HMGN5 is a typical member of the HMGN (high mobility group nucleosome-binding protein) family which may function as a nucleosomal binding and transcriptional activating protein. Overexpression of HMGN5 has been observed in several human tumors but its role in tumorigenesis has not been fully clarified. To investigate its significance for human lung cancer progression, we successfully constructed a shRNA expression lentiviral vector in which sense and antisense sequences targeting the human HMGN5 were linked with a 9-nucleotide loop. Inhibitory effects of siRNA on endogenous HMGN5 gene expression and protein synthesis were demonstrated via real-time RT-PCR and western blotting. We found HMGN5 silencing to significantly inhibit A549 and H1299 cell proliferation assessed by MTT, BrdU incorporation and colony formation assays. Furthermore, flow cytometry analysis showed that specific knockdown of HMGN5 slowed down the cell cycle at the G0/G1 phase and decreased the populations of A549 and H1299 cells at the S and G2/M phases. Taken together, these results suggest that HMGN5 is directly involved in regulation cell proliferation in A549 and H1299 cells by influencing signaling pathways involved in cell cycle progression. Thus, our finding suggests that targeting HMGN5 may be an effective strategy for human lung cancer treatment.
Journal of the Korea Academia-Industrial cooperation Society
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v.18
no.12
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pp.93-99
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2017
The rate of traffic accidents that occurred in Korea last year is 10 out of every 100,000 people, ranking it 6th among the 35 OECD member countries. The accident rate of children with disabilities and elderly people is also high. The purpose of this study is to introduce traffic safety facilities which have been developed for the reduction of traffic accidents in non-urban areas in Korea through an analysis of the related literature, the accident factors using traffic accident analysis system data and traffic accident characteristics. Traffic safety integrated facilities for ICT-based pedestrian crossings are subject to cross-sectional coverage of child protection zones. The smart safety fence prevents vehicles from parking illegally and informs pedestrians that there is an access vehicle on the pedestrian crossing. The smart bump is designed to warn drivers who are not aware of the pedestrians. In order to standardize the appropriate form and size of the traffic safety facilities for pedestrian crossings, we constructed a standard model for each type, considering the road function, press classification, power, lane number, geometric form, etc. As a result, the rate of traffic accidents involving vulnerable people was reduced. In addition, it is anticipated that the maintenance costs will be reduced by the use of a solar power supply and their compatibility with the existing installed safety fences.
The estrogen receptor-related receptors (ERRs) are a group of nuclear receptor superfamily of transcription factors. ERRs and estrogen receptors (ERs) have overlapping affinities for coactivators and DNA binding sites, but differ markedly in ligand binding and activation. The three mammalian ERR genes have been implicated in diverse physiological processes ranging from placental development to maintenance of bone density, whereas the molecular diversity, function, and regulation of ERRs in non-mammalian species are not well understood. In the present study, to investigate the involvement of ERR in transcription and embryogenesis in marine invertebrates, a cDNA encoding ERR (SnERR) was cloned from the gonad in Strongylocentrotus nudus, by polymerase chain reaction (PCR). The amino acid sequence of SnERR showed high homology with that of S. purpuratus (91%). A phylogenetic tree clearly showed that SnERR is a member of the ERR family and clustered in echinodermata group as supported by a high bootstrap value. We examined gene expression of SnERR during embryonic development of S. nudus using real-time PCR. During the embryonic development, the mRNA of ERR was significantly high levels in early development stages (4~64 cell) and larval stages. The SnERR slightly activated transcription through the classical estrogen response elements (EREs) in the presence of genistein. In addition, peroxisome proliferator-activated receptor $\gamma$ coactivator (PGC)-$1\alpha$ knwon as a coactivator of ERR enhanced the snERR-mediated transactivation, suggesting that the PGC-$1\alpha$ is a coactivator of SnERR.
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.
