• Title/Summary/Keyword: Disease models

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Cell Culture Models of Human Norovirus: the End of the Beginning? (인간노로바이러스의 세포배양 기술개발 : 새로운 시작?)

  • Nguyen, Minh Tue;Park, Mi-Kyung;Ha, Sangdo;Choi, In-Soo;Choi, Changsun;Myoung, Jinjong
    • Microbiology and Biotechnology Letters
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    • v.45 no.2
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    • pp.93-100
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    • 2017
  • Human norovirus (hNoV) infection accounts for the vast majority of virus-mediated gastroenteritis cases worldwide. It causes self-limiting acute illnesses in healthy individuals lasting for a few days, however, in immunocompromised patients, hNoV can establish chronic and potentially fatal infections. Since its discovery in 1968, much effort had been made to develop cell culture and animal infection models to no avail. Only recently, some promising breakthroughs in the development of in vitro infection models have been made. Here, we will contrast and compare those models and discuss what further needs to be done to develop a reliable and robust cell culture model.

Development of Long-Term Hospitalization Prediction Model for Minor Automobile Accident Patients (자동차 사고 경상환자의 장기입원 예측 모델 개발)

  • DoegGyu Lee;DongHyun Nam;Sung-Phil Heo
    • Journal of Korea Society of Industrial Information Systems
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    • v.28 no.6
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    • pp.11-20
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    • 2023
  • The cost of medical treatment for motor vehicle accidents is increasing every year. In this study, we created a model to predict long-term hospitalization(more than 18 days) among minor patients, which is the main item of increasing traffic accident medical expenses, using five algorithms such as decision tree, and analyzed the factors affecting long-term hospitalization. As a result, the accuracy of the prediction models ranged from 91.377 to 91.451, and there was no significant difference between each model, but the random forest and XGBoost models had the highest accuracy of 91.451. There were significant differences between models in the importance of explanatory variables, such as hospital location, name of disease, and type of hospital, between the long-stay and non-long-stay groups. Model validation was tested by comparing the average accuracy of each model cross-validated(10 times) on the training data with the accuracy of the validation data. To test of the explanatory variables, the chi-square test was used for categorical variables.

Current strategies using 3D organoids to establish in vitro maternal-embryonic interaction

  • Islam Mohamed Saadeldin;Seif Ehab;Ahmed Elsayed Noreldin;Ayman Abdel-Aziz Swelum;Seonggyu Bang;Hyejin Kim;Ki Young Yoon;Sanghoon Lee;Jongki Cho
    • Journal of Veterinary Science
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    • v.25 no.3
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    • pp.40.1-40.19
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    • 2024
  • Importance: The creation of robust maternal-embryonic interactions and implantation models is important for comprehending the early stages of embryonic development and reproductive disorders. Traditional two-dimensional (2D) cell culture systems often fail to accurately mimic the highly complex in vivo conditions. The employment of three-dimensional (3D) organoids has emerged as a promising strategy to overcome these limitations in recent years. The advancements in the field of organoid technology have opened new avenues for studying the physiology and diseases affecting female reproductive tract. Observations: This review summarizes the current strategies and advancements in the field of 3D organoids to establish maternal-embryonic interaction and implantation models for use in research and personalized medicine in assisted reproductive technology. The concepts of endometrial organoids, menstrual blood flow organoids, placental trophoblast organoids, stem cell-derived blastoids, and in vitro-generated embryo models are discussed in detail. We show the incorportaion of organoid systems and microfluidic technology to enhance tissue performance and precise management of the cellular surroundings. Conclusions and Relevance: This review provides insights into the future direction of modeling maternal-embryonic interaction research and its combination with other powerful technologies to interfere with this dialogue either by promoting or hindering it for improving fertility or methods for contraception, respectively. The merging of organoid systems with microfluidics facilitates the creation of sophisticated and functional organoid models, enhancing insights into organ development, disease mechanisms, and personalized medical investigations.

