• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.3035-3042
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• 2015

Background: Isorhamnetin (Iso), a novel and essential monomer derived from total flavones of Hippophae rhamnoides that has long been used as a traditional Chinese medicine for angina pectoris and acute myocardial infarction, has also shown a spectrum of antitumor activity. However, little is known about the mechanisms of action Iso on cancer cells. Objectives: To investigate the effects of Iso on A549 lung cancer cells and underlying mechanisms. Materials and Methods: A549 cells were treated with $10{\sim}320{\mu}g/ml$ Iso. Their morphological and cellular characteristics were assessed by light and electronic microscopy. Growth inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic characteristics of cells were determined by flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling (TUNEL). Tumor models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice, and the weights and sizes of tumors were measured. Results: Iso markedly inhibited the growth of A549 cells with induction of apoptotic changes. Iso at $20{\mu}g/ml$, could induce A549 cell apoptosis, up-regulate the expression of apoptosis genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1 and PCNA protein. The tumors in tumor-bearing mice treated with Iso were significantly smaller than in the control group. The results of apoptosis-related genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis cells were the same as those of A549 cells in vitro. Conclusions: Iso, a natural single compound isolated from total flavones, has antiproliferative activity against lung cancer in vitro and in vivo. Its mechanisms of action may involve apoptosis of cells induced by down-regulation of oncogenes and up-regulation of apoptotic genes.

• Molecules and Cells
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• v.37 no.3
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• pp.213-219
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• 2014

MicroRNAs (miRNAs) represent a class of small non-coding regulatory RNAs that play important roles in normal hematopoiesis, including erythropoiesis. Although studies have identified several miRNAs that regulate erythroid commitment and differentiation, we do not understand the mechanism by which the crucial erythroid transcription factors, GATA-1and NF-E2 directly regulate and control differentiation via miRNA pathways. In this study, we identified miR-199b-5p as a key regulator of human erythropoiesis, and its expression was up-regulated during the erythroid differentiation of K562 cells. Furthermore, the increase of miR-199b-5p in erythroid cells occurred in a GATA-1- and NF-E2-dependent manner during erythrocyte maturation. Both GATA-1 and NF-E2 bound upstream of the miR-199b gene locus and activated its transcription. Forced expression of miRNA-199b-5p in K562 cells affected erythroid cell proliferation and maturation. Moreover, we identified c-Kit as a direct target of miR-199b-5p in erythroid cells. Taken together, our results establish a functional link among the erythroid transcription factors GATA-1/NF-E2, miR-199b-5p and c-Kit, and provide new insights into the coupling of transcription and post-transcription regulation in erythroid differentiation.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.541-556
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• 2022

Myocardial fibrosis is a key link in the occurrence and development of diabetic cardiomyopathy. Its etiology is complex, and the effect of drugs is not good. Cardiomyocyte apoptosis is an important cause of myocardial fibrosis. The purpose of this study was to investigate the effect of gaseous signal molecule sulfur dioxide (SO₂) on diabetic myocardial fibrosis and its internal regulatory mechanism. Masson and TUNEL staining, Western-blot, transmission electron microscopy, RT-qPCR, immunofluorescence staining, and flow cytometry were used in the study, and the interstitial collagen deposition, autophagy, apoptosis, and changes in phosphatidylinositol 3-kinase (PI3K)/AKT pathways were evaluated from in vivo and in vitro experiments. The results showed that diabetic myocardial fibrosis was accompanied by cardiomyocyte apoptosis and down-regulation of endogenous SO₂-producing enzyme aspartate aminotransferase (AAT)_1/2. However, exogenous SO₂ donors could up-regulate AAT_1/2, reduce apoptosis of cardiomyocytes induced by diabetic rats or high glucose, inhibit phosphorylation of PI3K/AKT protein, up-regulate autophagy, and reduce interstitial collagen deposition. In conclusion, the results of this study suggest that the gaseous signal molecule SO₂ can inhibit the PI3K/AKT pathway to promote cytoprotective autophagy and inhibit cardiomyocyte apoptosis to improve myocardial fibrosis in diabetic rats. The results of this study are expected to provide new targets and intervention strategies for the prevention and treatment of diabetic cardiomyopathy.

