• Journal of the Korean Magnetic Resonance Society
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• v.12 no.1
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• pp.1-13
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• 2008

Acetyl-CoA carboxylase (ACC) catalyzes the first step in fatty acid biosynthesis: the synthesis of malonyl-CoA from acetyl-CoA. As essential regulators of fatty acid biosynthesis and metabolism, ACCs are regarded as therapeutic targets for the treatment of metabolic diseases such as obesity, In ACC, the biotinoyl domain performs a critical function by transferring an activated carboxyl group from the biotin carboxylase domain to the carboxyl transferase domain, followed by carboxyl transfer to malonyl-CoA. Despite the intensive research on this enzyme, only the bacterial and yeast ACC structures are currently available, To explore the mechanism of ACC holoenzyme function, we determined the structure of the biotinoyl domain of human ACC2 and analyze its characteristics using NMR spectroscopy. The 3D structure of the hACC2 biotinoyl domain has a similar folding topology to the previously determined domains from E. coli and P. Shermanii, however, the 'thumb' structure is absent in the hACC2 biotinoyl domain. Observations of the NMR signals upon the biotinylation indicate that the biotin group of hACC2 does not affect the structure of the biotinoyl domain, while the biotin group for E. coli ACC interacts directly with the thumb residues that are not present in the hACC2 structure. These results imply that, in the E. coli ACC reaction, the biotin moiety carrying the carboxyl group from BC to CT can pause at the thumb of the BCCP domain. The human biotinoyl domain, however, lacks the thumb structure and does not have additional non-covalent interactions with the biotin moiety; thus, the flexible motion of the biotinylated lysine residue must underlie the "swinging arm" motion. This study provides insight into the mechanism of ACC holoenzyme function and supports the "swinging arm" model in human ACCs.

• Journal of Life Science
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• v.17 no.3 s.83
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• pp.334-339
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• 2007

We evaluated the potential of 20 herbal medications (HMs), commonly used in Korea, to inhibit the catalytic activities of several cytochrome P450 (CYP) isoforms. The abilities of 500 ${\mu}g/ml$ of aqueous extracts of 20 HMs to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), rosiglitazone hydroxylation (CYP2C8), tolbutamide 4-methylhydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The HMs Woohwangcheongsimwon suspension and Hwanglyeonhaedok-Tang strongly inhibited CYP2B6 and CYP2D6 isoform activity, respectively. These results suggest that some of the HMs used in Korea have potential to inhibit CYP isoforms in vitro. Although the plasma concentrations of the active constituents of the HMs were not determined, some herbs could cause clinically significant interactions because the usual doses of those individual herbs are several grams of freeze-dried extracts.

• Polymer(Korea)
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• v.34 no.4
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• pp.300-305
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• 2010

Zaltoprofen is a propionic acid derivative of non-steroidal anti-inflammatory drugs (NSAIDs) and has been widely used in the treatment of a number of arthritic conditions or lumbago. Zaltoprofen has low water solubility and low bioavailability, therefore great efforts have been devoted to enhance the extent of drug adsorption. In this study, zaltoprofen was formulated into a tablet to enhance the bioavailability and to achieve sustained-release using additives such as lactose monohydrate, carboxymethylcellulose (CMC), hydroxypropylmethylcellulose (HPMC). Fourier transform-infrared (FTIR) and differential scanning calorimeter (DSC) were employed to study the structure and crystallization of zaltoprofen in the tablet with various contents of additives. It was found that additives had interactions with zaltoprofen and inhibited the crystallization of zaltoprofen. Tablets containing low viscosity HPMC showed a higher release than those containing high viscosity HPMC. Also, as the amount of CMC increased zaltoprofen release increased.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.553-561
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• 2022

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia. However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

• Asian-Australasian Journal of Animal Sciences
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• v.9 no.1
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• pp.1-25
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• 1996