The X-linked inhibitor of apoptosis (XIAP) is a member of a novel family of inhibitors of apoptosis and has several BIR domains (BIR1, BIR2, and BIR3) and a carboxy-terminal RING zinc-finger. Since suppressionof apoptosis is fundamentally important for carcinogenesis and tumor growth, we investigated the expression and function of XIAP in DEN-induced carcinogenesis using rat model. Wistar rats were injected intraperitoneally with DEN at a dose of 50 mg/kg in twice a week for 12 weeks (Group II) and 16 weeks (Group III) followed by the recovery periods, respectively. The evaluation of DEN-induced carcinogenesis carried out the blood, RT-PCR, histopathological and western blot analysis. The level of blood chemistry including GOT/GPT, albumin, and total bilirubin were significantly exchanged comparing to control and Group I/Group II. The expression of albumin and collagen mRNA were significantly exchanged (P<0.05) in both groups. In addition, AFP mRNA expression decreased more after recovery periods than Group II. XIAP was expressed constitutively in normal rat liver as well as DEN-induced Groups I and Group II. In addition, XIAP expression increased more in Group I with 4 weeks recovery periods than Group I. However, XIAP expression shown to increase in Group lI, otherwise, it was decreased in Group II with 10 weeks repair periods. Taken together, these results suggest the alteration of XIAP expression could be involved in hepatocellular carcinogenesis.
This work has been conducted as a part to set up the regulations and the scientific evaluation systems for the functional dairy products with health claims in Korea. Toward this end, current regulations, requirements, and all kinds of provisions related to the functional dairy products overseas were taken into accounts and feasible recommendations of new initiatives on the current regulations as well. By doing so, not only protecting hopefully the innocent consumers from the false labeling statements and fake advertisements, but also eventually to revitalize the stagnated domestic dairy industries. Currently, functional daily products are simply regarded as "Dietary Supplements" in the United States, and subjected to the regulations under the Dietary Supplement Health and Education Act, established m 1994. Manufacturers and sales distributors should notify their products to the FDA, which is in charge of the dietary supplements on nutrition and labeling, in advance when they start marketing a new dietary ingredient or any foods containing it in the States. For EU countries, there exists keen interests about the functional food products between the member countries of the European Union even though the products are categorized into "Food Supplements" similar to those in the United States. Therefore, they maintain a cautious attitude in applying the health claims to the functional food products. On the other hand, under the Japanese health food system, functional foods are qualified to the functional health foods in terms of legal status as long as any traditional foods can meet the legal standards in its effectiveness, safety as well as quality, along with significant scientific evidences related to the products, thus categorized into "Foods for Specified Health Uses and "Foods with Nutrient Function Claims". Through this study, we may have some expectations and potential utilizations as follows: Legal regulations of dietary supplements especially for the dairy products will be implemented by the outcomes of this research and proposed a tentative amendment of functional ingredients for the sake of consumer protection from the false advertisements and overstatement labeling. Current regulations on the animal foods processing and advertisements will be amended and supplemented in order to revitalize the current downturn dairy sales and to harmonize the international Codex recommendations. The results obtained from this study will make the consumers a wise selection of the dairy products with health claims and be utilized for consumer education and advertisement of the functional products as well.
Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF protein family which is highly synthesized in the liver, pancreas, and adipose tissue. Depending on the expression tissue, FGF21 uses endo- or paracrine features to regulate several metabolic pathways including glucose metabolism and energy homeostasis. Different physiologically stressful conditions such as starvation, a ketogenic diet, extreme cold, and mitochondrial dysfunction are known to induce FGF21 synthesis in various tissues to exert either adaptive or defensive mechanisms. More specifically, peroxisome proliferator-activated receptor gamma and peroxisome proliferator-activated receptor alpha control FGF21 expression in adipose tissue and liver, respectively. In addition, the pharmacologic administration of FGF21 has been reported to decrease the body weight and improve the insulin sensitivity and lipoprotein profiles of obese mice and type 2 diabetes patients meaning that FGF21 has attracted huge interest as a therapeutic agent for type 2 diabetes, obesity, and non-alcoholic fatty liver disease. However, understanding FGF21 remains complicated due to the paradoxical condition of its tissue-dependent expression. For example, nutrient deprivation largely increases hepatic FGF21 levels whereas adipose tissue-derived FGF21 is increased under feeding condition. This review discusses the issues of interest that have arisen from existing publications, including the tissue-specific function of FGF21 and its action mechanism. We also summarize the current stage of a clinical trial using several FGF21 analogs.
