• Mass Spectrometry Letters
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• v.9 no.2
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• pp.61-65
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• 2018

KPLA-012, a benzopyranyl 1,2,3-triazole compound, is considered a potent $HIF-1{\alpha}$ inhibitor based on the chemical library screening, and is known to exhibit anti-angiogenetic and anti-tumor progressive effects. The aim of this study was to investigate the pharmacokinetic properties of KPLA-012 in ICR mice and to investigate in vitro characteristics including the intestinal absorption, distribution, metabolism, and excretion of KPLA-012. The oral bioavailability of KPLA-012 was 33.3% in mice. The pharmacokinetics of KPLA-012 changed in a metabolism-dependent manner, which was evident by the low recovery of parent KPLA-012 from urine and feces and metabolic instability in the liver microsomes. However, KPLA-012 exhibited moderate permeability in Caco-2 cells ($3.1{\times}10^{-6}cm/s$) and the metabolic stability increased in humans compared to that in mice (% remaining after 1 h; 47.4% in humans vs 14.8% in mice). Overall, the results suggest that KPLA-012 might have more effective pharmacokinetic properties in humans than in mice although further studies on its metabolism are necessary.

• Journal of Microbiology and Biotechnology
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• v.10 no.3
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• pp.321-326
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• 2000

To examine the feasibility of the long-term production of the human granulocyte colony stimulating factor (hG-CSF) using the $_{L}-arabinose$ promoter system of Escherichia coli, flask relay culture and cyclic fed-batch culture were performed. In the flask relay culture, it was found that the pismid was maintained stably up to about 170 generations in an uninduced condition, whereby the cells could also maintain the capability of expressing hG-CSF expression were maintained stably up to at least 100 generations. In contrast, in the cyclid fed-batch culture, segregational plasmid instability was observed within about 4 generations after induction, even though the cell growth and hG-CSF production reached their maximum balues, 78.0 g/l of dry cell weight and 7.0 g/l of hG-CSF, respectively. It would appear that, when compared to the flask relay culture, the high-cell density and high-level expression of hG-CSF in the cyclic fed-batch cultrure led to the segregational plasmid instability; in other words, a severe metabolic burden existe on the cells due to the high-level expression of hG-CSF. Accordingly, based on these long-term cultures, the segregational and structural plasmid instability was observed and a strategy to overcome such problems could be designed.

• The Korean Journal of Food And Nutrition
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• v.34 no.1
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• pp.88-95
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• 2021

This study compared the lifestyle patterns, dietary patterns, and health care practices of Korean middle-aged people by household type, and ultimately analyzed their relationship with different risk factors for the prevalence and severity of metabolic syndrome. We analyzed the data from 4,755 subjects who were from 40 to 64 years old, and gathered our sample from participants of the Korea National Health and Nutrition Examination Survey from 2013 to 2015. Our results showed that single-person households had lower economic income levels, lower subjective health statuses, and higher levels of food instability than households with two or more individuals. The incidence of metabolic syndrome was 1.64 times higher in single-person households than in households with two or more individuals. After adjusting for potential confounding factors (sex, age, education, household income, smoking status, health status, and dietary factors), single-person households showed 1.75 times higher hypertriglyceridemia ORs than non-single-person households. In the conclusion of our study, we suggest that middle-aged people in single-person households may be at greater risk for metabolic syndrome and hypertriglyceridemia.

• Molecules and Cells
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• v.38 no.9
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• pp.750-758
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• 2015

Genomic instability and altered metabolism are key features of most cancers. Recent studies suggest that metabolic reprogramming is part of a systematic response to cellular DNA damage. Thus, defining the molecules that fine-tune metabolism in response to DNA damage will enhance our understanding of molecular mechanisms of tumorigenesis and have profound implications for the development of strategies for cancer therapy. Sirtuins have been established as critical regulators in cellular homeostasis and physiology. Here, we review the emerging data revealing a pivotal function of sirtuins in genome maintenance and cell metabolism, and highlight current advances about the phenotypic consequences of defects in these critical regulators in tumorigenesis. While many questions should be addressed about the regulation and context-dependent functions of sirtuins, it appears clear that sirtuins may provide a promising, exciting new avenue for cancer therapy.