Forecasting hierarchical time series for foodborne disease outbreaks (식중독 발생 건수에 대한 계층 시계열 예측)

  • In-Kwon Yeo
    • The Korean Journal of Applied Statistics
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    • v.37 no.4
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    • pp.499 -508
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    • 2024
  • In this paper, we investigate hierarchical time series forecasting that adhere to a hierarchical structure when deriving predicted values by analyzing segmented data as well as aggregated datasets. The occurrences of food poisoning by a specific pathogen are analyzed using zero-inflated Poisson regression models and negative binomial regression models. The occurrences of major, miscellaneous, and overall food poisoning are analyzed using Poisson regression models and negative binomial regression models. For hierarchical time series forecasting, the MinT estimation proposed by Wickramasuriya et al. (2019) is employed. Negative predicted values resulting from hierarchical adjustments are adjusted to zero, and weights are multiplied to the remaining lowest-level variables to satisfy the hierarchical structure. Empirical analysis revealed that there is little difference between hierarchical and non-hierarchical adjustments in predictions based on pathogens. However, hierarchical adjustments generally yield superior results for predictions concerning major, miscellaneous, and overall occurrences. Without hierarchical adjustment, instances may occur where the predicted frequencies of the lowest-level variables exceed that of major or miscellaneous occurrences. However, the proposed method enables the acquisition of predictions that adhere to the hierarchical structure.

Inhibitory Effects of Schisandrae Fructus Ethanol Extract on the Production of Matrix Metalloproteinases in in vitro and in vivo Osteoarthritis Models (In vitro 및 in vivo 퇴행성관절염 모델에서 오미자 에탄올 추출물에 의한 matrix metalloproteinases의 생성 억제)

  • Jeong, Jin-Woo;Lee, Hye Hyeon;Kim, Hong Jae;Lee, Ki Won;Kim, Ki Young;Kim, Sung Goo;Hong, Su-Hyun;Kim, Bum Hoi;Park, Cheol;Choi, Yung Hyun
    • Journal of Life Science
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    • v.27 no.10
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    • pp.1207-1214
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    • 2017
  • Schisandrae Fructus (SF), the fruit of Schisandra chinensis (Turcz.) Baill., is widely used in traditional medicine for the treatment of a number of chronic diseases. SF extracts have been recently reported to attenuate the inflammatory responses in SW1353 human chondrocyte cells in in vitro and monosodium iodoacetate (MIA)-induced cartilage degradation in in vivo osteoarthritis (OA) models. However, their protective and therapeutic potentials against OA in primary culture chondrocytes and animal models remain unclear. Therefore, we investigated the effects of the ethanol extract of SF on the activity of matrix metalloproteinases (MMPs), biomarkers for diagnosis of OA, on interleukin $(IL)-1{\beta}-induced$ primary cultured rat cartilage chondrocytes and MIA-induced osteoarthritis in a rat model. Our data indicated that SF treatment significantly reduced the mRNA expression and enzyme activity of MMP-1, -3 and -13 in $IL-1{\beta}-induced$ primary cultured rat cartilage chondrocytes. The chondro-protective effects of SF were then analyzed in a rat OA model using a single intra-articular injection of MIA in the right knee joint. According to our results, the elevated levels of MMP-1 and -3 were markedly ameliorated by SF administration. Collectively, these findings indicate that SF could be a candidate for the treatment of OA.

NecroX-5 exerts anti-inflammatory and anti-fibrotic effects via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway in hypoxia/reoxygenation-treated rat hearts

  • Thu, Vu Thi;Kim, Hyoung Kyu;Long, Le Thanh;Thuy, To Thanh;Huy, Nguyen Quang;Kim, Soon Ha;Kim, Nari;Ko, Kyung Soo;Rhee, Byoung Doo;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.3
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    • pp.305-314
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    • 2016
  • Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating inflammation and fibrosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 ($10{\mu}mol/L$) treatment as experimental models. Addition of NecroX-5 significantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 ($TGF{\beta}1$) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, significantly increased production of tumor necrosis factor alpha ($TNF{\alpha}$), $TGF{\beta}1$, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of $TNF{\alpha}$, $TGF{\beta}1$, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the $TNF{\alpha}/Dcn/TGF{\beta}1/Smad2$ pathway.

