aims to verify that JDBM alloy can repair osteochondral defects in rats, which is realized by Wnt/β-catenin signaling pathway. In this study, the osteochondral defect model of the right femoral condyle non-weight-bearing area in rats was established and randomly divided into three groups: Control group, JDBM alloy implantation group and JDBM alloy implantation combined with signaling pathway inhibitor drug ICRT3 injection. It was found that after JDBM alloy implantation, the bone volume fraction (BVF) became larger, the bone trabeculae were increased, the relative expression of osteogenesis gene Runx2, Bmp2, Opn, Ocn and chondrogenesis gene Collagen II, Aggrecan were increased, and the tissue repair was obvious by HE and Masson staining, which could be inhibited by ICRT3.

• Molecules and Cells
• /
• v.46 no.11
• /
• pp.675-687
• /
• 2023

Accumulation of pathogenic amyloid-β disrupts the tight junction of retinal pigment epithelium (RPE), one of its senescence-like structural alterations. In the clearance of amyloid-β, the autophagy-lysosome pathway plays the crucial role. In this context, mammalian target of rapamycin (mTOR) inhibits the process of autophagy and lysosomal degradation, acting as a potential therapeutic target for age-associated disorders. However, efficacy of targeting mTOR to treat age-related macular degeneration remains largely elusive. Here, we validated the therapeutic efficacy of the mTOR inhibitors, Torin and PP242, in clearing amyloid-β by inducing the autophagy-lysosome pathway in a mouse model with pathogenic amyloid-β with tight junction disruption of RPE, which is evident in dry age-related macular degeneration. High concentration of amyloid-β oligomers induced autophagy-lysosome pathway impairment accompanied by the accumulation of p62 and decreased lysosomal activity in RPE cells. However, Torin and PP242 treatment restored the lysosomal activity via activation of LAMP2 and facilitated the clearance of amyloid-β in vitro and in vivo. Furthermore, clearance of amyloid-β by Torin and PP242 ameliorated the tight junction disruption of RPE in vivo. Overall, our findings suggest mTOR inhibition as a new therapeutic strategy for the restoration of tight junctions in age-related macular degeneration.

• Korean journal of applied entomology
• /
• v.52 no.1
• /
• pp.5-12
• /
• 2013

The Hawaiian beet webworm (Spoladea recurvalis) is one of the serious insect pests found on red beet (Beta vulgaris var. conditiva) in Korea. The study was conducted to investigate the development period of S. recurvalis at various constant temperatures, 15.0, 17.5, 20.0, 22.5, 25.0, 27.5, 30.0, 32.5 and $35.0^{\circ}C$, with $65{\pm}5%$ RH and a photoperiod of 16L:8D. The developmental period from egg to pre-adult was 51.0 days at $17.5^{\circ}C$ and 14.6 days at $35.0^{\circ}C$. The developmental period of S. recurvalis was decreased with increasing temperature. The relationship between the developmental rate and temperature was fitted well by linear regression analysis ($R^2{\geq}0.87$). The lower developmental threshold and effective accumulative temperature of the total immature stage were $10.4^{\circ}C$ and 384.7 degree days, respectively. The nonlinear relationship between the temperature and developmental rate was well described by the Lactin model. The relationship between the cumulative frequency and normalized distributions of the developmental period for each life stage were fitted to the Weibull function with $R^2=0.63{\sim}0.87$.

• Journal of Korean Society of Transportation
• /
• v.23 no.3 s.81
• /
• pp.95-108
• /
• 2005

The purpose of this study is to develop the ITS evaluation model using the Probabilistic Risk Analysis (PRA) methodology and to demonstrate the goodness-of-fit of the large ITS projects through the comparative analysis between DEA and PRA model. The results of this study are summarized below. First, the evaluation mode] using PRA with Monte-Carlo Simulation(MCS) and Latin-Hypercube Sampling(LHS) is developed and applied to one of ITS projects initiated by local government. The risk factors are categorized with cost, benefit and social-economic factors. Then, PDF(Probability Density Function) parameters of these factors are estimated. The log-normal distribution, beta distribution and triangular distribution are well fitted with the market and delivered price. The triangular and uniform distributions are valid in benefit data from the simulation analysis based on the several deployment scenarios. Second, the decision making rules for the risk analysis of projects for cost and economic feasibility study are suggested. The developed PRA model is applied for the Daejeon metropolitan ITS model deployment project to validate the model. The results of cost analysis shows that Deterministic Project Cost(DPC), Deterministic Total Project Cost(DTPC) is the biased percentile values of CDF produced by PRA model and this project need Contingency Budget(CB) because these values are turned out to be less than Target Value(TV;85% value), Also, this project has high risk of DTPC and DPC because the coefficient of variation(C.V) of DTPC and DPC are 4 and 15 which are less than that of DTPC(19-28) and DPC(22-107) in construction and transportation projects. The results of economic analysis shows that total system and subsystem of this project is in type II, which means the project is economically feasible with high risk. Third, the goodness-of-fit of PRA model is verified by comparing the differences of the results between PRA and DEA model. The difference of evaluation indices is up to 68% in maximum. Because of this, the deployment priority of ITS subsystems are changed in each mode1. In results. ITS evaluation model using PRA considering the project risk with the probability distribution is superior to DEA. It makes proper decision making and the risk factors estimated by PRA model can be controlled by risk management program suggested in this paper. Further research not only to build the database of deployment data but also to develop the methodologies estimating the ITS effects with PRA model is needed to broaden the usage of PRA model for the evaluation of ITS projects.