• Journal of Photoscience
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• v.9 no.2
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• pp.25-28
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• 2002

The chicken pineal gland has been used for studies on the circadian clock, because it retains an intracellular phototransduction pathway regulating the phase of the intrinsic clock oscillator. Previously, we identified chicken clock genes expressed in the gland (cPer2, cPer3, cBmal1, cBmal2, cCry1, cCry2, and cClock), and showed that a cBMALl/2-cCLOCK heteromer acts as a regulator transactivating cPer2 gene through the CACGTG E-box element found in its promoter. Notably, mRNA expression of cPer2 gene is up-regulated by light as well as is driven by the circadian clock, implying that light-dependent clock resetting may involve the up-regulation of cPer2 gene. To explore the mechanism of light-dependent gene expression unidentified in animals, we first focused on pinopsin gene whose mRNA level is also up-regulated by light. A pinopsin promoter was isolated and analyzed by transcriptional assays using cultured chicken pineal cells, resulting in identification of an 18-bp light-responsive element that includes a CACGTG E-box sequence. We also investigated a role of mitogen-activated protein kinase (MAPK) in the clock resetting, especially in the E-box-dependent transcriptional regulation, because MAPK is phospholylated (activated) in a circadian manner and is rapidly dephosphorylated by light in the gland. Both pulldown analysis and kinase assay revealed that MAPK directly associates with BMAL1 to phosphorylate it at several Ser/Thr residues. Transcriptional analyses implied that the MAPK-mediated phosphorylation may negatively regulate the BMAL-CLOCK-dependent transactivation through the E-box. These results suggest that the CACGTG E-box serves not only as a clock-controlled element but also as a light-responsive element.

• Development and Reproduction
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• v.17 no.1
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• pp.9-16
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• 2013

Coactivator-associated arginine methyltransferase 1 (CARM1) is included in the protein arginine methyltransferase (PRMT) family, which methylates histone arginine residues through posttranslational modification. It has been proposed that CARM1 may up-regulate the expression of pluripotency-related genes through the alteration of the chromatin structure. Mouse embryonic stem cells (mESCs) are pluripotent and have the ability to self-renew. The cells are mainly used to study the genetic function of novel genes, because the cells facilitate the transmission of the manipulated genes into target mice. Since the up-regulated methylation levels of histone arginine residue lead to the maintenance of pluripotency in embryos and stem cells, it may be suggested that CARM1 overexpressing mESCs elevate the expression of pluripotency-related genes in reconstituted embryos for transgenic mice and may resist the differentiation into trophectoderm (TE). We constructed a fusion protein by connecting CARM1 and 7X-arginine (R7). As a cell-penetrating peptide (CPP), can translocate CARM1 protein into mESCs. CPP-CARM1 protein was detected in the nuclei of the mESCs after a treatment of 24 hours. Accordingly, the expression of pluripotency-related genes was up-regulated in CPP-CARM1-treated mESCs. In addition, CPP-CARM1-treated mESC-derived embryoid bodies (EBs) showed an elevated expression of pluripotency-related genes and delayed spontaneous differentiation. This result suggests that the treatment of recombinant CPP-CARM1 protein elevates the expression of pluripotency-related genes of mESCs by epigenetic modification, and this protein-delivery system could be used to modify embryonic fate in reconstituted embryos with mESCs.

• Physical Therapy Korea
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• v.14 no.3
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• pp.72-80
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• 2007

The purpose of this study was to verify the effects on fine motor, muscle strength (hand-grip), explosive muscular strength (vertical jump) and muscular endurance (sit-up) after ingesting coffee. Hence this study targeted a sample group of 38 healthy men in their twenties, without cardiac disorders and muscle disorders and none of them were hypersensitive to caffeine with symptoms such as palpitation and dyspnea. Nineteen of them ingested coffee, whereas the other nineteen men ingested decaffeinated coffee at the same amount. The amount of coffee was controlled by weight so as to regulate intake to 6 mg caffeine per kg. Research material was evaluated through O'Conner's finger dexterity test, hand-grip strength test, vertical jump test and sit-up test. The data were analyzed by means of paired t-test and ANCOVA. The material was then, analyzed by means of two-way ANOVA in order to verify the effect of one or two cups of coffee on fine motor and hand-grip strength. All parameters were measured by an independent observer. The results were as follows: There were no significant differences to fine motor, hand-grip strength, vertical jump, sit-up before and after drinking decaffeinated coffee, but there was a difference to those before and after drinking caffeine coffee. There was no significant difference to hand dexterity and hand-grip strength in one or two cups of coffee. Intake of a certain dosage of caffeine effects activation of muscles working in a short period based on the results. As a consequence, intake of certain dosages of caffeine was beneficial to enhance efficiency of activity during exercises, but it is will be difficult to obtain the desired result with only one or two cups of coffee.

• Journal of Internet Computing and Services
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• v.17 no.4
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• pp.145-159
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• 2016

