• Journal of Life Science
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• v.30 no.4
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• pp.331-342
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• 2020

The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.

• Journal of Life Science
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• v.25 no.1
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• pp.68-74
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• 2015

Recently developed black waxy rice with a giant embryo ('Nunkeunheukchal', BGE) was selected and processed to produce high quality nutritional food. BGE contains high levels of several phytochemicals with antioxidant activities, as well as other reported health beneficial properties. In addition, the giant embryo has high protein, lipid, and amino acids contents. Within the free amino acids, ${\gamma}$-aminobutyric acid (GABA), a major inhibitory neurotransmitter, has long been used for treating the aftereffects of brain injuries and stroke. A method for manufacturing pop-rice and black rice tea by popping process in BGE is provided to increase a taste, nutrition and functionality. The produced 'pop-rice' showed increased protein (11.3%) and lipid (3.7%) contents compared with control variety, IB ('Ilmibyeo'). In addition, melanoidin related products, polyphenol and functional amino acid contents were increased by the popping process. Pop-rice tea made of BGE showed the highest extraction of total sugar, glucose, raffinose and sucrose (4 times higher than brown rice) by hot water. Scavenging activity ($SC_{50}$) of processed BGE rice powder showed strong antioxidative activity of 0.24 mg/ml using DPPH and 1.82 mg/ml using ABTs method. Thereafter, these results suggested that the popping processed rice of BGE could be one of the promising materials for healthy food development.

• Journal of Life Science
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• v.24 no.12
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• pp.1276-1283
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• 2014

Cell adhesion molecules determine the cell-cell binding and the interactions between cells and extracellular signals. Cell-cell junctional complexes, which maintain the structural integrity of tissues, consist of more than 50 proteins including multi-PDZ domain protein 1 (MUPP1). MUPP1 contains 13 postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains and serves a scaffolding function for transmembrane proteins and cytoskeletal proteins or signaling proteins, but the mechanism how MUPP1 links and stabilizes the juxtamembrane proteins has not yet been elucidated. We used the yeast two-hybrid system to identify proteins that interact with PDZ domains of MUPP1. We found an interaction between MUPP1 and cell adhesion molecule 1 (Cadm1, also known as SynCAM1, Necl-2, or TSLC1). Cadm1 bound to the second PDZ domain of MUPP1. The carboxyl (C)-terminal end of Cadm1 has a type II PDZ-association motif (-Y-F-I) which was essential for the interaction with MUPP1 in the yeast two-hybrid assay. MUPP1 also bound to the C-terminal cytoplasmic tail region of other Cadm family members (Cadm2, Cadm3, and Cadm4). In addition, these protein-protein interactions were observed in the glutathione S-transferase (GST) pull-down assay and by co-immunoprecipitation. Anti-MUPP1 antibody co-immunoprecipitated Cadm1 and Cadm4 with MUPP1 from mouse brain extracts. These results suggest that MUPP1 could mediate interaction between Cadms and cytoskeletal proteins.

• Journal of Life Science
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• v.24 no.4
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• pp.343-351
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• 2014

Phosphoinositide 3-kinase (PI3K) plays a central role in cell signaling and leads to cell proliferation, survival, motility, exocytosis, and cytoskeletal rearrangements, as well as specialized cell responses, superoxide production, and cardiac myocyte growth. PI3K is divided into three classes; type I PI3K is preferentially expressed in leukocytes and activated by ${\beta}{\gamma}$ subunits of heterotrimeric G-proteins. In this study, the cDNAs encoding the $PI3K{\gamma}$ gene were isolated from a brain cDNA library constructed using the flounder (Paralichthys olivaceus). The sequence of the isolated $PI3K{\gamma}$ was 1341 bp, encoding 447 amino acids. The nucleotide sequence of the $PI3K{\gamma}$ gene was analyzed with that of other species, including Oreochromis niloticus and Danio rerio, and it turned out to be well conserved during evolution. The $PI3K{\gamma}$ gene was subcloned into the expression vector pET-44a(+), and expressed in the E. coli BL21 (DE3) codon plus cell. The resulting protein was expressed as a fusion protein of approximately 49 kDa containing a C-terminal six-histidine extension that was derived from the expression vector. The expressed protein was purified to homogeneity by His-tag affinity chromatography and showed enzymatic activity corresponding to $PI3K{\gamma}$. The binding of wortmannin to $PI3K{\gamma}$, as detected by anti-wortmannin antisera, closely followed the inhibition of the kinase activities. The results obtained from this study will provide a wider base of knowledge on the primary structure and characterization of the $PI3K{\gamma}$ at the molecular level.