• Molecules and Cells
• /
• v.41 no.8
• /
• pp.742-752
• /
• 2018

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive degeneration of dopaminergic (DAergic) neurons, particularly in the substantia nigra (SN). Although circadian dysfunction has been suggested as one of the pathophysiological risk factors for PD, the exact molecular link between the circadian clock and PD remains largely unclear. We have recently demonstrated that $REV-ERB{\alpha}$, a circadian nuclear receptor, serves as a key molecular link between the circadian and DAergic systems. It competitively cooperates with NURR1, another nuclear receptor required for the optimal development and function of DA neurons, to control DAergic gene transcription. Considering our previous findings, we hypothesize that $REV-ERB{\alpha}$ may have a role in the onset and/or progression of PD. In the present study, we therefore aimed to elucidate whether genetic abrogation of $REV-ERB{\alpha}$ affects PD-related phenotypes in a mouse model of PD produced by a unilateral injection of 6-hydroxydopamine (6-OHDA) into the dorsal striatum. $REV-ERB{\alpha}$ deficiency significantly exacerbated 6-OHDA-induced motor deficits as well as DAergic neuronal loss in the vertebral midbrain including the SN and the ventral tegmental area. The exacerbated DAergic degeneration likely involves neuroinflammation-mediated neurotoxicity. The $REV-erb{\alpha}$ knockout mice showed prolonged microglial activation in the SN along with the over-production of interleukin $1{\beta}$, a pro-inflammatory cytokine, in response to 6-OHDA. In conclusion, the present study demonstrates for the first time that genetic abrogation of $REV-ERB{\alpha}$ can increase vulnerability of DAergic neurons to neurotoxic insults, such as 6-OHDA, thereby implying that its normal function may be beneficial for maintaining DAergic neuron populations during PD progression.

• The Korean Journal of Physiology and Pharmacology
• /
• v.25 no.2
• /
• pp.147-157
• /
• 2021

Coronary microembolization (CME) is associated with cardiomyocyte apoptosis and cardiac dysfunction. Puerarin confers protection against multiple cardiovascular diseases, but its effects and specific mechanisms on CME are not fully known. Hence, our study investigated whether puerarin pretreatment could alleviate cardiomyocyte apoptosis and improve cardiac function following CME. The molecular mechanism associated was also explored. A total of 48 Sprague-Dawley rats were randomly divided into CME, CME + Puerarin (CME + Pue), sham, and sham + Puerarin (sham + Pue) groups (with 12 rats per group). A CME model was established in CME and CME + Pue groups by injecting 42 ㎛ microspheres into the left ventricle of rats. Rats in the CME + Pue and sham + Pue groups were intraperitoneally injected with puerarin at 120 mg/kg daily for 7 days before operation. Cardiac function, myocardial histopathology, and cardiomyocyte apoptosis index were determined via cardiac ultrasound, hematoxylin-eosin (H&E) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Western blotting was used to measure protein expression related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. We found that, puerarin significantly ameliorated cardiac dysfunction after CME, attenuated myocardial infarct size, and reduced myocardial apoptotic index. Besides, puerarin inhibited cardiomyocyte apoptosis, as revealed by decreased Bax and cleaved caspase-3, and up-regulated Bcl-2 and PI3K/Akt/GSK-3β pathway related proteins. Collectively, puerarin can inhibit cardiomyocyte apoptosis and thus attenuate myocardial injury caused by CME. Mechanistically, these effects may be achieved through activation of the PI3K/Akt/GSK-3β pathway.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.6
• /
• pp.661-670
• /
• 2018

Fimasartan, a new angiotensin II receptor antagonist, reduces myocyte damage and stabilizes atherosclerotic plaque through its anti-inflammatory effect in animal studies. We investigated the protective effects of pretreatment with fimasartan on ischemia-reperfusion injury (IRI) in a mouse model of ischemic renal damage. C57BL/6 mice were pretreated with or without 5 (IR-F5) or 10 (IR-F10) mg/kg/day fimasartan for 3 days. Renal ischemia was induced by clamping bilateral renal vascular pedicles for 30 min. Histology, pro-inflammatory cytokines, and apoptosis assays were evaluated 24 h after IRI. Compared to the untreated group, blood urea nitrogen and serum creatinine levels were significantly lower in the IR-F10 group. IR-F10 kidneys showed less tubular necrosis and interstitial fibrosis than untreated kidneys. The expression of F4/80, a macrophage infiltration marker, and tumor necrosis factor $(TNF)-{\alpha}$, decreased in the IR-F10 group. High-dose fimasartan treatment attenuated the upregulation of $TNF-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 in ischemic kidneys. Fewer TUNEL positive cells were observed in IR-F10 compared to control mice. Fimasartan caused a significant decrease in caspase-3 activity and the level of Bax, and increased the Bcl-2 level. Fimasartan preserved renal function and tubular architecture from IRI in a mouse ischemic renal injury model. Fimasartan also attenuated upregulation of inflammatory cytokines and decreased apoptosis of renal tubular cells. Our results suggest that fimasartan inhibited the process of tubular injury by preventing apoptosis induced by the inflammatory pathway.

