• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.296-300
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• 2015

${\beta}$-Lapachone has drawn increasing attention as an anti-inflammatory and anti-cancer drug. However, its oral bioavailability has not been yet assessed, which might be useful to develop efficient dosage forms possibly required for non-clinical and clinical studies and future market. The aim of the present study was thus to investigate pharmacokinetic properties of ${\beta}$-lapachone as well as its first-pass metabolism in the liver, and small and large intestines after oral administration to measure the absolute bioavailability in rats. A sensitive HPLC method was developed to evaluate levels of ${\beta}$-lapachone in plasma and organ homogenates. The drug degradation profiles were examined in plasma to assess the stability of the drug and in liver and intestinal homogenates to evaluate first-pass metabolism. Pharmacokinetic profiles were obtained after oral and intravenous administration of ${\beta}$-lapachone at doses of 40 mg/kg and 1.5 mg/kg, respectively. The measured oral bioavailability of ${\beta}$-lapachone was 15.5%. The considerable degradation of ${\beta}$-lapachone was seen in the organ homogenates but the drug was quite stable in plasma. In conclusion, we suggest that the fairly low oral bioavailability of ${\beta}$-lapachone may be resulted from the first-pass metabolic degradation of ${\beta}$-lapachone in the liver, small and large intestinal tracts and its low aqueous solubility.

• Journal of Microbiology and Biotechnology
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• v.30 no.8
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• pp.1261-1271
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• 2020

Cytochrome c_L (Cytc_L) is an essential protein in the process of methanol oxidation in methylotrophs. It receives an electron from the pyrroloquinoline quinone (PQQ) cofactor of methanol dehydrogenase (MDH) to produce formaldehyde. The direct electron transfer mechanism between Cytc_L and MDH remains unknown due to the lack of structural information. To help gain a better understanding of the mechanism, we determined the first crystal structure of heme c containing Cytc_L from the aquatic methylotrophic bacterium Methylophaga aminisulfidivorans MP^T at 2.13 Å resolution. The crystal structure of Ma-Cytc_L revealed its unique features compared to those of the terrestrial homologues. Apart from Fe in heme, three additional metal ion binding sites for Na⁺, Ca⁺, and Fe²⁺ were found, wherein the ions mostly formed coordination bonds with the amino acid residues on the loop (G93-Y111) that interacts with heme. Therefore, these ions seemed to enhance the stability of heme insertion by increasing the loop's steadiness. The basic N-terminal end, together with helix α4 and loop (G126 to Y136), contributed positive charge to the region. In contrast, the acidic C-terminal end provided a negatively charged surface, yielding several electrostatic contact points with partner proteins for electron transfer. These exceptional features of Ma-Cytc_L, along with the structural information of MDH, led us to hypothesize the need for an adapter protein bridging MDH to Cytc_L within appropriate proximity for electron transfer. With this knowledge in mind, the methanol oxidation complex reconstitution in vitro could be utilized to produce metabolic intermediates at the industry level.

• Journal of Microbiology and Biotechnology
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• v.26 no.3
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• pp.572-578
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• 2016

Communication between endothelial cells (ECs) and smooth muscle cells (SMCs) via miR-143/145 clusters is vital to vascular stability. Previous research demonstrates that miR-143/145 released from ECs can regulate SMC proliferation and migration. In addition, a recent study has found that SMCs also have the capability of manipulating EC function via miR-143/145. In the present study, we artificially increased the expression of miR-143/145 in ECs, to mimic a similar change caused by miR-143/145 released by SMCs, and applied untargeted metabolomics analysis, aimed at investigating the consequential effect of miR-143/145 overexpression. Our results showed that miR-143/145 overexpression alters the levels of metabolites involved in energy production, DNA methylation, and oxidative stress. These changed metabolites indicate that metabolic pathways, such as the SAM cycle and TCA cycle, exhibit significant differences from the norm with miR-143/145 overexpression.

