• Title/Summary/Keyword: disease model animal

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Improvement of Motor Behavior of Parkinson′s Disease Animal Model by Nurr1-Transfected Human Embryonic Stem Cells.

  • Lee, Chang-Hyun;Cho, Hwang-Yoon;Kil, Kwang-Soo;Lee, Gun-Soup;Yoon, Ji-Yeon;Lee, Young-Jae;Kim, Eun-Young;Park, Se-Pill;Lim, Jin-Ho
    • Proceedings of the Korean Society of Developmental Biology Conference
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    • 2003.10a
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    • pp.103-103
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    • 2003
  • The purpose of this study is to evaluate an efficacy of in vitro differentiated human embryonic stem (hES, MB03) cells expressing Nurr1 in relief of symptomatic motor behavior of Parkinson's disease (PD) animal models MB03 was genetically modified to express Nurr1 protein and was induced to differentiate according to 2-/4+ protocol using retinoic acid and ascorbic acid. The differentiation-induced cells were selected for 10 to 20 days thereafter in N2 medium. Upon selection, cells expressing GFAP, TH, or NF200 were 38.8%, 11%, and 20.5%, respectively. in order to examine therapeutic effects of the differentiated cells in PD animal model, rats were unilaterally lesioned by administration of 6-kydroxydopamine HCI (6-OHDA) into medial forebrain region (MFB, AP -4.4 mm, ML 1.2 mm, DV 78 mm with incision bar set at -2.4 mm), as a reference to bregma and the surface of the skull. Confirmation of successful lesion by apomorphine-induced rotational behavior, differentiated cells were transplanted into the striatum (AP 1.0, ML 3.5, DV -5.0; AP 0.6, ML 2.5, DV -4.5). Improvements of asymmetric motor behavior by the transplantation were examined every two weeks after the surgery. In two weeks, numbers of rotation by the experimental rats were $-14.8 \pm 33.9%$ (P<0.05) of the number before transplantation, however, the ratio increased slightly to $13.6 \pm 56.3%$ in six weeks. In contrast, the ratio of sham-grafted animals ranged from 112.3+8.5% to 139.2+28.9% during the examination. Immunohistochemical studies further confirmed the presence, survival, migration, and expression of TH of the transplanted human cells.

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Induced neural stem cells from human patient-derived fibroblasts attenuate neurodegeneration in Niemann-Pick type C mice

  • Hong, Saetbyul;Lee, Seung-Eun;Kang, Insung;Yang, Jehoon;Kim, Hunnyun;Kim, Jeyun;Kang, Kyung-Sun
    • Journal of Veterinary Science
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    • v.22 no.1
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    • pp.7.1-7.13
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    • 2021
  • Background: Niemann-Pick disease type C (NPC) is caused by the mutation of NPC genes, which leads to the abnormal accumulation of unesterified cholesterol and glycolipids in lysosomes. This autosomal recessive disease is characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. Recently, the application of induced neural stem cells (iNSCs), converted from fibroblasts using specific transcription factors, to repair degenerated lesions has been considered a novel therapy. Objectives: The therapeutic effects on NPC by human iNSCs generated by our research group have not yet been studied in vivo; in this study, we investigate those effects. Methods: We used an NPC mouse model to efficiently evaluate the therapeutic effect of iNSCs, because neurodegeneration progress is rapid in NPC. In addition, application of human iNSCs from NPC patient-derived fibroblasts in an NPC model in vivo can give insight into the clinical usefulness of iNSC treatment. The iNSCs, generated from NPC patientderived fibroblasts using the SOX2 and HMGA2 reprogramming factors, were transplanted by intracerebral injection into NPC mice. Results: Transplantation of iNSCs showed positive results in survival and body weight change in vivo. Additionally, iNSC-treated mice showed improved learning and memory in behavior test results. Furthermore, through magnetic resonance imaging and histopathological assessments, we observed delayed neurodegeneration in NPC mouse brains. Conclusions: iNSCs converted from patient-derived fibroblasts can become another choice of treatment for neurodegenerative diseases such as NPC.