• The Korean Journal of Pesticide Science
• /
• v.9 no.2
• /
• pp.140-145
• /
• 2005

Quantitative Structure Activity Relationship (QSAR) assumes the relatedness between physical property and biological activity. However, activity data measured at single concentration such as percent activity have not been used extensively for modeling purpose. This probably comes from the fact that these values are qualitative instead of quantitative. To utilize percent activity data for molecular modeling, we classified the whole data into two classes. One class represents the active while the other signifies the inactive. The percent activity data of ${\beta}$-Ketoacetoanilides measured for TLB (Tomato Late Blight) were investigated. CoMFA (Comparative Molecular Field Analysis) was used as a discriminant function. Using CoMFA provides 3D (three dimensional) information, which is crucial for chemical insight. It can also serve as a predictive model. The resultant model classified the given data correctly (98%). When LOO (leave-one-out) crossvalidation procedure was applied, the classification accuracy was 69%. Therefore two class approximation of percent activity data with CoMFA can be utilized to understand the relationship between chemical structure and biological activity and design subsequent chemical analogs.

• Asian-Australasian Journal of Animal Sciences
• /
• v.30 no.12
• /
• pp.1684-1688
• /
• 2017

Objective: From a review of published information on genetic association studies, a meta-analysis was conducted to determine the influence of the genes ${\kappa}-casein$ (CSN3) and ${\beta}-lactoglobulin$ (LGB) on milk yield traits in Holstein, Jersey, Brown Swiss, and Fleckvieh. Methods: The GLIMMIX procedure was used to analyze milk production and percentage of protein and fat in milk. Models included the main effects and all their possible two-way interactions; not estimable effects and non-significant (p>0.05) two-way interactions were dropped from the models. The three traits analyzed used Poisson distribution and a log link function and were determined with the Interactive Data Analysis of SAS software. Least square means and multiple mean comparisons were obtained and performed for significant main effects and their interactions (p<0.0255). Results: Interaction of breed by gene showed that Holstein and Fleckvieh were the breeds on which CSN3 ($6.01%{\pm}0.19%$ and $5.98%{\pm}0.22%$), and LGB ($6.02%{\pm}0.19%$ and $5.70%{\pm}0.22%$) have the greatest influence. Interaction of breed by genotype nested in the analyzed gene indicated that Holstein and Jersey showed greater influence of the CSN3 AA genotype, $6.04%{\pm}0.22%$ and $5.59%{\pm}0.31%$ than the other genotypes, while LGB AA genotype had the largest influence on the traits analyzed, $6.05%{\pm}0.20%$ and $5.60%{\pm}0.19%$, respectively. Furthermore, interaction of type of statistical model by genotype nested in the analyzed gene indicated that CSN3 and LGB genes had similar behavior, maintaining a difference of more than 7% across analyzed genotypes. These results could indicate that both Holstein and Jersey have had lower substitution allele effect in selection programs that include CSN3 and LGB genes than Brown Swiss and Fleckvieh. Conclusion: Breed determined which genotypes had the greatest association with analyzed traits. The mixed model based in Bayesian or Ridge Regression was the best alternative to analyze CSN3 and LGB gene effects on milk yield and protein and fat percentages.

• Journal of Navigation and Port Research
• /
• v.37 no.5
• /
• pp.453-461
• /
• 2013

This paper describes evaluation procedures and experimental results for the estimation of Cumulative Distribution Functions (CDF) giving best-fit to the sample data in the Probability based risk Evaluation Techniques (PET) which is to assess the risks of a small-sized sea floater. The CDF in the PET is to provide the reference values of risk acceptance criteria which are to evaluate the risk level of the floater and, it can be estimated from sample data sets of motion response functions such as Roll, Pitch and Heave in the floater model. Using Maximum Likelihood Estimates and with the eight kinds of regulated distribution functions, the evaluation tests for the CDF having maximum likelihood to the sample data are carried out in this work. Throughout goodness-of-fit tests to the distribution functions, it is shown that the Beta distribution is best-fit to the Roll and Pitch sample data with smallest averaged probability errors $\bar{\delta}(0{\leq}\bar{\delta}{\leq}1.0)$ of 0.024 and 0.022, respectively and, Gamma distribution is best-fit to the Heave sample data with smallest $\bar{\delta}$ of 0.027. The proposed method in this paper can be expected to adopt in various application areas estimating best-fit distributions to the sample data.