• The Korean Journal of Physiology and Pharmacology
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• 제18권2호
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• pp.169-175
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• 2014

Human organic cation/carnitine transporter 1 (OCTN1) plays an important role in the transport of drugs and endogenous substances. It is known that a missense variant of OCTN1 is significantly associated with Crohn's disease susceptibility. This study was performed to identify genetic variants of the OCTN1 promoter in Korean individuals and to determine their functional effects. First, the promoter region of OCTN1 was directly sequenced using genomic DNA samples from 48 healthy Koreans. OCTN1 promoter activity was then measured using a luciferase reporter assay in HCT-116 cells. Seven variants of the OCTN1 promoter were identified, two of which were novel. There were also four major OCTN1 promoter haplotypes. Three haplotypes (H1, H3, and H4) showed decreased transcriptional activity, which was reduced by 22.9%, 23.0%, and 44.6%, respectively (p<0.001), compared with the reference haplotype (H2). Transcription factor binding site analyses and gel shift assays revealed that NF-Y could bind to the region containing g.-1875T>A, a variant present in H3, and that the binding affinity of NF-Y was higher for the g.-1875T allele than for the g.-1875A allele. NF-Y could also repress OCTN1 transcription. These data suggest that three OCTN1 promoter haplotypes could regulate OCTN1 transcription. To our knowledge, this is the first study to identify functional variants of the OCTN1 promoter.

• Applied Microscopy
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• 제24권2호
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• pp.12-25
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• 1994

This research was undertaken to determine the effects of the anticancer and immunosuppressive drug cyclophosphamide (CP) on the epididymis of the male rat in terms of ultrastructural alteration and protein analysis by SDS-PAGE at different groups; control group, 1 week group, 3 weeks group, 5 weeks group were treated with saline (control group) or CP at doses of 20mg/Kg/week, 1 time a week, respectively. In the cytoplasm of the principal cells on the epididymis, the mitochondrial outer and inner membranes were significantly swollen or disrupted. The cisterns of rough endoplasmic reticulum (rER) were also swollen, and a number of Golgi vesicles were increased, respectively. It is suggested that treatment with CP alters the specific cell organelles in all segments of the epididymis. CP caused changes in protein concentrations in cauda of epididymis after CP treatment. Total proteins of 30 to 39 species such as lactate dehydrogenase, carnitine acetyltransferase and acid phosphatase were expressed in the cauda fluid. Then the more CP was increased, the more concentration of proteins caused to decrease, synthesize or increase in epididymal cauda. In contrast to the control group, in particular 29KD and the other 10 proteins in the cauda fluid were decreased or disappeared, respectively, whereas 89KD and the other 6 proteins in the cauda, were increased or synthesized, respectively. The other proteins are not showed distinctive difference. Therefore, it is possible that CP at a high dose accumulation alters epididymal function with dose-related increase or decrease in specific activity of marked proteins for all regions of the epididymis (particularly, specific segment of cauda). These alterations could be mediated by direct, toxic effects of the drug on the epithelium or be secondary to changes in the spermatozoa as a result of the CP treatment.

• Toxicological Research
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• 제29권1호
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• pp.7-14
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• 2013

Betaine supplementation has been shown to alleviate altered glucose and lipid metabolism in mice fed a high-fat diet or a high-sucrose diet. We investigated the beneficial effects of betaine in diabetic db/db mice. Alleviation of endoplasmic reticulum (ER) and oxidative stress was also examined in the livers and brains of db/db mice fed a betaine-supplemented diet. Male C57BL/KsJ-db/db mice were fed with or without 1% betaine for 5 wk (referred to as the db/db-betaine group and the db/db group, respectively). Lean non-diabetic db/+ mice were used as the control group. Betaine supplementation significantly alleviated hyperinsulinemia in db/db mice. Betaine reduced hepatic expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha, a major transcription factor involved in gluconeogenesis. Lower serum triglyceride concentrations were also observed in the db/db-betaine group compared to the db/db group. Betaine supplementation induced hepatic peroxisome proliferator-activated receptor alpha and carnitine palmitoyltransferase 1a mRNA levels, and reduced acetyl-CoA carboxylase activity. Mice fed a betaine-supplemented diet had increased total glutathione concentrations and catalase activity, and reduced lipid peroxidation levels in the liver. Furthermore, betaine also reduced ER stress in liver and brain. c-Jun N-terminal kinase activity and tau hyperphosphorylation levels were lower in db/db mice fed a betaine-supplemented diet, compared to db/db mice. Our findings suggest that betaine improves hyperlipidemia and tau hyperphosphorylation in db/db mice with insulin resistance by alleviating ER and oxidative stress.

