• Title/Summary/Keyword: Animal disease model

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Tissue Distribution of HuR Protein in Crohn's Disease and IBD Experimental Model (염증성 장질환 모델 및 크론병 환자에서의 점막상피 HuR 단백질의 변화 분석)

  • Choi, Hye Jin;Park, Jae-Hong;Park, Jiyeon;Kim, Juil;Park, Seong-Hwan;Oh, Chang Gyu;Do, Kee Hun;Song, Bo Gyoung;Lee, Seung Joon;Moon, Yuseok
    • Journal of Life Science
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    • v.24 no.12
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    • pp.1339-1344
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    • 2014
  • Inflammatory bowel disease is an immune disorder associated with chronic mucosal inflammation and severe ulceration in the gastrointestinal tract. Antibodies against proinflammatory cytokines, including TNF${\alpha}$, are currently used as promising therapeutic agents against the disease. Stabilization of the transcript is a crucial post-transcriptional process in the expression of proinflammatory cytokines. In the present study, we assessed the expression and histological distribution of the HuR protein, an important transcript stabilizer, in tissues from experimental animals and patients with Crohn's disease. The total and cytosolic levels of the HuR protein were enhanced in the intestinal epithelia from dextran sodium sulfate (DSS)-treated mice compared to those in control tissues from normal mice. Moreover, the expression of HuR was very high only in the mucosal and glandular epithelium, and the relative localization of the protein was sequestered in the lower parts of the villus during the DSS insult. The expression of HuR was significantly higher in mucosal lesions than in normal-looking areas. Consistent with the data from the animal model, the expression of HuR was confined to the mucosal and glandular epithelium. These results suggest that HuR may contribute to the post-transcriptional regulation of proinflammatory genes during early mucosal insults. More mechanistic investigations are warranted to determine the potential use of HuR as a predictive biomarker or a promising target against IBD.

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.

Development and Animal Tests of Prototype Oxygen Concentrator (국산 산소 농축기의 개발 및 동물실험)

  • 변정욱;성숙환;이태수
    • Journal of Chest Surgery
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    • v.31 no.7
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    • pp.643-649
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    • 1998
  • Background: For the patient with chronic obstructive pulmonary disease requiring long-term oxygen therapy, oxygen concentrator machines are already widely available for use in home. In this study, we used mongrel dogs as test subjects to compare the functional efficiency and safety of the oxygen concentrator developed by our own research team with those of the imported FORLIFE(TM) machine made by AIRSEP Corp. Method and method: To test mechanical reliability, the concentrations of oxygen delivered were measured after 4 hours of continuous operation. Sixteen mongrel dogs were divided into two equal groups. Mongrel dogs in group A were given oxygen using the imported oxygen concentrator, and those in group B using the machine developed. 5 l/min of oxygen were given, after which vital signs were analyzed, arterial blood gases measured, and blood chemistry tests carried out. Results: After 4 hours of continuous operation, the imported model performed better, giving 98${\pm}$3% oxygen, compared to our model, which gave 91${\pm}$1%. In the animal experiments, oxygen concentrations were measured at the inlet of face mask 1, 2, 3, and 4 hours after continuous administration, and there was no statistically significant difference(repeated measures of analysis of variance p=0.70) between the values of 70.6${\pm}$2.5%, 67.1${\pm}$2.9%, 68.2${\pm}$2.6%, and 64.9${\pm}$3.9% that were measured from group A, and the values of 65.1${\pm}$4.8%, 65.2${\pm}$3.6%, 68.7${\pm}$4.3%, and 66.0${\pm}$5.0% measured from group B. Before oxygen administration, and at 1, 2, 3, and 4 hours after oxygen administration, arterial blood partial pressure of oxygen 87.2${\pm}$2.5 mmHg, 347.4${\pm}$29.3 mmHg, 353.4${\pm}$21.2 mmHg, 343.0${\pm}$28.8 mmHg, and 321.6${\pm}$24.4 mmHg, respectively, were read from group A, which were not statistically different (p=0.24) to the values of 102.5${\pm}$9.6 mmHg, 300.3${\pm}$17.1 mmHg, 321.6${\pm}$23.7 mmHg, 303.4${\pm}$27.4 mmHg, and 273.5${\pm}$25.9 mmHg read from group B. Nonetheless, the arterial blood partial pressure of oxygen values appear to be somewhat higher in dogs that were given oxygen using the imported oxygen concentrator. Conclusions: From these results the prototype oxygen concentrator developed appears to function relatively satisfactorily compared to the imported, established model, but may be criticized for the excessive noise generated and poor long-term endurance or consistency, which need improvement.