The pathogenesis of atherosclerosis can not be summarized as a single process. Lipid infiltration hypothesis and endothelial injury hypothesis have been proposed and investigated. Recent developments show that there are many points of potential interactions between them and that they can actually be regarded as two phases of a single, unifying hypothesis. Among the many risk factors of atherosclerosis, plasma homocysteine and lipoprotein(a) draw a considerable interest because they are independent indicators of atherogenicity. Triglyceride (TG)-rich lipoproteins (chylomicron and VLDL) are not considered to be atherogenic but they are related to the metabolism of HDL cholesterol and indirectly related to coronary heart disease (CHD). LDL can of itself be atherogenic but the oxidative products of this lipoprotein are more detrimental. HDL cholesterol has been considered to be a favorable cholesterol. The so-called 'causalist view' claims that HDL traps excess cholesterol from cellular membranes and transfers it to TG-rich lipoproteins that are subsequently removed by hepatic receptors. In the so-called 'noncausalist view', HDL does not interfere directly with cholesterol deposition in the arterial wall but instead reflects he metabolism of TG-rich lipoproteins and their conversion to atherogenic remnants. Approximately 70-80% of the human population shows an effective feedback control mechanism in cholesterol homeostasis. Type of dietary fat has a significant effect on the lipoprotein cholesterol metabolism and atherosclerosis. Generally, saturated fatty acids elevate and PUFA lower serum cholesterol, whereas MUFA have no specific effect. EPA and DHA inhibit the synthesis of TG, VLDL and LDL, and may have favourable effects on some of the risk factors. Phospholipids, particularly lecithin, have an antiatherosclerotic effect. Essential phospholipids (EPL) may enhance the formation of polyunsaturated cholesteryl ester (CE) which is less sclerotic and more easily dispersed via enhanced hydrolysis of CE in the arterial wall. Also, neutral fecal steroid elimination may be enhanced and cholesterol absorption reduced following EPL treatment. Antioxidants protect lipoproteins from oxidation, and cells from the injury of toxic, oxidized LDL. The rationale for lowering of serum cholesterol is the strong association between elevation of plasma or serum cholesterol and CHD. Cholesterol-lowing, especially LDL cholesterol, to the target level could be achieved using diet and combination of drug therapy. Information on the link between cholesterol and CHD has decreased egg consumption by 16-25%. Some clinical studies have indicated that dietary cholesterol and egg have a significant hypercholesterolemic effect, while others have indicated no effect. These studies differed in the use of purified cholesterol or cholesterol in eggs, in the range of baseline and challenge cholesterol levels, in the quality and quantity of concomitant dietary fat, in the study population demographics and initial serum cholesterol levels, and clinical settings. Cholesterol content of eggs varies to a certain extent depending on the age, breed and diet of hens. However, egg yolk cholesterol level is very resistant to change because of the particular mechanism involved in yolk formation. Egg yolk contains a factor of factors responsible for accelerated cholesterol metabolism and excretion compared with crystalline cholesterol. One of these factors could be egg lecithin. Egg lecithin may not be as effective as soybean lecithin in lowering serum cholesterol level due probably to the differences of fatty acid composition. However, egg lecithin may have positive effects in hypercholesterolemia by increasing serum HDL level and excretion of fecal cholesterol. The association of serum cholesterol with egg consumption has been widely studied. When the basal or control diet contained little or no cholesterol, consumption of 1 or 2 eggs daily increased the concentration of plasma cholesterol, whereas that of the normolipemic persons on a normal diet was not significantly influenced by consuming 2 to 3 eggs daily. At higher levels of egg consumption, the concentration of HDL tends to increase as well as LDL. There exist hyper-and hypo-responders to dietary (egg) cholesterol. Identifying individuals in both categories would be useful from the point of view of nutrition guidelines. Dietary modification of fatty acid composition has been pursued as a viable method of modifying fat composition of eggs and adding value to eggs. In many cases beneficial effects of PUFA enriched eggs have been demonstrated. Generally, consumption of n-3 fatty acids enriched eggs lowered the concentration of plasma TG and total cholesterol compared to the consumption of regular eggs. Due to the highly oxidative nature of PUFA, stability of this fat is essential. The implication of hepatic lipid accumulation which was observed in hens fed on fish oils should be explored. Nutritional manipulations, such as supplementation with iodine, inhibitors of cholesterol biosynthesis, garlic products, amino acids and high fibre ingredients, have met a limited success in lowering egg cholesterol.

• Journal of Microbiology and Biotechnology
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• v.25 no.10
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• pp.1751-1760
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• 2015

Mucin2 (MUC2), an important regulatory factor in the immune system, plays an important role in the host defense system against bacterial translocation. Probiotics known to regulate MUC2 gene expression have been widely studied, but the interactions among probiotic, pathogens, and mucin gene are still not fully understood. The aim of this study was to investigate the role of MUC2 in blocking effects of probiotics on meningitic E. coli-induced pathogenicities. In this study, live combined probiotic tablets containing living Bifidobacterium, Lactobacillus bulgaricus, and Streptococcus thermophilus were used. MUC2 expression was knocked down in Caco-2 cells by RNA interference. 5-Aza-2'-deoxycytidine (5-Aza-CdR), which enhances mucin-promoted probiotic effects through inducing production of Sadenosyl-L-methionine (SAMe), was used to up-regulate MUC2 expression in Caco-2 cells. The adhesion to and invasion of meningitic E. coli were detected by competition assays. Our studies showed that probiotic agents could block E. coli-caused intestinal colonization, bacteremia, and meningitis in a neonatal sepsis and meningitis rat model. MUC2 gene expression in the neonatal rats given probiotic agents was obviously higher than that of the infected and uninfected control groups without probiotic treatment. The prohibitive effects of probiotic agents on MUC2-knockdown Caco-2 cells infected with E44 were significantly reduced compared with nontransfected Caco-2 cells. Moreover, the results also showed that 5-Aza-CdR, a drug enhancing the production of SAMe that is a protective agent of probiotics, was able to significantly suppress adhesion and invasion of E44 to Caco-2 cells by upregulation of MUC2 expression. Taken together, our data suggest that probiotic agents can efficiently block meningitic E. coli-induced pathogenicities in a manner dependent on MUC2.

