• The Korean Journal of Nuclear Medicine
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• v.29 no.3
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• pp.294-306
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• 1995

There has recently been increasing interest in the use of NMDA receptor antagonists as potential neuroprotective agents for the treatment of ischemic stroke. To evaluate the neuroprotective effect of the selective non-competitive NMDA receptor antagonist MK-801 in focal cerebral ischemia, local cerebral glucose utilization (ICGU) was examined in 15 neuroanatomically discrete regions of the conscious rat brain using the 2-deoxy-D[$^{14}C$] glucose quantitative autoradiographic technique 24 hr after left middle cerebral artery occlusion (MCAO). Animals received MK-801 (5 mg/kg i.v.) or saline vehicle before (20-30 min) or after (30 min) MCAO. Both pretreatment and posttreatment of MK-801 increased occluded/non-occluded ICGU ratio in 7 and 5 of the 15 regions measured, respectively (most notably in cortical structures). Following MK-801 pretreatment, there was evidence of widespread increases in ICGU not only in the non-occluded hemisphere (12 of the 15 areas studied) but also in the occluded hemisphere (13 of the 15 areas studied), while MK-801 postreatment did not significantly increase ICGU both in the normal and occluded hemispheres. These data indicate that MK-801 has a neuroprotective effect in focal cerebral ischemia and demonstrate that MK-801 provides widespread alterations of glucose utilization in conscious animals.

• Journal of Veterinary Science
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• v.23 no.1
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• pp.4.1-4.15
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• 2022

Background: Flavonoids are natural polyphenols found widely in citrus fruit and peel that possess anti-adipogenic effects. On the other hand, the detailed mechanisms for the antiadipogenic effects of flavonoids are unclear. Objectives: The present study observed the anti-adipogenic effects of five major citrus flavonoids, including hesperidin (HES), narirutin (NAR), nobiletin (NOB), sinensetin (SIN), and tangeretin (TAN), on AMP-activated protein kinase (AMPK) activation in palmitate (PA)-treated HepG2 cells. Methods: The intracellular lipid accumulation and triglyceride (TG) contents were quantified by Oil-red O staining and TG assay, respectively. The glucose uptake was assessed using 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG) assay. The levels of AMPK, acetyl-CoA carboxylase (ACC), and glycogen synthase kinase 3 beta (GSK3β) phosphorylation, and levels of sterol regulatory element-binding protein 2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) expression were analyzed by Western blot analysis. The potential interaction between the flavonoids and the γ-subunit of AMPK was investigated by molecular docking analysis. Results: The flavonoid treatment reduced both intracellular lipid accumulation and TG content in PA-treated HepG2 cells significantly. In addition, the flavonoids showed increased 2-NBDG uptake in an insulin-independent manner in PA-treated HepG2 cells. The flavonoids increased the AMPK, ACC, and GSK3β phosphorylation levels and decreased the SREBP-2 and HMGCR expression levels in PA-treated HepG2 cells. Molecular docking analysis showed that the flavonoids bind to the CBS domains in the regulatory γ-subunit of AMPK with high binding affinities and could serve as potential AMPK activators. Conclusion: The overall results suggest that the anti-adipogenic effect of flavonoids on PA-treated HepG2 cells results from the activation of AMPK by flavonoids.

• Korean Journal of Microbiology
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• v.28 no.2
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• pp.174-179
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• 1990

In order to overproduce L-phenylalanine, various kind of regulatory mutants were isolated from parental Escherichia coli K-12. MWEC 83 Producing 7.4g/l of L-phenylalanine has been derived as a tyrosine and tryptophan double auxotrophic mutant. To produce L-phenylalanine without adding L-tyrosine and L-tryptophan, revertant strain MWEC 101 was isolated from MWEC 83. Further various analogues and valine resistant mutants were isolated from MWEC 101. MWEC 101-5 was the most excellent strain that produced 17.9g/l of L-phenylalanine after having been cultivated for 54 hours in 15% glucose medium. It was disclosed that activities of rate-limiting enzymes including chorismate mutase and prephenate dehydratase in MWEC 101-5 were desensitized to 2mM L-phenylalanine in the enzyme reaction mixture and that activities level of 3-deoxy-D-arabino-heptulosonic acid-7-phosphate synthase and prephenate dehydratase were increased more than 20 times over those of the parental strain.

• Journal of Korean Medicine for Obesity Research
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• v.18 no.2
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• pp.96-105
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• 2018

Objectives: The aim of this study was to examine the effect of Asparagus cochinchinensis (AC) and fermented AC (fAC) on microorganisms and efficacies. Methods: AC was fermented for four weeks without using any bacterial strains. Then we investigated fermentation characteristics including potential of hydrogen (pH), total sugar, microbial profiling and antioxidant compound contents such as total polyphenol and total flavonoid. The anti-obesity effects of AC and fAC were evaluated by using Oil Red O staining in 3T3-L1 adipocyte. Also anti-diabetic effects of them were evaluated by using 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG) uptake in C2C12 skeletal muscle cell. Results: Both pH and total sugar of fAC were decreased significantly compared to unfermented AC. And the abundance of total bacteria and lactic acid bacteria increased during fermentation, especially Lactobacillus plantarum. Also fermentation of AC increased the content of total polyphenol. On the metabolic aspects, we found that AC and fAC suppressed fat accumulation. Conclusions: After four weeks of fermentation, AC increased concentrations of active compounds, altered microbial composition, and inhibited fat accumulation such as triglyceride. These results indicate that fermentation of AC might be a beneficial therapeutic approach for obesity.