This study points out the problems of absence of the legislation for standard regulation on Video on Demand(VoD) advertisement which grows so fast lately, for this it recommends making legal references, which have the definition of non-linear broadcasting & VoD advertisement and VoD advertisement standard regulation in the merged Broadcasting Act, and adopting co-regulation system. Pay TV operators providing VoD service have the opportunities to make money as subscribers uses it increasingly. In case of linear service, the Broadcasting Act regulates the advertisement strictly, but not the VoD ads. The reason why is that Korean legislation including the Broadcasting Act does not have legal reference to regulate it, instead of that, it rely on the self-regulation system which is operated by pay-tv players who provide the VoD ads. So, there is the limitation to protect the minors such as children and youth from the harmful VoD ads, to be invulnerable for advertisers to influence to advertising agents, and to ensure the regulatory effectiveness under player-centric self-regulatory regime. In this context, this study analyses the how to regulate VoD ads standard with a three-pronged approach. First, it analyses the VoD ads regulation system in overseas countries, UK, Canada, EU and Ireland. Each country has the legal reference to regulate it in the Broadcasting Act or lower statures and adopts the co-regulatory regime the NRA and the 3rd entity operate together. Second, it reviews the objectives and scope of VoD ads standard. This study recommends that the objective of it is users protection and the scope of it is standard regulation not commercial practice. Third, this study researches how to legislate for regulation of VoD ads standard. Considering VoD service's characteristics(non-linear service) and legal position of Ads agency(i.e. pay tv operators), it suggest that legal reference will be in the integrated Broadcasting bill, which is the general law, not individual. If it is available to regulate VoD ads standard with co-regulatory regime, it expects the enhancement of user protection from the harmful VoD ads and make up sustainability of the pay-tv players' self-regulation.

• Journal of Photoscience
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• v.9 no.2
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• pp.201-204
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• 2002

Epidermal cells produce a panel of antioxidants as well as cytokines after UVB irradiation, which counteract reactive oxygen species, however, how these antioxidants might regulate melanogenesis is unclear. An important constituent of the cellular antioxidant buffering system which controls the redox state of proteins is thioredoxin (TRX), a 13-kD protein that catalyzes thiol-disulfide exchange reactions, regulates activation of transcription factors, and possesses several other biological functions similar to cytokines. TRX suppressed the UVB-induced production and secretion of $\alpha$-melanocyte stimulating hormone ($\alpha$-MSH) and of adrenocorticotropic hormone (ACTH), and also suppressed proopiomelanocortin (POMC) mRNA expression by normal human keratinocyte (KC)s. Further, L-cysteine, N-acetyl-cysteine, $\alpha$-tocopheryl ferulate showed suppressive effect on UVB-induced POMC mRNA expression. However, TRX released from UVB-irradiated KCs stimulated melanogenesis by up-regulating MSH receptor expression and its binding activity in melanocyte (MC)s. UVB-induced KC derived cytokines such as IL1, IL6, and ET1 upregulated MSH-receptor binding ability as well as MCl-R mRNA expression in cultured normal human MCs. MCl-R has a tendency to be upregulated by UVB-induced KC-derived cytokines as well as by direct UVB irradiation. These results suggest that antioxidants such as TRX suppresses UVB induction of POMC, but in the case of MCl-R, this gene can be mainly in the trend of upregulation by UVB-induced KC-derived factors including TRX.

• Reproductive and Developmental Biology
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• v.31 no.1
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• pp.55-60
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• 2007

Aging causes thymus involution, and genes in thymus play an important role in the development of the immune system. In this study, we compared genes expressed in thymus of neonatal and peripubertal rats using annealing control primers (ACPs)-based GeneFishing polymerase chain reaction (PCR) and semiquantitative reverse transcription (RT)-PCR. We identified 10 differentially expressed genes (DEGs) with 20 ACPs. Of 10 DEGs, bystin-like, collagen type V alpha 1 (COL5A1), and T-cell receptor beta-chain segment 2 (TCRB2) that are related to immune-function were detected in rat thymus. Bystin-like and TCRB2 were up-regulated, while COL5A1 was down-regulated in peripubertal thymus. Semiquantitative RT-PCR confirmed postnatal changes in expression of bystin-like, COL5A1, and TCRB2. These results suggest that bystin-like, COL5A1, and TCRB2 could regulate immune function controlled in thymus as age increases.

• The Bulletin of The Korean Astronomical Society
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• v.40 no.2
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• pp.32.1-32.1
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• 2015

The gradual infall of small dark matter halos onto larger ones has become a relatively straightforward aspect of the standard hierarchical formation paradigm. What happens to the baryons they contain, however, is less well understood. Of special relevance are the processes that regulate and ultimately suppress star formation in galaxies in the early universe. The z=1.5-2.5 epoch is then particularly interesting as a transition period when global star-formation in the universe starts peaking but also where the first ostensibly collapsed and virialized galaxy clusters appear, along with segregated galaxy populations. From a theoretical point of view, the mode of gas accretion in massive halos is also expected to change around this time, switching from a cold to a hot phase and affecting the build-up and evolution of the galaxies they host. A lot of effort has thus been devoted to the search for high-redshift structures, in particular galaxy clusters, through a variety of methods. However, as the limited area for which deep datasets are available remains relatively limited, only few massive z>1.5 structures have been found so far. Here I will instead discuss the regulation of star-formation in lower-mass, X-ray detected halos at z~2 and its implication for galaxy quenching at high redshift. As these smaller, group-size halos are vastly more abundant and structurally simpler than massive clusters, they allow for true statistical studies and offer a novel way to probe environmental effects in this transitional epoch.