• Journal of Korean Academy of Nursing
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• v.24 no.1
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• pp.58-69
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• 1994

In order to see the development of Nursing related research activities in Korea over the last three decades, abstracts of almost all of the Master and Ph.D theses that appeared from 1961 up to August 1991 were collected. The number of theses was 2354, from which an index of key words has been constructed. Key words were defined as those terms in each thesis title that convey major objectives of the given thesis study and the important nursing concepts dealt with in the thesis. Although all the key words were picked from the thesis title only, full use was made of the abstracts in deciding the principal objectives and essential contents of the thesis studies and their important concepts as well. In total, 539 kinds of key words were identified from the 2354 titles, and the identified words were all found to be in the International Nursing Index. On an average each title has two key words. Which key words were most frequently used, how they have changed with time, what kind of concept is preferably dealt with by each graduate school, and the concepts to which a given key word is likely to be connected were examined. The results are summerized below : 1) For each decade the theses numbers were as follows : 54(2.3%) from the 60’s, 413(17.5%) from the 70’s, 1523(64.7%) from the 80’s, and 364(15.5%) from the 90’s. Master’s thesis contributed 96% (2252) of the papers and Ph. D’s theses filled the remaining 4%(102). 2) A total of 539 key words were used, averaging about 2 for each thesis. The most frequently used key words were ‘Nurse’, ‘Anxiety’, ‘Knowledge / Attitude /Practice’, ‘Stress /Stressor’, ‘Attitude’, ‘Job-Satisfaction’, ‘Mental Disorder’, ‘Operation’, ‘Elderly’, ‘Nursing Role’. 3) Each decades key words can be classified as : the 60’s : ‘Nursing Education’, ‘Pulmonary Tuberculosis’, ‘Mother-Child Health’, ‘Growth & Development’, ‘Public Facilities’, ‘Mental Disorder’ : the 70’s : ‘Nurse’, ‘Family Planning’, ‘Attitude’ / ‘Knowledge, Attitude / Practice’, ‘Curriculum in Nursing Education’, ‘Clinical Practice in Nursing’, ‘Analysis of the Work of the Nurse’, ‘Health Education of School’, : the 80’s : ‘Nurse’, ‘Anxiety’, ‘Stress /Stressor’, ‘Operation’, ‘Nursing Role’, ‘Job Satisfaction’ : the 90’s : ‘Nurse’, ‘Elderly’, ‘Family-Support’, ‘Stress /Stressor’, ‘Home Care’. Key word ‘Nurse’ appears continuously and most frequently through the years, which indicates that there has been active study of the characteristics of nurses and related fields. The concept ‘Anxiety’ has been studied steadly from the 80’s and it shows that interest in health and disease are increasing Which comes as a result of society changing to an industrial and informational community. 4) Looking into each graduate school’s study area key words ‘Anxiety’, ‘Nurse’, ‘Mental Disorder’, ‘Stress /Stressor’, ‘Operation’, ‘Attitude’, ‘Hemo-dialysis’, were studied in the regular graduate school : ‘Family Planning /Contraception’, ‘Knowledge / Attitude /Practice’, ‘Physical Health-State /Physical Health Examination’, ‘Nurse’, ‘Using Clinical Facilities’, ‘Health Education of School’, were studied in the Graduate School of Public Health’ ; ‘Nurse’, ‘Anxiety’, ‘Stress / Stressor’, ‘Job-Satisfaction’, ‘Clinical Practice Education’, ‘Nursing Education’, were studied in the Graduate School of Education : ‘Nurse’, ‘Job Satisfaction’, ‘Nursing Role’, ‘Administration - Employment /Employment Management’, ‘Leadership’, ‘Personnel Profile’, ‘Nursing Manpower / Changing Working Place’, were studied in the Graduate School of Public Administration. 5) The Connection between key words were : ‘Nurse Job Satisfaction’, ‘Stress / Stressor ⇔ Coping / Ajustment’, ‘Nurse ⇔ Nursing Role’, ‘Anxiety ⇔ Giving Information’, ‘Nurse ⇔ Stress / Stressor’, ‘Anxiety ⇔ Operation’, ‘Nurse ⇔ Burnout’, ‘Knowledge, Attitude, Practice ⇔ Family Planning’, ‘Nurse Administration ⇔ Employment’, ‘Anxiety Muscle ⇔ Relaxation Technic’, ‘Anxiety ⇔ Mental Disorder’. From the above it can be noted that many nursing concepts were handled in the thesis titles. But there were more than enough papers on the characteristics of the nurse. It is suggested that in depth research be made on ‘Nursing Accidents’, t-‘Ethics’, ‘Nurse - Patient Interactions’, ‘Spritual Care’, ‘Dying’, ‘Hospice’, ‘Resident Helper’ and that there should be in depth research relating to the physical and mental development of youth and in particular physical concepts like ‘Drug - Abuse’, ‘Child -Abuse and Teaching’.