• Title/Summary/Keyword: laboratory model

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CRISPR/Cas9-mediated knockout of CD47 causes hemolytic anemia with splenomegaly in C57BL/6 mice

  • Kim, Joo-Il;Park, Jin-Sung;Kwak, Jina;Lim, Hyun-Jin;Ryu, Soo-Kyung;Kwon, Euna;Han, Kang-Min;Nam, Ki-Taek;Lee, Han-Woong;Kang, Byeong-Cheol
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.302-310
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    • 2018
  • CD47 (integrin-associated protein), a multi-spanning transmembrane protein expressed in all cells including red blood cells (RBCs) and leukocytes, interacts with signal regulatory protein ${\alpha}$ ($SIRP{\alpha}$) on macrophages and thereby inhibits phagocytosis of RBCs. Recently, we generated a novel C57BL/6J CD47 knockout ($CD47^{-/-}$ hereafter) mouse line by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease, and here report their hematological phenotypes. On monitoring their birth and development, $CD47^{-/-}$ mice were born viable with a natural male-to-female sex ratio and normally developed from birth through puberty to adulthood without noticeable changes in growth, food/water intake compared to their age and sex-matched wild-type littermates up to 26 weeks. Hematological analysis revealed a mild but significant reduction of RBC counts and hemoglobin in 16 week-old male $CD47^{-/-}$ mice which were aggravated at the age of 26 weeks with increased reticulocyte counts and mean corpuscular volume (MCV), suggesting hemolytic anemia. Interestingly, anemia in female $CD47^{-/-}$ mice became evident at 26 weeks, but splenomegaly was identified in both genders of $CD47^{-/-}$ mice from the age of 16 weeks, consistent with development of hemolytic anemia. Additionally, helper and cytotoxic T cell populations were considerably reduced in the spleen, but not in thymus, of $CD47^{-/-}$ mice, suggesting a crucial role of CD47 in proliferation of T cells. Collectively, these findings indicate that our $CD47^{-/-}$ mice have progressive hemolytic anemia and splenic depletion of mature T cell populations and therefore may be useful as an in vivo model to study the function of CD47.

Change Pattern of Heart Age in Korean Population Using Heart Age Predictor of Framingham Heart Study (Framingham Heart Study의 Heart Age Predictor를 활용한 한국인 심장나이 추이분석)

  • Cho, Sang Ok
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.20 no.8
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    • pp.331-343
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    • 2019
  • The purpose of this study is to observe the trends of heart age of Koreans by using the predictor of heart age of the Framingham Heart Study. The subjects were 20,012 adults aged 30~74 years who were enrolled in the Korean National Health and Nutrition Examination Survey from 2005~2013. They filled in the determinants data and they had no history of cardiovascular disease (CVD). The heart age was calculated using a non-laboratory based model of prediction. The difference of heart age and chronological age, and the rate of excessive heart age over 10 years were calculated. The annual trend, the difference according to gender, the age bracket and geographic region, the heart age were all evaluated. Data analysis performed using the SAS program (version 9.3). Complex designed analysis was done. The heart age showed differences according to gender, age bracket and geographic region. The heart age is a useful comprehensive indicator for predicting the CVD events in the near future. So, it could be used for the purposes of exercising caution and guidance on CVD for administering medical care. It is strongly recommended to use heart age as an indicator for customized medical management to focus efforts on relatively vulnerable subjects and their factors for CVD. Further study on Koreans' customized heart age is needed.

Protein molecular structure, degradation and availability of canola, rapeseed and soybean meals in dairy cattle diets

  • Tian, Yujia;Zhang, Xuewei;Huang, Rongcai;Yu, Peiqiang
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.9
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    • pp.1381-1388
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    • 2019
  • Objective: The aims of this study were to reveal the magnitude of the differences in protein structures at a cellular level as well as protein utilization and availability among soybean meal (SBM), canola meal (CM), and rapeseed meal (RSM) as feedstocks in China. Methods: Experiments were designed to compare the three different types of feedstocks in terms of: i) protein chemical profiles; ii) protein fractions partitioned according to Cornell Net Carbohydrate and Protein System; iii) protein molecular structures and protein second structures; iv) special protein compounds-amino acid (AA); v) total digestible protein and energy values; vi) in situ rumen protein degradability and intestinal digestibility. The protein second structures were measured using FT/IR molecular spectroscopy technique. A summary chemical approach in National Research Council (NRC) model was applied to analyze truly digestible protein. Results: The results showed significant differences in both protein nutritional profiles and protein structure parameters in terms of ${\alpha}-helix$, ${\beta}-sheet$ spectral intensity and their ratio, and amide I, amide II spectral intensity and their ratio among SBM, CM, and RSM. SBM had higher crude protein (CP) and AA content than CM and RSM. For dry matter (DM), SBM, and CM had a higher DM content compared with RSM (p<0.05), whereas no statistical significance was found between SBM and CM (p = 0.28). Effective degradability of CP and DM did not demonstrate significant differences among the three groups (p>0.05). Intestinal digestibility of rumen undegradable protein measured by three-step in vitro method showed that there was significant difference (p = 0.05) among SBM, CM, and RSM, which SBM was the highest and RSM was the lowest with CM in between. NRC modeling results showed that digestible CP content in SBM was significantly higher than that of CM and RSM (p<0.05). Conclusion: This study suggested that SBM and CM contained similar protein value and availability for dairy cattle, while RSM had the lowest protein quality and utilization.