• Journal of Radiation Industry
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• v.5 no.4
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• pp.313-316
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• 2011

[$^{18}F$]FDG (2-[$^{18}F$] Fluoro-2-deoxy-D-Glucose), which is required Automated Synthetic Module for production, is most often used Radiopharmaceuticals in nuclear medicine. In this study, an Automated Synthesis Module was developed to produce FDG in two consecutive time when F-18 feds continuously by modifying a domestic FDG Automated Synthetic Module on structural geometry and control system. The results were showed that the Average Synthesis Yields on the developed Automated Synthetic Module were $45{\pm}3%$ (n=20), $50{\pm}3%$ (n=20) respectively. The Quality Control results, such as Radio TLC, Radiochemical purity, Gamma-counter, pH, LAL Test, Micro bacteria test, showed in same level with domestic [$^{18}F$]FDG Auto-Synthetic modules. Therefore, if some features were improved by considering the components life time and appearance, commercial sales can be expected because of low price and easy maintenance compared with foreign products.

• Journal of radiological science and technology
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• v.29 no.4
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• pp.249-255
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• 2006

Purpose: The diagnostic utility of fluorine-18 2-deoxy-D-glucose positron emission tomograhpy ($^{18}F-FDG $PET) for the non-invasive differentiation of focal lung lesions originated from cancer or inflammation disease by combined visual image interpretation and semi-quantitative uptake value analysis has been documented. In general, Standardized Uptake Value(SUV) is used to diagnose lung disease. But SUV does not contain dynamic information of lung tissue for the glucose. Therefore, this study was undertaken to hypothesis that analysis of dynamic kinetics of focal lung lesions base on $^{18}F-FDG$ PET may more accurately determine the lung disease. So we compared Time Activity Curve(TAC), Standardized Uptake Value-Dynamic Curve(SUV-DC) graph pattern with Glucose Metabolic Rate(MRGlu) from Patlak analysis. Methods: With lung disease, 17 patients were examined. They were injected with $^{18}F-FDG$ over 30-s into peripheral vein while acquisition of the serial transaxial tomographic images were started. For acquisition protocol, we used twelve 10-s, four 30-s, sixteen 60-s, five 300-s and one 900-s frame for 60 mins. Its images were analyzed by visual interpretation TAC, SUV-DC and a kinetic analysis(Patlak analysis). The latter was based on region of interest(ROIs) which were drawn with the lung disease shape. Each optimized patterns were compared with itself. Results: In TAC patterns, it hard to observe cancer type with inflammation disease in early pool blood area but over the time cancer type slope more remarkably increased than inflammation disease. SUV-DC was similar to TAC pattern. In the result of Patlak analysis, In time activity curve of aorta, even though inflammation disease showed higher blood activity than cancer, at first as time went by, blood activity of inflammation disease became the lowest. However, in time activity curve of tissue, cancer had the highest uptake and inflammation disease was in the middle. Conclusion: Through the examination, TAC and SUV-DC could approached the results that lung cancer type and inflammation disease type has it's own difference shape patterns. Also, it has outstanding differentiation between cancer type and inflammation in Patlak and MRGlu analysis. Through these analysis methods, it will helpful to separation lung disease.

• Journal of Gastric Cancer
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• v.17 no.4
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• pp.384-393
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• 2017

Purpose: The tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-($^{18}F$)fluoro-D-glucose ($^{18}F-FDG$) positron emission tomography (PET)-computed tomography (CT) ($^{18}F-FDG$ PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs). Materials and Methods: We retrospectively reviewed 56 patients who underwent $^{18}F-FDG$ PET-CT prior to gastrectomy. In resected tumor specimens, TIL subsets, including cluster of differentiation (CD) 3, CD4, CD8, Forkhead box P3 (Foxp3), and granzyme B, were subjected to immunohistochemical analysis. The prognostic nutritional index (PNI) was calculated as: ($10{\times}serum$ albumin value)+($0.005{\times}peripheral$ lymphocyte counts). Additionally, the maximum standard uptake value ($SUV_{max}$) was calculated to evaluate the metabolic activity of cancer cells. Results: The $SUV_{max}$ was positively correlated with larger tumor size (R=0.293; P=0.029) and negatively correlated with PNI (R=-0.407; P=0.002). A higher $SUV_{max}$ showed a marginal association with higher CD3 (+) T lymphocyte counts (R=0.227; P=0.092) and a significant association with higher Foxp3 (+) T lymphocyte counts (R=0.431; P=0.009). No other clinicopathological characteristics were associated with $SUV_{max}$ or TILs. Survival analysis, however, indicated that neither $SUV_{max}$ nor Foxp3 held prognostic significance. Conclusions: FDG uptake on PET-CT could be associated with TILs, especially regulatory T cells, in gastric cancer. This finding may suggest that PET-CT could be of use as a non-invasive tool for monitoring the tumor microenvironment in patients with gastric cancer.

