• Title/Summary/Keyword: Animal models

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The Effect of Genetically Modified Lactobacillus plantarum Carrying Bone Morphogenetic Protein 2 Gene on an Ovariectomized Rat

  • Jin, Eun-Sun;Kim, Ji Yeon;Yang, Jung-Mo;Kim, Jun-Sub;Min, JoongKee;Jeon, Sang Ryong;Choi, Kyoung Hyo;Moon, Gi-Seong;Jeong, Je Hoon
    • Journal of Korean Neurosurgical Society
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    • v.65 no.2
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    • pp.204-214
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    • 2022
  • Objective : Osteoporosis result from age-related decline in the number of osteoblast progenitors in the bone marrow. Probiotics have beneficial effects on the host, when administered in appropriate amounts. This study investigated the effects of probiotics expressing specific genes, especially the effects of genetically modified bone morphogenetic protein (BMP)-2-expressing Lactobacillus plantarum CJNU 3003 (LP) on ovariectomized rats. Methods : Twenty-eight female Wistar rats (250-300 g, 12 weeks old) were divided into four groups : the sham (control), the ovariectomy (OVX)-induced osteoporosis group (OVX), the OVX and LP (OVX/LP), OVX and genetically modified BMP-2-expressing LP (OVX/LP with BMP) groups. The three groups underwent bilateral OVX and two of these groups were administered two different types of LP via oral gavage daily. At 16 weeks post-OVX, blood was collected from the heart and the bilateral tibiae were extracted and were scanned by ex-vivo micro-computed tomography and stained with hematoxylin-and-eosin (H&E) and Masson's trichrome stain for pathological assessment. The serum levels of osteocalcin (OC), rat C-telopeptide of type I collagen (CTX-I), BMP-2, and receptor activator of nuclear factor-ĸB ligand (RANKL) were measured. Results : The 3D-micro-computed tomography images showed that the trabecular structure in the OVX/LP with BMP group was maintained compared with OVX and OVX/LP groups. No significant differences were detected in trabecular thickness (Tb.Th) between control and OVX/LP with BMP groups (p>0.05). Furthermore, a tendency toward increased BMD, trabecular bone volume, Tb.Th, and trabecular number and decreased trabecular separation was found in rats in the OVX/LP with BMP groups when compared with the OVX and OVX/LP groups (p>0.05). The H&E and Masson's trichrome stained sections showed a thicker trabecular bone in the OVX/LP with BMP group compared with the OVX and OVX/LP groups. There was no difference in serum levels of OC, CTX and RANKL control and OVX/LP with BMP groups (p>0.05). In contrast, significant differences were found in OC and CTX-1 levels between the OVX and OVX/LP with BMP groups (p<0.05). Conclusion : Our results showed that the expression of genetically modified BMP-2 showed inhibition effect for bone loss in a rat model of osteoporosis.

Ginsenoside Rg3 ameliorates myocardial glucose metabolism and insulin resistance via activating the AMPK signaling pathway

  • Ni, Jingyu;Liu, Zhihao;Jiang, Miaomiao;Li, Lan;Deng, Jie;Wang, Xiaodan;Su, Jing;Zhu, Yan;He, Feng;Mao, Jingyuan;Gao, Xiumei;Fan, Guanwei
    • Journal of Ginseng Research
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    • v.46 no.2
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    • pp.235-247
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    • 2022
  • Background: Ginsenoside Rg3 is one of the main active ingredients in ginseng. Here, we aimed to confirm its protective effect on the heart function in transverse aortic coarctation (TAC)-induced heart failure mice and explore the potential molecular mechanisms involved. Methods: The effects of ginsenoside Rg3 on heart and mitochondrial function were investigated by treating TAC-induced heart failure in mice. The mechanism of ginsenoside Rg3 for improving heart and mitochondrial function in mice with heart failure was predicted through integrative analysis of the proteome and plasma metabolome. Glucose uptake and myocardial insulin sensitivity were evaluated using micro-positron emission tomography. The effect of ginsenoside Rg3 on myocardial insulin sensitivity was clarified by combining in vivo animal experiments and in vitro cell experiments. Results: Treatment of TAC-induced mouse models with ginsenoside Rg3 significantly improved heart function and protected mitochondrial structure and function. Fusion of metabolomics, proteomics, and targeted metabolomics data showed that Rg3 regulated the glycolysis process, and Rg3 not only regulated glucose uptake but also improve myocardial insulin resistance. The molecular mechanism of ginsenoside Rg3 regulation of glucose metabolism was determined by exploring the interaction pathways of AMPK, insulin resistance, and glucose metabolism. The effect of ginsenoside Rg3 on the promotion of glucose uptake in IR-H9c2 cells by AMPK activation was dependent on the insulin signaling pathway. Conclusions: Ginsenoside Rg3 modulates glucose metabolism and significantly ameliorates insulin resistance through activation of the AMPK pathway.