The Effect of Combined Exercise on Brain Function and Sleep Disorder of Sleep Disturbance Rats (복합운동프로그램이 수면장애 모델 쥐의 뇌기능과 수면장애에 미치는 영향)

  • Kim, Dong-Hyun
    • The Journal of Korean society of community based occupational therapy
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    • v.8 no.3
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    • pp.69-76
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    • 2018
  • Objective : The study was to investigate the neurophysiological approach to the effect of complex exercise on memory, one of brain functions, and the degree of sleep disorder using experimental animals with sleep disorders. Methods : This study carried out a complex exercise that designed in an animal laboratory for 4 days to 16 sleep - disordered model rats. After the exercise, brain function was confirmed with the changes of BDNF in the hippocampus and the change of sleep level was confirmed with the concentration of melatonin in the blood. Results : First, the effect of the complex exercise program on brain function was significantly increased in the experimental group(p<0.01). Second, the effect of complex exercise program on sleep disturbance was significantly increased in the experimental group and control group(p<0.01)(p<0.05). Conclusion : The rate of increase of the elderly in the community is rapidly increasing, and the sleep disorder of the elderly can affect the quality of life of these elderly people. Secondary memory impairment due to sleep disturbances can also be a problem. Although there are many ways to improve sleep disturbance, it has been scientifically proven through experimental animals that sleep and memory can be improved with complex exercise that is not economically, spatially burdensome.

Inhibition of endoplasmic reticulum stress in high-fat-diet-induced obese C57BL/6 mice: Efficacy of a novel extract from mulberry (Morus alba) leaves fermented with Cordyceps militaris

  • Lee, Mi Rim;Bae, Su Ji;Kim, Ji Eun;Song, Bo Ram;Choi, Jun Young;Park, Jin Ju;Park, Ji Won;Kang, Mi Ju;Choi, Hyeon Jun;Choi, Young Whan;Kim, Kyung Mi;Hwang, Dae Youn
    • Laboraroty Animal Research
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    • v.34 no.4
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    • pp.288-294
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    • 2018
  • A few clues about correlation between endoplasmic reticulum (ER) stress and mulberry (Morus alba) leaves were investigated in only the experimental autoimmune myocarditis and streptozotocin-induced diabetes. To investigate whether a novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) could suppress ER in fatty liver, alterations in the key parameters for ER stress response were measured in high fat diet (HFD)-induced obese C57L/6 mice treated with EMfC for 12 weeks. The area of adipocytes in the liver section were significantly decreased in the HFD+EMfC treated group as compared to the HFD+Vehicle treated group, while their level was higher in HFD+Vehicle treated group than No treated group. The level of the eukaryotic initiation factor 2 alpha ($eIF2{\alpha}$) and inositol-requiring enzyme 1 beta ($IRE1{\alpha}$) phosphorylation and CCAAT-enhancer-binding protein homologous protein (CHOP) expression were remarkably enhanced in the HFD+Vehicle treated group. However, their levels were restored in the HFD+EMfC treated group, although some differences were detected in the decrease rate. Similar recovery was observed on the ER stress-induced apoptosis. The level of Caspase-3, Bcl-2 and Bax were decreased in the HFD+EMfC and HFD+orlistat (OT) treated group compared to the HFD+Vehicle treated group. The results of the present study therefore provide first evidence that EMfC with the anti-obesity effects can be suppressed ER stress and ER stress-induced apoptosis in the hepatic steatosis of HFD-induced obesity model.