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Pharmacokinetics of amoxicillin trihydrate in cultured eel Anguilla japonica by single oral and intravenous administrations (Amoxicillin trihydrate의 단독 경구투여 및 정맥투여에 따른 뱀장어, Anguilla japonica 체내 약물동태학적 특성)

  • Jeon, Eun-Ji;Seo, Jeong-Soo;Kim, Jin-Do;Jung, Sung-Hee;Kim, Myoung-Sug;Hwang, Jee-Youn;Park, Myoung-Ae;Jee, Bo-Young;Kim, Jin-Woo;Kim, Yi-Cheong
    • Journal of fish pathology
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    • v.23 no.3
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    • pp.357-367
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    • 2010
  • The pharmacokinetic properties of amoxicillin trihydrate (Amox) were studied after single oral administration and single intravenous injection to cultured eel, Anguilla japonica, respectively (average $220{\pm}10\;g$, $28{\pm}1^{\circ}C$). Plasma samples were taken at 3, 5, 10, 15, 24, 30, 48, 96 and 144 h post-dose. The kinetic profile of absorption, distribution and elimination of Amox in plasma were analyzed fitting to a two-compartment model by WinNonlin program. In oral dosage of 40 and 80 mg/kg body weight, the peak plasma concentrations of Amox, which attained at 3~12 h post-dose, were 3.4 and $3.3\;{\mu}g/ml$, respectively. In intravenous injection with 1 mg/kg, the peak plasma concentrations of Amox, which attained at 9 h post-dose, was $7.2\;{\mu}g/ml$. The following parmeters were calculated for a single oral dosage of 40 and 80 mg/kg body weight, respectively: AUC (the area under the concentration-time curve)= 464 and $667\;{\mu}g{\cdot}h/ml$; $T_{max}$ (time for maximum concentration)= 2.1 and 3.6 h; $C_{max}$ (maximum concentration)= 3.04 and $3.4\;{\mu}g/ml$. Following intravenous injection at 1 mg/kg, this parameters were AUC= $748\;{\mu}g{\cdot}h/ml$; $C_{max}=4.2\;{\mu}g/ml$. The apparent oral bioavailability at 40 and 80 mg/kg were 1.6 and 1.1%, respectively. Despite using the trihydrate form of amoxicillin, the oral bioavailability was low in eel.

Transfer of Isolated Mitochondria to Bovine Oocytes by Microinjection (미세주입을 이용한 난자로의 분리된 미토콘드리아 전달)

