• The Korean Journal of Physiology and Pharmacology
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• v.14 no.4
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• pp.229-233
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• 2010

Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of amyloid precursor protein and serves as a bipartite activation enzyme for the ubiquitin-like protein, NEDD8. Previously, it has been reported that APP-BP1 rescues the cell cycle S-M checkpoint defect in Ts41 hamster cells, that this rescue is dependent on the interaction of APP-BP1 with hUba3. The exogenous expression of APP-BP1 in neurons has been reported to cause DNA synthesis and apoptosis via a signaling pathway that is dependent on APP-BP1 binding to APP. These results suggest that APP-BP1 overexpression contributes to neurodegeneration. In the present study, we explored whether APP-BP1 expression was altered in the brains of Tg2576 mice, which is an animal model of Alzheimer's disease. APP-BP1 was found to be up-regulated in the hippocampus and cortex of 12 month-old Tg2576 mice compared to age-matched wild-type mice. In addition, APP-BP1 knockdown by siRNA treatment reduced cullin-1 neddylation in fetal neural stem cells, suggesting that APP-BP1 plays a role in cell cycle progression in the cells. Collectively, these results suggest that increased expression of APP-BP1, which has a role in cell cycle progression in neuronal cells, contributes to the pathogenesis of Alzheimer's disease.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.134-144
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• 2019

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and $3{\beta}$, $7{\alpha}$-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and ${\alpha}/{\gamma}$-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

• 한국생물공학회:학술대회논문집
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• 2003.10a
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• pp.347-350
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• 2003

Dialysis and renal transplantation, the current therapies for end-stage renal disease (ESRD), have many limitations including severe complications, organ shortage, and graft failure. To overcome the limitations, the present study investigated the reconstruction of renal tissue in vivo by transplanting isolated fetal renal cells using fibrin gel to the kidney of renal failure rat model. After 4 weeks from the transplantation, blood urea nitrogen(BUN) and creatinine were examined from blood samples and histological examination of the implanted tissues revealed formation of renal-like structures and restoration of renal function.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.1
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• pp.49-56
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• 2013

Chrysanthemum boreale(CB) is an oriental medicinal herb which has been used traditionally for the treatment of various brain disease including headache, dizziness and sedation. In order to examine the mechanism of anti-parkinsonism effect, water extract of CB(100 mg and 200 mg/kg of b.w.) were administered orally during 28 days in MPTP-induced parkisonism mice model. Water extract of CB increased the motor activities. CB did not affect total MAO and MAO-B activity in the brain of MPTP-induced mice. CB significantly increased the concentration of lipid peroxidation in the mid brain. Also, CB significantly increased antioxidant enzyme including were SOD, catalase and glutathione peroxidase in the mid brain activity. CB significantly increased the concentration of dopamine and homovanillic acid in the brain. These results suggest that the anti-parkinsonism effect of CB is possibly due to the antioxidative effects at mid brain in MPTP-induced animal model.

• Food Science and Biotechnology
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• v.16 no.1
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• pp.43-48
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• 2007

Collagen-induced arthritis (CIA) is a model for some types of human autoimmune rheumatoid arthritis (RA). In this study, we examined whether ethanol extract of potato (Solanum tuberosum) is efficacious against CIA in mice. Potato extracts (100 and 200 mg/kg) were orally administered to DBA/1J mice once daily for 49 day after initial immunization with type II collagen. Clinical assessment of disease and measurement of paw edema were conducted throughout the study. The production of CIA-related rheumatoid factor, anti-type II collagen antibody, and cytokines were examined in DBA/1J mice. Serum levels of AST, ALT, creatinine, and lipids were measured, and antioxidant enzyme activity in the spleen was also determined. The arthritis score and paw edema were markedly suppressed in the groups treated with potato extract. Levels of rheumatoid factor, anti-type II collagen antibody, interleukin (IL)-1, IL-6, LDL-cholesterol, and malondialdehyde in sera were also reduced by potato extract treatment. The activities of glutathione peroxidase and glutathione reductase were increased in the spleens of CIA mice treated with potato extract. These findings suggest that potato extract has suppressive effects on type II collagen-induced arthritis, an animal model for human RA.