• 한국축산식품학회지
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• 제40권6호
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• pp.924-937
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• 2020

The purpose of this study was to investigate the meat metabolite profiles related to differences in beef quality attributes (i.e., high-marbled and low-marbled groups) using nuclear magnetic resonance (NMR) spectroscopy. The beef of different marbling scores showed significant differences in water content and fat content. High-marbled meat had mainly higher taste compounds than low-marbled meat. Metabolite analysis showed differences between two marbling groups based on partial least square discriminant analysis (PLS-DA). Metabolites identified by PLS-DA, such as N,N-dimethylglycine, creatine, lactate, carnosine, carnitine, sn-glycero-3-phosphocholine, betaine, glycine, glucose, alanine, tryptophan, methionine, taurine, tyrosine, could be directly linked to marbling groups. Metabolites from variable importance in projection plots were identified and estimated high sensitivity as candidate markers for beef quality attributes. These potential markers were involved in beef taste-related pathways including carbohydrate and amino acid metabolism. Among these metabolites, carnosine, creatine, glucose, and lactate had significantly higher in high-marbled meat compared to low-marbled meat (p<0.05). Therefore, these results will provide an important understanding of the roles of taste-related metabolites in beef quality attributes. Our findings suggest that metabolomics analysis of taste compounds and meat quality may be a powerful method for the discovery of novel biomarkers underlying the quality of beef products.

• Archives of Pharmacal Research
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• 제27권6호
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• pp.676-681
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• 2004

Acetyl-L-camitine (ALC), a naturally occurring endogenous compound, has been shown to improve the cognitive performance of patients with senile dementia Alzheimer＇s type, and to be involved in cholinergic neurotransmission. Because ALC is an endogenous compound, valida-tion of the analytical methods of ALC in the biological fluids is very important and difficult. This study was presented validation and correction for plasma ALC concentrations and pharmacok-inetics after oral administration of ALC to human volunteers. ALC concentrations in human plasma were corrected by subtracting the concentration of blank plasma from each sample. Precision and accuracy (bias %) for uncorrected ALC concentrations were below 2.6 and 6.5% for intra-days, and 4.0 and 9.4% for inter-days, respectively. Precision and accuracy (bias %)for corrected ALC concentrations were below 10.9 and 6.0% for intra-days, and 10.5 and 16.9% for inter-days, respectively. Quantitation limit was $0.1{\;}\mu\textrm{g}／mL$. After oral administration of a 500 mg ALC tablet to 8 healthy volunteers, the principle pharmacokinetic parameters were 4.2 h of the half-life$ (t_{1/2},{\beta})$, the area under the curve $(AUC_{0{\rightarrow}8){\;}of{\;}9.88{\;}\mu\textrm{g}{\cdot}h/mL$, and 3.1 h of the time ($T_{max}$) to reach $C_{max}$. This study first describes the pharmacokinetic study after oral admin-istration of a single dose of ALC in human volunteers.