  • Baek, Sang-Ki;Byun, June-Ho;Kim, Bo Gyu;Lee, A ram;Cho, Young-Soo;Kim, Ik-Sung;Seo, Gang-Mi;Chung, Se-Kyo;Lee, Joon-Hee;Woo, Dong Kyun
    • Journal of Life Science
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    • v.27 no.12
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    • pp.1445-1451
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    • 2017
  • Mitochondria play a central role in energy generation by using electron transport coupled with oxidative phosphorylation. They also participate in other important cellular functions including metabolism, apoptosis, signaling, and reactive oxygen species production. Therefore, mitochondrial dysfunction is known to contribute to a variety of human diseases. Furthermore, there are various inherited diseases of energy metabolism due to mitochondrial DNA (mtDNA) mutations. Unfortunately, therapeutic options for these inherited mtDNA diseases are extremely limited. In this regard, mitochondrial replacement techniques are taking on increased importance in developing a clinical approach to inherited mtDNA diseases. In this study, green fluorescence protein (GFP)-tagged mitochondria were isolated by differential centrifugation from a mammalian cell line. Using microinjection technique, the isolated GFP-tagged mitochondria were then transferred to bovine oocytes that were triggered for early development. During the early developmental period from bovine oocytes to blastocysts, the transferred mitochondria were observed using fluorescent microscopy. The microinjected mitochondria were dispersed rapidly into the cytoplasm of oocytes and were passed down to subsequent cells of 2-cell, 4-cell, 8-cell, morula, and blastocyst stages. Together, these results demonstrate a successful in vitro transfer of isolated mitochondria to oocytes and provide a model for mitochondrial replacement implicated in inherited mtDNA diseases and animal cloning.

Utility of Micro CT in a Murine Model of Bleomycin-Induced Lung Fibrosis (Bleomycin 유도 폐 섬유화 쥐 모델에서 미세 전산화단층촬영의 유용성)

  • Lee, Jae A;Jin, Gong Yong;Bok, Se Mi;Han, Young Min;Park, Seoung Ju;Lee, Yong Chul;Chung, Myung Ja;Youn, Gun Ha
    • Tuberculosis and Respiratory Diseases
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    • v.67 no.5
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    • pp.436-444
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    • 2009
  • Background: Micro computed tomography (CT) is rapidly developing as an imaging tool, especially for mice, which have become the experimental animal of choice for many pulmonary disease studies. We evaluated the usefulness of micro CT for evaluating lung fibrosis in the murine model of bleomycin-induced lung inflammation and fibrosis. Methods: The control mice (n=10) were treated with saline. The murine model of lung fibrosis (n=60) was established by administering bleomycin intra-tracheally. Among the 70 mice, only 20 mice had successful imaging analyses. We analyzed the micro CT and pathological findings and examined the correlation between imaging scoring in micro CT and histological scoring of pulmonary inflammation or fibrosis. Results: The control group showed normal findings on micro CT. The abnormal findings on micro CT performed at 3 weeks after the administration of bleomycin were ground-glass opacity (GGO) and consolidation. At 6 weeks after bleomycin administration, micro CT showed various patterns such as GGO, consolidation, bronchiectasis, small nodules, and reticular opacity. GGO (r=0.84) and consolidation (r=0.69) on micro CT were significantly correlated with histological scoring that reflected pulmonary inflammation (p<0.05). In addition, bronchiectasis (r=0.63) and reticular opacity (r=0.83) on micro CT shown at 6 weeks after bleomycin administration correlated with histological scoring that reflected lung fibrosis (p<0.05). Conclusion: These results suggest that micro CT findings from a murine model of bleomycin-induced lung fibrosis reflect pathologic findings, and micro CT may be useful for predicting bleomycin-induced lung inflammation and fibrosis in mice.

Recent Trends of Immunologic Studies of Herbal Medicine on Rheumatoid Arthritis (류마티스 관절염에 대한 한약의 면역학적 연구동향)