• BMB Reports
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• v.32 no.3
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• pp.273-278
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• 1999

Cytolysin produced by Vibrio vulnificus has been known to be lethal to mice by increasing vascular permeability and neutrophil sequestration in the lung. In the present study, a cytotoxic mechanism of V. vulnificus cytolysin on the neutrophil was investigated. Cytolysin rapidly bound to neutrophils and induced cell death, as determined by the trypan blue exclusion test. V. vulnificus cytolysin caused the depletion of cellular ATP without the release of ATP or lactate dehydrogenase. Formation of transmembrane pores was evidenced by the rapid efflux of potassium and 2-deoxy-D-[$^3H$]glucose from cytolysin-treated neutrophils. It was further confirmed by the rapid flow of monovalent ions in the patch clamp of cytolysin-treated neutrophil membrane. The pore formation was accompanied by the oligomerization of cytolysin monomers on the neutrophil membrane as demonstrated by immunoblot, which exhibited a 210 kDa band corresponding to a tetramer of the native cytolysin of $M_r$ 51,000. These findings indicate that V. vulnificus cytolysin rapidly binds to the neutrophil membrane and oligomerizes to form small transmembrane pores, which induce the efflux of potassium and the depletion of cellular ATP leading to cell death without cytolysis.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.9-16
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• 2005

Purpose : To prospectively evaluate the use of positron emission tomography with the glucose analog fluoro-deoxyglucose (FDG-PET) to deoxyglucose (FDG-PET) to predict disease-free survival (DFS) after concurrent chemo-radiotherapy (CCRT) in patients with non-disseminated nasopharyngeal carcinoma (NPC). Materials and Methods : We studied 41 patients with non-disseminated NPC scheduled to undergo platinum-based CCRT were eligible for this study. Patients were studied by FDG-PET prior to the CCRT. FDG uptake of tumors were measured with the maximal standardized uptake value (SUV). Results : Complete response rate was $100\%$. In ten patients who presented with any component of treatment failure, the median $SUV_{max}$ was 8.55 (range: $2.49\~14.81$) in any component of failure and the median $SUV_{max}$ was 5.48 (range: $2.31\~26.07$) In the remaining patients without any such failure. Patients having tumors with high FDG uptake had a significantly lower 3-year DFS ($51\%\;{\nu}91\%$, p=0.0070) compared with patients having low uptake tumors. Conclusion : FDG uptake, as measured by the SUV, has potential value in predicting DFS in NPC treated by CCRT, High FDG uptake may be a useful parameter for Identifying patients requiring more aggressive treatment approaches.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.8
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• pp.1197-1203
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• 2013

This study investigated the effects of endurance exercise and ginsenoside $Rb_1$ on AMP-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K) protein expression and glucose uptake in the skeletal muscle of rats. A total of 32 rats were randomly divided into four groups: CON (Control group, n=8), Ex (Exercise group; 25 m/min for 1 h, 6 days/week, 2 weeks, n=8), $Rb_1$ (Ginsenoside $Rb_1$ group; n=8), and $Rb_1/Ex$ ($Rb_1$+Exercise group, n=8). The $Rb_1$ and $Rb_1/Ex$ groups were incubated in ginsenoside $Rb_1$ (KRBP buffer, $100{\mu}g/mL$) for 60 min after a 2-week experimental treatment. After 2 weeks, the expression of phosphorylated $AMPK{\alpha}$ $Thr^{172}$, total $AMPK{\alpha}$, the p85 subunit of PI3K, pIRS-1 $Tyr^{612}$, and pAkt $Ser^{473}$ were determined in the soleus muscle. Muscle glucose uptake was measured using 2-deoxy-D-[$^3H$] glucose in epitroclearis muscle. Muscle glucose uptake was significantly higher in the three experimental groups (Ex, $Rb_1$, $Rb_1/Ex$) compared to the CON group (P<0.05). The expression of $tAMPK{\alpha}$ and $pAMPK{\alpha}$ $Thr^{172}$ was significantly higher in the Ex, $Rb_1$, and $Rb_1/Ex$ groups compared to the CON group (P<0.05). The expression of pAkt $Ser^{473}$ was significantly higher in the $Rb_1$ group compared to the CON and EX groups. However, the expression of pIRS-1 $Tyr^{612}$ and the p85 subunit of PI3K were not significantly different between the four groups. Overall, these results suggest that ginsenoside $Rb_1$ significantly stimulates glucose uptake in the skeletal muscle of rats through increasing phosphorylation in the AMPK pathway, similar to the effects of exercise.