Prediction of the human in vivo antiplatelet effect of S- and R-indobufen using population pharmacodynamic modeling and simulation based on in vitro platelet aggregation test

  • Noh, Yook-Hwan;Han, Sungpil;Choe, Sangmin;Jung, Jin-Ah;Jung, Jin-Ah;Hwang, Ae-Kyung;Lim, Hyeong-Seok
    • Translational and Clinical Pharmacology
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    • v.26 no.4
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    • pp.160-165
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    • 2018
  • Indobufen ($Ibustrin^{(R)}$), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using $NONMEM^{(R)}$ and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0-128 mg/L. Collagen-induced platelet aggregation in platelet-rich plasma was determined using a Chrono-log Lumi-Aggregometer. Inhibitory sigmoid $I_{max}$ model adequately described the anti-platelet effect. The S-form was more potent, whereas the R-form showed less inter-individual variation. No significant interaction was observed between the two enantiomers. The anti-platelet effect of multiple treatments with 200 mg indobufen twice daily doses was predicted in the simulation study, and the effect of S- or R-indobufen alone at various doses was predicted to define optimal dosing regimen for each enantiomer. Simulation study predicted that 200 mg twice daily administration of S-indobufen alone will produce more treatment effect than S-and R-mixture formulation. S-indobufen produced treatment effect at lower concentration than R-indobufen. However, inter-individual variation of the pharmacodynamic response was smaller in R-indobufen. The present study suggests the optimal doses of R-and S-enantioselective indobufen formulations in terms of treatment efficacy for patients with thromboembolic problems. The proposed methodology in this study can be applied to the develop novel enantio-selective drugs more efficiently.

Wind load and wind-induced effect of the large wind turbine tower-blade system considering blade yaw and interference

  • Ke, S.T.;Wang, X.H.;Ge, Y.J.
    • Wind and Structures
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    • v.28 no.2
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    • pp.71-87
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    • 2019
  • The yaw and interference effects of blades affect aerodynamic performance of large wind turbine system significantly, thus influencing wind-induced response and stability performance of the tower-blade system. In this study, the 5MW wind turbine which was developed by Nanjing University of Aeronautics and Astronautics (NUAA) was chosen as the research object. Large eddy simulation on flow field and aerodynamics of its wind turbine system with different yaw angles($0^{\circ}$, $5^{\circ}$, $10^{\circ}$, $20^{\circ}$, $30^{\circ}$ and $45^{\circ}$) under the most unfavorable blade position was carried out. Results were compared with codes and measurement results at home and abroad, which verified validity of large eddy simulation. On this basis, effects of yaw angle on average wind pressure, fluctuating wind pressure, lift coefficient, resistance coefficient,streaming and wake characteristics on different interference zone of tower of wind turbine were analyzed. Next, the blade-cabin-tower-foundation integrated coupling model of the large wind turbine was constructed based on finite element method. Dynamic characteristics, wind-induced response and stability performance of the wind turbine structural system under different yaw angle were analyzed systematically. Research results demonstrate that with the increase of yaw angle, the maximum negative pressure and extreme negative pressure of the significant interference zone of the tower present a V-shaped variation trend, whereas the layer resistance coefficient increases gradually. By contrast, the maximum negative pressure, extreme negative pressure and layer resistance coefficient of the non-interference zone remain basically same. Effects of streaming and wake weaken gradually. When the yaw angle increases to $45^{\circ}$, aerodynamic force of the tower is close with that when there's no blade yaw and interference. As the height of significant interference zone increases, layer resistance coefficient decreases firstly and then increases under different yaw angles. Maximum means and mean square error (MSE) of radial displacement under different yaw angles all occur at circumferential $0^{\circ}$ and $180^{\circ}$ of the tower. The maximum bending moment at tower bottom is at circumferential $20^{\circ}$. When the yaw angle is $0^{\circ}$, the maximum downwind displacement responses of different blades are higher than 2.7 m. With the increase of yaw angle, MSEs of radial displacement at tower top, downwind displacement of blades, internal force at blade roots all decrease gradually, while the critical wind speed decreases firstly and then increases and finally decreases. The comprehensive analysis shows that the worst aerodynamic performance and wind-induced response of the wind turbine system are achieved when the yaw angle is $0^{\circ}$, whereas the worst stability performance and ultimate bearing capacity are achieved when the yaw angle is $45^{\circ}$.