Effects of aged garlic extract and endurance exercise on skeletal muscle FNDC-5 and circulating irisin in high-fat-diet rat models

  • Seo, Dae Yun;Kwak, Hyo Bum;Lee, Sung Ryul;Cho, Yeun Suk;Song, In-Sung;Kim, Nari;Bang, Hyun Seok;Rhee, Byoung Doo;Ko, Kyung Soo;Park, Byung Joo;Han, Jin
    • Nutrition Research and Practice
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    • v.8 no.2
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    • pp.177-182
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    • 2014
  • BACKGROUND/OBJECTIVES: Irisin, a newly identified hormone, is associated with energy homeostasis. We investigated whether aged garlic extract (AGE) and exercise training intervention could improve body weight, insulin sensitivity, skeletal muscle fibronectin domain containing protein 5 (FNDC-5) levels, and plasma irisin in high-fat diet (HFD). MATERIALS/METHODS: Male Sprague Dawley rats were fed a ND (normal diet, n=5) or HFD (n=28) for 6 weeks. After 6 weeks, all rats were divided into 5 groups for the next 4 weeks: ND, (normal diet, n=5), HFD (high-fat diet, n=7), HFDA (high-fat diet + aged garlic extract, n=7), HFDE (high-fat diet + exercise, n=7), and HFDEA (high-fat diet + exercise + aged garlic extract, n=7). Exercise groups performed treadmill exercises for 15-60 min, 5 days/week, and AGE groups received AGE (2.86 g/kg, orally injected) for 4 weeks. RESULTS: Significant decreases in body weight were observed in the ND, HFDE, and HFDEA groups, as compared with the HFD group. Neither intervention affected the masses of the gastrocnemius muscle or liver. There were no significant differences in glucose levels across the groups. The homeostatic model assessments of insulin resistance were significantly higher in the HFD group, as compared with the ND, HFDA, HFDE, and HFDEA groups. However, skeletal muscle FNDC-5 levels and plasma irisin concentrations were unaffected by AGE or exercise in obese rats. AGE supplementation and exercise training did not affect skeletal muscle FNDC-5 or plasma irisin, which are associated with insulin sensitivity in obese rats. CONCLUSION: Our results suggest that the protection against HFD-induced increases in body fat/weight and insulin resistance that are provided by AGE supplementation and exercise training may not be mediated by the regulation of FNDC-5 or irisin.

Associations Between Body Fat Percentage and Fitness among Police Officers: A Statewide Study

  • Violanti, John M.;Ma, Claudia C.;Fekedulegn, Desta;Andrew, Michael E.;Gu, Ja K.;Hartley, Tara A.;Charles, Luenda E.;Burchfiel, Cecil M.
    • Safety and Health at Work
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    • v.8 no.1
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    • pp.36-41
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    • 2017
  • Background: Police work is generally sedentary although there may be situations that require physical endurance and strength, such as foot chases and arresting suspects. Factors such as excessive body fat can impede an officer's physical ability to deal with such occurrences. Our objective was to examine associations between officers' body fat percentage (BF%) and performance on a standardized fitness protocol. Methods: Data were obtained from fitness screening among 1,826 male and 115 female officers in a large US police agency. The screening consisted of a 2.4-km run, push-ups, sit-ups, and sit-and-reach test. Sex-specific body fat percentages were estimated from skinfold thickness measured using calipers. Linear regression models were used to examine unadjusted and adjusted mean scores of fitness tests across BF% tertiles. Results: The prevalence of overall fitness was 4.3 times greater in male officers and 3.6 times greater in female officers having the lowest BF% tertile compared with the highest tertile (30.3% vs 7.1% and 46.0% vs 12.8%, respectively). BF% was linearly and positively associated with the time of 2.4-km run (p < 0.001), and linearly and inversely associated with the number of push-ups (p < 0.001), sit-ups (p < 0.001), and the distance of sit-and-reach (p < 0.001) in men. Similar associations were observed in women with the exception of sit-and-reach (p = 0.122). Associations were independent of age, race/ethnicity, rank, and duty station. Conclusion: Overall, BF% was inversely associated with fitness levels in male and female officers. Future longitudinal studies should be initiated to explore the potentially causal relationship between BF% and fitness in law enforcement officers.

Neuro-Restorative Effect of Nimodipine and Calcitriol in 1-Methyl 4-Phenyl 1,2,3,6 Tetrahydropyridine-Induced Zebrafish Parkinson's Disease Model