• Korean journal of applied entomology
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• v.31 no.3
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• pp.314-327
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• 1992

Insecticide resistance is a serious is a serious threat to IPM, resulting in various adverse effects not to mention the loss of yield in agriculture. One approach to counter the problem is the disruption of resistance mechanisms. This can be achieved by (1) compounds which show a negative correlation with resistance at the site of action, (2) specific metabolic inhibitors which serve as synergists, or (3) a certain combination of two insecticides producing a joint action. This approach, however, requires certain precautions for the side effects may cause an increase in toxicity to mammals. Owing to the recent advances in theoretical studies on resistance management employing computer simulation and mathematical models, a few principles to reduce the risk of development of resistance have been clarified. They are helpful in designing operational strategies with regard to, for instance, insecticide doses to be applied, mode of application, and choice and nature of the insecticide(s) to be used. For restoration of insecticide susceptibility of a resistant population, reintroduction of susceptible individuals to the resistant population is feasible when certain conditions are met. Natural enemies which developed resistance to insecticides can be an important component of IPM as has been shown in the pest management in apple orchards. After all, the implementation of a successful resistance management program depends upon cooperation between different sigments of the agricutural community. Although resistance is a preadaptive phenomenon, in some cases spontaneous loss of resistance does occur without contamination by susceptible individuals. The instability of resistance in these insects implies the possible existence of a switch machanism controlling the expression of resistance gene(s). Elucidation of such a mechanism may eventually provide us with a new technical approach with which we can combat the problem of insecticide resistance.

• Toxicological Research
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• v.30 no.3
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• pp.211-220
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• 2014

Resveratrol has received considerable attention as a polyphenol with various biological effects such as anti-inflammatory, anti-oxidant, anti-mutagenic, anti-carcinogenic, and cardioprotective properties. As part of the overall safety assessment of HS-1793, a novel resveratrol analogue free from the restriction of metabolic instability and the high dose requirement of resveratrol, we assessed genotoxicity in three in vitro assays: a bacterial mutation assay, a comet assay, and a chromosomal aberration assay. In the bacterial reverse mutation assay, HS-1793 did not increase revertant colony numbers in S. typhimurium strains (TA98, TA100, TA1535 and TA1537) or an E. coli strain (WP2 uvrA) regardless of metabolic activation. HS-1793 showed no evidence of genotoxic activity such as DNA damage on L5178Y $Tk^{+/-}$ mouse lymphoma cells with or without the S9 mix in the in vitro comet assay. No statistically significant differences in the incidence of chromosomal aberrations following HS-1793 treatment was observed on Chinese hamster lung cells exposed with or without the S9 mix. These results provide additional evidence that HS-1793 is non-genotoxic at the dose tested in three standard tests and further supports the generally recognized as safe determination of HS-1793 during early drug development.

• The Journal of Internal Korean Medicine
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• v.11 no.2
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• pp.80-93
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• 1990

Review of Literature on Languor and fatigue. According to comparative studies of Oriental and Western medical Literature on the Languor and fatigue on causes and symptom, flowing results were obtained. 1. Common etiologies of the Languor and fatigue in Western medicine are firstly exhaustion of energy, secondly variation of control center-neurotic and body fluid control-, thirdly variation of a living body physico chemical state, forthly production of middle metabolic product, fifthly psychological instability. 2. The expression of the Languor and fatigue in Oriental medicine are consumption, dificiency of vital energy(氣虛), illness caused by overexertion and dificiency of essence of life(精虛). The caure of the Languor and fatigue are dificiency in spleen and stomach(脾胃虛弱), dificiency of both the lung and kidney(肺腎兩虛), the six excessive(六淫), irregular life and excessive mental labor. 3. The symptomes of the Languor and fatigue in western medicine are systemic feeling of fatigue, dislike of work, Dizziness, general fatigue, anorexia, painful body, nerveous prostration. anxiety and decrese of energy, and in oriental medicine dificiency of vital energy, general pain, sinking of vital energy(氣虛下階) in adequate nutrition, confusion and slow speaking.

