• 제목/요약/키워드: Experimental animal models

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A comparison study of pathological features and drug efficacy between Drosophila models of C9orf72 ALS/FTD

  • Davin Lee;Hae Chan Jeong;Seung Yeol Kim;Jin Yong Chung;Seok Hwan Cho;Kyoung Ah Kim;Jae Ho Cho;Byung Su Ko;In Jun Cha;Chang Geon Chung;Eun Seon Kim;Sung Bae Lee
    • Molecules and Cells
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    • v.47 no.1
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    • pp.100005.1-100005.15
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    • 2024
  • Amyotrophic lateral sclerosis is a devastating neurodegenerative disease with a complex genetic basis, presenting both in familial and sporadic forms. The hexanucleotide (G4C2) repeat expansion in the C9orf72 gene, which triggers distinct pathogenic mechanisms, has been identified as a major contributor to familial and sporadic Amyotrophic lateral sclerosis cases. Animal models have proven pivotal in understanding these mechanisms; however, discrepancies between models due to variable transgene sequence, expression levels, and toxicity profiles complicate the translation of findings. Herein, we provide a systematic comparison of 7 publicly available Drosophila transgenes modeling the G4C2 expansion under uniform conditions, evaluating variations in their toxicity profiles. Further, we tested 3 previously characterized disease-modifying drugs in selected lines to uncover discrepancies among the tested strains. Our study not only deepens our understanding of the C9orf72 G4C2 mutations but also presents a framework for comparing constructs with minute structural differences. This work may be used to inform experimental designs to better model disease mechanisms and help guide the development of targeted interventions for neurodegenerative diseases, thus bridging the gap between model-based research and therapeutic application.

A murine periodontitis model using coaggregation between human pathogens and a predominant mouse oral commensal bacterium

  • Liu, Mengmeng;Choi, Youngnim
    • Journal of Periodontal and Implant Science
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    • v.52 no.2
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    • pp.141-154
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    • 2022
  • Purpose: C57BL/6 mice, which are among the most common backgrounds for genetically engineered mice, are resistant to the induction of periodontitis by oral infection with periodontal pathogens. This study aimed to develop a periodontitis model in C57BL/6 mice using coaggregation between human pathogens and the mouse oral commensal Streptococcus danieliae (Sd). Methods: The abilities of Porphyromonas gingivalis ATCC 33277 (Pg33277), P. gingivalis ATCC 49417 (Pg49417), P. gingivalis KUMC-P4 (PgP4), Fusobacterium nucleatum subsp. nucleatum ATCC 25586 (Fnn), and F. nucleatum subsp. animalis KCOM 1280 (Fna) to coaggregate with Sd were tested by a sedimentation assay. The Sd-noncoaggregating Pg33277 and 2 Sd-coaggregating strains, PgP4 and Fna, were chosen for animal experiments. Eighty C57BL/6 mice received oral gavage with Sd once and subsequently received vehicle alone (sham), Fna, Pg33277, PgP4, or Fna+PgP4 6 times at 2-day intervals. Mice were evaluated at 5 or 8 weeks after the first gavage of human strains. Results: Fnn, Fna, and PgP4 efficiently coaggregated with Sd, but Pg33277 and Pg49417 did not. Alveolar bone loss was significantly higher in the PgP4 group at both time points (weeks 5 and 8) and in all experimental groups at week 8 compared with the sham group. The PgP4 group presented greater alveolar bone loss than the other experimental groups at both time points. A higher degree of alveolar bone loss accompanied higher bacterial loads in the oral cavity, the invasion of not only PgP4 but also Sd and Fna, and the serum antibody responses to these bacteria. Conclusions: Periodontitis was successfully induced in C57BL/6 mice by oral infection with a P. gingivalis strain that persists in the oral cavity through coaggregation with a mouse oral commensal bacterium. This new model will be useful for studying the role of human oral bacteria-host interactions in periodontitis using genetically engineered mice.