Effect of Polylysine on Scrapie Prion Protein Propagation in Spleen during Asymptomatic Stage of Experimental Prion Disease in Mice

  • Titlow, William B.;Waqas, Muhammad;Lee, Jihyun;Cho, Jae Youl;Lee, Sang Yeol;Kim, Dae-Hwan;Ryou, Chongsuk
    • Journal of Microbiology and Biotechnology
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    • v.26 no.9
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    • pp.1657-1660
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    • 2016
  • Prion diseases are incurable neurodegenerative disorders. Our previous study demonstrated that polylysine was effective in prolonging the incubation period in a rodent model and in alleviating the scrapie prion protein (PrPSc) burden in the brain at the terminal stage of the disease. Here, we report that intraperitoneal administration of polylysine suppresses the accumulation of prions in the spleen during the early stages of the disease. This study supports the congruence of PrPSc inhibition by polylysine in both the spleen and brain.

Combination Treatment with SIP-3 Herb Formula and Donepezil: An NGS Study in the Mouse Model of Alzheimer's Disease Induced by Amyloid-β (SIP-3 한약 처방 및 도네페질의 병용 치료: 아밀로이드 베타로 유도된 알츠하이머병 생쥐 모델에서의 NGS 연구)

  • Oh, Young-je;Song, Sue-jin;Liu, Quan Feng;Son, Tae-kwon;Kim, Geun-woo;Koo, Byung-soo
    • Journal of Oriental Neuropsychiatry
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    • v.30 no.4
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    • pp.327-340
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    • 2019
  • Objectives: Alzheimer's disease (AD) is a complex disease accompanied by slow impairment of memory and coordination leading to behavioral changes. To date, the only treatment option is to delay the progress of the disease. The purpose of this study was to investigate the synergistic effects of combination treatment with donepezil and three herbal extracts SIP-3 in the AD mouse model induced by amyloid-β (Aβ). Methods: We tested SIP-3 extracts for the cytotoxicity on Aβ-treated SH-SY5Y cells. Then the synergistic effects of SIP-3 and donepezil were evaluated in the AD mouse model using animal experiments and the next generation sequencing (NGS) study. Results: We found that co-treatment with SIP-3 extracts and donepezil increased the viability in Aβ-treated SH-SY5Y cells. The beneficial effects of the co-treatment were also observed in the Aβ-induced AD mouse model. The NGS study was performed to show that the co-treatment of SIP-3 and donepezil restored the disease phenotype closely to the normal level in the AD mouse model in terms of mRNA expression. However, the phenotypes were only partially restored. Conclusions: This study suggests that the combination treatment has a potential to be used for the treatment of AD. However, longer periods of treatment may be required.

Protective Effects of SAPP, a Novel Herbal Complex, in Acute Hepatotoxic Mouse Model

  • Lee, Geum Seon;Lee, Ki Man;Kim, Seung Hyun;Jeong, Nam-Joo;Kim, Young-Jung;Jung, Ju-Young;Kang, Tae Jin
    • Natural Product Sciences
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    • v.19 no.2
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    • pp.173-178
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    • 2013
  • The protective effect of SAPP, an extract from a novel herbal complex, on acute liver injury was investigated using mouse animal model in this study. The content of total phenol in SAPP was increased at dose dependent manner. Consistent with the content of total phenol, SAPP showed the significant anti-oxidative effects on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) method. Acute liver injury was induced by D-galactosamine (D-GalN) in mouse. Treatment with SAPP significantly reduced the level of alanine transaminase (ALT) and aspartate transaminase (AST) in serum. Histological observation revealed that whereas D-GalN treated mouse showed vacuolization of hepatocytes, sinusoidal dilation and congestion, loss of cell boundaries and ballooning degeneration, loss of architecture and cell necrosis, treatment with SAPP improved D-GalN-induced liver injury. These results suggest that SAPP shows protective effects against D-GalN-induced hepatotoxicity in vivo acute mouse model.

CP-690550 Treatment Ameliorates Established Disease and Provides Long-Term Therapeutic Effects in an SKG Arthritis Model

  • Oh, Keunhee;Seo, Myung Won;Kim, In Gyu;Hwang, Young-Il;Lee, Hee-Yoon;Lee, Dong-Sup
    • IMMUNE NETWORK
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    • v.13 no.6
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    • pp.257-263
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    • 2013
  • Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signaling mediators have been shown to play critical roles. An increasing numbers of therapeutic options have been added for the effective control of RA. Nevertheless, there is still a category of patients that fails treatment and suffers from progressive disease. The recently developed immunosuppressant CP-690550, a small molecule JAK kinase inhibitor, has been implicated as an important candidate treatment modality for autoimmune arthritis. In this study, we evaluated the therapeutic effect of CP-690550 on established arthritis using an SKG arthritis model, a pathophysiologically relevant animal model for human RA. CP-690550 treatment revealed remarkable long-term suppressive effects on SKG arthritis when administered to the well-advanced disease (clinical score 3.5~4.0). The treatment effect lasted at least 3 more weeks after cessation of drug infusion, and suppression of disease was correlated with the reduced pro-inflammatory cytokines, including IL-17, IFN-${\gamma}$, and IL-6 and increased level of immunoregulatory IL-10.