• Preventive Nutrition and Food Science
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• v.7 no.4
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• pp.454-460
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• 2002

While atherosclerosis is a major killer, there is now concern that mortality from the disease will increase due to the rising incidence of type II diabetes. Because diet can potentially influence both diseases, it is important to elucidate the role of diet in the progression of atherosclerosis. In addition, the mechanisms involved in dietary-related alterations of the disease need to be defined to guide public health recommendations to reduce athero-sclerosis incidence and limiting unwanted side effects. Since diet is thought to play a role in atherosclerosis even without added complications due to type II diabetes, reducing the incidence of that metabolic disease will not be enough. While evidence is increasing that high intake of carbohydrate can lead to type II diabetes and atherosclerosis, the preponderance of existing evidence indicates that intake of specific fats as a major dietary causal factor. It has recently been hypothesized that a dietary fat link to atherosclerosis may depend partly on the activity of a transcriptional regulator, the peroxisome proliferator activated receptors (PPAR). Thusfar, PPAR $\alpha$, $\beta$/$\delta$ and ${\gamma}$, have been shown to play a major role in metabolism, inflammation, and cancer. Furthermore, PPAR may regulate specific processes associated with atherosclerosis such as triglyceride and low density lipoprotein (LDL) metabolism; the reverse cholesterol transport pathway; lipid accumulation within plaques; the local inflammatory response and plaque stability. Synthetic ligands for PPAR have been developed; however, natural ligands include specific fatty acids and their metabolites. Though the role of PPAR in atherosclerosis has been reported with respect to synthetic ligands, additional studies need to be done with established and possible natural ligands. In this review, we will focus on the relation of dietary fat to PPAR alteration of atherosclerosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.6
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• pp.823-833
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• 2012

Now a days, number of non alcoholic fatty liver patients are increasing more rapidly compare to past rate, and the average age of patients is getting younger, but there are no appropriate therapeutics in non alcoholic fatty liver disease. This study was aimed to analyze relationship between non alcoholic fatty liver disease and Injinho-tang. The papers were collected and analysed from domestic and international journals. The effects of Injinho-tang and constituent-herb were researched. Non-alcoholic fatty liver disease was induced complex causes of the metabolic syndrome. Medications that can be used in non-alcoholic fatty liver disease, it should be have many effects such as anti-hepatic fibrosis, hepatocyte protection, liver cancer inhibitory effect, inflammatory cytokine regulation, improving hyperlipidemia, weight control, decrease the toxicity of the drug, antioxidant. Injinho-tang (Artemisia capillaris Thunb, Gardenia fructus, Rhei rhizome) has been widely used in disease that causes jaundice and liver biliary disease. Drugs for standardization of Injinho-tang index components(6,7-Dimethylesculetin, geniposide, rhein) have been presented. And Injinho-tang has been proven reliability in the administration of single dose toxicity. Also clinical stability in the administration of four years was reported. Injinho-tang has been reported some effects which anti-hepatic fibrosis, hepatocyte protection, liver cancer inhibitor, inflammatory cytokine regulation, improving hyperlipidemia, weight control, decrease the toxicity of the drug, and antioxidant. Therefore, Injinho-tang can be used in Non alcoholic fatty liver disease without Syndrome Differentiation.

• Biomedical Science Letters
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• v.18 no.4
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• pp.384-390
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• 2012

Diabetes mellitus (DM) is considered to be a serious metabolic disease which may cause systemic complications. The present study was designed to clarify a difference on stress, physiological variables and their correlation between diabetic (DM group) and nondiabetic adults (control group). The levels of body weight, waist circumference, blood pressure, body mass index, body fat mass, total cholesterol (TcH), triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total bilirubin (TB), autonomic balance (AB), stress index (SI), fatigue index (FI), and heart rate (HR) were all significantly higher in the DM group than in the control group. However, the levels of autonomic activity (AA), stress resistance (SR), and electrocardiac stability (ES) were significantly lower in the DM group than in the control group. The percentages of persons with abnormal levels in the Tch, high density lipoprotein, low density lipoprotein, TG, AST, ALT and GGT were significantly greater in the DM group than in the control group. In the correlation of glucose and hemoglobin A1c (HBA1c) to stress indices, the DM group had a significant relationship with AB, SR, SI, FI, ES, and HR, whereas the control group had no significant relationship with these, excepting AB. These results suggest that DM was harmfully associated with body, biochemical and stress indices and that blood glucose and HBA1c levels must be exhaustively regulated.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.457-465
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• 2018

