• BMB Reports
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• v.47 no.9
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• pp.494-499
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• 2014

NADH:quinone oxidoreductase 1 (NQO1) is known to be involved in the regulation of energy synthesis and metabolism, and the functional studies of NQO1 have largely focused on metabolic disorders. Here, we show for the first time that compared to NQO1-WT mice, NQO1-KO mice exhibited a marked increase of permeability and spontaneous inflammation in the gut. In the DSS-induced colitis model, NQO1-KO mice showed more severe inflammatory responses than NQO1-WT mice. Interestingly, the transcript levels of claudin and occludin, the major tight junction molecules of gut epithelial cells, were significantly decreased in NQO1-KO mice. The colons of NQO1-KO mice also showed high levels of reactive oxygen species (ROS) and histone deacetylase (HDAC) activity, which are known to affect transcriptional regulation. Taken together, these novel findings indicate that NQO1 contributes to the barrier function of gut epithelial cells by regulating the transcription of tight junction molecules.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.2
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• pp.163-173
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• 2020

Purpose: This study aimed to investigate the clinical and metabolic determinants of circulating soluble leptin receptor (CSLR) and free leptin index (FLI) in pre-pubertal obese male children. Methods: We conducted a preliminary cross-sectional study at three tertiary hospitals and one public primary school. Eighty obese male children without growth and developmental abnormalities aged 5-9 years were recruited. In these children, obesity was solely caused by excessive food intake, and not by acute illness, medications, endocrine abnormalities, or any syndrome. Body mass index (BMI), body fat mass, carbohydrate intake, fat intake, high density lipoprotein cholesterol level, low density lipoprotein cholesterol level, triglyceride level, and Homeostatic Model Assessment for Insulin Resistance are the potential determinants for leptin regulation, which is represented by CSLR level and FLI. Results: Carbohydrate was the main source of energy. BMI and body fat mass had negative weak correlation with CSLR and positive weak correlation with FLI. Furthermore, carbohydrate intake was found to be independently associated with CSLR based on the results of the multiple linear regression analysis. Following an increase in carbohydrate intake, CSLR level decreased progressively without any negative peak. Conclusion: Leptin regulation in prepubertal obese male children is associated with body composition and dietary intake. Carbohydrate intake is useful for predicting CSLR. Lipid profiles and insulin resistance are not related to both CSLR and FLI. Treatment and prevention of leptin resistance in obese children should focus on reducing BMI, fat mass, and carbohydrate intake.

• Journal of Pharmaceutical Investigation
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• v.37 no.2
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• pp.73-78
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• 2007

The aim of this study was to investigate the absorption properties of ketoprofen. The in-situ perfusion model has advantages over in vitro models as it provides intact lymphatic and blood flow circulation. The absorption properties of six different concentrations of ketoprofen have been studied in single pass in-situ rat intestine model. $^{14}C-PEG$ 4000 was used as a permeability marker and the possibility of an energy dependent contribution to ketoprofen absorption was also Investigated using the metabolic inhibitor sodium azide. Three different concentrations of sodium azide were studied to examine its effect on absorption of ketoprofen from the rat intestine. The findings of this study suggest that mono-carboxylic type drugs like ketoprofen cause permeability changes in the intestine. This is shown by the increase in absorption of $^{14}C-PEG$ 4000 as the concentration of ketoprofen is increased. However, the trend for ketoprofen permeability is to decrease over the concentration ranges. It was observed that the Papp values for ketoprofen with sodium azide shows a trend towards reduction in the amount of ketoprofen absorbed from the rat intestine which was significantly different (p<0.05) from that of ketoprofen with sodium azide 3.0mM. This indicates that sodium azide has an affect on the absorption of ketoprofen. The pH of all the perfusion solutions was altered to ${\sim}pH\;6.7$ by the buffering capacity of the small intestine secretions. The results suggest that mechanisms other than passive diffusion may be involved in ketoprofen absorption. This would be consistent with the involvement of active transport or saturatable processes in the absorption of drugs containing monocarboxylic acid group, as has been previously suggested from in vitro data.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.11
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• pp.1555-1565
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• 2009

Anaerobic rumen fungi have been regarded as good genetic resources for enzyme production which might be useful for feed supplements, bio-energy production, bio-remediation and other industrial purposes. In this study, an expressed sequence tag (EST) library of the rumen anaerobic fungus Neocallimastix frontalis was constructed and functional genes from the EST library were analyzed to elucidate carbohydrate metabolism of anaerobic fungi. From 10,080 acquired clones, 9,569 clones with average size of 628 bp were selected for analysis. After the assembling process, 1,410 contigs were assembled and 1,369 sequences remained as singletons. 1,192 sequences were matched with proteins in the public data base with known function and 693 of them were matched with proteins isolated from fungi. One hundred and fifty four sequences were classified as genes related with biological process and 328 sequences were classified as genes related with cellular components. Most of the enzymes in the pathway of glucose metabolism were successfully isolated via construction of 10,080 ESTs. Four kinds of hemi-cellulase were isolated such as mannanase, xylose isomerase, xylan esterase, and xylanase. Five $\beta$-glucosidases with at least three different conserved domain structures were isolated. Ten cellulases with at least five different conserved domain structures were isolated. This is the first solid data supporting the expression of a multiple enzyme system in the fungus N. frontalis for polysaccharide hydrolysis.

