• Molecules and Cells
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• v.39 no.5
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• pp.395-402
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• 2016

Identifying Hoxc8 target genes is at the crux of understanding the Hoxc8-mediated regulatory networks underlying its roles during development. However, identification of these genes remains difficult due to intrinsic factors of Hoxc8, such as low DNA binding specificity, context-dependent regulation, and unknown cofactors. Therefore, as an alternative, the present study attempted to test whether the roles of Hoxc8 could be inferred by simply analyzing genes frequently coexpressed with Hoxc8, and whether these genes include putative target genes. Using archived gene expression datasets in which Hoxc8 was differentially expressed, we identified a total of 567 genes that were positively coexpressed with Hoxc8 in at least four out of eight datasets. Among these, 23 genes were coexpressed in six datasets. Gene sets associated with extracellular matrix and cell adhesion were most significantly enriched, followed by gene sets for skeletal system development, morphogenesis, cell motility, and transcriptional regulation. In particular, transcriptional regulators, including paralogs of Hoxc8, known Hox co-factors, and transcriptional remodeling factors were enriched. We randomly selected Adam19, Ptpn13, Prkd1, Tgfbi, and Aldh1a3, and validated their coexpression in mouse embryonic tissues and cell lines following $TGF-{\beta}2$ treatment or ectopic Hoxc8 expression. Except for Aldh1a3, all genes showed concordant expression with that of Hoxc8, suggesting that the coexpressed genes might include direct or indirect target genes. Collectively, we suggest that the coexpressed genes provide a resource for constructing Hoxc8-mediated regulatory networks.

• Journal of Microbiology and Biotechnology
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• v.28 no.1
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• pp.165-174
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• 2018

Glioblastoma multiforme is the most lethal malignant brain tumor. Despite many intensive studies, the prognosis of glioblastoma multiforme is currently very poor, with a median overall survival duration of 14 months and 2-year survival rates of less than 10%. Although viral infections have been emphasized as potential cofactors, their influences on pathways that support glioblastoma progression are not known. Some previous studies indicated that human Kaposi's sarcoma-associated herpesvirus (KSHV) was detected in healthy brains, and its microRNA was also detected in glioblastoma patients' plasma. However, a direct link between KSHV infection and glioblastoma is currently not known. In this study, we infected glioblastoma cells and glioma stem-like cells (GSCs) with KSHV to establish an in vitro cell model for KSHV-infected glioblastoma cells and glioma stem-like cells in order to identify virologic outcomes that overlap with markers of aggressive disease. Latently KSHV-infected glioblastoma cells and GSCs were successfully established. Additionally, using these cell models, we found that KSHV infection modulates the proliferation of glioma stem-like cells.

• Korean Journal of Community Nutrition
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• v.6 no.3
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• pp.507-515
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• 2001

The elevation of plasma total homocysteine(tHcy) is now established as a risk factro for cardiovascular disease. It is also well known that plasma levels of folate and vitamin $B_{12}$ influences homocysteine metabolism as cofactors. Recently, the effects of health-related lifestyle factors, such as smoking, alcohol drinking coffee consumption, regular exercise, and etc, on plasma tHcy have been determined. The Hordalane Homocysteine Study revealed that smoking and coffee consumption are major deter minants of plasma tHcy as well as folate levels; however, the influence of alcohol intake is still controversial. In Koreans, the effects of lifestyle factors of plasma tHcy have not yet been determined. Thus, we investigated the relationships of various lifestyle determinants with plasma tHcy, folate, and vitamin $B_{12}$ levels and the erythrocyte folate concentrations in Korean adults (99 males and 96 fermales). Plasma tHcy levels were significantly hight in male subjects. On the contrary, plasma levels of folate and vitamin $B_{12}$ and erythrocyte folate concentration of the females were significantly higher than those of the males. Among the five lifestyle factors determined in the study, regular exercise significantly affects plasma tHcy levels only in the females, Contrary to the expectation, there were on significant differences in plasma tHcy levels between alcohol drinkers and non-alcohol drinkers as well as smokers and non-smokers. And also, plasma tHcy leverls were not different between coffee consumers and non-coffee consumer and between green tea consumers and non-green tea consumers. Although alcohol intake did not influence plasma tHcy levels, the duration, frequency, and amount of alcohol drinking showed significant negative relationships with plasma folate levers. These results indicate the regular exercise and alcohol intake might influence plasma levels of tHcy and folate in Koreans, although the results were not reveled in both sexes.

