• IMMUNE NETWORK
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• v.19 no.1
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• pp.2.1-2.13
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• 2019

The enhanced differentiation and activation of osteoclasts (OCs) in the inflammatory arthritis such as rheumatoid arthritis (RA) and gout causes not only local bone erosion, but also systemic osteoporosis, leading to functional disabilities and morbidity. The induction and amplification of NFATc1, a master regulator of OC differentiation, is mainly regulated by receptor activator of NF-κB (RANK) ligand-RANK and calcium signaling which are amplified in the inflammatory milieu, as well as by inflammatory cytokines such as TNFα, IL-1β and IL-6. Moreover, the predominance of CD4⁺ T cell subsets, which varies depending on the condition of inflammatory diseases, can determine the fate of OC differentiation. Anti-citrullinated peptide antibodies which are critical in the pathogenesis of RA can bind to the citrullinated vimentin on the surface of OC precursors, and in turn promote OC differentiation and function via IL-8. In addition to adaptive immunity, the activation of innate immune system including the nucleotide oligomerization domain leucine rich repeat with a pyrin domain 3 inflammasome and TLRs can regulate OC maturation. The emerging perspectives about the diverse and close interactions between the immune cells and OCs in inflammatory milieu can have a significant impact on the future direction of drug development.

• Korean Journal of Veterinary Service
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• v.38 no.3
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• pp.199-203
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• 2015

An 8-year old intact female poodle was presented to clinics due to abdominal distension, anorexia, and labored breath associated with pleural effusion. Intra-operative findings revealed multiple neoplasm of the greater omentum, involving anterolateral abdominal wall, sterna surface in the pleural cavity and diaphragm. These masses were 0.1~0.5 cm in diameter and extended to ovaries, pancreas, and serosal surface of stomach. Microscopically, most neoplastic cells had oval nuclei with prominent nucleoli and abundant eosinophilic cytoplasm. In deeper area, neoplastic acinus or glandular structures showed invaginated growth resembling adenocarcinoma. High mitotic figures were observed. By immunohistochemistry, the neoplastic cells were strong positive both cytokeratin and vimentin. The present case described for malignant mesothelioma in a dog. Our findings might be helpful for diagnosis and information and helped the clinics choose the treatment including chemotherapy such as cisplatin.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3625-3630
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• 2013

Reactive oxygen species (ROS) are known to promote mesothelial carcinogenesis that is closely associated with asbestos fibers and inflammation. Epithelial to mesenchymal cell transition (EMT) is an important process involved in the progression of tumors, providing cancer cells with aggressiveness. The present study was performed to determine if EMT is induced by $H_2O_2$ in human malignant mesothelioma (HMM) cells. Cultured HMM cells were treated with $H_2O_2$, followed by measuring expression levels of EMT-related genes and proteins. Immunohistochemically, TWIST1 expression was confined to sarcomatous cells in HMM tissues, but not in epithelioid cells. Treatment of HMM cells with $H_2O_2$ promoted EMT, as indicated by increased expression levels of vimentin, SLUG and TWIST1, and decreased E-cadherin expression. Expression of stemness genes such as OCT4, SOX2 and NANOG was also significantly increased by treatment of HMM cells with $H_2O_2$. Alteration of these genes was mediated via activation of hypoxia inducible factor 1 alpha (HIF-$1{\alpha}$) and transforming growth factor beta 1 (TGF-${\beta}1$). Considering that treatment with $H_2O_2$ results in excess ROS, the present study suggests that oxidative stress may play a critical role in HMM carcinogenesis by promoting EMT processes and enhancing the expression of stemness genes.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.90-90
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• 2003

