• Title/Summary/Keyword: Branched Chain

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Valproic Acid-induced PPAR-alpha and FGF21 Expression Involves Survival Response in Hepatocytes (Valproic acid에 의해 증가하는 PPAR-alpha 및 FGF21의 발현이 간세포 생존에 미치는 영향)

  • Bakhovuddin Azamov;Yeowon Kang;Chanhee Lee;Wan-Seog Shim;Kwang Min Lee;Parkyong Song
    • Journal of Life Science
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    • v.34 no.4
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    • pp.227-235
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    • 2024
  • Hepatocyte damage caused by medications or herbal products is one of the important problem when these compounds are chronically administrated. Thus, improving hepatocyte survival during treatment offers a wide range of opportunities. Valproic acid (VPA), a branched short-chain fatty acid derived from naturally occurring valeric acid, is commonly used to treat epilepsy and seizures. Although VPA exerts numerous effects in cancer, HIV therapy, and neurodegenerative disease, its effects on the liver and its mechanism of action have not been fully elucidated. Here, we demonstrated that VPA caused moderate liver cell toxicity and apoptosis. Interestingly, VPA treatment increased transcription levels of PPAR alpha (PPAR-α) and fibroblast growth factor 21 (FGF21) in murine (Hepa1c1c7) hepatoma cells in a time and concentration dependent manner. VPA-induced FGF21 expression was significantly weaker under PPAR-α silencing condition than in cells transfected with non-targeting control siRNA. Subsequent experiments showed that cell viability was significantly lowered when the FGF21 signaling pathway was blocked by FGF receptor antagonist. Finally, we further determined that AMPK phosphorylation was not responsible for VPA-induced FGF21 expression and PPAR-a increments. These results indicate that increases of FGF21 expression alleviate VPA-induced hepatic toxicity, thereby making FGF21 a potential biomarker for predicting liver damage during VPA treatments.

Studies on the Chemical Structure of the New Polysaccharide C - (The New Polysaccharides of Gum Tragacanth. II) - (Tragacanth gum 의 신다당류(新多糖類) C 의 화학구조(化學構造) - Tragacanth gum의 신다당류(新多糖類)에 관(關)한 연구(硏究) 제2보(第二報) -)

  • Lee, Sung-Hwan
    • Applied Biological Chemistry
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    • v.3
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    • pp.25-48
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    • 1962
  • The polysaccharide C prepared from gum tragacanth powder (U. S. P. grade) by the precipitation method with 85% ethanol was a neutral polysaccharide, $[{\alpha}]^{30}_D-72.2$. The polysaccharide C consisted of L-rhamnose, D-xylose, L-arabinose and D-galactose in the molar ratio 2:1:17:9 (Table 1, 2, 3, ). The polysaccharide C was methylated with dimethylsulphate and 40% NaOH, and Purdies regent. The hydrolyzate of fully methlated product ($[{\alpha}]^{22}_D-102$ in chloroform, the methoxy content 40.6%) was composed of 2, 3, 5-tri-O-methyl-L-arabofuranose (I), 3,4-di-O-methyl-L-rhamnopyranose (II), 2,3-di-O-methyl-D-xylose (III), 2,3,4-tri-O-methyl-D-galactopyranose (IV), 2,4-di-O-methyl-L-arabopyranose (?), 2,4-di-O-methyl-D-galactose(VI), 2-O-methyl-D-arabinose (VII), and L-arabopyranose(VIII) (Table 4, 5, and Fig. 4). The first partial hydrolysis (A) of the polysaccharide C with 0.05N-HCl for 4.5 hours at $80-85^{\circ}C$ released only L-arabinose: the second hydrolysis (B) with 0.1N-HCl for 5 hours at $80-85^{\circ}C$, L-arabinose and D-galactose; and the third hydrolysis (C) with 0.3N-HCl at $90-95^{\circ}C$ in sealed tube, L-rhamnose, D-xylose, L-arabinose and D-galactose. From the unhydrolyzate A' were found L-rhamnose, D-xylose, L-arabinose, and D-galactose; from B' L-rhamnose, d-xylose, L-arabinose and D-galactose; and from C' D-xylose and D-galactose respectively (Table 6). The periodate consumption and formic acid production of the polysaccharide C were measured at various time intervals. After 120 hours periodat was consumed by 1.23 mole per $C_5H_8O_4$ and formic acid was produced 0.78 mole per $C_5H_8O_4$ (Table 7). Although a definite chemical structure for this polysaccharide C may not be formulated, experimental data, especially, from methylation, partial hydrolysie and determination of its molar ratio, and periodate analysis showed that the polysaccharide C is a highly branched polysaccharide and would be constructed of galactoaraban as a main chain residue and L-arabofuranose, D-galactopyranosyl $(1{\rightarrow}1)$-L-arabofuranose, D-xylopyranosyl $(1{\rightarrow}2)$-L-rhamnopyranosyl $(1{\rightarrow}1)$-L-arabofuranose, and L-rhamnopyranosyl $(1{\rightarrow}1)$-arabofuranose, and D-galactopyranosyl-$(1{\rightarrow}2)$-L-arabopyranosyl-$(1{\rightarrow}1)$-I-arabofuranose as a branch chain or end group (page 21).