• Journal of Life Science
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• v.29 no.12
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• pp.1371-1377
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• 2019

Oxidative stress induced by the over-production of reactive oxygen species (ROS) in the brain is the most common cause of neurodegenerative diseases such as Alzheimer's. In the present study, we investigated the protective effects of flavonoids and their glycosides, namely kaempferol, kaempferol-3-O-glucoside, quercetin, and quercetin-3-β-D-glucoside, against H₂O₂-induced oxidative stress in the C6 glial cells. The H₂O₂-treated glial cells exhibited decreased cell viability and increased ROS production when compared with normal cells. However, cells treated with each of the four flavonoids/glycosides demonstrated significantly increased viability and suppressed ROS production when compared with the H₂O₂-treated control group. These results indicate that flavonoids/glycosides attenuate oxidative stress induced by H₂O₂ in C6 glial cells. To confirm the protective molecular mechanisms, we measured pro-inflammatory factors such as inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1β. H₂O₂ treatment was seen to elevate these factors and decrease IκB-α in the C6 glial cells, while the flavonoids/glycosides induced a down-regulation of the pro-inflammatory factors and increased IκB-α, indicating a neuroprotective effects through attenuation of the inflammation. In particular, quercetin and its glycoside showed a higher neuroprotective effect than the kaempferol treatments. These results suggest that these flavonoids and their glycosides could be promising therapeutic agents for neurodegenerative diseases via the attenuation of oxidative stress.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.23-34
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• 2012

Purpose: Acute symptomatic seizures are caused by structural changes, inflammation or metabolic changes of brain, such as tumor, stroke, meningitis, encephalitis and metabolic disorders. Inherited metabolic disorders that can cause seizures are organic acidopathies, lysosomal storage disorders, peroxisomal disorders and mineral disorders. We have done this study to find out the importance of organic acidopathies causing seizure disorders in Korean childhood and adolescent patients. Method: Retrograde analysis for 1,306 patients with seizure disorders whose clinical informations are available and have done urine organic acid analysis for 5 years period, between Jan. 1st 2007 to Dec. 31th 2011. Statistical analysis was done with Student's t test using SPSS. Result: Out of 1,306 patients, 665 patients (51%) showed abnormalities on urine organic acid analysis. The most frequent disease was mitochondrial respiratory chain disorders (394, 30.1%), followed by mandelic aciduria (127, 9.7%), ketolytic defects (81, 6.2%), 3-hydroxyisobutyric aciduria (19, 1.4%), glutaric aciduria type II (10, 0.8%), ethylmalonic aciduria (4), propionic aciduria (4), methylmalonic aciduria (3), glutaric aciduria type I (3), pyruvate dehydrogenase deficiency (3), pyruvate carboxylase deficiency (3), isovaleric aciduria (2), HMG-CoA lyase deficiency (2), 3-methylcrotonylglycinuria (2), fatty acid oxidation disorders (2), fumaric aciduria (1), citrullinemia (1), CPS deficiency (1), MCAD deficiency (1). Conclusion: On neonatal period, mandelic aciduria due to infection was found relatively frequently. Mitochondrial disorders are most frequent etiologic disease on all age group, followed by ketolytic defects and various organic acidopathies. The number and diversities of organic acidopathies emphasize meticulous evaluation of basic routine laboratory examinations and organic acid analysis with initial sample on every seizure patient.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.14-22
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• 2012

Objectives: This study was performed to review clinical manifestations of hyperphenylalaninemia patients in Korean. Methods: 178 cases of hyperphenyalaninemia were diagnosed at department of pediatrics, Soonchunhyang University Hospital from January, 1983 to August. We reviewed DNA analysis, MR imaging, EEG, radiography of the left hand and wrist, bone densitometry (BMD), IQ test of hyperphenyalaninemia patients. Results: Out of 178 cases, 161 cases were diagnosed classic phenylketonuria and 17 cases were diagnosed BH4 deficiency. 122 cases performed DNA analysis. R243Q (10.3%), Y204C (9.9%), and IVS4-1G>A (8.1%) mutations were predominant. 22 cases underwent MR imaging. Varying degrees of symmetrical high signal intensity were noted on T2-weighted sequences in the periventricular deep white matter of 15 cases. 23 cases were performed EEG. 12 cases (52.3%) showed abnormal pattern. EEG abnormalities showed in 11 cases. On lumbar BMD four of 11 cases (36%) showed reduced bone density of more than 1 S.D. in four of 11 cases, bone age was less than chronological age by at least one year. 18 cases were performed IQ test. Mean IQ scores was $84{\pm}21.6$. Among older than 15 years (9 cases), Mean IQ scores was $72{\pm}21.2$. PTPS deficiency was 14 cases, DHPR deficiency was 2 cases, and GTPCH deficiency was 1 case. Conclusion: We confirmed there were varieties of DNA mutations. And MR imaging and EEG were nonspecific in PKU patients. Older children showed lower IQ score. Low phenylalanine diet prevents brain damage in PKU patient. Not only first few years of life but also lifetime, Keeping low phenylalanine diet is important.