The expression of BCL-2 interacting cell death suppressor (BIS), an anti-stress or anti-apoptotic protein, has been shown to be regulated at the transcriptional level by heat shock factor 1 (HSF1) upon various stresses. Recently, HSF1 was also shown to bind to BIS, but the significance of these protein-protein interactions on HSF1 activity has not been fully defined. In the present study, we observed that complete depletion of BIS using a CRISPR/Cas9 system in A549 non-small cell lung cancer did not affect the induction of heat shock protein (HSP) 70 and HSP27 mRNAs under various stress conditions such as heat shock, proteotoxic stress, and oxidative stress. The lack of a functional association of BIS with HSF1 activity was also demonstrated by transient downregulation of BIS by siRNA in A549 and U87 glioblastoma cells. Endogenous BIS mRNA levels were significantly suppressed in BIS knockout (KO) A549 cells compared to BIS wild type (WT) A549 cells at the constitutive and inducible levels. The promoter activities of BIS and HSP70 as well as the degradation rate of BIS mRNA were not influenced by depletion of BIS. In addition, the expression levels of the mutant BIS construct, in which 14 bp were deleted as in BIS-KO A549 cells, were not different from those of the WT BIS construct, indicating that mRNA stability was not the mechanism for autoregulation of BIS. Our results suggested that BIS was not required for HSF1 activity, but was required for its own expression, which involved an HSF1-independent pathway.

• Bulletin of the Korean Chemical Society
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• v.28 no.9
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• pp.1535-1538
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• 2007

The work presented in this paper represents a study of the rate and extent of transdermal penetration of three synthetic hexapeptides consisting only of glycine (Gly) and phenylalanine (Phe) as the constituent amino acids and they include Phe-Gly-Gly-Gly-Gly-Gly (Pep-1), Phe-Phe-Gly-Gly-Gly-Gly (Pep-2), and Phe-Phe-Phe- Gly-Gly-Gly (Pep-3). The present study demonstrated the extent to which the peptides having a high metabolic stability were transdermally transported from the various vehicles. The results of this study appear to indicate that minor differences in the lipophilicity of the synthetic hexapeptides have a slight influence on the rate and extent of transport. In the presence of terpene permeation enhancers, together with ethanol (i.e., menthone/ EtOH, carveol/EtOH or cineole/EtOH), the peptides were more rapidly penetrated through the skin and among the terpenes tested, cineole was the most effective for all three peptides. The maximum enhancement ratio of approximately 2 was achieved by cineole in 50% ethanol solution.

• Korean Journal of Plant Resources
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• v.28 no.1
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• pp.135-144
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• 2015

The Korean daily intake of vegetable oils has increased about 2.5-fold from 17 g/day to 46 g/day for the last several decades. Perilla (Perilla frutescens var. frutescens) has been cultivated in Korea for a long time as a dietary oil seed which has the highest content of ${\alpha}$-linolenic acid, accounting for nearly 60%. It is known that the main role of ALA is as a precursor to the longer-chain ${\omega}-3$, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), the metabolic products of ${\alpha}$-linolenic acid (ALA, ${\omega}-3$). Dietary ${\omega}-3$ fatty acids reduce inflammation and the risk of chronic diseases such as heart disease, cancer, and arthritis, but they also may act as functional components for cognitive and behavioral function. Thus, ${\alpha}$-linolenic acid is one of the essential nutrients in modern dietary patterns in which much linoleic acid is consumed. Nevertheless, perilla oil, rich in ${\alpha}$-linolenic acid, can be easily oxidized, giving rise to controversies with respect to shelf life, the deterioration of the product's commercial value, and further related toxicity. Recent research using genetic modifications has tried to develop new plant oil seeds that balance the ratio of ${\omega}-6/{\omega}-3$ fatty acids. Such trials could be a strategy for improving an easily oxidizable property of perilla oil due to high ${\alpha}$-linolenic acid. Alternatively, appropriate application of antioxidant to the oil can be considerable.

• YAKHAK HOEJI
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• v.57 no.6
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• pp.400-405
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• 2013

In this study, we measured the complex efficiency of a physiologically active antibody, a chelator and radiosiotopes using the ESI-TOF/Ms system for develop good radiopharmaceuticals. For a precise measurement, TLC is a low accuracy method. Loading of same amount of sample is difficult for each test, and work to quantify accurately the results obtained through TLC cannot be afforded compared to the use of other analytical instruments. The method of analysis using a mass spectrometer is capable of a mass analysis of proteins for quantitative analysis. The conjugates of the chelator (CHX-A- DTPA) and the antibody (IgG) were separated through MWCO, and were analyzed using ESI-TOF and MALDI-TOF mass spectrometry. The analysis using MALDI-TOF is roughly divided into measurements on mass spectrometry. When conjugating a small molecular weight of CHX-A-DTPA and a large molecular weight of IgG, distinguishing the peak of the conjugate and the peak of IgG was difficult. However, an ESI-TOF mass spectrometer system is capable of an analysis of mass by decentralizing the IgG. It is utilized as a technique for measuring the metabolic processes during conjugation and the stability evaluation of radiopharmaceuticals. When establishing this technique, the accuracy of the overall radiophar-maceutical analysis is expected to be able to be improved.