체세포 핵이식에 의한 복제기술은 매우 낮은 성공률 나타내고 있어 실용화에 지장을 초래하고 있다. 이것은 후생적인 유전현상인 reprogramming이 불완전하게 이루어지기 때문인 것으로 추측되어지고 있다(Reik et al., Theriogenology 2003, 59: 21-32; Han et al, Theriogenology 2003, 59: 33-44). 체세포 핵이식 후에 태아사망의 원인이 태반의 비정상적인 기능과 관계가 있는 것으로 추정되는데 복제시 태아사망의 원인을 찾기 위해 본 연구를 시행하였다. 한우에서 체세포 복제 후 임신 말기에 태아가 사망한 태반조직 3개와 IVF 수정란 이식 후 동일한 시기에 제왕절개술을 실시한 태반조직 2개를 실험에 이용하였다. 태반 protein을 Two-Dimensional electrophoresis와 Mass spectrometer를 이용하여 분석 비교하였다. IPG-system을 이용하여 pH 4~7, pH 6~9에서 1차 전기영동을 한 후, 8~l6%의 SDS-PAGE gel에 2차 전기영동을 실시하였고 G-250 Coomassie로 염색하였다. gel 이미지는 Malanie III program을 이용하여 분석하였다. 전체 gel에서 약 1800개의 구분 가능한 protein spot이 나타났다. pH 4~7 범위에서 양적으로 차이나는 것 15개 중 복제한우 태반에서 증가되는 protein spot 5개와 감소하는 protein spot 10개를 골라 protein identification을 실시하였다. MALDI-TOF-MS를 이용하여 동정한 결과 phosphatidylinositol transfer protein-$\alpha$와 interleukin-18 등의 protein이 복제태반에서 발현이 증가되었고, 복제한우에서 발현이 감소되는 것으로는 vimentin, Rho-GDI-$\beta$, TRAST $\beta$-chain, ovarian sterol carrier protein 2, triosephosphate isomerase, tropemyosin beta chain, Aldose reductase 등으로 나타났다. 이러한 protein들은 inositol 지질 신호전달과 면역시스템, 세포분열, 산소 운반, steroidogenic 세포에서의 콜레스테롤 이동, 촉매 작용, 대사 작용 등에 중요한 역할을 하는 것으로 알려져 체세포 복제에 의한 태아사망 원인은 태반에서 이러한 protein들의 비정상적인 발현에 기인된 것으로 추정된다.

• Molecules and Cells
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• v.43 no.5
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• pp.438-447
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• 2020

The aim of this study was to explore the role of IL-6-miR-210 in the regulation of Tregs function and atrial fibrosis in atrial fibrillation (AF). The levels of interleukin (IL)-6 and IL-10 in AF patients were detected by using ELISA. Proportions of Treg cells were detected by fluorescence activated cell sorting analysis in AF patients. The expression of Foxp3, α-SMA, collagen I and collagen III were determined by western blot. The atrial mechanocytes were authenticated by vimentin immunostaining. The expression of miR-210 was performed by quantitative real-time polymerase chain reaction (qRT-PCR). TargetScan was used to predict potential targets of miR-210. The cardiomyocyte transverse sections in AF model group were observed by H&E staining. The myocardial filaments were observed by masson staining. The level of IL-6 was highly increased while the level of IL-10 (Tregs) was significantly decreased in AF patients as compared to normal control subjects, and IL-6 suppressed Tregs function and promoted the expression of α-SMA, collagen I and collagen III. Furthermore, miR-210 regulated Tregs function by targeting Foxp3, and IL-6 promoted expression of miR-210 via regulating hypoxia inducible factor-1α (HIF-1α). IL-6-miR-210 suppresses regulatory T cell function and promotes atrial fibrosis by targeting Foxp3.

• The Journal of Internal Korean Medicine
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• v.30 no.2
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• pp.375-387
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• 2009

Objective : Gyehyuldeung (GHD) has been widely used in oriental medicine for the treatments of cardiovascular and neurological disorders. Thus, its potential facilitatory activity on axonal regeneration was investigated in the rats. Methods: Sprague-Dawley rats were given crush injury at the sciatic nerve and the changes of axon growth after nerve injury on each nerve injury model were investigated with anti-NF-200 antibody, DiI, GAP-43 protein and Cdc2 protein Results : GHD-mediated enhancement of axonal regeneration after crush injury was measured in both qualitative and quantitative ways by immunofluorescence staining with anti-NF-200 antibody and retrograde tracing of fluorescence dye DiI. GAP-43 protein levels were elevated by GHD treatments in the distal injured sciatic nerve and DRG sensory neurons. The neurite outgrowth of DRG sensory neurons was facilitated by GHD treatment when co-cultured with Schwann cells and astrocytes prepared from injured sciatic nerves and injured spinal cord tissues, respectively. It was observed that Cdc2 protein was up-regulated in co-cultured Schwann cells or astrocytes and Cdc2 protein signals were co-localized to a certain extent with those of phospho-vimentin protein. Conclusions : These results suggest that GHD may play a facilitatory role in axonal regeneration by acting on the injured axons and adjacent non-neuronal cells. The current findings may be useful for the development of therapeutic targets through more specific explorations on molecular interactions between herbal components and endogenous factors.

• The Korean Journal of Cytopathology
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• v.7 no.1
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• pp.69-74
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• 1996