Kinematic Analysis of Drag Flick Shooting Motion for Training Shooters Specializing in Penalty Corners in Women's Field Hockey: A Case Study (여자 필드하키 페널티코너 전문 슈터 양성을 위한 Drag Flick 슈팅 동작의 운동학적 분석: 사례 연구)

  • Park, Jongchul;Byun, Kyungseok;Kim, Eonho
    • Korean Journal of Applied Biomechanics
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    • v.29 no.2
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    • pp.43-51
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    • 2019
  • Objective: This study aims to propose an efficient technical model through a kinematic analysis of field hockey drag flick shooting motion in laboratory situations and game situations and to build up the basic data on drag flick shooting technique through a comparative analysis of a Korean specialized shooter and specialized shooters of competing Asian countries. Method: This study selected one Korean female national specialized shooter and seven specialized shooters of competing countries, China, Japan, India, and Malaysia, who participated in the 2018 Asian Hockey Champions Trophy as research subjects. In exercise situations, a 3-D motion analysis utilizing an infrared camera was conducted, while in game situations, an image-based 3-D motion analysis utilizing a digital camera was conducted. Results: The Korean specialized shooter had smaller changes in the angles of the trunk and the stick in game situations than in exercise situations. She had a high angular velocity of the trunk and the stick head, and the maximum speed of the ball was high. The Korean specialized shooter had the maximum angular velocity of the trunk higher than the specialized shooters of the competing countries did, and the angular velocity of the stick head and the maximum speed of the ball were in the average level. Conclusion: As for drag flick shooting in game situations, changes in the angle of the trunk and the stick were small, and the angular velocity was high due to the pressure that the shooters should perform the motion fast with the defenders' interruptions, and this high angular velocity of the trunk and the stick head affected the movement of the ball. Thus, the maximum speed of the ball was higher in game situations than in exercise situations. The Korean specialized shooter had the maximum angular velocity higher than the specialized shooters of the competing countries did; however, the maximum speed of the ball was average, and it turned out that the maximum speed of the ball was associated with the angular velocity of the stick head in P3. Therefore, Korean specialized shooters need complementary training for a change to the torque of the stick head, using the strong torque of the trunk.

Upregulation of Carbonyl Reductase 1 by Nrf2 as a Potential Therapeutic Intervention for Ischemia/Reperfusion Injury during Liver Transplantation

  • Kwon, Jae Hyun;Lee, Jooyoung;Kim, Jiye;Kirchner, Varvara A.;Jo, Yong Hwa;Miura, Takeshi;Kim, Nayoung;Song, Gi-Won;Hwang, Shin;Lee, Sung-Gyu;Yoon, Young-In;Tak, Eunyoung
    • Molecules and Cells
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    • v.42 no.9
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    • pp.672-685
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    • 2019
  • Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygen-glucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation.

Effect of milling tool wear on the internal fit of PMMA implant interim prosthesis (밀링 공구의 마모가 PMMA 임플란트 임시보철물 변연 및 내면적합도에 미치는 영향)

  • Shin, Mi-sun
    • Journal of Technologic Dentistry
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    • v.41 no.2
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    • pp.63-69
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    • 2019
  • Purpose: The purpose of this study is to evaluate the effect of CAD/CAM system milling tool wear on the marginal and internal fit of PMMA implant interim prosthesis three-dimensional manner. Methods: A total of 20 crowns were fabricated with CAD/CAM method. Their designs were unified to first molar of the left maxilla. The Customized abutments were prepared and scanned with on optical model scanner. Five crowns were milled by the newly replaced tool (1st milling), and 15 crowns were milled by 2nd, 3rd, 4th milling tool. The marginal and internal fit of 20 interim crowns were measured using the triple-scan protocol. Results: Statistically significant difference was found between the $1^{st}$ milling group ($51.8{\pm}14.6{\mu}m$) and the $3^{rd}$, $4^{th}$ milling group ($128.6{\pm}43.8{\mu}m$, $146.2{\pm}38.1{\mu}m$, respectively) at the distal margins. In the mesial margins, There was a statistically significant difference between the $1^{st}$ milling group ($63.6{\pm}25.9{\mu}m$) and the $3^{rd}$, $4^{th}$ milling group ($137.2{\pm}25.9{\mu}m$, $186.8{\pm}70.6{\mu}m$, respectively). In the distal line angle, significant difference was found between the $1^{st}$, $2^{nd}$, $3^{rd}$ milling groups and the $4^{th}$ milling group. In the mesial axial wall, significant difference was found between the $1^{st}$ milling group ($52.2{\pm}20.3{\mu}m$) and the $3^{rd}$, $4^{th}$ milling groups ($22.8{\pm}8.8{\mu}m$, $7.8{\pm}5.7{\mu}m$). Conclusion: As a result of the experiment, decrease of the marginal and internal fit was statistically significant as the number of machining cycles increased. In order to produce clinically excellent restorations, it is recommandable to consider the condition of the milling tool wear, when designing the restoration with CAD program.