• Journal of Microbiology and Biotechnology
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• v.32 no.2
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• pp.212-219
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• 2022

Recently, the efficacy of probiotics in treatment of neurodegenerative disorders has been reported in animal and clinical studies. Here, we assessed the effects of Bacillus coagulans JA845 in counteracting the symptoms of D-galactose (D-gal)/AlCl₃-induced Alzheimer's disease (AD) in a mice model through behavioral test, histological assessment and biochemical analysis. Ten weeks of pre-treatment with B. coagulans JA845 prevented cognitive decline, attenuated hippocampal lesion and protected neuronal integrity, which demonstrated the neuroprotective features of B. coagulans JA845 in vivo. We also found that supplementation of B. coagulans JA845 alleviated amyloid-beta deposits and hyperphosphorylated tau in hippocampus of D-gal/AlCl₃-induced AD model mice. Furthermore, B. coagulans JA845 administration attenuated oxidative stress and decreased serum concentration of inflammatory cytokines by regulating the Nrf2/HO-1 and MyD88/TRAF6/NF-κB pathway. Our results demonstrated for the first time that B. coagulans has the potential to help prevent cognitive decline and might be a novel therapeutic approach for the treatment of neurodegenerative diseases.

• Clinical Endoscopy
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• v.57 no.1
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• pp.73-81
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• 2024

Background/Aims: Upper gastrointestinal bleeding (UGIB) is a life-threatening condition that necessitates early identification and intervention and is associated with substantial morbidity, mortality, and socioeconomic burden. However, several diagnostic challenges remain regarding risk stratification and the optimal timing of endoscopy. The PillSense System is a noninvasive device developed to detect blood in patients with UGIB in real time. This study aimed to assess the safety and performance characteristics of PillSense using a simulated bleeding model. Methods: A preclinical study was performed using an in vivo porcine model (14 animals). Fourteen PillSense capsules were endoscopically placed in the stomach and blood was injected into the stomach to simulate bleeding. The safety and sensitivity of blood detection and pill excretion were also investigated. Results: All the sensors successfully detected the presence or absence of blood. The minimum threshold was 9% blood concentration, with additional detection of increasing concentrations of up to 22.5% blood. All the sensors passed naturally through the gastrointestinal tract. Conclusions: This study demonstrated the ability of the PillSense System sensor to detect UGIB across a wide range of blood concentrations. This ingestible device detects UGIB in real time and has the potential to be an effective tool to supplement the current standard of care. These favorable results will be further investigated in future clinical studies.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.71-81
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• 2005

Objective : Dear antler (Cervus korean TEMMINCK var. mantchuricus Swinhoe) used for traditional immunosuppressive and immuno-activating action. The effect of deer antler herbal-acupuncture(DAH) solution, prepared by water extract method, on cathepsin activities in bone tissues (cartilage and synovial) cells from mouse rheumatoid arthritis (RA) model was studied. The cysteine endoprotease cathepsin mediates degradation of the MHC class II invariant chain (Ii) in human and mouse antigen-presenting cells. The studies described here examine the functional significance of cathepsin inhibition on autoantigen presentation and organ-specific autoimmune diseases in a murine model for RA. Methods : An animal model for RA in BALB/c mice thymectomized 3 days after birth (3d-Tx) was constructed All 3d-Tx BALB/c mice developed autoimmune lesions in the bone tissue cells, starting at 3 weeks of age, and the disease mediated by CD4+ T cells was chronic and progressive. Significant inhibitory effects of DAH solution on cathepsin S and L were observed in each organ in a dose-dependent manner. Moreover, we confirmed that cathepsin S and L activity in each organ were clearly inhibited by DAB solution. When we examined the inhibitory effects of DAH solution against autoantigen-specific T cell responses in vitro, in regional lymph node cells, but not in spleens, from model mice, a significant inhibitory effect of DAB solution was observed in a dose-dependent manner. DAH solution do not block T cell proliferation to Con A, indicated that the dose of DAB solution 10 to $20\;{\mu}g/m{\ell}$ was sufficient to inactivate the autoantigen-specific T cell responses in vitro. In vivo therapeutic effects of DAB solution were examined in a murine model for RA, autoantigen-specific (C-II-specific) T cell response were significantly inhibited in LNCs from DAH solution-treated mice. Results : Iinhibition of cathepsin S and L in vivo alters autoantigen presentation and development of organ-specific autoimmunity in RA model. Conclusion : These data identify selective inhibition of cysteine protease cathepsin S and L as a potential therapeutic strategy for autoimmune disease process such RA. Thus, DAH solution will served as a potent anti-inflammatory and anti-arthritic agents for treatment of human RA.

