• Natural Product Sciences
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• v.11 no.2
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• pp.103-108
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• 2005

Bioflavone quercetin is thought to have an important role to inhibit bone loss by affecting osteoclastogenesis and regulating a number of systemic and local factors such as hormones and cytokines. In this study, we examined how quercetin acts on cytokine production and mineralization of osteoblast in the presence of tumor necrosis factor-alpha $(TNF-{\alpha})$ which has been known to play a pivotal role in bone metabolic diseases. Quercetin inhibited $TNF-{\alpha}-induced$ secretion of $IFN-{\gamma}$ and IL-6 in differentiated MC3T3-E1 cells. As indicated by the markers that are characteristics of the osteoblast phenotype, such as alkaline phosphatase (ALP) activity and calcium deposition, quercetin treatment slightly prevented the $TNF-{\alpha}-induced$ dramatic inhibition of differentiation and mineralization of MC3T3-E1 cells. Further, quercetin inhibited the production of nitric oxide induced by $TNF-{\alpha}$ in the cells. Collectively, our findings indicate that quercetin inhibites $TNF-{\alpha}-induced$ secretion of inflammatory cytokines in differentiated MC3T3-E1 cells without any cytotoxic effects.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2002.07a
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• pp.113-113
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• 2002

Phylogenetically conserved Bcl-2 family proteins play a pivotal role in the regulation of apoptosis from virus to human. Members of the Bcl-2 family consist of antiapoptotic proteins such as Bcl-2, Bcl-xL, and Bcl-w, and proapoptotic proteins such as BAD, Bax, BOD, and Bok. It has been proposed that anti- and proapoptotic Bcl-2 proteins regulate cell death by binding to each other and forming heterodimers. A delicate balance between anti- and proapoptotic Bcl-2 family members exists in each cell and the relative concentration of these two groups of proteins determines whether the cell survives or undergoes apoptosis. Mcl-1 (Myeloid cell :leukemia-1) is a member of the Bcl-2 family proteins and was originally cloned as a differentiation-induced early gene that was activated in the human myeloblastic leukemia cell line, ML-1 . Mcl-1 is expressed in a wide variety of tissues and cells including neoplastic ones. We recently identified a short splicing variant of Mcl-1 short (Mcl-IS) and designated the known Mcl-1 as Mcl-1 long (Mcl-lL). Mcl-lL protein exhibits antiapoptotic activity and possesses the BH (Bcl-2 homology) 1, BH2, BH3, and transmembrane (TM) domains found in related Bcl-2 proteins. In contrast, Mcl-1 S is a BH3 domain-only proapoptotic protein that heterodimerizes with Mcl-lL. Although both Mc1-lL and Mcl-lS proteins contain BH domains fecund in other Bcl-2 family proteins, they are distinguished by their unusually long N-terminal sequences containing PEST (proline, glutamic acid, serine, and threonine) motifs, four pairs of arginine residues, and alanine- and glycine-rich regions. In addition, the expression pattern of Mcl-1 protein is different from that of Bcl-2 suggesting a unique role (or Mcl-1 in apoptosis regulation. Tankyrasel (TRF1-interacting, ankyrin-related ADP-related polymerasel) was originally isolated based on its binding to TRF 1 (telomeric repeat binding factor-1) and contains the sterile alpha motif (SAM) module, 24 ankyrin (ANK) repeats, and the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP). Previous studies showed that tankyrasel promotes telomere elongation in human cells presumably by inhibiting TRFI though its poly(ADP-ribosyl)action by tankyrasel . In addition, tankyrasel poly(ADP-ribosyl)ates Insulin-responsive amino peptidase (IRAP), a resident protein of GLUT4 vesicles, and insulin stimulates the PARP activity of tankyrase1 through its phosphorylation by mitogen-activated protein kinase (MAPK). ADP-ribosylation is a posttranslational modification that usually results in a loss of protein activity presumably by enhancing protein turnover. However, little information is available regarding the physiological function(s) of tankyrase1 other than as a PARP enzyme. In the present study, we found tankyrasel as a specific-binding protein of Mcl-1 Overexpression of tankyrasel led to the inhibition of both the apoptotic activity of Mel-lS and the survival action of Mcl-lL in mammalian cells. Unlike other known tankyrasel-interacting proteins, tankyrasel did not poly(ADP-ribosyl)ate either of the Mcl-1 proteins despite its ability to decrease Mcl-1 proteins expression following coexpression. Therefore, this study provides a novel mechanism to regulate Mcl-1-modulated apoptosis in which tankyrasel downregulates the expression of Mcl-1 proteins without the involvement of its ADP-ribosylation activity.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.1
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• pp.69-75
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• 2006