Effects of the Constituents of Melonis Pedicellus in the Animal Models of Hepatic Diseases (과체 성분의 간질환 모델에서의 효과)

  • 최선희;이석용;조태순
    • YAKHAK HOEJI
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    • v.44 no.1
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    • pp.87-94
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    • 2000
  • In order to investigate the hepatoprotective constituents, Melonis Pedicellus was systematically extracted and fractionated with n-hexane, ethyl acetate, butanol and water Treatment of rats with ethyl acetate fraction reduced hepatic injuries induced by $\alpha$-naphthylisothiocyanate or D-galactosamine, whereas the components in water fraction showed protective effect only against D-galactosamine-induced hepatitis in rats. Two cucurbitacins and three sterols were isolated from ethylacetate fraction and their chemical structures were identified as cucurbitacin B, isocucurbitacin B, $\alpha$-spinasterol, stigmast-7-en-3-ol and stigmast-7-en-3-ol-0-$\beta$-D-glucopyranoside. Cucurbitacin B at the dose of 1 mg/kg (p.o.) signifcantly increased in bile flow in rats with ANIT-induced cholestasis. Isocucurbitacin B at 5 mg/hg (p.o.) showed signilicant protective effects against ANIT-induced cholestasis. These results showed that cucurbitacin B and isocucurbitacin B from Melonis Pedicellus may have hepatoprotective effect in rats with experimental cholestasis.

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The Effect of Dietary Fat on Immune Response and Cytokine Production (식이 지방이 면역반응과 Cytokine생성에 미치는 영향)

  • 김우경
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.25 no.2
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    • pp.352-366
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    • 1996
  • The nutritional status of host has a profound effect on immune response and its ability to defend aganinst invading pathogen. Almost all nutrient dificiencies impaired host defence, and more than recommended levels of certain nutrient enhance immune response beyond that observed with 'adequate'. But high-fat diets have been associated with various types of immune dysfunction in experimental animal models and humans. Also, high linoleic acid suppressed immune function and growth and metastasis of tumor than saturated fatty acids. The present review focused on the effect of dietary lipid on immune fuction, cytokine production and clinical conditions like infection, autoimmune disease and cancer.

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Lung Regeneration Therapy for Chronic Obstructive Pulmonary Disease

  • Oh, Dong Kyu;Kim, You-Sun;Oh, Yeon-Mok
    • Tuberculosis and Respiratory Diseases
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    • v.80 no.1
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    • pp.1-10
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    • 2017
  • Chronic obstructive pulmonary disease (COPD) is a critical condition with high morbidity and mortality. Although several medications are available, there are no definite treatments. However, recent advances in the understanding of stem and progenitor cells in the lung, and molecular changes during re-alveolization after pneumonectomy, have made it possible to envisage the regeneration of damaged lungs. With this background, numerous studies of stem cells and various stimulatory molecules have been undertaken, to try and regenerate destroyed lungs in animal models of COPD. Both the cell and drug therapies show promising results. However, in contrast to the successes in laboratories, no clinical trials have exhibited satisfactory efficacy, although they were generally safe and tolerable. In this article, we review the previous experimental and clinical trials, and summarize the recent advances in lung regeneration therapy for COPD. Furthermore, we discuss the current limitations and future perspectives of this emerging field.

Antioxidant Effects of Berchemia berchemiaefolia in Nerve Pain Models

  • Lee, Gil-Hyun;Hyun, Kyung-Yae;Choi, Seok-Cheol
    • Biomedical Science Letters
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    • v.23 no.4
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    • pp.380-387
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    • 2017
  • Berchemia berchemiaefolia (BB) are climbing plants or small to medium-sized trees that live in Africa, Asia and America. We performed the present study to investigate whether oral administration of Berchemia berchemiaefolia extract (BBE) protects SD rats from pain. The SD rat experimental groups were divided into four groups. Two of the animal model groups were fed on BBE (200 mg/kg or 100 mg/kg). We performed oral acute toxicity test to determine the optimal oral dose of BBE. To explore if BBE alleviated pain in the SD rat, we undertook the tail flick latency test and formalin test. Additionally, we conducted the anti-oxidative test. The findings of the present study suggest that Berchemia berchemiaefolia extract exhibits strong antioxidant and analgesic activities.