The ProtectiveEffect of Oryeongsan, Geumgwe-sinkihwan, and Jwagwieum on Renal Injury in Rats with Unilateral Ureteral Obstruction (편측성 요관폐색으로 유발된 신장 질환 백서 모델에서 오령산, 금궤신기환, 좌귀음의 보호효과)

  • Byung Hyuk Han;Je Kuk Yu;Youn Jae Jang;Hye Yoom Kim;Jung Joo Yoon;Nam Geun Cho;Ho Sub Lee;Dae Gill Kang
    • Herbal Formula Science
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    • v.31 no.3
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    • pp.133-144
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    • 2023
  • Ureteral obstruction can be causes of renal dysfunction and renal injury at late period of kidney pathology. The purpose of this study was to determine the protective effects of Oryeongsan (ORS), Geumgwe-sinkihwan (GSH), and Jwagwieum (JGE) in rats with unilateral ureteral obstruction (UUO). The animal models were divided into five groups randomly at the age of 5 weeks; Control group: SD male rats (n=10), UUO group: SD male rats with UUO surgery (n=10), ORS group: SD male rats with UUO surgery + ORS 200 mg/kg/day (n=10), GSH group: SD male rats with UUO surgery + GSH 200 mg/kg/day (n=10), JGE group: SD male rats with UUO surgery + JGE 200 mg/kg/day (n=10). Treatment with ORS, GSH, and JGE significantly ameliorate creatinine clearance(Ccr). The present results also showed that ORS, GSH, and JGE improved the morphological aspects of renal tissues. These prescriptions also reduced the expression levels of cytokines such as TNF-α, IL-1β, and IL-6. In Kidney, UUO increased the expression levels of inflamasome markers such as NLRP3, ASC, and Caspase-1. However, ORS, GSH, and JGE suppressed these levele. Treatment with these prescriptions reduced kidney inflammation markers such as Neutrophil Gelatinase Associated Lipocalin (NGAL) and kidney injury molecule -1 (KIM-1). Therefore, these findings suggest that ORS, GSH, and JGE has a protective effect on renal injury by alleviating renal inflammation and improving renal function in rats with UUO.

Cardioprotective Potential of Gracilaria Verrucosa Extract in Myocardial Infarction-Induced Heart Failure Model (심근 경색 유발 심부전 모델에서 강리 추출물의 심장 보호 가능성)

  • Youn Jae Jang;Hye Yoom Kim;Jung Joo Yoon;Byung Hyuk Han;Je Kuk Yu;Nam Geun Cho;Ho Sub Lee;Dae Gill Kang
    • Herbal Formula Science
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    • v.31 no.3
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    • pp.157-169
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    • 2023
  • Gracilaria Verrucosa (GV), a seaweed used in traditional Korean medicine, was studied for its effects on MI-induced heart failure in rats. MI is caused by a blocked coronary artery, leading to severe cardiac dysfunction. The study used a rat model to assess cardiac changes over time and evaluate the impact of GV on heart failure. Ischemia was induced through LAD ligation surgery, and the extent of ischemic area was measured as a prognostic factor. GV extract administration significantly improved cardiac morphology and reduced cardiac weight compared to the MI group. GV treatment also improved cardiac function, as evidenced by positive effects on chamber dilation during MI-induced heart failure. Parameters such as ejection fraction (EF) and fractional shortening (FS) were measured. The MI group showed decreased EF and FS compared to the sham group, while these parameters improved in the GV group. GV treatment also reduced levels of LDH, CPK, and CK-MB in the serum, indicating reduced myocardial damage. Histological analysis revealed that GV treatment attenuated cardiac hypertrophy and fibrosis, with reduced collagen deposition in the myocardium. Immunohistochemistry analysis showed suppressed expression of TGF-β1 and collagen 1, involved in fibrosis. In conclusion, GV showed potential in improving cardiac function in a rat model of MI-induced heart failure. It alleviated myocardial damage, attenuated cardiac hypertrophy and fibrosis, and suppressed fibrotic markers. Further studies are needed to explore its clinical efficacy and underlying mechanisms in cardiac diseases beyond animal models.