Journal of the Korean Society for Advanced Composite Structures
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v.2
no.3
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pp.1-11
/
2011
The typical truss-lattice material successively packed by repeated cubic symmetric unit cells consists of sub-elements (SE) proposed in this study. The representative continuum model for this truss-lattice material such as the effective strain and stress relationship can be formulated by the homogenization procedure based on the notation of averaged mechanical properties. The volume fractions of micro-scale struts have a significant influence on the effective strength as well as the relative density in the lattice plate with replicable unit cell structures. Most of the strength contribution in the lattice material is induced by axial stiffness under uniform stretching or compression responses. Therefore, continuum based constitutive models composed of homogenized member stiffness include these mechanical characteristics with respect to strength, internal stress state, material density based on the volume fraction and even failure modes. It can be also recognized that the stress state of micro-scale struts is directly associated with the continuum constitutive model. The plastic flow at the micro-scale stress can extend the envelope of the analytical stress function on the surface of macro-scale stress derived from homogenized constitutive equations. The main focus of this study is to investigate the basic topology of unit cell structures with the cubic symmetric system and to formulate the plastic models to predict pressure dependent macro-scale stress surface functions.
Park, Se-Hwan;Ahn, Seong-Kyu;Chang, Hong Lae;Han, Bo Young;Kim, Bong Young;Kim, Dongseon;Kim, Ho-Dong;Lee, Chaehun;Oh, Jong-Myeong;Seo, Hee;Shin, Hee-Sung;Won, Byung-Hee;Ku, Jeong-Hoe
Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
/
v.15
no.3
/
pp.191-197
/
2017
The Korea Atomic Energy Research Institute (KAERI) has developed a safeguards technology for pyroprocessing based on the Safeguards-By-Design (SBD) concept. KAERI took part in a Member-State Support Program (MSSP) to establish a pyroprocessing safeguards approach. A Reference Engineering-scale Pyroprocessing Facility (REPF) concept was designed on which KAERI developed its safeguards system. Recently the REPF is being upgraded to the REPF+, a scaled-up facility. For assessment of the nuclear-material accountancy (NMA) system, KAERI has developed a simulation program named Pyroprocessing Material Flow and MUF Uncertainty Simulation (PYMUS). The PYMUS is currently being upgraded to include a Near-Real-Time Accountancy (NRTA) statistical analysis function. The Advanced Spent Fuel Conditioning Process Safeguards Neutron Counter (ASNC) has been updated as Non-Destructive Assay (NDA) equipment for input-material accountancy, and a Hybrid Induced-fission-based Pu-Accounting Instrument (HIPAI) has been developed for the NMA of uranium/transuranic (U/TRU) ingots. Currently, performance testing of Compton-suppressed Gamma-ray measurement, Laser-Induced Breakdown Spectroscopy (LIBS), and homogenization sampling are underway. These efforts will provide an essential basis for the realization of an advanced nuclear-fuel cycle in the ROK.
Kim, Eun-Sook;Hwang, Jae-Ho;Lee, Jin-Moo;Lee, Chang-Hoon;Cho, Jung-Hoon;Jang, Jun-Bock;Lee, Kyung-Sub;Choi, Jae-Ho
Journal of Oriental Medical Thermology
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v.5
no.1
/
pp.1-13
/
2006
Objectives : This study was designed to analyze basic data for cold hypersensitivity patients with a questionnaire and investigate correlation between cold hypersensitivity and Heart Rate Variability(HRV). Methods : 49 patients who complain of cold hypersensitivity on hands and feet in ambulatory care were investigated in Oriental Gynecology, Kyunghee Oriental Medical Center and Women medical center, Kangnam Koreana hospital from May 1, 2006 to October 20, 2006. All patients were asked to answer a questionnaire. After careful I examination to rule out other disease which may affect Digital Infrared Thermal Imaging(DITI) and HRV data, patients were taken thermography for the diagnosis of cold hypersensitivity Based on the result of thermography, the patients were divided into two groups(Objective cold hypersensitivity and Subjective cold hypersensitivity). Then, these two groups were compared using HRV data which was measured in the supine position for 5 minutes. Results: 1. For most patients, cold hypersensitivity first developed during puberty. 2. The parts of the body that felt cold first time were hands and feet. 3. The cold sensation was increased in winter or at bedtime Showing that the sensation can be changed according to the level of coldness. 4. Among women who sufferfrom cold hypersensitivity, very few of them were treated. 5. More than half of cold hypersensitivity patients's family member also had a cold hypersensitivity. 6. The decrease in mean values of LF/HF ratio was observed in objective cold hypersensitivity group than subjective cold hypersensitivity group and the decrease was significant(P=0.014) when examined by Student t-test. Conclusions : It is necessary that the cold hypersensitivity patients should be treated carefully considering the facts mentioned above. And it can be suggested that dysautinomia be related with cold hypersensitivity and be evaluated by HRV.
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