• 대한본초학회지
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• 제35권5호
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• pp.23-31
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• 2020

Objectives : This study was conducted to evaluate the anti-hyperlipidemia effect of Scutellariae Radix, Aucklandiae Radix and Bupleuri Radix(SAB). Methods : FL83B cells were mouse liver hepatocytes, and we used this cell line. FL83B cells were treated with 0.5 mM oleic acid(OA) for 24 h, SAB extract was treated. After OA treatment, intracellular triglyceride (TG) and free fatty acid contents were measured with AdiopoRed™ assay and Free Fatty Acid Quantitation assay kit, respectively. Further, we evaluated several lipogenesis and metabolic markers such as sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), 3-hydroxy3-methyl-glutaryl CoA reductase (HMGCR), hormone-sensitive lipase (HSL), carnitine palmitoyltransferase (CPT-1), peroxisome proliferator activated receptor alpha (PPARα), and cluster of differentiation (CD36) using RT-PCR and Western-blot analysis. Results : OA markedly increased intracellular TG and free fatty acid, which plays a key role in reducing hepatic lipid accumulation, in FL83B cells. These increases were alleviated by SAB extract. The mRNA and protein expression of Fatty acid(FA) oxidation factors (CPT-1, PPARα), lipolysis factor(HSL), FA transporter(CD36), cholesterol synthesis factors (HMGCoA) and Lipodenesis (SREBP-1c, FAS, and ACC-1) were significantly increased by treatment of SAB extract in the OA-induced fatty liver cell model. Conclusions : In summary, the treat of SAB extract showed a significant reduction of the influx of fatty acids into hepatocytes, promoted the oxidation of fatty acids, and regulated fat synthesis-related factors, thereby regulating the accumulation of TG and free fatty acids.

• 한국조리학회지
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• 제23권7호
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• pp.42-49
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• 2017

This study was conducted to determine the nutritional value of domestic cherry tomato varieties (Summerking, Qutiquti, and Minichal). The levels of amino acids, amino acid derivatives, and ${\gamma}-aminobutyric-acid$ (GABA) were analyzed using ion chromatography. In domestic cherry tomatoes, eighteen free amino acids were found including L-glutamic acid (L-Glu), L-glutamine (L-Gln), and L-aspartic acid (L-Asp). L-Glu was the most abundant amino acid, ranging from 1,533.17 mg/100 g to 1,920.65 mg/100 g (dry weight). The next abundant amino acids were L-Gln, ranging from 784.68 mg/100 g to 1,164.36 mg/100 g and L-Asp, ranging from 320.73 mg/100 g to 387.22 mg/100 g. Domestic cherry tomatoes contained eight essential amino acids except tryptophan and the total essential amino acid content was 297.30~432.43 mg/100 g (dry weight), which was 8.92~10.61% of total free amino acid. Several amino acid derivatives were found: L-carnitine (L-Car), hydroxylysine (Hyl), o-phosphoethanolamine (o-Pea), phosphoserine (p-Ser), ${\beta}-alanine$ (${\beta}-Ala$), N-methyl-histidine (Me-His), ethanolamine ($EtNH_2$), and L-citrulline (L-Cit). L-Car, transporting long-chain fatty acid into mitocondrial matrix, was the most abundant amino acid derivative in all domestic cherry tomatoes. A high level of GABA (313.18~638.57 mg/100 g), known as a neurotransmitter, was also found in all three domestic cherry tomatoes. These results revealed that domestic cherry tomatoes have a good balance of nutrient and bioactive compounds. Therefore, cherry tomatoes can be used as a functional food material.

• Clinical and Experimental Reproductive Medicine
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• 제31권3호
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• pp.177-182
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• 2004

Purpose: To determine the efficacy of $Carnitil^{(R)}$ (acetylcarnitine, Hanmi, Korea) therapy in idiopathic oligoasthenospermic men. Materials and Methods: Forty-four subfertile men with abnormal semen parameters were treated between March, 2003 and March, 2004 with 3 g of $Carnitil^{(R)}$ daily for 3 months. Changes in semen parameters were evaluated 3 months after this therapy. Results: The mean age was 34.2 years and the mean follow-up duration was 3.7 months. In asthenospemic patients (n=28), semen analysis before and after $Carnitil^{(R)}$ treatment showed an increase in volume ($2.64{\pm}1.65\;ml$ vs. $3.10{\pm}1.60\;ml$), motility ($35.1{\pm}17.7%$ vs. $45.9{\pm}20.4%$) and viability ($51.4{\pm}20.3%$ vs. $59.3{\pm}13.6%$) respectively. In oligoasthenospermic patients (n=16), semen analysis before and after $Carnitil^{(R)}$ treatment showed an increase in sperm count ($10.7{\pm}54.4\;million/ml$ vs. $38.4{\pm}32.5\;million/ml$) respectively. Conclusions: These results suggested that in idiopathic oligoasthenospermic men the empirical medical therapy with acetylcarnitine may be considered as primary treatment.