• Journal of Applied Biological Chemistry
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• v.52 no.1
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• pp.15-20
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• 2009

Poplar contains various flavonoids including naringenin, kaempferol, myricetin, apigenin, luteolin, rhamnetin, and quercetin. These flavonoids are synthesized from naringenin with various enzymes. However, none of genes from poplar involved in flavonoid biosynthesis have been biochemically characterized. We cloned PFNS I-1 from Populus deltoids by RT-PCR method. The open reading frame of PFNS I-1 consisted of 1,017-bp and it showed high similarity with other FNS genes. The purified recombinant PFNS I-1, expressed in Escherichia coli, catalyzed the reaction from flavanone (naringenin) to flavone (apigenin). The reaction of PFNS I-1 was enhanced by cofactors such as oxoglutarate, $Fe^{2+}$, ascorbate and catalase. Thus, it is concluded that PFNS N-1 encodes a flavone synthase I.

• KSBB Journal
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• v.11 no.2
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• pp.193-200
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• 1996

In molecular biology, type-II restriction endonuclease, which specifically recognize and cleave DNA at a limited number of sites, have been exploited as a means of characterizing DNA fragments, DNA mapping for genetic engineering. Type-II restriction endonucleases have been found to modulate their substrate specificity under modified conditions such as extreme pH, ionic strength, high enzyme concentration, substitution of metallic cofactors or addition of organic solvents. This study was initiated to investigate the modification of recognition specificity of BamHI according to the different pH and organic solvent under the given buffer condition. The specificity of BamHI is highly depends on the presence of hydrophobicity (LogP: partition coefficient) and pH of reaction solution. The specificity of BamHI is changed in range of LogP -1.03∼-1.35(at pH 7.5), -1.03∼-2.5 (at pH 8.0), -0.75∼-0.25(at pH 8.5), 0.32∼-2.5(at pH 8.9), respectively. Alteration of specificity appears in lower concentration of organic solvent when the reaction occurs in more alkali pH. For example, in DMSO solution, alteration of specificity appears in 20% concentration at pH 7.5 but in 4% concentration at pH 8.9.

• Korean Journal of Community Nutrition
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• v.10 no.6
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• pp.963-970
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• 2005

Recently elevated plasma homocysteine concentration is considered an independent risk factor for atherosclerosis and thrombosis with coronary artery disease. Folate and vitamin $B_{12}$ are cofactors and closely related with metabolism of homocysteine. The purpose of this study is to evaluate the correlation between homocysteine and folate and vitamin $B_{12}$ in patients with ischemic heart disease. Twenty-six patients, in whom coronary angiographic finding revealed more than $50\%$ of stenosis at least in one coronary vessel were enrolled as the patient group, and thirty subjects, in whom angiographic finding revealed in not significant stenosis, but complained of chest pain, were selected as the control group. Fasting venous blood was obtained and measured the concentration of plasma total homocysteine, folate and vitamin $B_{12}$ by high performance liquid chromatography and fluorescence detection method. We examined the correlation between homocysteine and folate and/or vitamin $B_{12}$ in the control group and the patient group, respectively. Compared with the control group, the patient group had relatively higher plasma total homocysteine concentration ($10.7\pm4.2\;vs\;9.6\pm3.5$ umol/L), but showed no significant difference. Folate and vitamin $B_{12}$ concentration are low in the patient group, but showed no significant difference between patient and control group. Plasma total homocysteine concentration showed negative correlation with folate and vitamin $B_{12}$ in both the control group and the patient group, and showed significantly negative correlation in patient group {r = -0.550 (p < 0.01) vs r = -0.609 (p < 0.01)}. We knew that the plasma total homocysteine concentration were relatively elevated in patient group compared with the control group. Because plasma total homocysteine concentrations are closely negative correlated with folate and vitamin $B_{12}$ in the patient group, folate and vitamin $B_{12}$ supplement can lower the mortality and morbidity of ischemic heart disease. (Korean J Community Nutrition 10(6) : $963\∼970$, 2005)

• Journal of Society of Preventive Korean Medicine
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• v.11 no.1
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• pp.45-53
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• 2007

Homocysteine is a sulfur amino-acid produced during the metabolism of the essential amino acid methionine. Moderately increased plasma total homocysteine concentration have been implicated as a risk factor for occlusive vascular disease. Smoking is known to be one of the most significant factors leading to elevated plasma homocysteine concentration. However, the main component of a cigarette, nicotine has been not studied whether it is linked directly to the increase of homocysteine concentration in blood. The metabolism of homocysteine is closely linked to that of its cofactors, folate. Here, the effects of nicotine and folic acid on amount of plasma homocysteine were studied. The concentration of homocysteine was increased by about 70% in rat plasma after nicotine treatment for one month. This increased concentration of homocysteine was reduced by about 60% at 6 hours later after folate treatment. Thus, nicotine should be directly involved in increasing the concentration of plasma homocysteine. Also it is suggested that these results can be and applied and used for controlling withdrawal symptoms after stopping smoking as one of oriental medicine formulas.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.11
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• pp.1527-1534
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• 2010