Analysis of Transfer Learning Effect for Automatic Dog Breed Classification (반려견 자동 품종 분류를 위한 전이학습 효과 분석)

  • Lee, Dongsu;Park, Gooman
    • Journal of Broadcast Engineering
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    • v.27 no.1
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    • pp.133-145
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    • 2022
  • Compared to the continuously increasing dog population and industry size in Korea, systematic analysis of related data and research on breed classification methods are very insufficient. In this paper, an automatic breed classification method is proposed using deep learning technology for 14 major dog breeds domestically raised. To do this, dog images are collected for deep learning training and a dataset is built, and a breed classification algorithm is created by performing transfer learning based on VGG-16 and Resnet-34 as backbone networks. In order to check the transfer learning effect of the two models on dog images, we compared the use of pre-trained weights and the experiment of updating the weights. When fine tuning was performed based on VGG-16 backbone network, in the final model, the accuracy of Top 1 was about 89% and that of Top 3 was about 94%, respectively. The domestic dog breed classification method and data construction proposed in this paper have the potential to be used for various application purposes, such as classification of abandoned and lost dog breeds in animal protection centers or utilization in pet-feed industry.

Research on the Bacillus-fermented Enzamin Administration on Human NK Cell Activity and Bone Density of Hamster: A Pilot Study (Bacillus 발효액 Enzamin의 투여가 인체의 NK세포 활성도와 Hamster의 골밀도에 미치는 탐색연구)

  • Won, Ryu Seo;Fujii, Tokio;Lee, Hyung H.
    • Journal of Naturopathy
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    • v.7 no.2
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    • pp.63-69
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    • 2018
  • Purpose: The purpose of this study was to investigate the effects of Bacillus fermentation broth (ENM) on the human NK cell activity, and bone matrix density, matrix content and area of hamsters fed ENM. Methods: NK cell activity was tested, and bone mineral density were measured by x-ray. Results: NK cell activity was significantly higher in the control group (644.71 pg/ml) and in the test group (1796.37 pg/ml) (p<.004). Test groups were significantly increased by 1110.37 pg/ml in the pre-test and 1796.37 pg/ml in the post-test(p<.001). Behavioral observations after feeding ENM to hamsters showed normal behavior with no difference between control and test groups. The hamster body weight of the control was 106 g at the initial and final 27 days. In the test group, the initial weight was 96.6 g and the final 27 days was 114 g. No morphological changes were observed in the X-ray photographs of the hamster hind legs. The bone matrix density was 0.059 g/cm3 in control and 0.062 g/cm3 in the test, which was increased by 0.003 g/cm3. The bone matrix content was 0.175 g in the control and 0.196 g in the test. The bone area was 2.95 cm2 in the control and 3.19 cm2 in the test, which was increased by 0.19 cm2. In the autopsy, neither the control nor the test group showed any remarkable abnormality, and each organ was normal. Conclusions: It is thought that ingestion of ENM is useful for immunity enhancement.

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Protective Effect of Rubus crataegifolius Extracts Against Obesity and Non-alcoholic Fatty Liver Disease via Promotion of AMPK/ACC/CPT-1 Pathway in HFD-induced C57BL/6J Obese Mice (HFD 유도 C57BL/6J 비만 mice에서 AMPK/ACC/CPT-1 경로 촉진을 통한 산딸기 추출물의 비만 및 비알코올성 지방간 질환에 대한 보호 효과)

  • Young Ik Lee;Hui Jin Lee;Su Jin Pyo;Yong Hyun Park;Myng Min Lee;Ho-Yong Sohn;Jin Sook Cho
    • Journal of Life Science
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    • v.33 no.12
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    • pp.967-977
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    • 2023
  • Rubus crataegifolius (RC) is a traditional Asian medicinal plant belonging to the Rosaceae family. The fruits of RC are known to prevent adult diseases through antioxidants. In this study, the effects of RC extract (RCex) on obesity and nonalcoholic fatty liver disease (NAFLD) were evaluated in animal models. Twenty-eight male C57BL/6J mice were induced to become obese for 8 weeks and then the extract was orally administered for 8 weeks. RCex reduced body weight, adipose tissue, liver weight. RCex improved biochemical biomarkers including lipid metabolism (alanine aminotransferase (ALT), aspartate aminotransferase (AST), plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol). The activation of AMP-activated protein kinase (AMPK) reduced the expression of adipogenesis genes (liver × receptor (LXR), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthesis (FAS), acetyl-CoA carboxylase 1 (ACC1) and the effect of enhancing carnitine palmitoyltransferase (CPT) activity by RCex was verified. RCex also influence on plasma production of hormones (adiponectin & leptin) related on energy expenditure and metabolism. In addition, we confirmed that RCex improved glucose intolerance in HFD-induced obese rats. RCex was first demonstrated to have anti-obesity as well as anti-NAFLD effects by regulating fatty acid oxidation and fatty acid synthesis by phosphorylation of AMPK. This suggests that RCex could be a good supplement for the prevention of obesity and related NAFLD.