• Journal of Periodontal and Implant Science
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• v.43 no.4
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• pp.147-152
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• 2013

Purpose: An animal periodontitis model is essential for research on the pathogenesis and treatment of periodontal disease. In this study, we have introduced a lipopolysaccharide (LPS) of a periodontal pathogen to the alveolar bone defect of experimental animals and investigated its suitability as a periodontitis model. Methods: Alveolar bone defects were made in both sides of the mandibular third premolar region of nine beagle dogs. Then, the animals were divided into the following groups: silk ligature tied on the cervical region of tooth group, Porphyromonas gingivalis LPS (P.g. LPS)-saturated collagen with silk ligature group, and no ligature or P.g. LPS application group as the control. The plaque index and gingival index were measured at 0 and 4 weeks postoperatively. The animals were then euthanized and prepared for histologic evaluation. Results: The silk ligature group and P.g. LPS with silk ligature group showed a significantly higher plaque index at 4 weeks compared to the control (P<0.05). No significant difference was found in the plaque index between the silk ligature group and P.g. LPS with silk ligature group. The P.g. LPS with silk ligature group showed a significantly higher gingival index compared to the silk ligature group or the control at 4 weeks (P<0.05). Histologic examination presented increased inflammatory cell infiltration in the gingival tissue and alveolar bone of the P.g. LPS with silk ligature group. Conclusions: An additional P.g. LPS-saturated collagen with silk ligature ensured periodontal inflammation at 4 weeks. Therefore, P.g. LPS with silk ligature application to surgically created alveolar bone defects may be a candidate model for experimental periodontitis.

• Reproductive and Developmental Biology
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• v.35 no.1
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• pp.123-129
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• 2011

The pig has been considered to serve as an appropriate model of human disease. Therefore, establishment of porcine embryonic stem cell lines is important. The purpose of the present study was to further work in this direction. We produced porcine parthenogenetic embryos, and separately aggregated two of each of two-cell ($2{\times}2$), four-cell ($2{\times}4$), and eight-cell ($2{\times}8$) embryos derived by parthenogenesis. After culture for 4 days, the developmental ability of the aggregates and total blastocyst cell numbers were evaluated. The percentage of blastocysts was significantly higher in both $2{\times}4$- and $2{\times}8$-aggregated embryos ($58.3{\pm}1.9%$ and $37.2{\pm}2.8%$, respectively) than in the control or $2{\times}2$-aggregated embryos ($23.6{\pm}1.1%$ and $12.5{\pm}2.4%$, respectively). Total blastocyst cell numbers were increased in the $2{\times}4$- and $2{\times}8$-aggregated embryos (by $44{\pm}3.0%$ and $45{\pm}3.3%$, respectively) compared with those of control or $2{\times}2$-aggregated embryos ($30.5{\pm}2.1%$ and $30.7{\pm}2.6%$, respectively; p<0.05). The levels of mRNA encoding Oct-4 were higher in both the $2{\times}4$- and $2{\times}8$-aggregated embryos than in the control. When blastocysts derived from $2{\times}4$- aggregated embryos or intact normal embryos were cultured on mouse embryonic fibroblast feeder cells to obtain porcine stem cells, blastocysts from aggregated embryos formed colonies that were better in shape compared with those derived from intact blastocysts. Together, the data show that aggregation of porcine embryos not only improves blastocyst quality but also serves as an efficient procedure by which porcine embryonic stem cells can become established.