  • Choi, Do-young;Lee, Jae-dong;Back, Yong-hyeon;Lee, Song-shil;Yoo, Myung-chul;Han, Chung-soo;Yang, Hyung-in;Park, Sang-do;Ryu, Mi-hyun;Park, Eun-kyung;Park, Dong-seok
    • Journal of Acupuncture Research
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    • v.21 no.4
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    • pp.177-196
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    • 2004
  • Objective : Rheumatoid arthritis is an autoimmune disease that pathogenesis is not fully understood and one of the most intractable musculoskeletal diseases. The concern in the immunopathogenesis of rheumatoid arthritis has been increased since 1980's and many immunotherapeutic agents including disease-modifying antirheumatic drugs (DMARDs) were developed and became the mainstay of treatment of rheumatoid arthritis. However, the cure of the disease has hardly been achieved. In oriental medicine, rheumatoid arthritis is related to Bi-Zheng(痺證), that presents pain, swelling, andlor loss of joint function as major clinical manifestations, and also known to be deeply involved in suppression of immune function related to weakness of Jung-Ki(正氣). The herbal medicine, empirically used, could be a potential resource of development of new immunotherapeutic agents for rheumatoid arthritis. Methods : We developed a search strategy using terms to include "rheumatoid arthritis and herbal medicine" combined with "Chinese medicine" and/or "Oriental medicine". The search was focused on experimental studies of herbal medicine (January 1999 to May 2004), which is known to have effects on immune function of patients with rheumatoid arthritis. Computerized search used Internet databases including KISS and RISS4U (Korea), CNKI (China), MOMJ (Main Oriental Medicine Journal, Japan), and PubMed. The articles were selected from journals of universities or major research institutes. Results : The literature search for experimental studies on effects of herbal medicine on immunity of rheumatoid arthritis retrieved a total of 21 articles (Korea; 8, China ; 12, Japan ; 1). Of 21 articles, 10 were related to single-drug formula, 2 to drug interaction, and 9 to multi-drug formula. Single-drug formula was mainly used for aqua-acupuncture and researches on active components. Studies of drug interaction emphasized harmony of Ki-Hyul(氣血) and balance of Han-Yeul(寒熱). Multi-drug regimen was mainly found among formulas for Bo-Ki-Hyul(補氣血) and Bo-Sin(補腎). Conclusion : Studies on rheumatoid arthritis were performed both in vitro and in vivo in vitro study, LPS-stimulated splenocytes and synoviocytes were treated with herbal medicine, resulting in proliferation and activation of immune cells and suppression of cytokine activities in vivo study CIA animal model demonstrated that herbal medicine decreased antibody production and improved function of immune cells. In cellular and molecular study herbal medicine showed profound effects on the level of mRNA expression of certain cytokines related to immune function. This study revealed that herbal medicine has significant immune modulatory action and could be used for recovery of immune dysfunction of rheumatoid arthritis patients.

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Effect of Kami-KangHwalSan on atopic dermatitis-like skin lesions induced in NC/Nga mice by mite antigen stimulation (가미강활산(加味羌活散)이 NC/Nga mice의 아토피 발진 억제에 미치는 실험적 연구)

  • Kim, Yun-Hee;Han, Jae-Kyung;Kim, Yun-Hee
    • Journal of Haehwa Medicine
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    • v.16 no.1
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    • pp.81-91
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    • 2007
  • Objective : We wished to examine closely effect that Kami-KangHwalSan medicines used to atopy dermatitis disease patient get in atopy eruption control experimentally. Materials and Methods : Atopic dermatitis (AD) usually develops in patients with an individual or family history of allergic diseases, and is characterized by chronic relapsing inflammation seen specially in childhood, association with IgE hyperproduction and precipitation by environmental factors. However, the exact etiology of AD has been unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is required. We found that skin lesions, which were chnically and histologically very simlar to human AD, mite antigen-induced dermatitis on the face, neck, ears and dorsal skin of inbred NC/Nga mice. Results and Conclusion : Kami-KangHwalSan medicines controlled CD3+/CD69+, CD4+/CD25+, B220+/IgE+, and B220+/CD23+ revelation that an experiment that motive allergy immune reponse because an in vitro experiment stimulates splenocytes of a NC/Nga mouse same t1me by PWM, and interleukin-4, eotaxin 2, CCR3, TARC mRNA outturn that bear in splenocytes decreased remarkably by Kami-KangHwalSan medicines. Th1 cell and Th2 cell observe to be shifted by secretion amount of IL-4 and IFN-$\gamma$ by Kami-KangHwalSan medicines could know that Kami-KangHwalSan medicines can use usefully in allergy autoimmnune diease.