• Childhood Kidney Diseases
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• v.6 no.2
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• pp.251-258
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• 2002

We report the experiences of pump-driven continuous venovenous hemofiltration therapy in three children with acute renal failure. The all three patients required mechanical ventilation and needed the support of vasopressors. Renal replacement therapy was needed to meet the metabolic and fluid balance, but intermittent hemodialysis and peritoneal dialysis were not feasible because of hemodynamic instability and concurrent infection. We instituted pump-driven continuous venovenous hemofiltratlon (CVVH), and immediate improvement of pulmonary edema and successful removal of retained fluid were observed. Urea clearance also was satisfactory. During the filter running time, significant thromboembolic event or rapid drop of systemic blood pressure were absent. We concluded that the CVVH is an effective and safe method of renal support for critically ill pediatric patient.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.572-584
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• 2002

Rapid development in molecular biology and recent advancement in recombinant technology increase identification and commercialization of potential protein drugs. Traditional forms of administrations for the peptide and protein drugs often rely on their parenteral injection, since the bioavailability of these therapeutic agents is poor when administered nonparenterally. Tremendous efforts by numerous investigators in the world have been put to improve protein formulations and as a result, a few successful formulations have been developed including sustained-release human growth hormone. For a promising protein delivery technology, efficacy and safety are the first requirement to meet. However, these systems still require periodic injection and increase the incidence of patient compliance. The development of an oral dosage form that improves the absorption of peptide and especially protein drugs is the most desirable formulation but one of the greatest challenges in the pharmaceutical field. The major barriers to developing oral formulations for peptides and proteins are metabolic enzymes and impermeable mucosal tissues in the intestine. Furthermore, chemical and conformational instability of protein drugs is not a small issue in protein pharmaceuticals. Conventional pharmaceutical approaches to address these barriers, which have been successful with traditional organic drug molecules, have not been effective for peptide and protein formulations. It is likely that effective oral formulations for peptides and proteins will remain highly compound specific. A number of innovative oral drug delivery approaches have been recently developed, including the drug entrapment within small vesicles or their passage through the intestinal paracellular pathway. This review provides a summary of the novel approaches currently in progress in the protein oral delivery followed by factors affecting protein oral absorption.

• Communications for Statistical Applications and Methods
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• v.28 no.4
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• pp.339-350
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• 2021

In medical research, the risk factors associated with human diseases need to be identified to predict the incidence rate and determine the treatment plan. Logistic regression analysis is primarily used in order to select risk factors. However, individuals who are unfamiliar with statistics outcomes have trouble using these methods. In this study, we develop a nomogram that graphically represents the numerical association between the disease and risk factors in order to identify the risk factors for delirium and to interpret and use the results more effectively. By using the logistic regression model, we identify risk factors related to delirium, construct a nomogram and predict incidence rates. Additionally, we verify the developed nomogram using a receiver operation characteristics (ROC) curve and calibration plot. Nursing home, stroke/epilepsy, metabolic abnormality, hemodynamic instability, and analgesics were selected as risk factors. The validation results of the nomogram, built with the factors of training set and the test set of the AUC showed a statistically significant determination of 0.893 and 0.717, respectively. As a result of drawing the calibration plot, the coefficient of determination was 0.820. By using the nomogram developed in this paper, health professionals can easily predict the incidence rate of delirium for individual patients. Based on this information, the nomogram could be used as a useful tool to establish an individual's treatment plan.