Trace minerals such as zinc, copper, and manganese are essential cofactors for hundreds of cellular enzymes and transcription factors in all animal species, and thus participate in a wide variety of biochemical processes. Immune development and response, tissue and bone development and integrity, protection against oxidative stress, and cellular growth and division are just a few examples. Deficiencies in trace minerals can lead to deficits in any of these processes, as well as reductions in growth performance. As such, most animal diets are supplemented with inorganic and/or organic forms of trace minerals. Inorganic trace minerals (ITM) such as sulfates and oxides form the bulk of trace mineral supplementation, but these forms of minerals are well known to be prone to dietary antagonisms. Feeding high-quality chelated trace minerals or other classes of organic trace minerals (OTM) can provide the animal with more bioavailable forms of the minerals. Interestingly, many, if not most, published experiments show little or no difference in the bioavailability of OTMs versus ITMs. In some cases, it appears that there truly is no difference. However, real differences in bioavailability can be masked if source comparisons are not made on the linear portion of the dose-response curve. When highly bioavailable chelated minerals are fed, they will better supply the biochemical systems of the cells of the animal, leading to a wide variety of benefits in both poultry and swine. Indeed, the use of certain chelated trace minerals has been shown to enhance mineral uptake, and improve the immune response, oxidative stress management, and tissue and bone development and strength. Furthermore, the higher bioavailability of these trace minerals allows the producer to achieve similar or improved performance, at reduced levels of trace mineral inclusion.

• Nutrition Research and Practice
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• v.14 no.2
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• pp.95-101
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• 2020

BACKGROUND/OBJECTIVES: Folate plays a critical role in DNA synthesis and methylation. Intracellular folate homeostasis is maintained by the enzymes folylpolyglutamate synthase (FPGS) and γ-glutamyl hydrolase (GGH). FPGS adds glutamate residues to folate upon its entry into the cell through a process known as polyglutamylation to enhance folate retention in the cell and to maintain a steady supply of utilizable folate derivatives for folate-dependent enzyme reactions. Thereafter, GGH catalyzes the hydrolysis of polyglutamylated folate into monoglutamylated folate, which can subsequently be exported from the cell. The objective of this review is to summarize the scientific evidence available on the effects of intracellular folate homeostasis-associated enzymes on cancer chemotherapy. METHODS: This review discusses the effects of FPGS and GGH on chemosensitivity to cancer chemotherapeutic agents such as antifolates, such as methotrexate, and 5-fluorouracil. RESULTS AND DISCUSSION: Polyglutamylated (anti)folates are better substrates for intracellular folate-dependent enzymes and retained for longer within cells. In addition to polyglutamylation of (anti)folates, FPGS and GGH modulate intracellular folate concentrations, which are an important determinant of chemosensitivity of cancer cells toward chemotherapeutic agents. Therefore, FPGS and GGH affect chemosensitivity to antifolates and 5-fluorouracil by altering intracellular retention status of antifolates and folate cofactors such as 5,10-methylenetetrahydrofolate, subsequently influencing the cytotoxic effects of 5-fluorouracil, respectively. Generally, high FPGS and/or low GGH activity is associated with increased chemosensitivity of cancer cells to methotrexate and 5-fluorouracil, while low FPGS and/or high GGH activity seems to correspond to resistance to these drugs. Further preclinical and clinical studies elucidating the pharmocogenetic ramifications of these enzyme-induced changes are warranted to provide a framework for developing rational, effective, safe, and customized chemotherapeutic practices.

• BMB Reports
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• v.38 no.6
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• pp.650-660
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• 2005

Proteins accumulated in dry, stratified Arabidopsis seeds or young seedlings, totaled 1100 to 1300 depending on the time of sampling, were analyzed by using immobilized pH gradient 2-DE gel electrophoresis. The molecular identities of 437 polypeptides, encoded by 355 independent genes, were determined by MALDI-TOF or TOF-TOF mass spectrometry. In the sum, 293 were present at all stages and 95 were accumulated during the time of radicle protrusion while another 18 appeared in later stages. Further analysis showed that 226 of the identified polypeptides could be located in different metabolic pathways. Proteins involved in carbohydrate, energy and amino acid metabolism constituted to about 1/4, and those involved in metabolism of vitamins and cofactors constituted for about 3% of the total signal intensity in gels prepared from 72 h seedlings. Enzymes related to genetic information processing increased very quickly during early imbibition and reached highest level around 30 h of germination.