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Effect of Jeseupwiryeongtang-Kamibang(JWRTK) on atopic dermatitis-like skin lesions induced in NC/Nga mice by mite antigen stimulation (제습위령탕가미방(除濕胃笭湯加味方)이 NC/Nga mice의 아토피 발진 억제에 미치는 실험적 연구)

  • Na, Dong-Kyu;Kim, Yun-Hee;Han, Jae-Kyung;Kim, Yun-Hee
    • Journal of Haehwa Medicine
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    • v.16 no.1
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    • pp.93-105
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    • 2007
  • Objective : We wished to examine closely effect that Kami-JeSeubUilYeongTang medicines used to atopy dermatitis disease patient get in atopy eruption control experimentally. Materials and Methods : Atopic dermatitis (AD) usually develops in patients with an individual or family history of allergic diseases, and is characterized by chronic relapsing inflammation seen specially in childhood, association with IgE hyperproduction and precipitation by environmental factors. However, the exact etiology of AD has been unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is required. We found that skin lesions, which were clinically and histologically very similar to human AD, mite antigen-induced dermatitis on the face, neck, ears and dorsal skin of inbred NC/Nga mice. Result and Conclusion : Kami-jeseupwiryeongtang(JWRTK) medicines controlled CD3+/CD69+, CD4+/CD25+, B220+/IgE+, and B220+/CD23+ revelation that an experiment that motive allergy immune reponse because an in vitro experiment stimulates splenocytes of a NC/Nga mouse same time by PWM, and interleukin-4, eotaxin 2, CCR3, TARC mRNA outturn that bear in splenocytes decreased remarkably by Jeseupwiryeongtang-Kamibang(JWRTK) medicines. Th1 cell and Th2 cell observe to be shifted by secretion amount of IL-4 and IFN-$\gamma$ by Jeseupwiryeongtang-Kamibang(JWRTK) medicines could know that Jeseupwiryeongtang-Kamibang(JWRTK) medicines can use usefully in allergy autoimmnune diease.

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Mind Bomb-Binding Partner RanBP9 Plays a Contributory Role in Retinal Development

  • Yoo, Kyeong-Won;Thiruvarangan, Maivannan;Jeong, Yun-Mi;Lee, Mi-Sun;Maddirevula, Sateesh;Rhee, Myungchull;Bae, Young-Ki;Kim, Hyung-Goo;Kim, Cheol-Hee
    • Molecules and Cells
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    • v.40 no.4
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    • pp.271-279
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    • 2017
  • Ran-binding protein family member, RanBP9 has been reported in various basic cellular mechanisms and neuropathological conditions including schizophrenia. Previous studies have reported that RanBP9 is highly expressed in the mammalian brain and retina; however, the role of RanBP9 in retinal development is largely unknown. Here, we present the novel and regulatory roles of RanBP9 in retinal development of a vertebrate animal model, zebrafish. Zebrafish embryos exhibited abundant expression of ranbp9 in developing brain tissues as well as in the developing retina. Yeast two-hybrid screening demonstrated the interaction of RanBP9 with Mind bomb, a component of Notch signaling involved in both neurogenesis and neural disease autism. The interaction is further substantiated by co-localization studies in cultured cells. Knockdown of ranbp9 resulted in retinal dysplasia with defective proliferation of retinal cells, downregulation of neuronal differentiation marker huC, elevation of neural proliferation marker her4, and alteration of cell cycle marker p57kip2. Expression of the $M{\ddot{u}}ller$ glial cell marker glutamine synthase was also affected in knockdown morphants. Our results suggest that Mind bomb-binding partner RanBP9 plays a role during retinal cell development of zebrafish embryogenesis.