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The Effect of the Addition of Carbohydrate Sources on the Concentration of Odorous Compounds for Recycling of Pig Slurry to Grassland (발효탄수화물 첨가 비육돈사료가 초지환원용 슬러리의 악취물질 농도에 미치는 영향)

  • Cho, Sung Back;Hwang, Ok Hwa;Park, Kyu Hyeun;Choi, Dong Yun;Yang, Seung Bong;Kim, Do Hwan;Park, Sung Kwon
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.33 no.4
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    • pp.257-262
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    • 2013
  • This study investigates the effect of fermentable carbohydrate on the concentration of odorous compounds in pig slurry. Four types of pig diet were studied: control, peanut hull (crude fiber 29.87, NDF 44.02%), golden fiber (crude fiber 48.77, NDF 65.88%), and almond hull (crude fiber 44.30, NDF 64.44%). Pigs (average BW 37.0 kg) were fed diets that met the Korean Feeding Standard (2012) and their excreta samples were collected from the slurry pits. Levels of volatile organic compounds (phenols and indoles) and volatile fatty acids were analyzed by gas chromatography. Phenol level was the lowest (p<0.05) in golden fiber (33.26 ppm) group and the highest in control (97.29 ppm). The concentration of indoles in the peanut hull (1.27 ppm), almond hull (1.20 ppm), and golden fiber (1.02 ppm) groups was lower (p < 0.05) than that of control (1.79 ppm). Levels of short chain fatty acid (SCFA) were lower (p < 0.05) in golden fiber (1,319 ppm) and almond hull (1,433 ppm) groups than in control (1,893 ppm). Concentration of branched chain fatty acid (BCFA) in the golden fiber group (74 ppm) was lower (p < 0.05) than that of control (98 ppm). Taken together, the concentration levels of phenols, indoles, and VFAs decreased on addition of peanut hull, golden fiber or almond hull to the diet, suggesting that fermentable carbohydrate may contribute to reducing odorous compounds in pig slurry.

Effects of Baicalin on Gene Expression Profiles during Adipogenesis of 3T3-L1 Cells (3T3-L1 세포의 지방세포형성과정에서 Baicalin에 의한 유전자 발현 프로파일 분석)

  • Lee, Hae-Yong;Kang, Ryun-Hwa;Chung, Sang-In;Cho, Soo-Hyun;Yoon, Yoo-Sik
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.1
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    • pp.54-63
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    • 2010
  • Baicalin, a flavonoid, was shown to have diverse effects such as anti-inflammatory, anti-cancer, anti-viral, anti-bacterial and others. Recently, we found that the baicalin inhibits adipogenesis through the modulations of anti-adipogenic and pro-adipogenic factors of the adipogenesis pathway. In the present study, we further characterized the molecular mechanism of the anti-adipogenic effect of baicalin using microarray technology. Microarray analyses were conducted to analyze the gene expression profiles during the differentiation time course (0 day, 2 day, 4 day and 7 day) in 3T3-L1 cells with or without baicalin treatment. We identified a total of 3972 genes of which expressions were changed more than 2 fold. These 3972 genes were further analyzed using hierarchical clustering analysis, resulting in 20 clusters. Four clusters among 20 showed clearly up-regulated expression patterns (cluster 8 and cluster 10) or clearly down-regulated expression patterns (cluster 12 and cluster 14) by baicalin treatment for over-all differentiation period. The cluster 8 and cluster 10 included many genes which enhance cell proliferation or inhibit adipogenesis. On the other hand, the cluster 12 and cluster 14 included many genes which are related with proliferation inhibition, cell cycle arrest, cell growth suppression or adipogenesis induction. In conclusion, these data provide detailed information on the molecular mechanism of baicalin-induced inhibition of adipogenesis.

Genotype and clinical features of Korean patients with methylmalonic aciduria and propionic aciduria (한국인 메틸말로닌산뇨증 및 프로피온산뇨증의 유전자형과 임상 양상)