EXPERIMENTAL STUDIES FOR PREVENTION OF LARGE BOWEL CARCINOGENESIS; A NEW BIOMARKER AND ITS ROLE

  • Mori, Hideki;Yamada, Yasuhiro;Hirose, Yoshinobu;Hara, Akira;Kuno, Toshiya
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.28-28
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    • 2001
  • Large bowel cancer is one of the major causes of increasing world-wide cancer mortality. Our group has found a variety of naturally-occurring and synthetic compounds which have chemopreventive potentials against the occurrence of large bowel cancers using animal models. Aberrant crypt foci (ACF) which develop in rodents soon after the carcinogen exposure have been used as a biomarker for screening effective agents for cancer chemoprevention.(omitted)

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Somatic Cell Nuclear Transfer in Rodents, the Little Big Animals

  • Roh, Sangho
    • Journal of Embryo Transfer
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    • v.27 no.4
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    • pp.205-209
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    • 2012
  • Transgenic rats and mice are useful experimental animal models for medical research including human disease model studies. Somatic cell nuclear transfer (SCNT) technology is successfully applied in most mammalian species including cattle, sheep, pig and mouse. SCNT is also considered to increase the efficacy of transgenic/knockout mouse and rat production. However, in the area of reproductive biotechnology, the rodent model is inadequate because of technical obstacles in manipulating the oocytes including intracytoplasmic sperm injection and SCNT. In particular, success of rat SCNT is very limited so far. In this review, the history of rodent cloning is described.

Adult Mesenchymal Stem Cells for Cell Therapy in Clinical Application (임상적용을 위한 세포치료제로서의 성체 중간엽줄기세포)

  • Song, In-Hwan
    • Journal of Yeungnam Medical Science
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    • v.26 no.1
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    • pp.1-14
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    • 2009
  • Human bone marrow-derived mesenchymal stem cells (MSCs) are a rare population of undifferentiated cells that have the capacity of self renewal and the ability to differentiate into mesodermal phenotypes, including osteocytes, chondrocytes, and adipocytes in vitro. Recently, MSCs have been shown to reside within the connective tissue of most organs, and their surface phenotype has been well analyzed. Many reports showed that transplanted MSCs enhanced regeneration as well as functional improvement of damaged organs and tissues. The wide differentiation plasticity of MSCs was expected to contribute to their demonstrated efficacy in a wide variety of experimental animal models and in human clinical trials. However, new findings suggest that the ability of MSCs to alter the tissue microenvironment via secretion of soluble factors may contribute more significantly than their capacity for differentiation in tissue repair. This review describes what is known about the cellular characteristics and differentiation potential of MSCs, which represent a promising stem cell population for further applications in regenerative medicine.

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Can antioxidants be effective therapeutics for type 2 diabetes?

  • Park, Soyoung;Park, So-Young
    • Journal of Yeungnam Medical Science
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    • v.38 no.2
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    • pp.83-94
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    • 2021
  • The global obesity epidemic and the growing elderly population largely contribute to the increasing incidence of type 2 diabetes. Insulin resistance acts as a critical link between the present obesity pandemic and type 2 diabetes. Naturally occurring reactive oxygen species (ROS) regulate intracellular signaling and are kept in balance by the antioxidant system. However, the imbalance between ROS production and antioxidant capacity causes ROS accumulation and induces oxidative stress. Oxidative stress interrupts insulin-mediated intracellular signaling pathways, as supported by studies involving genetic modification of antioxidant enzymes in experimental rodents. In addition, a close association between oxidative stress and insulin resistance has been reported in numerous human studies. However, the controversial results with the use of antioxidants in type 2 diabetes raise the question of whether oxidative stress plays a critical role in insulin resistance. In this review article, we discuss the relevance of oxidative stress to insulin resistance based on genetically modified animal models and human trials.