• Journal of Food Hygiene and Safety
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• v.24 no.4
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• pp.391-397
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• 2009

Carnosine is a dipeptide ($\beta$-alanyl-L-histidine) found in mammalian brain, eye, olfactory bulb and skeletal muscle at high concentrations. Its biological functions include antioxidant and anti-glycation activities. The objectives of this study were to investigate anti-diabetic effects of carnosine as determined by blood glucose levels in glucose tolerance test (GTT) and insulin tolerance test (ITT), insulin level and serum biochemical and lipid levels in male C57BL/6J db/db mice. There were five experimental groups including normal (C57BL/6J), control (vehicle), and three groups of carnosine at doses of 6, 30, and 150 mg/kg b.w. Carnosine was orally administered to the diabetic mice everyday for 8 weeks. There was no significant difference in body weight changes in carnosine-treated groups compared to the control. The treatments of carnosine significantly decreased the blood glucose level in the diabetic mice compared with the control (p < 0.05) after 5 weeks. The treatments of carnosine also significantly decreased the blood glucose levels in GTT and ITT and glycosylated hemoglobin (HbA1c), compared with the control (p < 0.05). Carnosine at the dose of 6 mg/kg significantly decreased the serum insulin level compared to the control (p < 0.05). Carnosine significantly increased total proteins but significantly decreased lactate dehydrogenase and blood urea nitrogen compared with the control (p < 0.05). Carnosine also significantly decreased glucose, LDL, and triglyceride in the serum of diabetic mice compared to the control (p < 0.05). These results suggest that carnosine has a hypoglycermic effect resulting from reduction of glucose and lipid levels and that high carnosine-containing diets or drugs may give a benefit for controlling diabetes mellitus in humans.

• Journal of Korean Society of Transportation
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• v.24 no.2 s.88
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• pp.91-100
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• 2006

This paper examines the situation and tasks of UK rail privatization, especially focusing on after the Hatfield rail accident. Earlier research which focused on the UK's Privatization had little knowledge of the explanations for recent changes. Moreover they had difficulty making a direct comparison between national rail and the privatized rail. Therefore we aye left without a good explanation which has a comprehensive perspective. I attempt to show the change in the rail privatization Process and its outcome, focusing on after the Hatfield rail accident. This Paper argues that the UK's vail privatization process has a regulatory framework which is too complicated with overlapping responsibilities that brought about inefficiency, increasing costs and a superficial safety regime. Especially the planning of rail and infrastructure maintenance did not come to play an appropriate role. However after 2000, the government took charge of setting the strategy for railways, and the Office of Rail Regulation covered safety performance and cost. explain that these changes present a good opportunity to solve the problem of passing the buck for poor performance. Through the analysis, I find that the passenger rail network is well-suited to deliver long distance business and commuters and that the subsidy from the government is decreasing. However, performance, for example punctuality and reliability. should be improved. Especially the Hatfield rail accident caused a reduction in the satisfaction of passengers. In future. the problems of rising costs and monopoly franchise system should be addressed.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.287-296
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• 1997

Purpose : This is study of whether 3-D conformal radiotherapy for carcino-mas of the ethmoid sinus were better than those treated with conventional 2-D plan, Materials and Methods : The 3-D conformal treatment Plans were compared with conventional 2-D plans in 4 patients with malignancy of the ethmoid sinus. Isodose distribution, dose statistics, and dose volume histogram of the planning target volume were used to evaluate differences between 2-D and 3-D plans. In addition. the risk of radiation exposure of surrounding normal critical organs are evaluated by means of point dose calculation and dose volume histogram. Results : 3-D conformal treatment plans for each patient that the better tumor coverages by the planning target volume with improved dose homo-geneity, compared to 2-D conventional treatment Plans in the same Patient. On the other hand, the radiation dose distributions to the surrounding nor-mal tissue organs, such as the orbit and optic nerves are not significantly reduced with our technique, but a substantial sparing in the brain stem and optic chiasm for each patient. Conclusion : Our findings represented the potential advantage of 3-D treatment planning for dose homogeniety as well as sparing of the normal tissue surrounding the tumor. However, further investigational studies are required to define the clinical benefit.