Latilactobacillus curvatus BYB3 Isolated from Kimchi Alleviates Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice by Inhibiting IL-6 and TNF-R1 Production

  • Wang, Xing;Li, Dingyun;Meng, Ziyao;Kim, Kiyeop;Oh, Sejong
    • Journal of Microbiology and Biotechnology
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    • v.32 no.3
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    • pp.348-354
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    • 2022
  • Recent studies have shown that probiotics have health-promoting effects, particularly intestinal immune modulation. In this study, we focused on the immunomodulatory properties of Latilactobacillus curvatus BYB3, formerly called Lactobacillus curvatus, isolated from kimchi. In a mouse model of 14-day dextran sulfate sodium (DSS)-induced colitis, treatment with L. curvatus BYB3 significantly decreased the disease activity index, colon length, and weight loss. Moreover, histological analyses showed that L. curvatus BYB3 protected the structural integrity of the intestinal epithelial layer and mucin-secreting goblet cells from DSS-induced damage, with only slight infiltration by immune cells. To evaluate the molecular mechanisms underlying L. curvatus BYB3-driven inhibition of interleukin 6 production, possible in vivo anti-inflammatory effects of L. curvatus BYB3 were examined in the same mouse model. In addition, significantly lower levels of IL-6 and tumor necrosis factor receptor 1 upregulation were seen in the DSS+BYB3 group (compared to that in the DSS group). These results indicate that L. curvatus BYB3 exhibits health-promoting effects via immune modulation; and therefore, it can be used to treat various inflammatory diseases.

Biocompatibility Evaluation of Bent-Type Left Ventricular Assist Device During Long-Term Animal Experiment and Emergent Situation (장기 동물 실험 및 응급상황에서의 곡관형 좌심실보조장치의 생체적합성 평가)

  • Kang, Seong Min;Her, Keun;Choi, Seong Wok
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.38 no.9
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    • pp.739-745
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    • 2014
  • Although medication is given to heart disease patients, conventional medication alone is not sufficient to treat heart disease. However, it has been reported that left ventricular assist device (LVAD) transplantation is an effective bridge to heart transplantation by assisting cardiac function. This study used long-term animal testing and emergency situations with a bovine model (Holstein) and canine model (Labrador-retriever) to evaluate the biocompatibility of LibraHeart-I (LH-1), which is a bent-tube type of LVAD that was developed in a previous study. In the long-term animal testing with the bovine model, the subjects survived for 49 days with no irregularities observed in their complete blood cell counts or the vital sign tests that were carried out during the test period. In short-term animal testing with the canine model, it was observed that blood did not remain inside the LH-I even without power support from an external drive source. In this study, the biocompatibility of the LH-I that was developed in a previous study was verified by the ejection performance during long-term animal testing and emergency situations.

Application of HACCP System in the Pork Industry in Korea - Review -

  • Chung, M.S.
    • Asian-Australasian Journal of Animal Sciences
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    • v.12 no.2
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    • pp.253-260
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    • 1999
  • Occurrences of foodborne disease outbreaks are increasing in Korea. Among the outbreaks, Salmonella, Staphylococcus aureus, Vibrio parahaemolyticus are the most important organisms and meat and meat product the major sources of infection. Hazard Analysis Critical Control Point system is a process control system designed to identify and prevent microbial and other hazards in food production. It is considered to be the best process management system by the National Advisory Committee for Microbiological Criteria for Foods, the National Academy of Science, and the Codex Alimentarius Commission. The Korean Ministry of Health and Welfare established a legal basis for the implementation of the HACCP system in Article 32-2 (Hazard Analysis Critical Control Point) of the Food Sanitation Act in December 1995. The Ministry of Agriculture and Forestry has granted research funds for the development of this model system for application to traditional food products and processed fishery products as well as to raw meats. Implementation of the HACCP system is an important step and the Korean food industry and the Government are focused on ensuring food safety in Korea.