  • Myung Ji Kim; Su Hee Cho; Yongbo Seo; Sang-Dae Kim; Hae-Chul Park; Bum-Joon Kim
    • Journal of Korean Neurosurgical Society
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    • v.67 no.5
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    • pp.510-520
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    • 2024
  • Objective : Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The treatment of PD aims to alleviate motor symptoms by replacing the reduced endogenous dopamine. Currently, there are no disease-modifying agents for the treatment of PD. Zebrafish (Danio rerio) have emerged as an effective tool for new drug discovery and screening in the age of translational research. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause a similar loss of dopaminergic neurons in the human midbrain, with corresponding Parkinsonian symptoms. L-type calcium channels (LTCCs) have been implicated in the generation of mitochondrial oxidative stress, which underlies the pathogenesis of PD. Therefore, we investigated the neuro-restorative effect of LTCC inhibition in an MPTP-induced zebrafish PD model and suggested a possible drug candidate that might modify the progression of PD. Methods : All experiments were conducted using a line of transgenic zebrafish, Tg(dat:EGFP), in which green fluorescent protein (GFP) is expressed in dopaminergic neurons. The experimental groups were exposed to 500 μmol MPTP from 1 to 3 days post fertilization (dpf). The drug candidates : levodopa 1 mmol, nifedipine 10 μmol, nimodipine 3.5 μmol, diethylstilbestrol 0.3 μmol, luteolin 100 μmol, and calcitriol 0.25 μmol were exposed from 3 to 5 dpf. Locomotor activity was assessed by automated tracking and dopaminergic neurons were visualized in vivo by confocal microscopy. Results : Levodopa, nimodipine, diethylstilbestrol, and calcitriol had significant positive effects on the restoration of motor behavior, which was damaged by MPTP. Nimodipine and calcitriol have significant positive effects on the restoration of dopaminergic neurons, which were reduced by MPTP. Through locomotor analysis and dopaminergic neuron quantification, we identified the neuro-restorative effects of nimodipine and calcitriol in zebrafish MPTP-induced PD model. Conclusion : The present study identified the neuro-restorative effects of nimodipine and calcitriol in an MPTP-induced zebrafish model of PD. They restored dopaminergic neurons which were damaged due to the effects of MPTP and normalized the locomotor activity. LTCCs have potential pathological roles in neurodevelopmental and neurodegenerative disorders. Zebrafish are highly amenable to high-throughput drug screening and might, therefore, be a useful tool to work towards the identification of disease-modifying treatment for PD. Further studies including zebrafish genetic models to elucidate the mechanism of action of the disease-modifying candidate by investigating Ca2+ influx and mitochondrial function in dopaminergic neurons, are needed to reveal the pathogenesis of PD and develop disease-modifying treatments for PD.

MicroRNA Expression Profiling in Cell and Mouse Models of Fabry Disease to Identify Biomarkers for Fabry Disease Nephropathy (파브리병의 바이오마커 발굴을 위한 파브리 마우스와 세포모델에서의 microRNA 발현 분석)

  • Jung, Namhee;Park, Saeyoung;Jeon, Yeo Jin;Choi, Yoonyoung;Jung, Sung-Chul
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.15 no.3
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    • pp.127-137
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    • 2015
  • Purpose: The main aim of this study was to compare and analyze expression profiles of microRNAs (miRNAs) to establish miRNA signature of Fabry nephropathy related epithelial mesenchymal transition (EMT). Methods: Expression profiles of miRNAs in kidney tissue samples and cell lines from normal and Fabry disease mouse model were examined by miRNA expression microarray analysis followed by quantitative real-time polymerase chain reaction analysis (qRT-PCR). Results: In the miRNA expression microarray analysis of Fabry mouse kidney tissues compared to wild type mouse, 5 and 3 miRNAs among 1,247 miRNAs examined were up- and down-regulated, respectively. Among them, miR-149-5p was down-regulated about 2-fold in Fabry kidney samples. The down-regulations of miR-149-5p were observed in kidney tissues of under 35 week-old-Fabry mice. However, this down-regulation was not observed in kidney tissues of 42 week-old Fabry mice. In SV40 MES 13 cells, mouse mesangial cells, treated with globotriaosylsphingosine (lyso-Gb3), miR-149-5p was also downregulated. The down-regulation of miR-149-5p induced up-regulation of its target genes related to EMT. Conclusion: The miRNA expression array and qRT-PCR results show that miR-149-5p expression was decreased in kidney tissues of Fabry mice compared to wild type mice under 35 weeks of age. Along with the observation of miR-149-5p expression in Fabry disease cell models, these results indicate that the down-regulated miR-149-5p were related to the biological response of mesangial cells to lyso-Gb3 and also have influence to the transcriptional up-regulation of its target genes. These results suggest miR-149-5p might play important roles in the Fabry nephropathy.