Head and neck squamous cell carcinoma(HNSCC) is the sixth most common cancer among men in the developed world affecting the tongue, pharynx, larynx and oral cavity. HNSCC is thought to represent a multistep process whereby carcinogen exposure leads to genetic instability in the tissue and accumulation of specific genetic events, which result in dysregulation of proliferation, differentiation, and cell loss and the acquisition of invasive capacity. Despite therapeutic and diagnostic progress in oncology during the past decades, the prognosis of HNSCC remains poor. Thus it seems that finding a biological tumor markers which will increase the early diagnosis and treatment monitoring rates, is of paramount importance in respect to improving prognosis. In an effort to identify gene expression signatures that may serve as biomarkers, this study several genes were selected, such as H3,3A, S100A7, UCHL1, GSTP1, PAI-2, PLK, TGF${\beta}$1 and bFGF, and used 7 HNSCC cell lines that were established various anatomical sites, and also 17 other cancer cell lines were used for control group using real-time quantitative RT-PCR and immunocytochemical analysis with a monoclonal antibody. In this study, S100A7 showed a clearly restricted occurrence in tongue originated cell line, and GSTP1 expression level in the pharynx originated cell line was very increased, relative to corresponding other cell lines. These results suggest that S100A7 and GSTP1 genes' expression can occur during tongue and pharynx originated head and neck tumorigenesis and that genetic change is an important driving force in the carcinogenesis process. This data indicate that S100A7 and GSTP1 expression pattern in HNSCC reflect both diagnostic clue and biological marker. And this is provides a foundation for the development of site-specific diagnostic strategies and treatments for HNSCC.

• The Journal of Korean Medicine
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• v.19 no.2
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• pp.194-210
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• 1998

The main purpose of this work is the study on the etiology and pathology of the anorexia in oriental and western medicine. An appetite is stimulated by the need of supply of nutrition for life and the physical desire of hunger which appeared as the alternative of taste. In this paper, I investigated the anatomical and the physiological function system, the Piwei functional system and meridian distribution, and the differentiation of the disease according to the Zangfu(internal organs) in association with the anorexia. And conclusion could be summarized as follows : 1. The tongue, one of the Piwei functional system(脾胃機能系), is connected with Pi(脾), Xin(心), Gan(肝) and Shen(腎) meridian. Especially Pi and Xin meridian have the close relations with taste. 2. The appetite has the close relations with Piwei. The appetite and digestion is influenced by the function of smoothing and regulating and bloodflow of Ki(肝主疏泄), warming the Shen to activate the function of Pi(腎主溫養), cleansing the inspired air and keeping the Ki flowing downward(肺主肅降). 3. The cause of anorexia is the insufficiency of Ki of Piwei(脾胃氣虛), the attack of Wei by hyperactive Gan Ki(脾氣犯胃), the insufficiency of Wei Yin(胃陰不足), the declination of the fire from the vital gate(命門火衰) and the retention or stagnancy of undigested food (飮食停滯). Especially, the main cause of anorexia is the insufficiency of Ki of the Piwei(脾胃氣虛). 4. Recently the attack of Wei by hyperactive Gan Ki(脾氣犯胃) is raised by the main cause of anorexia. 5. The mental function of anorexia, which is induced by the unbalance of Pi, is directly associated with Xin(心) and Xin meridia(心經). 6. The goal of the treatment of the anorexia is dependent on the recovery of the weakness of the Pi. And for this goal, the disorders of the other organs is also treated. 7. In the point of the anatomy and physiology, the main cause of anorexia is the loss of function of the autonomic nerve system and the vagus nerve.

• Journal of Gastric Cancer
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• v.1 no.2
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• pp.92-99
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• 2001

Purpose: E-cadherin is an adhesion molecule essential for tight connection between cells, forming the cadherin/catenin complex. Truncated $\beta$-catenin disrupts the interaction between E-cadherin and $\alpha$-catenin, leading to the loss of intercellular adhesion. Met protein, the hepatocyte growth factor receptor, plays important roles in signal transduction. We investigated the relationships between the expressions of E-cadherin, $\beta$-catenin, and c-met protein and the clinicopathological and prognostic parameters in gastric adenocarcinomas. Materials and Methods: The patterns of E-cadherin, $\beta$-catenin, and c-met protein expression were studied using immunohistochemistry in formalin-fixed, paraffin-embedded archival tissues from 76 surgically resected gastric adenocarcinomas. Results: Increased expressions of E-cadherin, $\beta$-catenin, and c-met were more significantly correlated in early gastric cancers (EGC) than in advanced gastric cancers (AGC) (P=0.002, P=0.003 and P=0.026). The positive immunoreactivities of all three markers were markedly lower in signet ring-cell type and poorly differentiated type lesions than in intestinal-type lesions. Decreased expression of the $\beta$-catenin protein correlated well with increased tumor invasion depth (P=0.039), and increased lymph node metastasis correlated well with reduced expression of c-met (P=0.046). Conclusion: In gastric cancers, reduced expressions of the E-cadherin, $\beta$-catenin, and c-met proteins may play some role in poorer tumor differentiation, deeper tumor invasion, and increased lymph node metastasis. Also, the c-met gene is thought to play a specific role in the mechanism of the yet unknown catenin action.