Evaluation of Biological Activity of Veronica incana Extracts (Veronica incana 추출물의 생물학적 활성 평가)

  • Mi-Rae Shin;Mi Yeong Yoon;Min Ju Kim;Il-Ha Jeong;Hui Yeon An;Ji-Won Jung;Seong-Soo Roh
    • The Korea Journal of Herbology
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    • v.39 no.3
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    • pp.57-67
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    • 2024
  • Objectives : The aim of this study is to evaluate the potential biological activity of Veronica incana extracts (VIE) through in vitro, ex vivo, and in vivo experiments. Methods : In vitro, we conducted analyses on the total polyphenol (TP) and total flavonoid (TF) levels, alongside DPPHand ABTS radical scavenging activities. Ex vivo evaluations on adipose tissue measured glycerol release as a marker of lipolysis. In LPS-induced RAW 264.7 cells, we quantified nitric oxide (NO) production. Following H2O2 induction in U2OS cells, we performed mitochondrial assays such as MitoSox and MitoTracker. Moreover, Bodipy assays were conducted in 3T3-L1 cells. In vivo, we performed anti-osteoarthritis effect of VIE against monosodium iodoacetate (MIA)-induced osteoarthritis in rats. Results : The results presented encompass a myriad of models, from cell culture to animal experiments as well as ex vivo studies. VIE demonstrated high TP and TF contents, potent DPPH and ABTS scavenging activities, and regulated glycerol release. Moreover, the inhibition of NO production in LPS-induced inflammation was notably confirmed and the reduction of lipid droplets was distinctly shown. Furthermore, in H2O2-induced U2OS cells, MitoSox was effectively reduced while MitoTracker noticeably increased. In vivo assays confirmed a significant increase in hindpaw weight distribution (HWD) decreased by MIA after VIE treatment. Additionally, VIE inhibited serum inflammatory cytokines (TNF-𝛼, IL-6, and IL-1𝛽) and MDA levels in joint tissue. Conclusion : In conclusion, Veronica incana exhibited various pharmacological effects including antioxidant, anti-obesity, and anti-inflammatory properties.

Analysis of SARS-CoV-2 Mutations after Nirmatrelvir Treatment in a Lung Cancer Xenograft Mouse Model

  • Bo Min Kang;Dongbum Kim;Jinsoo Kim;Kyeongbin Baek;Sangkyu Park;Ha-Eun Shin;Myeong-Heon Lee;Minyoung Kim;Suyeon Kim;Younghee Lee;Hyung-Joo Kwon
    • Biomolecules & Therapeutics
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    • v.32 no.4
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    • pp.481-491
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    • 2024
  • Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (Mpro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in Mpro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the Mpro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC50 values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

Effects of sucralose on memory and cognitive function relief in a scopolamine-induced amnesia model (Scopolamine으로 인한 건망증 모델에서 sucralose의 기억력 및 인지기능 완화 효과)

  • Eun-mi Jung;Eunhong Lee;Hyun-Ji Kwon;Jihye Lee;Hye-jeong Kim;Jinhan Park;Jongwon Lee;Ji Wook Jung
    • Journal of the Korean Applied Science and Technology
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    • v.40 no.6
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    • pp.1567-1579
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    • 2023
  • Sucralose is used as a sucrose alternative in the food sector and is a globally approved pyrogenic, high-intensity artificial sweetener. However, due to the lack of studies on the effects of sweeteners on the brain, this study confirmed whether short-term consumption of sucralose has cognitive and memory protective effects in scopolamine-induced memory-injured animal models. After oral administration of sucralose 2, 5, and 10 mg/kg, scopolamine (1 mg/kg) was administered to the control group and the drug group 30 minutes later, and saline was administered intraperitoneally to the normal group, followed by behavioral experiments As a result of the experiment, Y-Maze, passive avoidance, and Morris WaterMaze recovered more than 10% of cognitive function compared to the control group. In addition, as a result of measuring proinflammatory cytokines, sucralose was found to inhibit IL-6 and TNF-α by more than 30%, and we observed that the expression level of ERK-CREB with intracellular signaling mechanisms increased in a concentration-dependent manner. Therefore, it suggests that sucralose is associated with functional foods for the prevention of functional food patients.