Malignant rhabdold tumor is a distinct renal tumor in the pediatric age group. It was originally described as a rhabdomyosarcomatold variant of Wilms' tumor. However, subsequent studies fatted to confirm myogenous differentiation, so it is now considered to be a distinct and unique type of highly malignant tumor, histogenetically unrelated. Although extrarenal forms of this tumor are rare, several examples have been described in other sites, especially the liver, prostate, paravertebral area, urinary bladder and soft tissue. We experienced a case of malignant rhabdiod tumor located in the intraabdominal cavity in a 10 month-old boy. Smear of peritoneal fluid showed round, polygonal and irregular shaped cells with large nuclei, ample cytoplasm containing light pink to purple cytoplasmic inclusions, and one or a few prominent nucleoli. Immunocytochemistry revealed positivity to cytokeratin, epithelial membrane antigen and vimentin, and negativity to desmin and neuron-specific enolase. These distinct cytologic appearance and immunophenotypes were most consistent with a diagnosis of extrarenal malignant rhabdoid tumor. The cytoplasmic inclusions were correlated with eosinophilic inclusions seen in histologic section and electron microscopy confirmed this interpretation, showing filamentous aggregations in the cytoplasms of the tumor cells.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.2
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• pp.349-359
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• 2020

Objective: Orchastric changes in the mammary glands are vital, especially during lactation. The secretary epithelial cells together with the supporting myoepithelial and stromal cells function cordially to secrete milk. Increase in the number of luminal epithelial cells and a decrease in adipocytes are visible during lactation, whereas the reverse happens in the involution. However, an early involution occurs if the epithelial cells transdifferentiate towards adipocytes during the lactation period. We aimed to inhibit the adipocyte transdifferentiation of luminal cells by restraining the peroxisomal proliferator-activated receptor γ (PPARγ) pathway. Methods: Linolenic acid (LA) and thiazolidinediones (TZDs) induced adipogenesis in mammary epithelial cells were conducted in monolayer, mixed culture as well as in transwell plate co-culture with mammary myoepithelial cells. Results: Co-culture with myoepithelial cells showed higher adipogenic gene expression in epithelial cells under LA+TZDs treatment. Increase in the expressions of PPARγ, CCAAT/enhancer-binding protein α and vimentin in both mRNA as well as protein levels were observed. Whereas, bisphenol A diglycidyl ether treatment blocked LA+TZDs induced adipogenesis, as it could not show a significant rise in adipose related markers. Although comparative results were found in both mixed culture and monolayer conditions, co-culture technic was found to work better than the others. Conclusion: Antagonizing PPARγ pathway in the presence of myoepithelial cells can significantly reduce the adipogenisis in epithelial cells, suggesting therapeutic inhibition of PPARγ can be considered to counter early involution or excessive adipogenesis in mammary epithelium in animals.

• Journal of Pharmacopuncture
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• v.12 no.3
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• pp.49-59
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• 2009

Background : Anticancer effects of herbal medicine have been reported in various types of cancer, but the systematic approaches to explain molecular mechanism(s) are not established yet. Objective : The purpose of this study is to investigate the apoptotic cell death by Egg White combined Chalcanthite in NCI-H460 human lung cancer cells. Methods : Inhibitory effects were estimated by the MTT-assay. Cancer cells were stained with DAPI and showed condensed and fragmented nuclei. The expression of cleaved caspase-3, bcl-2, and bax was detected by western blotting. To establish a basis of understanding for anti-cancer mechanism, whole proteins have been obtained from NCI-H460 harvested at 24 hrs after the treatment of Egg White combined Chalcanthite, protein expression has been profiled by 2DE-based proteomic approach. Results : NCI-H460 human lung cancer cells were treated by three samples of IS3, IS4 and IS5. IS4 inhibited most effectively the growth of NCI-H460 human lung cancer cells. The expression of cleaved caspase-3 increased in IS4 in a concentration-dependent manner. Various changes of the protein expression have been monitored, and most frequent dysregulation was found in Vimentin, Lamin-A/C. Conclusion : Egg White combined-Chacanthite inhibited the growth of NCI-H460 human lung cancer cells by inducing the apoptotic cell death via caspase-3 activation. Based upon the present findings, the further study will focus on monitoring various cancer survival factors after artificial regulation of the proteins identified, and it would be the basis for the understanding of the Chacabthite anticancer effect(s) at the molecular level.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.44 no.2
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• pp.66-72
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• 2018

Objectives: Desmoplastic melanoma of the oral cavity is an extremely rare condition that is often confused on initial diagnosis with non-melanotic benign lesion or spindle cell tumors. The purpose of this article was to raise awareness of the disease using a literature review. Materials and Methods: We analyzed 19 desmoplastic melanoma cases reported in the literature and added our experience. Data on clinical, histopathology, treatment, and survival were retrieved and analyzed. Survival analysis was by the Kaplan-Meier method. Results: Initial clinical and histopathological features were indistinctive, and a definite diagnosis of desmoplastic melanoma at initial assessment was possible in only 23.5% of cases. Among tests, immunohistochemical studies for S-100 and vimentin were all positive. The 5-year disease-free survival rate for oral desmoplastic melanoma was 0%, and the 5-year overall survival rate was 55.0%. Conclusion: Oral desmoplastic melanoma has a high percentage of initial misdiagnosis and propensity for local recurrence. Thus, careful initial diagnosis and adequate surgery may result in improved overall survival.