• Journal of Gastric Cancer
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• v.17 no.2
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• pp.132-144
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• 2017

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

• Animal cells and systems
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• v.14 no.4
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• pp.305-313
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• 2010

Pacific abalone Haliotis discus discus is an important fisheries resource in Jeju, Korea. For basic information about its current genetic status in relation to stock enhancement, the level and distribution of genetic variation between wild and released stocks of Pacific abalone in Jeju were examined at nine cross-species microsatellite markers including the use of two novel primers. High levels of polymorphism were observed between the two populations. A total of 146 different alleles were found at all loci, with some alleles being unique. The allelic variability ranged from five to 27 in the wild population and from four to 16 in the released sample. The average observed and expected heterozygosities were estimated to be 0.74 and 0.84 in the wild sample and 0.70 and 0.78 in the released sample, respectively. Although a considerable loss of rare alleles was observed in the released sample, no statistically significant reductions were found in heterozygosity or allelic diversity in the released sample compared to the wild population. Low but significant genetic differentiation was found between the wild and released populations. These results suggest that the intensive breeding practices for stock enhancement may have resulted in a further decrease in genetic diversity, and that the cross-species microsatellite markers used in this study represent a potentially efficient means for further genetic studies, providing beneficial information for the protection and management of H. discus discus.

• Archives of Pharmacal Research
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• v.29 no.8
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• pp.666-676
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• 2006

Gangliosides are widely distributed in mammalian cells and play important roles in various functions such as cell differentiation and growth control. In addition, diabetes and obesity cause abnormal development of reproductive processes in a variety of species. However, the mechanisms underlying these effects, and how they are related, are not fully understood. This study examined whether the differential expression of gangliosides is implicated in the abnormal follicular development and uterine architecture of streptozotocin (STZ)-induced and db/db diabetic mice. Based upon the mobility on high-performance thin-layer chromatography, mouse ovary consisted of at least five different ganglioside components, mainly gangliosides GM3, GM1, GD1a and GT1b, and diabetic ovary exhibited a significant reduction in ganglioside expression with apparent changes in the major gangliosides. A prominent immunofluorescence microscopy showed a dramatic loss of ganglioside GD1a expression in the primary, secondary and Graafian follicles of STZ-induced and db/db diabetic mice. A significant decrease in ganglioside GD3 expression was also observed in the ovary of db/db mice. In the uterus of STZ-induced diabetic mice, expression of gangliosides GD1a and GT1b was obviously reduced, but gangliosides GM1, GM2 and GD3 expression was increased. In contrast, the uterus of db/db mice showed a significant increase in gangliosides GM1, GD1a and GD3 expression. Taken together, a complex pattern of ganglioside expression was seen in the ovary and uterus of normoglycemic ICR and $db/^+$ mice, and the correspoding tissues in diabetic mice are characterized by appreciable changes of the major ganglioside expression. These results suggest that alterations in ganglioside expression caused by diabetes mellitus may be implicated in abnormal ovarian development and uterine structure.

• Korean Journal of Environment and Ecology
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• v.26 no.4
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• pp.475-483
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• 2012

Tribolodon hakonensis(Cypriniformes; Leuciscinae) is anadromous; they are born in freshwater, migrate back to the ocean, then return to their home stream for spawning from mid-March to early-June. Here, five microsatellites were used to assess the level of gene flow among T. hakonensis populations from the Samcheok-Oship Stream, South Korea. The frequencies of dominant alleles across several loci differed between down-and upstream populations divided by several weirs, and pairwise multilocus $F_{ST}$ estimate was significantly high(0.083). However, there were no signs of any loss of genetic variation in the upstream population. Assignment tests of individuals in admixture model(K=2) to a set of baseline samples showed fairly correct assignment to each cluster; all of upstream individuals sere included in the first cluster, while the majority of downstream individuals(65%) comprise the second cluster. These results indicate reduced gene flow between up- and downstream populations but allowing passive downstream drift. It is likely that man-made structures might at least partially be a factor for creating and consolidating the current distribution patterns of genetic variation among T. hakonensis populations in the Samcheok-Oship Stream. This information will assist governing agencies in making informed decisions regarding conservation of anadromous fishes in Korean drainage systems.

• The Journal of Korean Institute of Communications and Information Sciences
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• v.29 no.9B
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• pp.778-790
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• 2004

In this paper, we propose the functional models of optical burst switching (OBS) routers to apply GMPLS (Generalized Multiprotocol Label Switching) to optical networks based on OBS. In addition, we introduce a connection admission control (CAC) algorithms which are operated in this models and can accommodate the required QoS. Firstly, the characteristics of current GMPLS and OBS for the optical Internet are basically considered. With this consideration, the models are proposed to accept OBS features which include the recognition of data bounda η with control information and the statistical multiplexing in terms of bursts. Secondly, we use an offset time decision (OTD) algorithm on behalf of controlling the connection admission with taking QoS parameters such as burst loss rate(BLR) and service-differentiation ratio(SDR) into consideration. The proposed CAC algorithms use the offered load of LSP (Label Switched Path), wavelength information, and QoS parame ‘ ers as inputs of OTD algorithm. A call setup request will be accepted when the offset time decided by OTD algorithm is reasonable for guaranteeing its requested QoS. Simulation is used for performance evaluation Results show the proposed schemes can guarantee the required QoS and those are better than the previous one in terms of channel utilization.