  • Lee, Eun Hye;Ko, Jung Min;Kim, Jae-Min;Yoo, Han-Wook
    • Clinical and Experimental Pediatrics
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    • v.51 no.9
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    • pp.964-970
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    • 2008
  • Purpose : Methylmalonic aciduria (MMA) and propionic aciduria (PA) are inborn errors in the catabolism of branched-chain amino acids. The study was undertaken to investigate the genotypes and clinical features of Korean patients with MMA and PA. Methods : This study examined 12 patients with MMA and eight with PA. We analyzed various clinical features, laboratory findings, treatments, and neuro-developmental outcomes. Diagnoses were based on the presence of characteristic compounds detected by amino acid analysis in serum and organic acid analysis in urine. Mutation analysis was performed in the genes of MUT, MMAA, MMAB, and MMACHC for MMA and PCCA and PCCB for PA. Results : Among the 20 patients, six patients were diagnosed before one month of age and nine patients were diagnosed after the newborn period. Five patients were diagnosed via a neonatal screening test. Patients with early-onset forms had more severe illness at presentation and generally poor outcomes. A favorable outcome was obtained in 55% patients; most of them were of a late-onset type or diagnosed by neonatal mass screening test without symptoms. Genotypes were confirmed in all patients with MMA. We detected 11 different mutations by MUT gene analysis in 10 patients, and three different mutations in MMACHC genes in two patients. PCCA and PCCB gene mutations were identified in 14 of the 16 alleles, in eight patients with PA. Conclusion : Organic aciduria is a fatal disease; however, better outcomes are expected whenever early diagnosis and prompt management are made possible. Mutation analysis is useful for confirming diagnoses and planning management strategies.

Comparison of Volatile Organic Compound and Volatile Fatty Acid Concentration in Feces and Urine of Finishing Pigs (초지환원용 비육돈의 분과 뇨에 있어서 휘발성유기물과 휘발성지방산 농도 비교)

  • Cho, Sung Back;Hwang, Ok Hwa;Yang, Seung Hak;Kwag, Jeong Hoon;Choi, Dong Yun;Yang, Sung Bong;Kim, Doo Hwan;Park, Sung Kwon
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.34 no.2
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    • pp.120-124
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    • 2014
  • This study was performed to compare the level of odorous compounds in feces and urine of finishing pigs. Feces and urine from 16 finishing pigs were separately collected for 28-d. Concentrations of volatile organic compound (VOC; phenols and indoles) and volatile fatty acid (VFA; SCFA and BCFA) were measured in feces and urine. Amount of phenols and p-cresol was higher (P<0.05) in urine than in feces. Urinal levels of phenols and p-cresol were 257.8 ppm and 250.9 ppm, and those of fecal phenols and p-cresol were 0.50 ppm and 0.05 ppm, respectively. There was no difference in concentration of indoles from feces (1.0 ppm) and urine (1.8 ppm). Short chain fatty acid (SCFA) level in urine was higher (P<0.05) than in feces showing 4,547 ppm and 863 ppm, respectively. Proportion of acetic acid to total SCFA was higher in urine (94%) than in feces (66%). However, level of branched fatty acid (BCFA) was greater in feces (118 ppm) compare to that of urine (87 ppm). Odorous compounds analyzed in the current study, phenols and SCFA, were contained more in urine than in feces. Greater amount of VFA is typically found in feces than in urine since it is generated in the large intestine. However, urine contained more VFA than feces in the current study. Therefore, it will be necessary to exploit odor reducing techniques especially for pig urine as grassland fertilizer.

Long-term Clinical Consequences in Patients with Urea Cycle Disorders in Korea: A Single-center Experience (요소회로대사 질환 환자들의 장기적인 임상 경과에 대한 단일 기관 경험)

  • Lee, Jun;Kim, Min-ji;Yoo, Sukdong;Yoon, Ju Young;Kim, Yoo-Mi;Cheon, Chong Kun
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.21 no.1
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    • pp.15-21
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    • 2021
  • Purpose: Urea cycle disorder (UCD) is an inherited inborn error of metabolism, acting on each step of urea cycle that cause various phenotypes. The purpose of the study was to investigate the long-term clinical consequences in different groups of UCD to characterize it. Methods: Twenty-two patients with UCD genetically confirmed were enrolled at Pusan National University Children's hospital and reviewed clinical features, biochemical and genetic features retrospectively. Results: UCD diagnosed in the present study included ornithine transcarbamylase deficiency (OTCD) (n=10, 45.5%), argininosuccinate synthase 1 deficiency (ASSD) (n=6, 27.3%), carbamoyl-phosphate synthetase 1 deficiency (CPS1D) (n=3, 13.6%), hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHHS) (n=2, 9.1%), and arginase-1 deficiency (ARG1D) (n=1, 4.5%). The age at the diagnosis was 32.7±66.2 months old (range 0.1 to 228.0 months). Eight (36.4%) patients with UCD displayed short stature. Neurologic sequelae were observed in eleven (50%) patients with UCD. Molecular analysis identified 37 different mutation types (14 missense, 6 nonsense, 6 deletion, 6 splicing, 3 delins, 1 insertion, and 1 duplication) including 14 novel variants. Progressive growth impairment and poor neurological outcomes were associated with plasma isoleucine and leucine concentrations, respectively. Conclusion: Although combinations of treatments such as nutritional restriction of proteins and use of alternative pathways for discarding excessive nitrogen are extensively employed, the prognosis of UCD remains unsatisfactory. Prospective clinical trials are necessary to evaluate whether supplementation with BCAAs might improve growth or neurological outcomes and decrease metabolic crisis episodes in patients with UCD.