• 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.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.9
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• pp.1209-1216
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• 2005

This study aimed to use field data collected by the Hokkaido Dairy Cattle Milk Recording and Testing programs to estimate genetic parameters for concentration of milk urea nitrogen (MUN) and predicted Digestive Crude Protein Percentage of requirement (DCPun). Edited data consisted of 5,797,500 test-day records of MUN and yields of milk, fat, and protein obtained from 783,271cows in Holstein herds in Hokkaido, Japan. Data were divided into four datasets; for the first, second, third and fourth lactations. Two analyses were performed on data from each lactation. First, ANOVA was used to estimate the significance of the effects of several environmental factors on MUN and DCPun, after absorbing the Herd-Test-Day (HTD) effects. The effects of DIM and age.season effects had significant impact on MUN and DCPun. The second used a multi-traits repeatability model (MTRM) to estimate heritabilities and genetic correlations of milk with MUN and DCPun. Heritability estimates for MUN and DCPun in the first, second, and third lactations were 0.21:0.16, 0.20:0.16, and 0.20:0.18, respectively. Genetic correlations for milk with MUN and DCPun in the first, second, and third lactations were 0.02 - 0.17, and -0.25 - -0.39, respectively. The results indicate that MUN and DCPun are possibly effective tools for improving the energy balance, but that the relationships between MUN and other economically important traits such as feed efficiency, metabolic disease and fertility are still necessary.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.1
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• pp.116-123
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• 2003

Forages are the most important feed resource for ruminants worldwide, whether fed as pastures, forage crops or conserved hay, silage or haylage. There is large variability in the quality of forages so measurement and prediction of feeding value and nutritive value are essential for high levels of production. Within a commercial animal production system, methods of prediction must be inexpensive and rapid. At least 50% of the variation in feeding value of forages is due to variation in voluntary feed intake. Identification of the factors that constrain voluntary feed intake allows these differences to be managed and exploited in forage selection. Constraints to intake have been predicted using combinations of metabolic and physical factors within the animal while simple measurements such as the energy required to shear the plant material are related to constraints to intake with some plant material. Animals respond to both pre- and post-ingestive feedback signals from forages. Pre-ingestive signals may play a role in intake with signals including taste, odour and texture together with learned aversions to nutrients or toxins (post-ingestive feedback signals). The challenge to forage evaluation is identification of the factors which are most important contributors to these feedback signals. Empirical models incorporating chemical composition are also widely used. The models tend to be useful within the ranges of the datasets used in their development but none can claim to have universal application. Mechanistic models are becoming increasingly complex and sophisticated and incorporate both feed characteristics and use of biochemical pathways within the animal. Improvement in utilisation through the deliberate selection of pasture plants for high feeding value appears to have potential and has been poorly exploited. Use of Near Infrared Reflectance Spectroscopy is a simple method that offers significant potential for the preliminary screening of plants with genetic differences in feeding value. Near Infrared Reflectance Spectroscopy will only be as reliable as the calibration sets from which the equations are generated.

• Journal of Microbiology and Biotechnology
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• v.16 no.6
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• pp.993-998
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• 2006

We earlier suggested a hierarchical regulatory network using defined modeling symbols and weights in order to improve the flux balance analysis (FBA) with regulatory events that were represented by if-then rules and Boolean logic. In the present study, the simulation results of the models, which were developed and improved from the previou model by incorporating a hierarchical regulatory network into the FBA, were compared with the experimental outcome of an aerobic batch growth of E. coli on glucose and tryptophan. From the experimental result, a diauxic growth curve was observed, reflecting growth resumption, when tryptophan was used as an alternativee after the supply of glucose was exhausted. The model parameters, the initial concentration of substrates (0.92 mM glucose and 1 mM tryptophan), cell density (0.0086 g biomass/1), the maximal uptake rates of substrates (5.4 mmol glucose/g DCW h and 1.32 mmol tryptophan/g DCW h), and lag time (0.32 h) were derived from the experimental data for more accurate prediction. The simulation results agreed with the experimental outcome of the temporal profiles of cell density and glucose, and tryptophan concentrations.

• 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.

• Environmental Analysis Health and Toxicology
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• v.24 no.4
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• pp.287-292
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• 2009

Over the a few decades, the incidences of obesity and associated metabolic syndrome diseases have been increased dramatically and resulted in a global health crisis. Recent findings suggest endocrine disrupting chemicals (EDCs) as an obesogen, because they disrupt normal development and homeostatic controls over adipogenesis and energy balance in obesity. Furthermore, risk of cardiovascular disease and mortality is elevated among those who were obese during childhood. Thus, we focused on etiology of obesity in children and performed biological monitoring of bisphenol A (BPA), which is a broadly exposed EDC in environment. Study subjects were age and sex-matched obese and normal children in Seoul (N=52; age, $8.67{\pm}1.46$ years). Exposure levels of BPA were analyzed with HPLC/FLD as a conjugated form in urine. As results, ranges of urinary BPA were 0~54.38 ${\mu}g/g$ creatinine (median, 4.57 ${\mu}g/g$ creatinine). Levels of urinary BPA were 1.7 fold higher in the obese children than those in the controls (medians of obese and control children, 7.31 and 4.25 ${\mu}g/g$ creatinine, respectively, p=0.22). In the near future, enlarge scaled studies should be performed to confirm the risk of BPA for obesity.