• Journal of Ginseng Research
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• 제44권2호
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• pp.350-361
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• 2020

Background: Black ginseng (BG) is a type of Korean ginseng prepared by steaming and drying raw ginseng to improve the saponin content. This study examined the effects of BG on nonalcoholic fatty liver disease (NAFLD) in HepG2 cells and diet-induced obese mice. Methods: HepG2 cells were treated with free fatty acids to induce lipid accumulation before supplementation with BG. NAFLD-induced mice were fed different doses (0.5%, 1%, and 2%) of BG for 8 weeks. Results: BG significantly reduced lipid accumulation and expression of lipogenic genes, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, sterol regulatory element-binding protein-1c, and fatty acid synthase in HepG2 cells, and the livers of mice fed a 45% high-fat diet with 10% fructose in the drinking water (HFHF diet). BG supplementation caused a significant reduction in levels of aspartate aminotransferase and alanine aminotransferase, while antioxidant enzymes activities were significantly increased in 45% high-fat diet with 10% fructose in the drinking water diet-fed mice. Expression of proliferator-activated receptor alpha and carnitine palmitoyltransferase I were upregulated at the transcription and translation levels in both HepG2 cells and diet-induced obese mice. Furthermore, BG-induced phosphorylation of AMP-activated protein kinase and acetyl CoA carboxylase in both models, suggesting its role in AMP-activated protein kinase activation and the acetyl CoA carboxylase signaling pathway. Conclusion: Our results indicate that BG may be a potential therapeutic agent for the prevention of NAFLD.

• Nutrition Research and Practice
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• 제7권4호
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• pp.294-301
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• 2013

In this study, we examined the hepatic anti-steatosis activity of carnosic acid (CA), a phenolic compound of rosemary (Rosmarinus officinalis) leaves, as well as its possible mechanism of action, in a high-fat diet (HFD)-fed mice model. Mice were fed a HFD, or a HFD supplemented with 0.01% (w/w) CA or 0.02% (w/w) CA, for a period of 12 weeks, after which changes in body weight, blood lipid profiles, and fatty acid mechanism markers were evaluated. The 0.02% (w/w) CA diet resulted in a marked decline in steatosis grade, as well as in homeostasis model assessment of insulin resistance (HOMA-IR) index values, intraperitoneal glucose tolerance test (IGTT) results, body weight gain, liver weight, and blood lipid levels (P < 0.05). The expression level of hepatic lipogenic genes, such as sterol regulating element binding protein-1c (SREBP-1c), liver-fatty acid binding protein (L-FABP), stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FAS), was significantly lower in mice fed 0.01% (w/w) CA and 0.02% (w/w) CA diets than that in the HFD group; on the other hand, the expression level of ${\beta}$-oxidation-related genes, such as peroxisome proliferator-activated receptor ${\alpha}$ (PPAR-${\alpha}$), carnitine palmitoyltransferase 1 (CPT-1), and acyl-CoA oxidase (ACO), was higher in mice fed a 0.02% (w/w) CA diet, than that in the HFD group (P < 0.05). In addition, the hepatic content of palmitic acid (C16:0), palmitoleic acid (C16:1), and oleic acid (C18:1) was significantly lower in mice fed the 0.02% (w/w) CA diet than that in the HFD group (P < 0.05). These results suggest that orally administered CA suppressed HFD-induced hepatic steatosis and fatty liver-related metabolic disorders through decrease of de novo lipogenesis and fatty acid elongation and increase of fatty acid ${\beta}$-oxidation in mice.